The role of the probiotic Akkermansia muciniphila in brain functions: insights underpinning therapeutic potential.

The role of Akkermansia muciniphila, one of the most abundant microorganisms of the intestinal microbiota, has been studied extensively in metabolic diseases, such as obesity and diabetes. It is considered a next-generation probiotic microorganism. Although its mechanism of action has not been fully elucidated, accumulating evidence indicates the important role of A. muciniphila in brain functions via the gut-brain axis and its potential as a therapeutic target in various neuropsychiatric disorders. However, only a limited number of studies, particularly clinical studies, have directly assessed the therapeutic effects of A. muciniphila interventions in these disorders. This is the first review to discuss the comprehensive mechanism of A. muciniphila in the gut-brain axis via the protection of the intestinal mucosal barrier and modulation of the immune system and metabolites, such as short-chain fatty acids, amino acids, and amino acid derivatives. Additionally, the role of A. muciniphila and its therapeutic potential in various neuropsychiatric disorders, including Alzheimer's disease and cognitive deficit, amyotrophic lateral sclerosis, Parkinson's disease, and multiple sclerosis, have been discussed. The review suggests the potential role of A. muciniphila in healthy brain functions.

The Skeletal Oncology Research Group Machine Learning Algorithm (SORG-MLA) for predicting prolonged postoperative opioid prescription after total knee arthroplasty: an international validation study using 3,495 patients from a Taiwanese cohort.

BACKGROUND: Preoperative prediction of prolonged postoperative opioid use (PPOU) after total knee arthroplasty (TKA) could identify high-risk patients for increased surveillance. The Skeletal Oncology Research Group machine learning algorithm (SORG-MLA) has been tested internally while lacking external support to assess its generalizability. The aims of this study were to externally validate this algorithm in an Asian cohort and to identify other potential independent factors for PPOU. METHODS: In a tertiary center in Taiwan, 3,495 patients receiving TKA from 2010-2018 were included. Baseline characteristics were compared between the external validation cohort and the original developmental cohorts. Discrimination (area under receiver operating characteristic curve [AUROC] and precision-recall curve [AUPRC]), calibration, overall performance (Brier score), and decision curve analysis (DCA) were applied to assess the model performance. A multivariable logistic regression was used to evaluate other potential prognostic factors. RESULTS: There were notable differences in baseline characteristics between the validation and the development cohort. Despite these variations, the SORG-MLA ( https://sorg-apps.shinyapps.io/tjaopioid/ ) remained its good discriminatory ability (AUROC, 0.75; AUPRC, 0.34) and good overall performance (Brier score, 0.029; null model Brier score, 0.032). The algorithm could bring clinical benefit in DCA while somewhat overestimating the probability of prolonged opioid use. Preoperative acetaminophen use was an independent factor to predict PPOU (odds ratio, 2.05). CONCLUSIONS: The SORG-MLA retained its discriminatory ability and good overall performance despite the different pharmaceutical regulations. The algorithm could be used to identify high-risk patients and tailor personalized prevention policy.

Internet of Things: Development Intelligent Programmable IoT Controller for Emerging Industry Applications.

The Internet of Things (IoT) has become critical to the implementation of Industry 4.0. The successful operation of smart manufacturing depends on the ability to connect everything together. In this research, we applied the TOC (Theory of Constraints) to develop a wireless Wi-Fi intelligent programmable IoT controller that can be connected to and easily control PLCs. By applying the TOC-focused thinking steps to break through their original limitations, the development process guides the user to use the powerful and simple flow language process control syntax to efficiently connect to PLCs and realize the full range of IoT applications. Finally, this research uses oil-water mixer equipment as the target of continuous improvement and verification. The verification results meet the requirements of the default function. The IoT controller developed in this research uses a marine boiler to illustrate the application. The successful development of flow control language by TOC in this research will enable academic research on PLC-derivative applications. The results of this research will help more SMEs to move into smart manufacturing and the new realm of Industry 4.0.

