New mechanistic insights of anti-obesity by sleeve gastrectomy-altered gut microbiota and lipid metabolism.

Background: The obesity epidemic has been on the rise due to changes in living standards and lifestyles. To combat this issue, sleeve gastrectomy (SG) has emerged as a prominent bariatric surgery technique, offering substantial weight reduction. Nevertheless, the mechanisms that underlie SG-related bodyweight loss are not fully understood. Methods: In this study, we conducted a collection of preoperative and 3-month postoperative serum and fecal samples from patients who underwent laparoscopic SG at the First Affiliated Hospital of Shandong First Medical University (Jinan, China). Here, we took an unbiased approach of multi-omics to investigate the role of SG-altered gut microbiota in anti-obesity of these patients. Non-target metabolome sequencing was performed using the fecal and serum samples. Results: Our data show that SG markedly increased microbiota diversity and Rikenellaceae, Alistipes, Parabacteroides, Bactreoidales, and Enterobacteraies robustly increased. These compositional changes were positively correlated with lipid metabolites, including sphingolipids, glycerophospholipids, and unsaturated fatty acids. Increases of Rikenellaceae, Alistipes, and Parabacteroide were reversely correlated with body mass index (BMI). Conclusion: In conclusion, our findings provide evidence that SG induces significant alterations in the abundances of Rikenellaceae, Alistipes, Parabacteroides, and Bacteroidales, as well as changes in lipid metabolism-related metabolites. Importantly, these changes were found to be closely linked to the alleviation of obesity. On the basis of these findings, we have identified a number of microbiotas that could be potential targets for treatment of obesity.

Effect of oligofructose on resistance to postoperative high-fat diet-induced damage of metabolism in diabetic rats after sleeve gastrectomy.

BACKGROUND: Sleeve gastrectomy (SG) can induce prominent remission of type 2 diabetes mellitus. However, the long-term remission rate of diabetes usually decreases over time. Oligofructose has been verified to modulate host metabolism. The aim of this study was to explore the protective effect of oligofructose on high-fat diet (HFD)-induced metabolic dysfunction after SG. AIM: To study the effect and mechanism of oligofructose on diabetic remission in diabetic rats after SG. METHODS: SG and SHAM operation were performed on diabetes rats induced with an HFD, nicotinamide, and low-dose streptozotocin. Then the rats in the SHAM and SG groups were continuously provided with the HFD, and the rats in sleeve gastrectomy-oligofructose group were provided with a specific HFD containing 10% oligofructose. Body weight, calorie intake, oral glucose tolerance test, homeostasis model assessment of insulin resistance, lipid profile, serum insulin, glucagon-like peptide 1 (GLP-1), total bile acids, lipopolysaccharide (LPS), and colonic microbiota levels were determined and compared at the designated time points. All statistical analyses were performed using Statistic Package for Social Science version 19.0 (IBM, United States), and the statistically significant difference was considered at P < 0.05. RESULTS: At 2 wk after surgery, rats that underwent SG exhibited improved indexes of glucose and lipid metabolism. Compared with the SG group, the rats from SG-oligofructose group exhibited better parameters of glucose and lipid metabolism, lower body weight (526.86 ± 21.51 vs 469.25 ± 21.84, P < 0.001), calorie intake (152.14 ± 9.48 vs 129.63 ± 8.99, P < 0.001), homeostasis model assessment of insulin resistance (4.32 ± 0.57 vs 3.46 ± 0.52, P < 0.05), and LPS levels (0.19 ± 0.01 vs 0.16 ± 0.01, P < 0.05), and higher levels of insulin (1.17 ± 0.17 vs 1.58 ± 0.16, P < 0.001) and GLP-1 (12.39 ± 1.67 vs 14.94 ± 1.86, P < 0.001), and relative abundances of Bifidobacterium (0.0034 ± 0.0014 vs 0.0343 ± 0.0064, P < 0.001), Lactobacillus (0.0161 ± 0.0037 vs 0.0357 ± 0.0047, P < 0.001), and Akkermansia muciniphila (0.0050 ± 0.0024 vs 0.0507 ± 0.0100, P < 0.001) at the end of the study. However, no difference in total bile acids levels was observed between the two groups. CONCLUSION: Oligofructose partially prevents HFD-induced glucose and lipid metabolism damage after SG, which may be due to the changes of calorie intake, insulin, GLP-1, LPS, and the gut microbiota in rats.

