Gut microbial co-metabolite 2-methylbutyrylcarnitine exacerbates thrombosis via binding to and activating integrin α2ß1.

Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2ß1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2ß1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.

Male-Biased Gut Microbiome and Metabolites Aggravate Colorectal Cancer Development.

Men demonstrate higher incidence and mortality rates of colorectal cancer (CRC) than women. This study aims to explain the potential causes of such sexual dimorphism in CRC from the perspective of sex-biased gut microbiota and metabolites. The results show that sexual dimorphism in colorectal tumorigenesis is observed in both ApcMin/ + mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice with male mice have significantly larger and more tumors, accompanied by more impaired gut barrier function. Moreover, pseudo-germ mice receiving fecal samples from male mice or patients show more severe intestinal barrier damage and higher level of inflammation. A significant change in gut microbiota composition is found with increased pathogenic bacteria Akkermansia muciniphila and deplets probiotic Parabacteroides goldsteinii in both male mice and pseudo-germ mice receiving fecal sample from male mice. Sex-biased gut metabolites in pseudo-germ mice receiving fecal sample from CRC patients or CRC mice contribute to sex dimorphism in CRC tumorigenesis through glycerophospholipids metabolism pathway. Sexual dimorphism in tumorigenesis of CRC mouse models. In conclusion, the sex-biased gut microbiome and metabolites contribute to sexual dimorphism in CRC. Modulating sex-biased gut microbiota and metabolites could be a potential sex-targeting therapeutic strategy of CRC.

Plasma metabolic signatures for intracranial aneurysm and its rupture identified by pseudotargeted metabolomics.

BACKGROUND AND AIMS: The vital metabolic signatures for IA risk stratification and its potential biological underpinnings remain elusive. Our study aimed to develop an early diagnosis model and rupture classification model by analyzing plasma metabolic profiles of IA patients. MATERIALS AND METHODS: Plasma samples from a cohort of 105 participants, including 75 IA patients in unruptured and ruptured status (UIA, RIA) and 30 control participants were collected for comprehensive metabolic evaluation using ultra-high-performance liquid chromatography-mass spectrometry-based pseudotargeted metabolomics method. Furthermore, an integrated machine learning strategy based on LASSO, random forest and logistic regression were used for feature selection and model construction. RESULTS: The metabolic profiling disturbed significantly in UIA and RIA patients. Notably, adenosine content was significantly downregulated in UIA, and various glycine-conjugated secondary bile acids were decreased in RIA patients. Enriched KEGG pathways included glutathione metabolism and bile acid metabolism. Two sets of biomarker panels were defined to discriminate IA and its rupture with the area under receiver operating characteristic curve of 0.843 and 0.929 on the validation sets, respectively. CONCLUSIONS: The present study could contribute to a better understanding of IA etiopathogenesis and facilitate discovery of new therapeutic targets. The metabolite panels may serve as potential non-invasive diagnostic and risk stratification tool for IA.

Bibliometric Review on the Volatile Organic Compounds in Meat.

Meat flavor is an important aspect of meat quality that also influences consumer demand, and is therefore very important for the meat industry. Volatile organic compounds (VOCs) contribute in large part to the flavor of meat, and while increasing numbers of articles are published on this topic, reviews of these articles are very scarce. Therefore, our aim was to perform a bibliometric analysis of the scientific publications on VOCs in meat over the period 2000-2020. We selected 611 scientific sources from the Scopus database related to VOCs in meat (seafood excluded). The bibliometric information retrieved included journals, authors, countries, institutions, keywords, and citations. From this analysis, we drew up a list of the most important journals, authors, countries, and institutions, and the trends in VOC research on meat. We conducted a social network analysis (SNA) to identify the collaborations among the many authors and countries, and a keyword analysis to generate a network map of the authors' keywords. We also determined which meat species were most frequently chosen as research subjects, traced the evolution of the various methods/instruments used, and explored the research tendencies. Finally, we point out the need for further research in defining meat quality, improving meat flavor, identifying adulterants, and certifying the authenticity of meat.

Spatio-Temporal Evolution and Driving Factors of Rural Settlements in Low Hilly Region-A Case Study of 17 Cities in Hubei Province, China.