An atypical hyperosmolar hyperglycemic state and diabetic ketoacidosis induced by sodium-glucose cotransporter-2 inhibitors: A case report.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have become the best choice of second-line oral antidiabetic drugs for patients with heart or chronic kidney disease. However, it is not clear how safe this treatment is for elderly patients, especially Asians, who are known to be more insulin deficient than Caucasian individuals with a similar insulin resistance. Here, we report a case concerning an elderly patient with type 2 diabetes mellitus without insulin dependence, whose antidiabetic medication had recently been changed to include an SGLT-2 inhibitor. The patient presented with an atypical hyperosmolar hyperglycemic state and diabetic ketoacidosis but recovered after insulin pump treatment and fluid supplementation. The patient was discharged with a prescription of a mixed-type insulin injection instead of oral antidiabetic medications for diabetes control. Our case demonstrates that if SGLT-2 inhibitors are administered to elderly Asian patients, their benefits and adverse effects should be carefully monitored.

Lactic Acid Produced by Glycolysis Contributed to Staphylococcus aureus Aggregation Induced by Glucose.

High concentration of glucose induces Staphylococcus aureus (S. aureus) aggregation, but the mechanism of this is still unclear. In this study, the aggregation of S. aureus strains was induced by high concentration of glucose (>7.8 mM), and which was dose- and time-dependent. In addition, the large amount of lactate acid produced during S. aureus aggregation, induced by glucose, resulted in decreased pH value. Lactic acid, the end product of glycolysis, could quickly induce S. aureus aggregation. Except for lactic acid, acetic acid and HCl also induced S. aureus aggregation. In addition, the aggregation of S. aureus strains induced by glucose or lactic acid was completely inhibited in Tris-HCl buffer (pH 7.5), and inhibition of glycolysis by 2-deoxyglucose significantly decreased S. aureus aggregation. The aggregation induced by glucose was dispersed by periodate and proteinase K. In summary, lactate acid produced by glycolysis contributed to S. aureus aggregation induced by high concentration of glucose.

Brownian motion and Einstein relation for migration of coffee particles in coffee suspensions.

BACKGROUND: The migration of particles in a liquid plays an important role in determining the stability of the corresponding suspension. The preparation of a cup of coffee involves the migration/dispersion of coffee particles in aqueous solutions. We investigate the Brownian motion of coffee particles in coffee suspensions at different temperatures for three different coffee beans via the migration of the coffee particles of the coffee suspensions in water. RESULTS: The activation energies for the Brownian motion of the coffee particles are in the range 23.5-32.0 kJ mol-1 , relatively independent of the size of the coffee particles used in the present study. The viscosities of the coffee suspensions are measured as a function of temperature and then used to correlate with the gradient-diffusion coefficient for the Brownian motion of the coffee particles. The activation energies of the rate process controlling the viscous flow of the coffee suspensions are in the range 12.7-14.1 kJ mol-1 . CONCLUSION: The correlation between the viscosity and gradient-diffusion coefficient of the coffee suspensions generally follows the Einstein relation. A temperature dependence exists for the viscosity and gradient-diffusion coefficient of the coffee suspensions, which can be used to understand the brewing of coffee at high temperatures with respect to product refinement. © 2019 Society of Chemical Industry.

Exploring the Confinement Effect of Carbon Nanotubes on the Electrochemical Properties of Prussian Blue Nanoparticles.

A novel and efficient photochemical method has been proposed for the encapsulation of Prussian blue nanoparticles (PBNPs) inside the channels of carbon nanotubes (PB-in-CNTs) in an acidic ferrocyanide solution under UV/vis illumination, and the confinement effect of CNTs on the electrochemical properties of PBNPs is systematically explored. PB-in-CNTs show a faster electron-transfer process, an enhanced electrocatalytic activity toward the reduction of H2O2, and an increased anti-base ability compared to PBNPs loaded outside of CNTs (PB-out-CNTs). In addition, PB-in-CNTs show an increased electrochemical reversibility and an unexpected diameter-independent catalytic activity with the decrease of CNT diameters. The improved electrochemical properties of PB-in-CNTs are attributed to the modified electronic properties and dimensions of PBNPs induced by the confinement effect of CNTs. This work provides further insights into the confinement effect on the properties of nanomaterials and will inspire extensive relevant investigations in the development of novel composites or excellent catalysts.