Surface chemistry-dependent activity and comparative investigation on the enhanced photocatalytic performance of graphitic carbon nitride modified with various nanocarbons.

Organic contaminants, dyes and antibiotics, discharged in wastewater systems, have posed great threats to the sustainability of the ecosystem. This study was performed to prepare graphitic carbon nitride (GCN) nanocomposites modified by nanocarbons, including carbon quantum dots (CQD), carbon nanotube (CNT), reduced graphene oxide (rGO), and carbon nanospheres (CNS), by a straightforward one-pot method. The characterization results suggest that after the modification with nanocarbons, GCN demonstrated slight red shift and stronger light absorption. The resultant photocatalysts revealed prominent performances for total photodegradation of organic contaminants. The degradation processes were investigated by in situ electron paramagnetic resonance (EPR). The mechanistic studies on the enhanced photoelectrochemical and photocatalytic performances were also conducted. Results indicate that GCN modified by the nanocarbon spheres displayed a substantial improvement in the degradation of sulfachloropyridazine (SCP) and dyes, compared favourably with other GCN samples modified by carbon nanotubes, quantum dots and layered graphene oxide. The photocatalytic degradation difference is mainly stemmed from the higher contents of COOH and CO functional groups. The intimate contact or interaction between the two phases of GCN and nanocarbon in the nanocomposites may further improve the activity. This work provides insight in the design of highly efficient metal-free photocatalysts to better utilise the clean and free solar energy for environmental remediation.

Nitrogen-doped Carbon Nanospheres-Modified Graphitic Carbon Nitride with Outstanding Photocatalytic Activity.

Metals and metal oxides are widely used as photo/electro-catalysts for environmental remediation. However, there are many issues related to these metal-based catalysts for practical applications, such as high cost and detrimental environmental impact due to metal leaching. Carbon-based catalysts have the potential to overcome these limitations. In this study, monodisperse nitrogen-doped carbon nanospheres (NCs) were synthesized and loaded onto graphitic carbon nitride (g-C3N4, GCN) via a facile hydrothermal method for photocatalytic removal of sulfachloropyridazine (SCP). The prepared metal-free GCN-NC exhibited remarkably enhanced efficiency in SCP degradation. The nitrogen content in NC critically influences the physicochemical properties and performances of the resultant hybrids. The optimum nitrogen doping concentration was identified at 6.0 wt%. The SCP removal rates can be improved by a factor of 4.7 and 3.2, under UV and visible lights, by the GCN-NC composite due to the enhanced charge mobility and visible light harvesting. The mechanism of the improved photocatalytic performance and band structure alternation were further investigated by density functional theory (DFT) calculations. The DFT results confirm the high capability of the GCN-NC hybrids to activate the electron-hole pairs by reducing the band gap energy and efficiently separating electron/hole pairs. Superoxide and hydroxyl radicals are subsequently produced, leading to the efficient SCP removal.

Improved FGF21 Sensitivity and Restored FGF21 Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats After Duodenal-Jejunal Bypass and Sleeve Gastrectomy.

Objective: Bariatric surgery can profoundly improve glucose and lipid metabolism in diabetic rats. Fibroblast growth factor 21 (FGF21) is an important hormone with multiple metabolic beneficial effects. Alteration in serum FGF21 level after bariatric surgery has been reported with conflicting results. Here, we investigated the effect of bariatric surgeries on FGF21 expression and sensitivity. Methods: We performed duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG) and sham surgery in diabetic rats induced by high fat diet and streptozotocin. Metabolic parameters, including body weight, food intake, glucose tolerance, and lipid profiles, were monitored. FGF21 levels in both serum and liver were measured after surgery. FGF21 signaling pathway including FGF receptor 1 (FGFR1), ß-klotho (KLB), and phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) was detected in the liver and white adipose tissue (WAT). We also determined FGF21 sensitivity post-operatively by acute recombinant human FGF21 injection. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted immediately after FGF21 injection. Serum triglyceride (TG) and non-esterified fatty acid (NEFA) were measured and the mRNA levels of early growth response 1 (Egr1) and c-Fos in the liver and WAT were detected after FGF21 injection. Results: Improvements in glucose tolerance, insulin sensitivity, and lipid profiles were observed after bariatric surgeries along with ameliorated lipid metabolism in the liver and WAT. Serum and hepatic FGF21 levels decreased in both DJB and SG groups. FGFR1 and phosphorylated ERK1/2 levels increased in both DJB and SG groups 8 weeks after surgery. The expression of KLB was downregulated only in the WAT after DJB and SG. Significant alteration of OGTT and ITT were observed after acute FGF21 administration in DJB and SG groups. Serum TG and NEFA in DJB and SG groups also decreased after FGF21 administration. And increased mRNA levels of Egr1 and c-Fos were detected in the liver and WAT after DJB and SG surgeries. Conclusions: DJB and SG surgeries can downregulate hepatic expression of FGF21, restore FGF21 signaling pathway and improve FGF21 sensitivity in high-fat diet/streptozotocin-induced diabetic rats.

