Ketogenic diet-induced bile acids protect against obesity through reduced calorie absorption.

The low-carbohydrate ketogenic diet (KD) has long been practiced for weight loss, but the underlying mechanisms remain elusive. Gut microbiota and metabolites have been suggested to mediate the metabolic changes caused by KD consumption, although the particular gut microbes or metabolites involved are unclear. Here, we show that KD consumption enhances serum levels of taurodeoxycholic acid (TDCA) and tauroursodeoxycholic acid (TUDCA) in mice to decrease body weight and fasting glucose levels. Mechanistically, KD feeding decreases the abundance of a bile salt hydrolase (BSH)-coding gut bacterium, Lactobacillus murinus ASF361. The reduction of L. murinus ASF361 or inhibition of BSH activity increases the circulating levels of TDCA and TUDCA, thereby reducing energy absorption by inhibiting intestinal carbonic anhydrase 1 expression, which leads to weight loss. TDCA and TUDCA treatments have been found to protect against obesity and its complications in multiple mouse models. Additionally, the associations among the abovementioned bile acids, microbial BSH and metabolic traits were consistently observed both in an observational study of healthy human participants (n = 416) and in a low-carbohydrate KD interventional study of participants who were either overweight or with obesity (n = 25). In summary, we uncover a unique host-gut microbiota metabolic interaction mechanism for KD consumption to decrease body weight and fasting glucose levels. Our findings support TDCA and TUDCA as two promising drug candidates for obesity and its complications in addition to a KD.

Diets, Gut Microbiota and Metabolites.

The gut microbiota refers to the gross collection of microorganisms, estimated trillions of them, which reside within the gut and play crucial roles in the absorption and digestion of dietary nutrients. In the past decades, the new generation 'omics' (metagenomics, transcriptomics, proteomics, and metabolomics) technologies made it possible to precisely identify microbiota and metabolites and describe their variability between individuals, populations and even different time points within the same subjects. With massive efforts made, it is now generally accepted that the gut microbiota is a dynamically changing population, whose composition is influenced by the hosts' health conditions and lifestyles. Diet is one of the major contributors to shaping the gut microbiota. The components in the diets vary in different countries, religions, and populations. Some special diets have been adopted by people for hundreds of years aiming for better health, while the underlying mechanisms remain largely unknown. Recent studies based on volunteers or diet-treated animals demonstrated that diets can greatly and rapidly change the gut microbiota. The unique pattern of the nutrients from the diets and their metabolites produced by the gut microbiota has been linked with the occurrence of diseases, including obesity, diabetes, nonalcoholic fatty liver disease, cardiovascular disease, neural diseases, and more. This review will summarize the recent progress and current understanding of the effects of different dietary patterns on the composition of gut microbiota, bacterial metabolites, and their effects on the host's metabolism.

BCAA insufficiency leads to premature ovarian insufficiency via ceramide-induced elevation of ROS.

Premature ovarian insufficiency (POI) is a disease featured by early menopause before 40 years of age, accompanied by an elevation of follicle-stimulating hormone. Though POI affects many aspects of women's health, its major causes remain unknown. Many clinical studies have shown that POI patients are generally underweight, indicating a potential correlation between POI and metabolic disorders. To understand the pathogenesis of POI, we performed metabolomics analysis on serum and identified branch-chain amino acid (BCAA) insufficiency-related metabolic disorders in two independent cohorts from two clinics. A low BCAA diet phenotypically reproduced the metabolic, endocrine, ovarian, and reproductive changes of POI in young C57BL/6J mice. A mechanism study revealed that the BCAA insufficiency-induced POI is associated with abnormal activation of the ceramide-reactive oxygen species (ROS) axis and consequent impairment of ovarian granulosa cell function. Significantly, the dietary supplement of BCAA prevented the development of ROS-induced POI in female mice. The results of this pathogenic study will lead to the development of specific therapies for POI.

Impact of Land-Use Change on Ecosystem Services in the Wuling Mountains from a Transport Development Perspective.

Transportation significantly affects regional land-use changes and ecosystem service functions. Exploring the correlations among transport development, spatial pattern of land-use changes, and ecosystem service changes are important for mitigating the deterioration of regional ecosystems due to human activities. In this study, 2000-2020 was selected as the study period to explore the effects of land-use changes on the ecosystem service value (ESV) in the Wuling Mountains. The results showed that: (1) the Wuling Mountains have experienced four stages of transport development and (2) transportation development has contributed to land-use change. The spatial pattern associated with construction land growth has evolved due to transport development. Garden land has gradually spread into the entire region with transport development. Policies from different periods have had more of an effect on ecological land and cropland. (3) During the study period, the ESV first increased and then declined. The periphery of the transportation axis formed a concentration zone of ESV cold spots. In contrast, ESV hot spots were more concentrated in areas along the Yangtze River. The results of this study provide guidance for land-use policy and spatial planning under the concept of green development.

