Prospective study of ALDH1A1 gene polymorphisms associated with antituberculosis drug-induced liver injury in western Chinese Han population.

Antituberculosis drug-induced liver injury (ATDILI) has received increasing attention globally, which may limit the effectiveness of antituberculosis (anti-TB) treatment. Many host genetic determinants of ATDILI have been identified recently. As little knowledge is currently available about the association between aldehyde dehydrogenase 1 family member A1 (ALDH1A1) polymorphisms and ATDILI, the association between their variants and the susceptibility to ATDILI was investigated. A total of 747 patients with TB treated by first-line anti-TB drugs were prospectively enrolled at West China Hospital. Genomic DNA was extracted from the peripheral blood sample of each patient and seven single-nucleotide polymorphisms (SNPs) of ALDH1A1 gene were screened and genotyped with a custom-designed 2×48-plex SNP Scan TM kit. The patients were followed up monthly to monitor the development of ATDILI. The C allele and the CA genotype of rs7852860 were significantly associated with an elevated risk for ATDILI (p = .006 and 0.005, respectively), which was consistent with the results in the dominant and additive models. No allele, genotype, or genetic model of the other six SNPs (rs3764435, rs348471, rs63319, rs610529, rs7027604, rs8187876) were found to be associated with susceptibility to ATDILI. The findings first demonstrate that rs7852860 variants in ALDH1A1 gene is associated with susceptibility to ATDILI in the Chinese Han population. Validation studies with larger sample sizes and other ethnic groups are needed to confirm the findings.

Titanium-defected undoped anatase TiO2 with p-type conductivity, room-temperature ferromagnetism, and remarkable photocatalytic performance.

Defects are critically important for metal oxides in chemical and physical applications. Compared with the often studied oxygen vacancies, engineering metal vacancies in n-type undoped metal oxides is still a great challenge, and the effect of metal vacancies on the physiochemical properties is seldom reported. Here, using anatase TiO2, the most important and widely studied semiconductor, we demonstrate that metal vacancies (VTi) can be introduced in undoped oxides easily, and the presence of VTi results in many novel physiochemical properties. Anatase Ti0.905O2 was synthesized using solvothermal treatment of tetrabutyl titanate in an ethanol-glycerol mixture and then thermal calcination. Experimental measurements and DFT calculations on cell lattice parameters show the unstoichiometry is caused by the presence of VTi rather than oxygen interstitials. The presence of VTi changes the charge density and valence band edge of TiO2, and an unreported strong EPR signal at g = 1.998 presents under room temperature. Contrary to normal n-type and nonferromagnetic TiO2, Ti-defected TiO2 shows inherent p-type conductivity with high charge mobility, and room-temperature ferromagnetism stronger than Co-doped TiO2 nanocrystalline. Moreover, Ti-defected TiO2 shows much better photocatalytic performance than normal TiO2 in H2 generation (4.4-fold) and organics degradation (7.0-fold for phenol), owing to the more efficient charge separation and transfer in bulk and at semiconductor/electrolyte interface. Metal-defected undoped oxides represent a unique material; this work demonstrates the possibility to fabricate such material in easy and reliable way and thus provides new opportunities for multifunctional materials in chemical and physical devices.

Study on the thermal behaviour of spontaneous combustion of open-pit minerals.

