High paternal homocysteine causes ventricular septal defects in mouse offspring.

Maternal hyperhomocysteinemia is widely considered as an independent risk of congenital heart disease (CHD). However, whether high paternal homocysteine causes CHD remains unknown. Here, we showed that increased homocysteine levels of male mice caused decreased sperm count, sperm motility defect and ventricular septal defect of the offspring. Moreover, high levels of paternal homocysteine decrease sperm DNMT3A/3B, accompanied with changes in DNA methylation levels in the promoter regions of CHD-related genes. Folic acid supplement could decrease the occurrence of VSD in high homocysteine male mice. This study reveals that increased paternal homocysteine level increases VSD risk in the offspring, indicating that decreasing paternal homocysteine may be an intervening target of CHD.

Proteome profiling of early gestational plasma reveals novel biomarkers of congenital heart disease.

Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid-gestational age-the sensitivity of which varies among centers and practitioners. An objective method for early diagnosis is needed. Here, we conducted a case-control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis.

Refinement of nanoporous copper by dealloying the Al-Cu alloy in NaOH solution containing sodium dodecyl sulfate.

This work reports the refinement of nanoporous copper (NPC) ligaments by introducing the sodium dodecyl sulfate (SDS) surfactant in the dealloying process. The Al80Cu20 (at%) alloy precursor is chemically dealloyed in a mixed solution of NaOH and SDS surfactant, producing NPC with a hierarchical microstructure. Micron-scaled skeletons that build up higher level networks consist of geometrically similar nano-scaled bi-continuous ligament-pore networks at the lower level. It has been found that the size of the ligaments in the lower level networks reduces from ∼32 nm to ∼24 nm with increasing SDS concentration to 1 mM. Further increasing the SDS concentration to 5 mM only leads to a slight ligament size decrease to ∼21 nm. Remarkably, nano-sized cones are formed on the lower level network surface in the dealloying solution containing 1 mM SDS, and the cone number greatly rises when the SDS concentration increases to 5 mM. The surface diffusivity of Cu adatoms is evaluated based on the experimental data, and the refinement of the ligament as well as the formation of cones are associated with the decreased surface diffusivity and the retarded Cu adatom motions with the addition of SDS. Quantum chemical calculations and molecular dynamics simulations are performed to model the adsorption behavior of SDS. It has been found that the SDS-substrate interaction increases with the number of SDS molecules before SDS reaches saturation.

Homocysteine inhibits pro-insulin receptor cleavage and causes insulin resistance via protein cysteine-homocysteinylation.

Elevation in homocysteine (Hcy) level is associated with insulin resistance; however, the causality between them and the underlying mechanism remain elusive. Here, we show that Hcy induces insulin resistance and causes diabetic phenotypes by protein cysteine-homocysteinylation (C-Hcy) of the pro-insulin receptor (pro-IR). Mechanistically, Hcy reacts and modifies cysteine-825 of pro-IR in the endoplasmic reticulum (ER) and abrogates the formation of the original disulfide bond. C-Hcy impairs the interaction between pro-IR and the Furin protease in the Golgi apparatus, thereby hindering the cleavage of pro-IR. In mice, an increase in Hcy level decreases the mature IR level in various tissues, thereby inducing insulin resistance and the type 2 diabetes phenotype. Furthermore, inhibition of C-Hcy in vivo and in vitro by overexpressing protein disulfide isomerase rescues the Hcy-induced phenotypes. In conclusion, C-Hcy in the ER can serve as a potential pharmacological target for developing drugs to prevent insulin resistance and increase insulin sensitivity.

A newly developed molecularly imprinted polymer on the surface of TiO2 for selective extraction of triazine herbicides residues in maize, water, and soil.

A new surface molecularly imprinted polymer (MIP) based on nano-TiO2 was developed using propazine (Pro) as a template molecule, ethyleneglycol dimethacrylate (EGDMA) as a crosslinker, methacrylic acid (MAA) as a functional monomer, and 2,2'-azobis (isobutyronitrile) (AIBN) as an initiator. Structures of the newly synthesized surface MIPs were characterized by Fourier transmission infrared spectrometry (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). The MIP had a good adsorption capacity and high recognition selectivity to propazine. Meanwhile, it exhibited a cross-selectivity for simazine (Sim) and atrazine (Atr). The MIPs were used as a solid phase extraction (SPE) material. Concomitant extraction, purification, and determination of three pesticides (Pro, Sim, and Atr) residues in water, soil, and maize plant and grain samples were performed by MIP-SPE coupled with high performance liquid chromatography (HPLC). The highly selective separation and enrichment of Pro, Atr, and Sim from the complex environmental media can be achieved. Thus, the newly developed technique provides an analytical platform to quantify the trace amount of Pro, Sim, and Atr residues in multi environmental media and food source.

Preparation of Dufulin imprinted polymer on surface of silica gel and its application as solid-phase extraction sorbent.

A new molecularly imprinted polymer (MIP) based on silica-gel surface was developed using Dufulin (Duf) as a template, methacrylic acid (MAA) as a functional monomer, ethyleneglycol dimethacrylate (EGDMA) as a crosslinker, and azodiisobutyronitrile (AIBN) as an initiator. The synthetic samples were characterized by the techniques of Fourier transmission infrared spectrometry (FT-IR) and scanning electron microscope (SEM). Batch experiments were performed to evaluate adsorption isotherms, adsorption kinetics and selective recognition of the MIP. Binding experiments demonstrated that the MIP had a good adsorption capacity, fast mass transfer rate and high recognition selectivity to Dufulin. When the MIP was used as a solid-phase extraction (SPE) material, the recoveries of Dufulin for spiked water, soil and wheat samples were 88.98-102.16%, 85.31-99.57% and 87.84-100.19%, along with LOD of 0.0008 mg L(-1), 0.010 mg kg(-1) and 0.023 mg kg(-1), respectively. Compared with direct determination of HPLC without MIP-SPE, the highly selective separation and enrichment of Dufulin from the complex environmental media can be achieved by the newly developed molecular imprinting at the surface of silica gel.

Development of a molecularly imprinted polymer for prometryne clean-up in the environment.

Molecularly imprinted polymers (MIPs) are prepared on the surface of modified silica gel using prometryne as a template, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as a crosslinker, and 2,2-azobisisobutyronitrile as an initiator. The structure of the MIPs was characterized using SEM and FTIR spectroscopy. The selectivity of the MIPs for the template molecule prometryne was proven by adsorption experiments. Highly selective SPE cartridges of MIP particles were developed and an optimized prometryne procedure was developed for the enrichment and clean-up of prometryne residues in water, soil, and wheat samples. The concentrations of prometryne in the samples were analyzed by HPLC. The average recoveries of prometryne spiked for water at 0.05∼0.8 mg/L were 101.47-106.65% and the RSD was 2.63-4.71%. The average recoveries of prometryne spiked for soil at 0.05∼0.8 mg/L were 87.34-94.91% with the RSD being 2.77-8.41%. The average recoveries of prometryne spiked for wheat plant at 0.2∼2.0 mg/kg were 91.04-97.76% with the RSD being 6.53-10.69%. The method developed here can be regenerated and repeatedly used more than two dozen times.