Quantitative Simulation of Enzymatic Breakdown of Alcohol in Human Metabolism.

The breakdown of ethanol, the active chemical in alcohol, is tightly regulated by the body, yet alcohol intoxication occurs in thousands of Americans annually. Many factors contribute to the concentration of ethanol in the bloodstream and the tolerance an individual has, including body size, previous drinking experience, and liver functionality. We propose a model that estimates both the blood alcohol concentration and the concentration of acetaldehyde (the toxic intermediate during catabolism) in the liver over time to quantify organ damage for an average person. From the current literature, we derived ordinary differential equations that govern the absorption of ethanol in the body and extended it with the metabolic enzyme mechanisms. We also altered the parameters of our system in order to show the effects of Asian flush, which impairs the body's processing of acetaldehyde. We demonstrated the accumulation of acetaldehyde in Asian flush patients was about 660 times higher compared to those without the disease.Clinical relevance-With further improvements and personalization, our model would be able to quantitatively describe the effects of alcohol consumption without having volunteers go through repetitive trials with extensive exposure to alcohol. Liver damage can also be estimated with the acetaldehyde buildup predicted by the model.

Altered oral microbiota and immune dysfunction in Chinese elderly patients with schizophrenia: a cross-sectional study.

Schizophrenia (SZ) is a complex psychiatric neurodevelopmental disorder with uncertain etiology and pathogenesis. Increasing evidence has recognized the key role of the gut microbiota in SZ. However, few studies have investigated the potential link between oral microbiota and SZ. We studied the tongue coating microbiota and inflammatory profiles of 118 elderly SZ patients and 97 age-matched healthy controls using Illumina MiSeq sequencing and multiplex immunoassays, respectively. Reduced α-diversity, along with a significant difference in ß-diversity, were observed in patients with SZ. We have identified SZ-associated oral dysbiosis, characterized by increased Streptococcus and Fusobacterium, as well as decreased Prevotella and Veillonella. These differential genera could potentially serve as biomarkers for SZ, either alone or in combination. Additionally, an elevated Streptococcus/Prevotella ratio could indicate oral dysbiosis. These differential genera formed two distinct clusters: Streptococcus-dominated and Prevotella-dominated, which exhibited different correlations with the altered immunological profiles. Furthermore, we also observed disruptions in the inferred microbiota functions in SZ-associated microbiota, particularly in lipid and amino acid metabolism. Our study provides novel insights into the characteristics of tongue coating microbiota and its associations with immunological disturbances in elderly SZ patients, which offer new targets for the diagnosis and treatment of SZ in the elderly.

Iodometric spectrophotometric determination of peroxydisulfate in hydroxylamine-involved AOPs: 15 min or 15 s for oxidative coloration?

In this study, iodometric spectrophotometry, the most-used method for detecting peroxydisulfate (PDS), was modified by increasing the concentration of potassium iodide (KI) for realizing the immediate PDS determination and avoiding the interference of hydroxylamine. Kinetic studies showed that the reaction between PDS and I- to generate the yellow-colored I3- followed the kinetic equation as [Formula: see text] . Detection time of the iodometric spectrophotometry was shortened from 15 min to 15 s when KI concentration was increased from 0.6 M to 4.8 M. Different with the previous iodometric spectrophotometry, the modified method using 4.8 M KI as the indicator was well tolerable to the interference of hydroxylamine at acidic pH conditions. The calibration curve of the modified method showed a well linear relationship (R2 = 0.999) between the absorbance of I3- at 352 nm and PDS concentration in the range of 0-80 µM. The modified method was highly sensitive with the absorptivity of 2.5 × 104 M-1 cm-1 and the limit of detection of 0.11 µM. Moreover, the modified method was successfully applied for monitoring the change of PDS concentration during the degradation of diclofenac with four different PDS-based AOPs, the calculated reaction stoichiometric efficiency (RSE(%)=DiclofenacdegradedPDSconsumed×100%) followed the order as heat/PDS system > hydroxylamine/Fe2+/PDS system > hydroxylamine/Cu2+/PDS system > Fe2+/PDS system.

Cu(II)-enhanced degradation of acid orange 7 by Fe(II)-activated persulfate with hydroxylamine over a wide pH range.

The activation of persulfate by Fe(II) coupled with hydroxylamine (the HA/Fe(II)/PS system) was highly effective for the degradation of refractory organic contaminants under acidic pH conditions. However, owing to the precipitation of ferric hydroxide and/or the slow reduction from Fe(III) to Fe(II), the HA/Fe(II)/PS system was invalid under neutral and alkaline pH conditions. In this study, it was observed that the degradation of acid orange 7 (AO7) was strongly enhanced over the wide pH range of 2-9 when trace Cu(II) (0.5-5 µM) was spiked into the HA/Fe(II)/PS system. It was evident that Cu(I) was generated via the reduction of Cu(II) by HA in the bimetallic system at both pH 3 and pH 8, and the steady concentration of Fe(II) in the bimetallic system was much higher than that in the HA/Fe(II)/PS system due to the rapid reaction between Fe(III) and Cu(I). Quenching experiments using tert-butyl alcohol, methanol and sodium bromide as the scavengers and electron spin resonance experiments confirmed that the primary reactive species responsible for AO7 degradation were sulfate radical at both pH 3 and pH 8, rather than hydroxyl radical and Cu(III). Nevertheless, sulfate radical was mainly produced by Fe(II)-activated PS at pH 3, while both Cu(I) and Fe(II) made important contributions to the generation of sulfate radical at pH 8. The bimetallic system was also highly effective in degrading other organic contaminants, such as phenol, diclofenac, reactive red 2 and orange G. This study might provide a promising idea based on Fe(II)-activated PS for degrading organic contaminants over a wide pH range.

Linking the low-density lipoprotein receptor-binding segment enables the therapeutic 5-YHEDA peptide to cross the blood-brain barrier and scavenge excess iron and radicals in the brain of senescent mice.

INTRODUCTION: Iron accumulates in the brain during aging, which catalyzes radical formation, causing neuronal impairment, and is thus considered a pathogenic factor in Alzheimer's disease (AD). To scavenge excess iron-catalyzed radicals and thereby protect the brain and decrease the incidence of AD, we synthesized a soluble pro-iron 5-YHEDA peptide. However, the blood-brain barrier (BBB) blocks large drug molecules from entering the brain and thus strongly reduces their therapeutic effects. However, alternative receptor- or transporter-mediated approaches are possible. METHODS: A low-density lipoprotein receptor (LDLR)-binding segment of Apolipoprotein B-100 was linked to the 5-YHEDA peptide (bs-5-YHEDA) and intracardially injected into senescent (SN) mice that displayed symptoms of cognitive impairment similar to those of people with AD. RESULTS: We successfully delivered 5-YHEDA across the BBB into the brains of the SN mice via vascular epithelium LDLR-mediated endocytosis. The data showed that excess brain iron and radical-induced neuronal necrosis were reduced after the bs-5-YHEDA treatment, together with cognitive amelioration in the SN mouse, and that the senescence-associated ferritin and transferrin increase, anemia and inflammation reversed without kidney or liver injury. DISCUSSION: bs-5-YHEDA may be a mild and safe iron remover that can cross the BBB and enter the brain to relieve excessive iron- and radical-induced cognitive disorders.