Restoration of myocardial glucose uptake with facilitated myocardial glucose transporter 4 translocation contributes to alleviation of diabetic cardiomyopathy in rats after duodenal-jejunal bypass.

AIMS/INTRODUCTION: Duodenal-jejunal bypass (DJB) surgery has been reported to effectively relieve diabetic cardiomyopathy (DCM). However, the specific mechanisms remain largely unknown. The present study was designed to determine the alterations of myocardial glucose uptake (MGU) after DJB and their effects on DCM. MATERIALS AND METHODS: Duodenal-jejunal bypass and sham surgeries were carried out in diabetic rats induced by a high-fat diet and a low dose of streptozotocin, with chow-diet fed rats as controls. Bodyweight, food intake, glucose homeostasis and lipid profiles were measured at indicated time-points. Cardiac function was evaluated by transthoracic echocardiography and hemodynamic measurement. Cardiac remodeling was assessed by a series of morphometric analyses along with transmission electron microscopy. Positron-emission tomography with fluorine-18 labeled fluorodeoxyglucose was carried out to evaluate the MGU in vivo. Furthermore, myocardial glucose transporters (GLUT; GLUT1 and GLUT4), myocardial insulin signaling and GLUT-4 translocation-related proteins were investigated to elucidate the underlying mechanisms. RESULTS: The DJB group showed restored systolic and diastolic cardiac function, along with significant remission in cardiac hypertrophy, cardiac fibrosis, lipid deposit and ultrastructural disorder independent of weight loss compared with the sham group. Furthermore, the DJB group showed upregulated myocardial insulin signaling, hyperphosphorylation of AKT substrate of 160 kDa (AS160) and TBC1D1, along with preserved soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins, facilitating the GLUT-4 translocation to the myocardial cell surface and restoration of MGU. CONCLUSIONS: The present findings provide evidence that restoration of MGU is implicated in the alleviation of DCM after DJB through facilitating GLUT-4 translocation, suggesting a potential choice for treatment of human DCM if properly implemented.

Sleeve Gastrectomy with Bypass of Proximal Small Intestine Provides Better Diabetes Control than Sleeve Gastrectomy Alone Under Postoperative High-Fat Diet.

BACKGROUND: Sleeve gastrectomy (SG) plus procedures have been developed to strengthen the effect of SG on diabetes control. The aim of this study was to compare diabetes control after SG plus bypass of the proximal small intestine with SG alone under adverse conditions for diabetes remission. METHODS: SG plus duodenojejunal bypass (SG-DJB), SG plus jejunojejunal bypass (SG-JJB), SG alone, and sham surgeries were performed in diabetic rats. A high-fat diet (HFD) was fed postoperatively to induce diabetes recurrence. Body weight, food intake, glucose tolerance, insulin sensitivity, serum hormones, hepatic function, and lipid profiles were measured postoperatively. RESULTS: SG-DJB, SG-JJB, and SG groups exhibited significant improvement in glucose tolerance and insulin sensitivity compared with the sham-operated group at 2 weeks postoperatively. Postoperative HFD induced obvious diabetes relapse and re-impaired insulin sensitivity at 16 weeks postoperatively. The SG-DJB and SG-JJB groups exhibited superior glucose tolerance and similar insulin sensitivity to SG alone at 16 weeks postoperatively. Compared with the SG alone, the SG-DJB and SG-JJB groups exhibited similar food intake, weight loss, fasting ghrelin, glucose-stimulated insulin secretion, and higher glucose-stimulated GLP-1 secretion. CONCLUSION: SG-DJB and SG-JJB provided better diabetes control than SG alone in rats fed a HFD postoperatively. Further clinical studies are expected to confirm the superiority of SG plus bypass of proximal small intestine.