[Research strategies and application of reference Dao-di herbs].

Establishing evaluation system of Dao-di herbs has been a problem to be solved in the field of traditional Chinese medicine (TCM), and is also a difficult problem in restricting the realization of TCM quality. On the basis of national drug standard substance requirements, this paper puts forward to set up reference Dao-di herbs in the first step of the evaluation system of Dao-di herbs, and discusses the properties, evaluation index system and its development requirements of reference Dao-di herbs, aiming at supporting the modern research and characteristics identification of Dao-di herbs in the future.

In vitro and in vivo antitumour activities of puerarin 6″-O-xyloside on human lung carcinoma A549 cell line via the induction of the mitochondria-mediated apoptosis pathway.

Context Pueraria lobata (Leguminoseae) shows cytotoxic effects against cancer cells; however, its active components remain unclear. Objective This study investigated the antitumour activity of puerarin 6″-O-xyloside (POS) on the human lung carcinoma A549 cell line. Materials and methods The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the cytotoxicity of POS (at 10, 20 and 40 µM) in vitro, and xenograft nude mice were established to evaluate the antitumour effect of POS (at 40 mg/kg/d) in vivo by 15 days intraperitoneal injection (ip). To explore its mechanism of action, flow cytometry was performed to determine the pro-apoptotic effect of POS (at 10, 20 and 40 µM). Subsequently, the expression of caspase-3, caspase-7, caspase-9, Bcl-2 and Bax in A549 cells were determined. Results POS showed significant cytotoxicity toward A549 cells (p < 0.05) by inducing apoptosis. Treatment with POS significantly upregulated the levels of caspase-3 (p < 0.01), caspase-7 (p < 0.01), caspase-9 (p < 0.01) and Bax (p < 0.01) in A549 cells, and Bcl-2 was downregulated (p < 0.01). Additionally, the in vivo animal study showed that POS significantly inhibited tumour growth in A549 cells (p < 0.01). Conclusion Our study demonstrated the POS has significant antitumour activities. The mechanisms are related to increased levels of caspase-3, caspase-7, caspase-9 and Bax, and reduced levels Bcl-2.

Hepatoprotective effect of ganoderma triterpenoids against oxidative damage induced by tert-butyl hydroperoxide in human hepatic HepG2 cells.

CONTEXT: Ganoderma triterpenoids (GTs) have been recognised as an important bioactive ingredient in Ganoderma Lucidum (Leyss. ex Fr.) Karst. (Polyporaceae), widely used for treating and preventing chronic hepatopathy of various etiologies. OBJECTIVE: The objective of this study is to better understand the hepatoprotective effect of GTs and to enhance their use in food supplement pharmaceutical and medical industries. MATERIALS AND METHODS: HepG2 cells were pretreated in the presence or absence of GTs (50, 100 and 200 µg/ml) for 4 h, then exposed with 60 µmol/L of t-BHP for an additional 4 h. The cell viability was evaluated by MTT method. ALT, AST and LDH production in culture medium and intracellular MDA, GSH and SOD levels were determined. Moreover, the total triterpenoid content and chemical constituents in GTs were detected by ultraviolet spectrophotometry and HPLC/Q-TOF-MS, respectively. RESULTS: GTs (50, 100 and 200 µg/ml) significantly increased the relative cell viability by 4.66, 7.78 and 13.46%, respectively, and reduced the level of ALT by 11.44%, 33.41% and 51.24%, AST by 10.05%, 15.63% and 33.64%, and LDH by 16.03%, 23.4% and 24.07% in culture medium, respectively. GTs could also remarkably decrease the level of MDA and increase the content of GSH and SOD in HepG2 cells. Furthermore, the total triterpenoid content in GTs was 438 mg GAAEs/g GTs. And 16 triterpenoids in GTs were identified or tentatively characterised. DISCUSSION AND CONCLUSION: Our results showed that GTs had potent cytoprotective effect against oxidative damage induced by t-BHP in HepG2 cells, thus suggesting their potential use as liver protectant.