With the rapid development of the social economy, factors of social and economic development in China's rural areas have been continuously reorganized, and the pattern and distribution of rural residential areas have undergone significant changes. In rural areas, there have been many peculiar phenomena of "reducing people but not reducing land in rural areas, which has caused tremendous pressure on land resource protection. We used geographic detectors and a geographically temporally weighted regression model (GTWR) to explore the rural settlements' evolution and driving mechanism in Hubei Province from 1990 to 2015. The results show that the kernel density of rural settlements decreased from 1.62 villages/km2 in 1990 to 1.60 villages/km2 in 2015. The scale of rural residential patches has obvious regional differentiation characteristics. From southeast to northwest, there is a wave-like distribution structure of "high-low-high-low-high", and the clustering characteristics of "cold and hot spots" are strengthened with time. Based on GTWR analysis, the total rural population, total power of agricultural machinery, and rural electricity consumption have promoted the expansion of rural settlements, with the regression coefficients 0.096, 0.484, and 0.878, respectively. Cultivated land, agricultural output value, and rural labor force have negative impacts on the expansion, the regression coefficients of the village were -0.584, -0.510, and -0.109, respectively.

Purebreeding with sexed semen and crossbreeding with semen from double-muscled sires to improve beef production from dairy herds: Live and slaughter performances of crossbred calves.

The use of sexed semen to produce purebred replacement heifers allows a large proportion of dairy cows to be mated to beef sires, and quantitative and qualitative improvements to be made to beef production from dairy herds. The major dairy and beef breeds are undergoing rapid genetic improvement as a result of more efficient selection methods, prompting a need to evaluate the meat production of crossbred beef × dairy cattle produced using current genetics. As part of a large project involving 125 commercial dairy farms, we evaluated the combined use of purebreeding with sexed semen and crossbreeding with semen from beef sires, particularly double-muscled breeds. A survey of 1,530 crossbred calves revealed that, whereas purebred dairy calves are destined almost exclusively for veal production, beef × dairy crossbred calves are also destined for beef production after fattening on either the dairy farm of birth or by specialized fatteners. In veal production, compared with Belgian Blue-sired calves (taken as the reference), double-muscled INRA 95-sired calves had a lighter slaughter weight (303 vs. 346 kg), but a greater dressing percent (62.3 vs. 58.4%). Limousin (also known as Limousine)-sired calves had a smaller average daily gain (1.26 vs. 1.34 kg/d), and lighter slaughter (314 vs. 346 kg) and carcass weights (182 vs. 201 kg). Last, Simmental-sired calves had a similar growth rate, but lighter carcass weight (177 vs. 201 kg), smaller dressing percentage (55.3 vs. 58.4%), and smaller muscularity scores (3.25 vs. 3.72). In the case of young bulls and heifers fattened on the dairy farm of birth, Belgian Blue-, Piemontese (also known as Piedmontese)-, and Limousin-sired calves performed similarly; the only exception was that Piemontese-sired calves had a greater dressing percentage. Belgian Blue- and Limousin-sired calves performed similarly when fattened by specialized beef producers. In both veal and beef production, the effects of dam breed were less important than sire breed. Considering the entire project, we can conclude that the combined use of sexed semen for purebreeding and conventional beef semen for terminal crossbreeding improves meat production from dairy herds, especially when the sires are double-muscled beef breeds.

Rapid Profiling of the Volatilome of Cooked Meat by PTR-ToF-MS: Characterization of Chicken, Turkey, Pork, Veal and Beef Meat.

This study aimed to compare the volatile organic compound (VOC) profiles of cooked meat from different species. Four burgers were prepared and cooked from each of 100 meat samples obtained from 100 animals of five species/categories (chicken, turkey, pork, veal and beef) sourced from five supermarkets and five local butchers. Two burgers were cooked in a water bath and two were grilled. Direct proton-transfer-reaction time-of-flight mass-spectrometry (PTR-ToF-MS) analysis of the sample headspace yielded 129 mass peaks, 64 of which were tentatively identified. The results showed that turkey and chicken had the largest and the smallest total concentrations of all VOCs, respectively. Of the mammalian meats, veal and beef had greater total VOC concentrations than pork. The proportions of the amounts of all the individual VOCs differed significantly according to species. Additionally, 14 of 17 independent latent explanatory factors (LEFs) identified by multivariate analysis exhibited significant differences between meat species/categories, and therefore helped to characterize them. PTR-ToF-MS has been used for the first time for the rapid and non-invasive profiling of cooked meat of different species/categories. Knowledge of specific VOC profiles paves new avenues for research aimed at characterizing species through sensory description, at authenticating species or at identifying abnormalities or fraud.