Bile acid profiles within the enterohepatic circulation in a diabetic rat model after bariatric surgeries.

Bile acids (BAs), which are synthesized in the liver and cycled in the enterohepatic circulation, have been recognized as signaling molecules by activating their receptors in the intestine and liver. Serum taurine-conjugated BAs have been shown to be elevated after bariatric surgeries although the postoperative BA profiles within the enterohepatic circulation have not been investigated. Clarification of these profiles could help explain the mechanisms by which bariatric surgery leads to BA profile alterations and subsequent metabolic effects. We performed duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham procedures in an obese diabetic rat model induced by high-fat diet and streptozotocin. The weight loss and antidiabetic effects were evaluated postsurgery. BA profiles in the systemic serum and within the enterohepatic circulation were analyzed, together with the expression of related BA transporters and enzymes at week 12 after surgery. Compared with sham, SG induced sustained weight loss, and both DJB and SG significantly improved glucose tolerance and insulin sensitivity with enhanced glucagon-like peptide 1 secretion. Similar to changes in the serum, BAs, especially taurine-conjugated species, were also elevated in the enterohepatic circulation (bile and portal vein) after DJB and SG. In addition, the expression of key BA transporters and conjugational enzymes was elevated postoperatively, whereas the enzymes responsible for BA synthesis were decreased. In conclusion, DJB and SG elevated BA levels in the systemic serum and enterohepatic circulation, especially taurine-conjugated species, which likely indicates increased ileal reabsorption and hepatic conjugation rather than synthesis. NEW & NOTEWORTHY Bile acids (BAs) have been implicated as potential mediators of the weight-independent effects of bariatric surgery. For the first time, we discovered that duodenal-jejunal bypass and sleeve gastrectomy elevated BAs, particularly the taurine-conjugated species in the enterohepatic circulation, likely through the promotion of ileal reabsorption and hepatic conjugation rather than BA synthesis. These findings will improve our understanding of BA metabolism after bariatric surgery and their subsequent metabolic effects.

Egg-shaped core/shell α-Mn2O3@α-MnO2 as heterogeneous catalysts for decomposition of phenolics in aqueous solutions.

Novel uniform ellipsoid α-Mn2O3@α-MnO2 core/shell (McMs) nanocomposites were prepared via a hydrothermal process with a shape-control protocol followed by calcination at different temperatures. The properties of the composites were characterized by a number of techniques such as thermogravimetric analysis (TGA), X-ray diffraction (XRD), N2 adsorption, and scanning electron microscopy (SEM). The core/shell materials were much effective in heterogeneous oxone(®) activation to generate sulfate and hydroxyl radicals for degradation of aqueous phenol. The McMs composites demonstrated catalytic activity for 100% phenol decomposition in short duration varying between 20 and 120 min, much higher than that of homogeneous Mn(2+) system with 95% phenol degradation in 120 min. They also showed a higher activity than single-phase α-Mn2O3 or α-MnO2. The catalytic activity of phenol degradation depends on temperature, oxone(®) concentration, phenol concentration, and catalyst loading. The catalysts also showed a stable activity in several cycles. Kinetic study demonstrated that phenol degradation reactions follow a first order reaction on McMs catalysts giving activation energies at 32.1-68.8 kJ/mol. With the detection of radicals by electron paramagnetic resonance (EPR), the generation mechanism was proposed.

Role of spinal GABAA receptor reduction induced by stress in rat thermal hyperalgesia.

The mechanisms underlying stress-induced hyperalgesia (SIH) remain poorly understood. Recent findings have provided strong evidence indicating that SIH could be related, at least in part, to alterations in spinal cord GABA activity. In the present study, we first investigated how acute restraint stress impacted pain responses as assessed using the tail flick immersion test. These results showed that rats developed hyperalgesia at 6 h after being subjected to 1-h acute restraint stress. Second, we measured the activation of spinal neurons and alterations in expression of GABAA receptor ß2 and ß3 subunits as related to stress-induced hyperalgesia. Results from Western blot and immunofluorescence assays showed that c-fos protein increased in the dorsal horn of the lumbar spinal cord and GABAA receptor ß2 and ß3 subunit proteins decreased significantly at 6 h after exposure to 1 h of acute restraint stress. Finally, the effects of spinal GABAA receptor alteration on SIH were evaluated. These results showed that intrathecal administration of muscimol inhibited hyperalgesia induced by stress while bicuculline enhanced hyperalgesia in the control groups. Taken together, the present data reveal that GABAA receptor ß2 and ß3 decrease following 1 h of acute restraint stress and may play a critical role in SIH.