[Germplasm identification of Lonicerae Japonicae Flos by DNA melt curve analysis].

To establish a new high resolution melting analytical method for identification of Lonicera japonica germplasm, the screening of 7 pairs of SSR (simple sequence repeats) primers, determining the suitable diagnostic primers by the differences of peak pattern and Tm was conducted. Then into the DNA template concentration, annealing temperature and the suitable range of cycle number were investigated. Combined with SIMCA-P software for data processing analysis, the results show that three main germplasm honeysuckle could be divided by four sets of primers. It provides methodology for improving L. japonica germplasm identification.

Akkermansia muciniphila Improves Depressive-Like Symptoms by Modulating the Level of 5-HT Neurotransmitters in the Gut and Brain of Mice.

Accumulating evidence has suggested that the gut microbiome plays an important role in depression. Akkermansia muciniphila (AKK), a next-generation probiotic, shows a beneficial effect on immune and metabolic homeostasis. The relative abundance of AKK was found negatively correlated with depressive symptoms in both clinical and pre-clinical studies. To evaluate the potential antidepressant effect of AKK and explore the possible mechanism, we used chronic alcohol exposure and chronic unpredictable mild stress (CUMS) to induce depressive-like behaviors in mice. We found that oral AKK administration significantly reduced the immobility time in the force swimming test (FST) and tail suspension test (TST) in the mice with chronic alcohol exposure and the CUMS mice. The sucrose preference in the mice receiving AKK was significantly increased in the sucrose preference test (SPT). More importantly, AKK implantation significantly increased the level of 5-HT in the gut and PFC of both the alcohol exposure mice and the CUMS mice. Furthermore, AKK had inhibited the expression of SERT in the gut but not in the brain for both NIAAA and the CUMS model mice. Interestingly, the expression of cFos in enteric nerves in the gut significantly decreased after AKK administration. In conclusion, our study demonstrated the antidepressant effect of AKK in mice exposed to alcohol exposure and CUMS, with the potential mechanism that AKK implantation might lead to an increased level of 5-HT and inhibited SERT expression in the gut, and might alter the gut-to-brain signal through suppression of enteric nerves activation.

Microstructure and Magnetic Properties of Fe67.6-Pd32-In0.4 (at.%) Shape Memory Melt-Spun Ribbons.

Fe-~30 at.%Pd is a ferromagnetic shape memory alloy (SMA) with a reversible thermoelastic fcc-fct phase transformation. The advantage of adding a small amount of Indium to Fe-Pd SMAs is, among other things, the upward shift of the transformation temperatures, which allows us to maintain the material in the martensitic state (fct structure) at room temperature. In this work, we study the microstructure and the magnetic properties of nominally Fe67.6-Pd32-In0.4 (at.%) melt-spun ribbons. Energy-dispersive spectroscopy analysis showed a certain level of non-uniformity of Indium distribution in the as-spun ribbon. However, the attempt to homogenize the ribbon by annealing at 1273 K for 120 h resulted in an unfavoured structural change to bct martensite. Magneto strains induced by a 9 kOe magnetic field reached over 400 ppm for certain field orientations, which is around four times more than the magneto strains of near-binary Fe-Pd shape memory alloys.

Quantitative and chemical fingerprint analysis for the quality evaluation of Receptaculum Nelumbinis by RP-HPLC coupled with hierarchical clustering analysis.