To study thermal behaviour during spontaneous combustion of an open-pit coal mine, mixed slag (coal, oil shale, and coal gangue) was taken as the research object. Laser thermal conductivity analyser and differential scanning calorimetry were used to test thermophysical parameters and heat release characteristics of the minerals. The parameters can be employed to calculate the apparent activation energy using the Arrhenius equation and evaluate the thermal behaviour of open-pit mixed slag. The results indicate that thermophysical parameters have stage characteristics. Thermal diffusivity and thermal conductivity of minerals, especially mixed slag, have a strong correlation with temperature. Heat flow of minerals exhibits five characteristic stages, and heat flow of the samples is consistent with the change in heating rate. During the heating process, thermal diffusivity and heat flow of the mixed slag are between those of a single mineral. Except for the mixed slag at 15 and 20 °C/min, the initial exothermic temperature of the other samples is mainly concentrated at 50-80 °C. Thermal energy release of the sample is mainly concentrated in the accelerated exothermic stage and rapid exothermic stage. Thermal energy release of mixed slag in rapid exothermic stage is always greater than that in accelerated exothermic stage, and the proportion of thermal energy release in these two stages exceeds 98 %. The apparent activation energy during the accelerated exothermic stage is lower, making it easier to release heat, and rapid exothermic stage is relatively high, which can readily lead to heat accumulation. Thermal analysis reveals that the thermal behaviour of mixed slag is significantly different from that of a single mineral. Its unique exothermic characteristics can provide a more accurate theoretical basis for the prevention and control of environmental pollution caused by slag spontaneous combustion.

Correlation between glycated hemoglobin A1c, urinary microalbumin, urinary creatinine, ß2 microglobulin, retinol binding protein and diabetic retinopathy.

BACKGROUND: Retinopathy is the most common microvascular disease of type 2 diabetes, and seriously threatens the life, health and quality of life of patients. It is worth noting that the development of diabetic retinopathy (DR) can be hidden, with few symptoms. Therefore, the preliminary screening of diabetic patients should identify DR as soon as possible, delay disease progression, and play a vital role in its diagnosis and treatment. AIM: To investigate the correlation between glycated hemoglobin A1c (HbA1c), urinary microalbumin (U-mALB), urinary creatinine (U-CR), mALB/U-CR ratio, ß2 microglobulin (ß2MG), retinol binding protein (RBP) and DR. METHODS: A total of 180 patients with type 2 diabetes mellitus attending the Second People's Hospital of Hefei from January 2022 to August 2022 were retrospectively enrolled by ophthalmologists. Based on whether they had combined retinopathy and its degree, 68 patients with diabetes mellitus without retinopathy (NDR) were assigned to the NDR group, 54 patients with non-proliferative DR (NPDR) to the NPDR group, and 58 patients with proliferative DR to the PDR group. General data, and HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR results were collected from the patients and compared among the groups. Pearson's correlation method was used to analyze the correlation between HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR indices, and multiple linear regression was applied to identify the risk factors for DR. Receiver operator characteristic (ROC) curves were also drawn. RESULTS: The differences in age, gender, systolic and diastolic blood pressure between the groups were not statistically significantly (P > 0.05), but the difference in disease duration was statistically significant (P < 0.05). The differences in fasting blood glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, and triglyceride between the groups were not statistically significant (P > 0.05). HbA1c in the PDR group was higher than that in the NPDR and NDR groups (P < 0.05). The levels of mALB, ß2MG, RBP, mALB/U-CR and U-CR in the PDR group were higher than those in the NPDR and NDR groups (P < 0.05). Multiple linear regression analysis showed that disease duration, HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR were risk factors for the development of DR. The ROC curve showed that the area under the curve (AUC) for the combination of indices (HbA1c + mALB + mALB/U-CR + U-CR + ß2MG + RBP) was 0.958, with a sensitivity of 94.83% and specificity of 96.72%, which was higher than the AUC for single index prediction (P < 0.05). CONCLUSION: HbA1c, mALB, mALB/U-CR, U-CR, ß2MG and RBP can reflect the development of DR and are risk factors affecting PDR, and the combination of these six indices has predictive value for PDR.

Correlation Analysis of the Change Law of Index Gas and Active Functional Groups in the Process of High-Temperature Spontaneous Combustion of Minerals in the Fushun West Mine.

