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The gut microbiota and microbial metabolites influence the enteric nervous system and the central nervous system via the microbial–gut–brain axis. Increasing body of evidence suggests that disturbances in the metabolism of peripheral branched-chain amino acids (BCAAs) can contribute to the development of neurodegenerative diseases through neuroinflammatory signaling. Preliminary research has shown that longitudinal changes in serum amino acid levels in mouse models of Parkinson’s disease (PD) are negatively correlated with disease progression. Therefore, the aim of the present study was to determine the changes in serum levels of short-chain fatty acids (SCFAs) in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD after dietary BCAA supplementation. In our research, gas chromatography–mass spectrometry was used to detect serum SCFA concentrations. The data were then analyzed with principal component analysis and orthogonal partial least squares discriminant analysis. Finally, the correlations of serum SCFA levels with gut and motor function in MPTP-induced PD mice were explored. Propionic acid, acetic acid, butyric acid, and isobutyric acid concentrations were elevated in MPTP + H-BCAA mice compared with MPTP mice. Propionic acid concentration was increased the most, while the isovaleric acid concentration was decreased. Propionic acid concentration was positively correlated with fecal weight and water content and negatively correlated with the pole-climbing duration. In conclusion, these results not only suggest that propionic acid may be a potential biomarker for PD, but also indicate the possibility that PD may be treated by altering circulating levels of SCFA.

C17H8Cl2N2O2, triclinic, P1‾$\overline{1}$ (no. 2), a = 7.9032(2) Å, b = 9.0843(3) Å, c = 10.8051(2) Å, α = 85.2310(10)°, β = 85.0270(10)°, γ = 71.013(2)°, V = 729.54(3) Å3, Z = 2, Rgt (F) = 0.0417, wRref (F2) = 0.1051, T = 293(2) K.

The transmission performance of the recirculating ball steering is closely related to the tooth profile shape of the rocker shaft non-circular gear sector. Aiming at the problem of the mesh clearance required by different angles is different between steering gear and rack,a means is proposed to repair the rocker arm shaft by using the varying-modification-coefficient modification method. The varying-modification-coefficient modification method is compared with eccentric modification method and the meshing motion of two kinds of gear rack pairs is analyzed,the related parameters of the gear sector is calculated,and two kinds of NC machining methods are given. The processing simulation is carried out in MATLAB,and the tooth profile coordinates of the two types of modification methods are obtained. Taking into account the actual assembly for the fixed axis transmission,two kinds of rack and pinion gear transmission clearance are calculated. Finally,the driving force which is analyzed by using ADAMS shows that,the two kinds of modification methods can effectively reduce the transmission of meshing force.

The prevalence of obesity, defined as the body mass index (BMI) ≥ 30 kg/m2, has reached epidemic levels. Obesity is associated with an increased risk of various cancers, including gastrointestinal ones. Recent evidence has suggested that obesity disproportionately impacts males and females with cancer, resulting in varied transcriptional and metabolic dysregulation. This study aimed to elucidate the differences in the metabolic milieu of adenocarcinomas of the gastrointestinal (GI) tract both related and unrelated to sex in obesity. To demonstrate these obesity and sex-related effects, we utilized three primary data sources: serum metabolomics from obese and non-obese patients assessed via the Biocrates MxP Quant 500 mass spectrometry-based kit, the ORIEN tumor RNA-sequencing data for all adenocarcinoma cases to assess the impacts of obesity, and publicly available TCGA transcriptional analysis to assess GI cancers and sex-related differences in GI cancers specifically. We applied and integrated our unique transcriptional metabolic pipeline in combination with our metabolomics data to reveal how obesity and sex can dictate differential metabolism in patients. Differentially expressed genes (DEG) analysis of ORIEN obese adenocarcinoma as compared to normal-weight adenocarcinoma patients resulted in large-scale transcriptional reprogramming (4029 DEGs, adj. p < 0.05 and |logFC| > 0.58). Gene Set Enrichment and metabolic pipeline analysis showed genes enriched for pathways relating to immunity (inflammation, and CD40 signaling, among others) and metabolism. Specifically, we found alterations to steroid metabolism and tryptophan/kynurenine metabolism in obese patients, both of which are highly associated with disease severity and immune cell dysfunction. These findings were further confirmed using the TCGA colorectal adenocarcinoma (CRC) and esophageal adenocarcinoma (ESCA) data, which showed similar patterns of increased tryptophan catabolism for kynurenine production in obese patients. These patients further showed disparate alterations between males and females when comparing obese to non-obese patient populations. Alterations to immune and metabolic pathways were validated in six patients (two obese and four normal weight) via CD8+/CD4+ peripheral blood mononuclear cell RNA-sequencing and paired serum metabolomics, which showed differential kynurenine and lipid metabolism, which corresponded with altered T-cell transcriptome in obese populations. Overall, obesity is associated with differential transcriptional and metabolic programs in various disease sites. Further, these alterations, such as kynurenine and tryptophan metabolism, which impact both metabolism and immune phenotype, vary with sex and obesity together. This study warrants further in-depth investigation into obesity and sex-related alterations in cancers that may better define biomarkers of response to immunotherapy.

Background and aims: atrophic gastritis (AG) and dysplasia are precancerous lesions, with which early surveillance of disease progression is particularly important for patients. The present study aimed to explore potential alarming signals for atrophic gastritis progression towards dysplasia. Methods: clinical data for patients with AG in the Digestive Endoscopy Center of Guangzhou Nanfang Hospital between 2001 and 2011 were retrospectively reviewed. Survival analysis, dichotomous logistic regression analysis and rank correlation analysis were carried out. Results: in 234 patients with atrophic gastritis, after follow up of 0.5, 1, 2, 5 and 10 years, the occurrence rates of dysplasia were respectively 2.3, 4.4, 9.6, 19.3, and 42.4%. Patients with AG combined with antral ulcer or gastric angle ulcer, had a higher risk for dysplasia than patients with simple AG (OR = 2.427, 95%Cl 1.069 ~ 5.511, p = 0.034; OR = 2.961, 95%Cl 1.336 ~ 6.564, p = 0.008). The constituent ratios of moderate to severe dysplasia were respectively 8.6, 2.7 and 1.2% (p = 0.000) in three patient groups: AG combined with antral ulcer/gastric angle ulcer (n = 255), antral ulcer/gastric angle ulcer alone (n = 1,389), and AG alone (n = 3,106). The Spearman correlation coefficients between a) Hp infection; and b) atrophy, intestinal metaplasia and dysplasia were -0.114 (p = 0.078), -0.169 (p = 0.009) and 0.064 (p > 0.05), respectively. Conclusions: long follow-up interval and gastric ulcer may be alarming signals for the progression of AG to dysplasia. But in patients with atrophy, intestinal metaplasia or dysplasia, Hp infection may not be a risk factor for these lesions aggravated, further studies are required to confirm it.

The sense of taste is an important sentinel governing what should or should not be ingested by an animal, with high pH sensation playing a critical role in food selection. Here we explore the molecular identities of taste receptors detecting the basic pH of food using Drosophila melanogaster as a model. We identify a chloride channel named alkaliphile (Alka), which is both necessary and sufficient for aversive taste responses to basic food. Alka forms a high-pH-gated chloride channel and is specifically expressed in a subset of gustatory receptor neurons (GRNs). Optogenetic activation of alka-expressing GRNs is sufficient to suppress attractive feeding responses to sucrose. Conversely, inactivation of these GRNs causes severe impairments in the aversion to high pH. Altogether, our discovery of Alka as an alkaline taste receptor lays the groundwork for future research on alkaline taste sensation in other animals.