A simple and reliable method of high-performance liquid chromatography with photodiode array detection (HPLC-DAD) was developed to evaluate the quality of Receptaculum Nelumbinis (dried receptacle of Nelumbo nucifera) through establishing chromatographic fingerprint and simultaneous determination of five flavonol glycosides, including hyperoside, isoquercitrin, quercetin-3-O-ß-d-glucuronide, isorhamnetin-3-O-ß-d-galactoside and syringetin-3-O-ß-d-glucoside. In quantitative analysis, the five components showed good regression (R > 0.9998) within linear ranges, and their recoveries were in the range of 98.31%-100.32%. In the chromatographic fingerprint, twelve peaks were selected as the characteristic peaks to assess the similarities of different samples collected from different origins in China according to the State Food and Drug Administration (SFDA) requirements. Furthermore, hierarchical cluster analysis (HCA) was also applied to evaluate the variation of chemical components among different sources of Receptaculum Nelumbinis in China. This study indicated that the combination of quantitative and chromatographic fingerprint analysis can be readily utilized as a quality control method for Receptaculum Nelumbinis and its related traditional Chinese medicinal preparations.

Role of sodium pyruvate in maintaining the survival and cytotoxicity of Staphylococcus aureus under high glucose conditions.

Glucose is a crucial carbon source for the growth of Staphylococcus aureus, but an excess of glucose is detrimental and even leads to cell death. Pyruvate, the central metabolite of glycolysis, has been shown to have anti-inflammatory and antioxidant properties. This study aimed to investigate the protective effect of pyruvate on S. aureus under high glucose conditions. Sodium pyruvate greatly increased the cytotoxicity of S. aureus strain BAA-1717 to human erythrocytes and neutrophils in vitro. However, the cytotoxicity and survival of S. aureus were significantly reduced by high glucose, which was restored to normal levels by the addition of sodium pyruvate. The expression of hlg and lukS in S. aureus was higher in the LB-GP cultures than that in LB-G cultures, but there was no significant difference in cytotoxicity between LB-GP and LB-G cultures. Furthermore, the hemolytic activity of S. aureus supernatants could be inhibited by the cell-free culture medium (CFCM) of LB-G cultures, suggesting that high levels of extracellular proteases were presence in the CFCM of LB-G cultures, resulting in degradation of the hemolytic factors. The expression of sarA, which negatively regulates extracellular protease secretion, was higher in LB-GP cultures than that in LB-G cultures. Additionally, sodium pyruvate increased acetate production in S. aureus, which helps maintain cell viability under acidic environment. In conclusion, pyruvate plays an important role in the survival and cytotoxicity of S. aureus under high glucose conditions. This finding may aid in the development of effective treatments for diabetic foot infections.

New insight into the virulence and inflammatory response of Staphylococcus aureus strains isolated from diabetic foot ulcers.

Staphylococcus aureus strains isolated from diabetic foot ulcers (DFUs) have less virulence, but still cause severe infections. Furthermore, hypovirulent S. aureus strains appear to be localized in the deep tissues of diabetic foot osteomyelitis, indicating that the unique environment within DFUs affects the pathogenicity of S. aureus. In this study, the cell-free culture medium (CFCM) of S. aureus strains isolated from DFUs exhibited higher cytotoxicity to human erythrocytes than those isolated from non-diabetic patients with sepsis or wounds. Among these S. aureus strains isolated from DFUs, ß-toxin negative strains have less virulence than ß-toxin positive strains, but induced a higher expression of inflammatory cytokines. Our study and previous studies have shown that the synergistic effect of phenol-soluble modulin α and ß-toxin contributes to the higher hemolytic activity of ß-toxin positive strains. However, lysis of human erythrocytes by the CFCM of ß-toxin negative strains was greatly inhibited by an autolysin inhibitor, sodium polyanethole sulfonate (SPS). A high level of glucose greatly reduced the hemolytic activity of S. aureus, but promoted the expression of interleukin-6 (IL-6) in human neutrophils. However, 5 mM glucose or glucose-6-phosphate (G6P) increased the hemolytic activity of SA118 (a ß-toxin negative strain) isolated from DFUs. Additionally, patients with DFUs with growth of S. aureus had lower level of serum IL-6 than those with other bacteria, and the CFCM of S. aureus strains significantly reduced lipopolysaccharide-induced IL-6 expression in human neutrophils. Therefore, the virulence and inflammatory response of S. aureus strains isolated from DFUs are determined by the levels of glucose and its metabolites, which may explain why it is the predominant bacteria isolated from DFUs.