The spontaneous combustion of underground minerals causes huge property losses and ecological damage. Coal and oil shale are co-associated minerals in the Fushun West Mine, and both have the ability to undergo oxidative spontaneous combustion. To study the effect of microstructure changes on the macroscopic gas product concentration during the mineral oxidation spontaneous combustion process in the Fushun West Mine, this study used a high-temperature temperature-programmed test to obtain the change trend of gas product concentration in different oxidation stages of minerals. Using Fourier transform infrared spectroscopy technology, the changes in active functional groups of surface molecules during the process of mineral oxidation and spontaneous combustion were identified. Finally, using the gray correlation degree, correlation analysis between the concentration of gas products and the concentration of active functional groups in different oxidation stages was carried out. The key reactive functional groups affecting mineral spontaneous combustion were identified. The essential reason for the change in the gas product was revealed.

Healthy Serum-Derived Exosomes Improve Neurological Outcomes and Protect Blood-Brain Barrier by Inhibiting Endothelial Cell Apoptosis and Reversing Autophagy-Mediated Tight Junction Protein Reduction in Rat Stroke Model.

Blood-brain barrier (BBB) dysfunction causing edema and hemorrhagic transformation is one of the pathophysiological characteristics of stroke. Protection of BBB integrity has shown great potential in improving stroke outcome. Here, we assessed the efficacy of exosomes extracted from healthy rat serum in protection against ischemic stroke in vivo and in vitro. Exosomes were isolated by gradient centrifugation and ultracentrifugation and exosomes were characterized by transmission electron microscopy (TEM) and nanoparticle tracking video microscope. Exosomes were applied to middle cerebral artery occlusion (MCAO) rats or brain microvascular endothelial cell line (bEnd.3) subjected to oxygen-glucose deprivation (OGD) injury. Serum-derived exosomes were injected intravenously into adult male rats 2 h after transient MCAO. Infarct volume and gross cognitive function were assessed 24 h after reperfusion. Poststroke rats treated with serum-derived exosomes exhibited significantly reduced infarct volumes and enhanced neurological function. Apoptosis was assessed via terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining and the expression of B-cell lymphoma-2 (Bcl-2), Bax, and cleaved caspase-3 24 h after injury. Our data showed that serum exosomes treatment strikingly decreased TUNEL+ cells in the striatum, enhanced the ratio of Bcl-2 to Bax, and inhibited cleaved caspase-3 production in MCAO rats and OGD/reoxygenation insulted bEnd.3 cells. Under the consistent treatment, the expression of microtubule-associated protein 1 light chain 3B-II (LC3B-II), LC3B-I, and Sequestosome-1 (SQSTM1)/p62 was detected by Western blotting. Autolysosomes were observed via TEM. We found that serum exosomes reversed the ratio of LC3B-II to LC3B-I, prevented SQSTM1/p62 degradation, autolysosome formation, and autophagic flux. Together, these results indicated that exosomes isolated from healthy serum provided neuroprotection against experimental stroke partially via inhibition of endothelial cell apoptosis and autophagy-mediated BBB breakdown. Intravenous serum-derived exosome treatment may, therefore, provide a novel clinical therapeutic strategy for ischemic stroke.

Effects of repetitive transcranial magnetic stimulation on children with low-function autism.

BACKGROUND: Autism spectrum disorder (ASD) is a very complex neurodevelopmental disorder, characterized by social difficulties and stereotypical or repetitive behavior. Some previous studies using low-frequency repetitive transcranial magnetic stimulation (rTMS) have proven of benefit in ASD children. METHODS: In this study, 32 children (26 males and six females) with low-function autism were enrolled, 16 children (three females and 13 males; mean ± SD age: 7.8 ± 2.1 years) received rTMS treatment twice every week, while the remaining 16 children (three females and 13 males; mean ± SD age: 7.2 ± 1.6 years) served as waitlist group. This study investigated the effects of rTMS on brain activity and behavioral response in the autistic children. RESULTS: Peak alpha frequency (PAF) is an electroencephalographic measure of cognitive preparedness and might be a neural marker of cognitive function for the autism. Coherence is one way to assess the brain functional connectivity of ASD children, which has proven abnormal in previous studies. The results showed significant increases in the PAF at the frontal region, the left temporal region, the right temporal region and the occipital region and a significant increase of alpha coherence between the central region and the right temporal region. Autism Behavior Checklist (ABC) scores were also compared before and after receiving rTMS with positive effects shown on behavior. CONCLUSION: These findings supported our hypothesis by demonstration of positive effects of combined rTMS neurotherapy in active treatment group as compared to the waitlist group, as the rTMS group showed significant improvements in behavioral and functional outcomes as compared to the waitlist group.