Mass spectrometry-based ganglioside profiling provides potential insights into Alzheimer's disease development.

Gangliosides are a family of glycosphingolipids which are particularly enriched in the nervous system. They play crucial roles in neuroprotection and neurological diseases. Alzheimer's disease (AD) is a neurodegenerative disease with cognitive, judgment and memory dysfunction. In this study, a mass spectrometry-based data-dependent acquisition method assisted with fragmentation characteristics screening by computer algorithm was developed for qualitative and quantitative analysis of gangliosides at low concentration. The developed method was applied to obtain detailed ganglioside species content in hippocampus of model mice (APPswe/PS1dE9 transgenic mice) with AD at 3- to 8-month-old. Up-regulated acetylated and N-acetylgalactosaminylated ganglioside species, and the down-regulated major gangliosides were observed with the development of AD from early to late stage. We speculated that deterioration of AD may be related to the acetylation/N-acetylgalactosaminylation transformation of complex gangliosides due to the inhibition of GD3 synthase activity. Moreover, the ganglioside species di-O-Ac-GT1a (d36:1), O-Ac-GD1b (d36:1) and O-Ac-GD1b (d36:0) were considered as the time-coursed biomarkers, and O-Ac-GT1a (d36:2) could be a candidate for early diagnosis of AD.

A fully integrated sample preparation strategy for highly sensitive intact glycoproteomics.

A fully integrated sample preparation technology, termed Intact GlycoSISPROT, was developed for the highly sensitive analysis of site-specific glycopeptides. Through integrating all glycoproteomic sample preparation steps into a single spintip, Intact GlycoSISPROT provided a tool for site-specific glycosylation analysis with low micrograms to even nanograms of protein sample.

Characterization and Manipulation of Carbon Precursor Species during Plasma Enhanced Chemical Vapor Deposition of Graphene.

To develop a synthesis technique providing enhanced control of graphene film quality and uniformity, a systematic characterization and manipulation of hydrocarbon precursors generated during plasma enhanced chemical vapor deposition of graphene is presented. Remote ionization of acetylene is observed to generate a variety of neutral and ionized hydrocarbon precursors, while in situ manipulation of the size and reactivity of carbon species permitted to interact with the growth catalyst enables control of the resultant graphene morphology. Selective screening of high energy hydrocarbon ions coupled with a multistage bias growth regime results in the production of 90% few-to-monolayer graphene on 50 nm Ni/Cu alloy catalysts at 500 °C. Additionally, synthesis with low power secondary ionization processes is performed and reveals further control during the growth, enabling a 50% reduction in average defect densities throughout the film. Mass spectrometry and UV-Vis spectroscopy monitoring of the reaction environment in conjunction with Raman characterization of the synthesized graphene films facilitates correlation of the carbon species permitted to reach the catalyst surface to the ultimate quality, layer number, and uniformity of the graphene film. These findings reveal a robust technique to control graphene synthesis pathways during plasma enhanced chemical vapor deposition.

Cavin1 Deficiency Causes Disorder of Hepatic Glycogen Metabolism and Neonatal Death by Impacting Fenestrations in Liver Sinusoidal Endothelial Cells.

It has been reported that Cavin1 deficiency causes lipodystrophy in both humans and mice by affecting lipid metabolism. The ablation of Cavin1 in rodents also causes a significant deviation from Mendelian ratio at weaning in a background-dependent manner, suggesting the presence of undiscovered functions of Cavin1. In the current study, the results show that Cavin1 deficiency causes neonatal death in C57BL/6J mice by dampening the storage and mobilization of glycogen in the liver, which leads to lethal neonatal hypoglycemia. Further investigation by electron microscopy reveals that Cavin1 deficiency impairs the fenestration in liver sinusoidal endothelial cells (LSECs) and impacts the permeability of endothelial barrier in the liver. Mechanistically, Cavin1 deficiency inhibits the RhoA-Rho-associated protein kinase 2-LIM domain kinase-Cofilin signaling pathway and suppresses the dynamics of the cytoskeleton, and eventually causes the reduction of fenestrae in LSECs. In addition, the defect of fenestration in LSECs caused by Cavin1 deficiency can be rescued by treatment with the F-actin depolymerization reagent latrunculin A. In summary, the current study reveals a novel function of Cavin1 on fenestrae formation in LSECs and liver glycogen metabolism, which provide an explanation for the neonatal death of Cavin1 null mice and a potential mechanism for metabolic disorders in patients with Cavin1 mutation.

Hypolipidemic effect of Fragarianilgerrensis Schlecht. medicine compound on hyperlipidemic rats.