Label-free strategy for in-situ analysis of protein binding interaction based on attenuated total reflection surface enhanced infrared absorption spectroscopy (ATR-SEIRAS).

A versatile ATR-SEIRAS methodology is described herein for highly sensitive analysis of immunoglobulin (IgG) recognition. This strategy allows in situ tracking of specific protein binding at the liquid-solid interface. Most importantly, interferential signal from environmental molecules (e.g., water, nonspecific binding molecules, and bulk molecules) can be eliminated to negligible levels by using the ATR analysis mode, and the sensitive IR structural information of target proteins is obtained simultaneously. A simplified numerical model has been established to quantitatively describe the kinetics and thermodynamics of protein recognition processes at surfaces. Compared with conventional label-free methods for protein binding study, experimental results obtained from IR spectroscopic information are more reliable. The presented ATR-SEIRAS method is powerful in studying surface limited protein binding reactions.

Antioxidant activities of extract and fractions from receptaculum nelumbinis and related flavonol glycosides.

The antioxidant activities of ethanolic crude extract (ECE) and its four different solvent sub-fractions (namely, petroleum ether fraction (PEF), ethyl acetate fraction (EAF), n-butanol fraction (BF) and the aqueous fraction (AF) from the receptacles of Nelumbo nucifera Gaertn. (Receptaculum Nelumbinis) were investigated using two in vitro antioxidant assays. BF showed the highest total phenolic content (607.6 mg/g gallic acid equivalents), total flavonoid content (862.7 mg/g rutin equivalents) and total proanthocyanidin content (331.0 mg/g catechin equivalents), accompanied with the highest antioxidant activity compared to other fractions through 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging assays. Five flavonol glycosides, namely hyperoside (1), isoquercitrin (2), quercetin-3-O-ß-d-glucuronide (3), isorhamnetin-3-O-ß-d-galactoside (4) and syringetin-3-O-ß-d-glucoside (5) were isolated from the Receptaculum Nelumbinis. Compounds 2-5 were isolated for the first time from the Receptaculum Nelumbinis. The five isolated flavone glycosides, particularly compounds 1-3, demonstrated significant DPPH and ABTS radical scavenging activity, with IC(50) values of 8.9 ± 0.2, 5.2 ± 0.2, 7.5 ± 0.1 for DPPH and 114.2 ± 1.7, 112.8 ± 0.8, 172.5 ± 0.7 µg/mL for ABTS, respectively. These results suggest that Receptaculum Nelumbinis has strong antioxidant potential and may be potentially used as a safe and inexpensive bioactive source of natural antioxidants.

Dataset for the analysis of stock price responses to African Swine Fever Outbreaks in China.

The African Swine Fever (ASF) outbreaks in China since 2018 caused a more than 100 million decline in its hog inventory. Leveraging publicly available announcements of ASF outbreaks and daily stock prices data from 25 major publicly listed hog companies from China and eight major hog exporting countries, we use the event study method to estimate firm-level abnormal stock price responses to China's ASF outbreak announcements for both Chinese and foreign hog companies. This article describes the data used in the research article "A Fortune from misfortune: Evidence from hog firms' stock price responses to China's African Swine Fever outbreaks" (Xiong et al., 2021). The daily stock price data in this article can be applied to other events that also occurred during the same sample period using a similar event study approach.