An "off-on" fluorescent and colorimetric probe bearing fluorescein moiety for Mg(2+) and Ca(2+) via a controlled supramolecular approach.

In the present work, a new kind of fluorescein-based chemosensor L was designed and synthesized to selectively recognize Ca(2+) or Mg(2+) over other competing ions. The chemosensor showed "off-on" fluorescent and color changes upon the addition of Ca(2+) and Mg(2+). The dynamic binding events with the formation of 1:1(L/M) and 1:2(L/M) complexes were examined. The cation-driven conformation changes of L were understood and proposed rationally by the UV-vis, FL, and (1)HNMR titrations. By this allosteric effect, Ca(2+) and Mg(2+) could be selectively recognized with the 1:2 stoichiometry by fluorescent changes, which were different from other known reports on chemosensors that the host-cation complexion was exploited for controlling chromophore interaction as the model of signaling.

A 15-year analysis of molecular epidemiology of avian infectious bronchitis coronavirus in China.

A comprehensive study of the epidemiology and pathogenicity of infectious bronchitis virus (IBV) in China was carried out by molecular characterization of the S1 gene from 46 isolates obtained for this study and 174 reference strains isolated over a 15-year period. Nine types were found according to sequence analysis and phylogenetic study of the S1 gene. The co-circulation of multiple IBV types and the ongoing emergence of IBV variants are the epidemiological challenges in China. Factors contributing to the continual emergence include mutations, insertions and deletions in the S1 protein genes; recombination between local IBV strains circulating in chicken flocks in China; and recombination between local strains and vaccine strains. Vaccination-challenge analysis between circulating field strains and Mass-type H120 vaccine indicated the need to develop new vaccines from local IBV strains. These results also emphasize the importance of continued IBV surveillance in China.

Evaluation of the protection conferred by commercial vaccines and attenuated heterologous isolates in China against the CK/CH/LDL/97I strain of infectious bronchitis coronavirus.

Avian infectious bronchitis virus (IBV) causes tremendous economic losses to the poultry industry worldwide. Different serotypes of this virus show little cross-protection. The present study investigated the genotypic relationship between CK/CH/LDL/97I-type strains and reference IBVs based on S1 gene comparisons and the protection provided by vaccination with commercial vaccines and attenuated homologous and heterologous strains. Phylogenetic analysis and the comparison of S1 showed that CK/CH/LDL/97I-type virus might be a new serotype compared to vaccine strains and other types of IBV isolates in China. Protection efficacy was evaluated by morbidity, mortality, and virus re-isolation from the challenged chicks. Complete protection by IBV vaccination was provided by the homologous strain but sufficient respiratory protection was not provided by the commercial vaccines. Heterologous strains against CK/CH/LDL/97I challenge and the development of a vaccine against CK/CH/LDL/97I-type IBV will be necessary to control infectious bronchitis disease in poultry. Further development of the attenuated CK/CH/LDL/97I strain may provide a valuable contribution towards this goal.

[Evaluation of the protection conferred by several avian infectious bronchitis attenuated vaccines against the field strain CK/CH/LDL/97 I in China].

The entire S1 protein gene of five infectious bronchitis (IB) vaccine strains (JAAS, IBN, Jilin, J9, H120) used in China were compared with that of the IB field isolate CK/CH/LDL/97 I present in China. The nucleotide and deduced amino acid similarities between the five IB vaccine strains and the field strain, CK/CH/LDL/97 I, were not more than 76.4% and 78.7%, respectively. Phylogenetic analysis based on the S1 gene showed that the vaccine strains and the field strain belonged to different clusters and had larger evolutionary distances, indicating that they were of different genotypes. The five vaccine strains were used for protection test against challenge of the field isolate CK/CH/LDL/97 I. The chickens inoculated with five vaccine strains showed morbidity as high as 30%-100% after challenged with the CK/CH/ LDL/97 I strain. The organ samples at 5 days post challenge showed that the viral detection rates were 50%-90% and 10%-30% for trachea and kidney, respectively. The live attenuated vaccines only provided partial protection to the vaccinated chickens against heterologous IBV infection, CK/CH/LDL/97 I.