Casein glycomacropeptide-derived peptide IPPKKNQDKTE ameliorates high glucose-induced insulin resistance in HepG2 cells via activation of AMPK signaling.

SCOPE: Recently, casein glycomacropeptide (GMP)-derived peptide was found to possess potent antioxidant and anti-inflammatory activities. In this study, the improvement effects and underlying molecular mechanisms of GMP-derived peptide on hepatic insulin resistance were investigated. METHODS AND RESULTS: The peptide IPPKKNQDKTE was identified from GMP papain hydrolysates by LC-ESI-MS/MS. Effects of IPPKKNQDKTE on glucose metabolism and expression levels of the hepatic insulin signaling proteins in high glucose-induced insulin-resistant HepG2 cells were evaluated. Results showed that IPPKKNQDKTE dose-dependently increased glucose uptake and intracellular glycogen in insulin-resistant HepG2 cells without affecting cell viability. IPPKKNQDKTE increased the phosphorylation of Akt and GSK3ß and decreased the expression levels of p-GS, G6Pase and PEPCK. These IPPKKNQDKTE-mediated protection effects were reversed by PI3K/Akt inhibitor LY294002, showing the mediatory role of PI3K/Akt. Moreover, treatment with IPPKKNQDKTE reduced IRS-1 Ser307 phosphorylation and increased phosphorylation of AMPK. Knockdown AMPK using siRNA in HepG2 cells increased Ser307 phosphorylation of IRS-1 and reduced Akt phosphorylation in IPPKKNQDKTE-treated insulin-resistant cells. CONCLUSION: IPPKKNQDKTE prevents high glucose-induced insulin resistance in HepG2 cells by modulating the IRS-1/PI3K/Akt signaling pathway through AMPK activation, indicating that IPPKKNQDKTE plays a potential role in the prevention and treatment of hepatic insulin resistance and type 2 diabetes.

Ca(2+) -induced binding of anticoagulation factor II from the venom of Agkistrodon acutus with factor IX.

Anticoagulation factor II (ACF II), a coagulation factor X- binding protein from the venom of Agkistrodon acutus has both anticoagulant and hypotensive activities. Previous studies show that ACF II binds specifically with activated factor X (FXa) in a Ca(2+) -dependent manner and inhibits intrinsic coagulation pathway. In this study, the inhibition of extrinsic coagulation pathway by ACF II was measured in vivo by prothrombin time assay and the binding of ACF II to factor IX (FIX) was investigated by native polyacrylamide gel electrophoresis and surface plasmon resonance (SPR). The results indicate that ACF II also inhibits extrinsic coagulation pathway, but does not inhibit thrombin activity. ACF II also binds with FIX with high binding affinity in a Ca(2+) -dependent manner and their maximal binding occurs at about 0.1 mM Ca(2+) . ACF II has similar binding affinity to FIX and FX as determined by SPR. Ca(2+) has a slight effect on the secondary structure of FIX as determined by circular dichroism spectroscopy. Ca(2+) ions are required to maintain in vivo function of FIX Gla domain for its recognition of ACF II. However, Ca(2+) at high concentrations (>0.1 mM) inhibits the binding of ACF II to FIX. Ca(2+) functions as a switch for the binding between ACF II and FIX. ACF II extends activated partial thromboplastin time more strongly than prothrombin time, suggesting that the binding of ACF II with FIX may play a dominant role in the anticoagulation of ACF II in vivo.