BACKGROUND: Fragarianilgerrensis Schlecht. medicine compound (FN-MC) is a kind of Chinese herbs' compound consisted of Fragarianilgerrensis Schlecht. and Centella asiatica (L.) Urban. The study was to investigate the hypolipidemia effect of FN-MC in a hypolipidemic rat model. METHODS: Male SD rats were randomly divided into five groups: normal-fat diet (NFD) group, high-fat diet (HFD) group, FN-MC (2 g/Kg) group, FN-MC (4 g/Kg) group and simvastatin (PDC) group. After FN-MC treatment, body weight, food intake, serum and hepatic biochemistry parameters of rats were measured and the pathological changes of liver and its cells were observed by optical microscope and transmission electron microscopy. RESULTS: The results showed that FN-MC significantly decreased the levels of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), apolipoprotein B (ApoB) and hepatic malondialdehyde (MDA), while increased serum high-density lipoprotein (HDL-C), apolipoprotein A1 (ApoA1) and hepatic Superoxide Dismutase (SOD). FN-MC also improved the structure of liver and decreased the lipid drops in the cytoplasm significantly. In addition, FN-MC significantly decreased the weight gain and had no significant effects on food intake. CONCLUSIONS: The study suggested that FN-MC exhibited strong ability to improve the dyslipidemia and prevent hepatic fatty deposition in rats fed with high-fat diet. Meanwhile, FN-MC exerted anti-obesity and antioxidant properties. HIGHLIGHTS: Fragarianilgerrensis Schlecht. medicine compound possesses a hypolipidemic effect on hyperlipidemic rat model Fragarianilgerrensis Schlecht. medicine compound administration improves the antioxidant capacity of rats Fragarianilgerrensis Schlecht. medicine compound prevents hepatic fatty deposition.

Comparison of the incidence of patient-reported post-operative dysphagia between ACDF with a traditional anterior plate and artificial cervical disc replacement.

PURPOSE: Compared with anterior cervical discectomy and fusion (ACDF), cervical disc replacement (CDR) has provided satisfactory clinical results. The incidence of post-operative dysphagia between ACDF with a traditional anterior plate and CDR remains controversial. Considering the limited studies and knowledge in this area, a retrospective study focusing on post-operative dysphagia was conducted. METHODS: The Bazaz grading system was used to assess the severity of dysphagia at post-operative intervals including 1 week, 1 month, 3 months, 6 months, 12 months and 24 months respectively. The Chi-square test, Student t-test, Mann-Whitney U tests and Ordinal Logistic regression were used for data analysis when appropriate. Statistical significance was accepted at a probability value of <0.05. RESULTS: Two hundred and thirty-one patients in the CDR group and one hundred and fifty-eight patients in Plate group were included in this study. The total incidences of dysphagia in the CDR and plate group were 36.58% and 60.43% at one week, 29.27% and 38.85% at one month, 21.95% and 31.65% at three months, 6.83% and 17.99% at six months, 5.85% and 14.39% at 12 months, and 4.39% and 10.07% at the final follow-up respectively (All P<0.05, Mann-Whitney U test). Ordinal Logistic regression analysis showed that female patients, two-level surgery, C4/5 surgery, and anterior cervical plating were significant risk factors for post-operative dysphagia (all P<0.05). CONCLUSION: Comparing ACDF with a plate, CDR with a Prestige LP can significantly reduce both transient and persistent post-operative dysphagia. Female patients, two-level surgery, C4/5 surgery and anterior cervical plating were associated with a higher incidence of dysphagia. Future prospective, randomized, controlled studies are needed to further validate these findings.

Papanicolaou smear screening of women with intellectual disabilities: a cross-sectional survey in Taiwan.

Although little is known about the incidence of cervical cancer in women with intellectual disabilities (ID), Pap smear screening is an effective public health program to prevent cervical cancer to this group of people. The purposes of this study were to identify and evaluate the factors regarding the utilization of the Pap smears in women with ID seen in the preventive health screening program. We employed a cross-sectional survey "2009 National Survey on Preventive Health Use and Determinants among People with Disabilities", with the study sample 508 women with ID (aged > or =15 years) participated in the research in Taiwan. Results showed that there were 22.1% women with ID had ever used Pap smear screening previously and mean age of the first screening was nearly 40 years old. Comparing to the general population in Taiwan, the ID women at age group <35 years was less likely to use screening and the age group > or =35 years was more likely to use Pap smears than did the general women. Finally, a logistic regression analysis showed that marital status and had experience of accepted tubal ligation surgery were two factors which predicted Pap smear test use in the study. Those women with ID who had marital status were 8.99 times (95% CI=1.65-49.15) more likely than those had not marital status to use Pap smear test. Women with ID had experience on tubal ligation surgery were 10.48 times (95% CI=1.40-78.26) more likely to use Pap smear test than their counterparts. This study highlights that to acknowledge the rights of women with ID to access Pap smear screening service, health professionals will need to become more flexible and competent in the service that they provide.