Rapid Profiling of the Volatilome of Cooked Meat by PTR-ToF-MS: Underlying Latent Explanatory Factors.

Volatile organic compounds (VOCs) are important contributors to meat aroma and are variably correlated with each other. To study the sources of variation and the correlations among meat VOCs, meat cuts from five animal species/categories (chicken, turkey, pork, veal, and beef; two animals/species/retailer: 100 meat cuts) were obtained by 10 retailers. Each cut was processed into four burgers, two of which were grilled and two were cooked in a water bath (400 meat burgers). VOCs were detected by Proton-Transfer-Reaction Time-of-Flight Mass-Spectrometry (PTR-ToF-MS). From these, 129 peaks were selected, of which 72 were tentatively identified as relevant VOCs. Pearson correlations revealed a large number of positive and negative relationships among the VOCs. A multivariate statistical analysis revealed that 87% of the matrix covariance was explained by 17 independent Latent Explanatory Factors (LEFs), which have been described and characterized. LEFs identified may be valuable tools for reducing the dimensionality of results from VOC analyses and can be useful for better understanding and interpreting the variation in the meat aroma profile, although further study is required to characterize their sensory meaning.

The volatile organic compound profile of ripened cheese is influenced by crude protein shortage and conjugated linoleic acid supplementation in the cow's diet.

A shortage in crude protein (CP) and supplementation of conjugated linoleic acids (CLA) in the diets of dairy cows could improve the dairy industry's ecological footprint and the nutritional value of milk, but it is not known what effect such a strategy might have on the aroma profiles of dairy products. The aim of this work was to study the effects of reducing the dietary CP content (from 150 to 123 g/kg of dry matter), with or without a supply of rumen-protected CLA (7.9 g/d C18:2 cis-9,trans-11 and 7.7 g/d C18:2 trans-10,cis-12), on the volatile organic compound (VOC) profile of cheeses ripened for 3 mo. Twenty mid-lactation Holstein-Friesian cows were reared in 4 pens (5 to a pen), and fed 4 different experimental diets over 4 periods of 3 wk each, following a 4 × 4 Latin square design. Twice in each period, 10-L milk samples were taken from each group and used to produce 32 cheeses, which we then analyzed for VOC by solid-phase microextraction and gas chromatography-mass spectrometry. We detected 48 VOC belonging to 10 chemical classes (11 alcohols, 8 ketones, 8 esters, 7 acids, 4 aldehydes, 4 sulfurs, 2 lactones, 2 phenolic, 1 monoterpene, 1 hydrocarbon); these were expressed as concentrations in cheese (quantitative data) or as proportions of total VOC (qualitative data). The results of mixed model analysis showed that the majority of VOC families and individual VOC in ripened cheese were affected by the dietary treatments: CP shortage depressed the concentrations of volatile aldehydes and increased the proportions of some esters and limonene, whereas CLA increased the concentration of total VOC, particularly several acids and esters, and decreased the proportions of ketones and phenolic compounds. The interaction between dietary CP and CLA affected the proportions of alcohols and acids. We performed a factor analysis to extract 5 latent explanatory variables from the individual VOC, which represented 79% of total VOC variance for the quantitative data and 78% for the qualitative data. Addition of CLA decreased the first qualitative factor (the "base aroma" of cheese, explaining 44% of total variance), whereas CP reduction increased the second quantitative factor ("ethyl esters," 15% of total variance) and the third qualitative factor ("butan-," 9% of total variance). In summary, the VOC profile of ripened cheese was heavily influenced by CP content and CLA supplementation in the diets of dairy cows, but the effect on sensorial properties of cheese is also worth considering.