The impact of heat treatment of bovine milk on gastric emptying and nutrient appearance in peripheral circulation in healthy females: a randomized controlled trial comparing pasteurized and ultra-high temperature milk.

BACKGROUND: Heat treatments of dairy, including pasteurization and ultra-high temperature (UHT) processing, alter milk macromolecular structures, and ultimately affect digestion. In vitro, animal, and human studies show faster nutrient release or circulating appearance after consuming UHT milk (UHT-M) compared with pasteurized milk (PAST-M), with a faster gastric emptying (GE) rate proposed as a possible mechanism. OBJECTIVES: To investigate the impact of milk heat treatment on GE as a mechanism of faster nutrient appearance in blood. We hypothesized that GE and circulating nutrient delivery following consumption would be faster for UHT-M than PAST-M. METHODS: In this double-blind randomized controlled cross-over trial, healthy female (n = 20; 27.3 ± 1.4 y, mean ± SD) habitual dairy consumers, consumed 500 mL of either homogenized bovine UHT-M or PAST-M (1340 compared with 1320 kJ). Gastric content volume (GCV) emptying half-time (T50) was assessed over 3 h by magnetic resonance imaging subjective digestive symptoms, plasma amino acid, lipid and B vitamin concentrations, and gastric myoelectrical activity were measured over 5 h. RESULTS: Although GCV T50 did not differ (102 ± 7 min compared with 89 ± 8 min, mean ± SEM, UHT-M and PAST-M, respectively; P = 0.051), GCV time to emptying 25% of the volume was 31% longer following UHT-M compared with PAST-M (42 ± 2 compared with 32 ± 4 min, P = 0.004). Although GCV remained larger for a longer duration following UHT-M (treatment × time interaction, P = 0.002), plasma essential amino acid AUC was greater following UHT-M than PAST-M (55,324 ± 3809 compared with 36,598 ± 5673 µmol·min·L-1, P = 0.006). Heat treatment did not impact gastric myoelectrical activity, plasma appetite hormone markers or subjective appetite scores. CONCLUSIONS: Contrary to expectations, GE was slower with UHT-M, yet, as anticipated, aminoacidemia was greater. The larger GCV following UHT-M suggests that gastric volume may poorly predict circulating nutrient appearance from complex food matrices. Dairy heat treatment may be an effective tool to modify nutrient release by impacting digestion kinetics. CLINICAL TRIAL REGISTRY: www.anzctr.org.au (ACTRN12620000172909).

Estimating surgical probability: Development and validation of a prognostic model for patients with lumbar disc herniation treated with acupuncture.

Lumbar disc herniation (LDH) is a common cause of pain in the lumbar spine and legs. While acupuncture has become the primary conservative treatment for LDH, some patients experience treatment failure and require surgery, causing substantial concern for clinicians. We developed an effective personalized clinical prediction model to identify the independent risk factors associated with acupuncture failure in patients with LDH. Our model aimed to predict the probability of surgery within 6 months of acupuncture failure in patients with LDH. A total of 738 patients with LDH who underwent acupuncture at 4 Chinese hospitals between January 2019 and October 2021 were selected. The patients were divided into training (n = 496) and validation (n = 242) cohorts. Seven predictive variables, including smoking, Oswestry Disability Index (ODI) score, lower-limb herniation, disc herniation type, lumbar spinal stenosis, lumbar lateral recess stenosis, and acupuncture frequency, were selected as risk factors using least absolute shrinkage and selection operato (LASSO) regression. A prediction model was developed using multivariate logistic regression analysis and a nomogram was constructed. The model exhibited good discrimination, with an area under the ROC curve (AUC) of 0.903 for the development cohort and 0.899 for the validation cohort. The Hosmer-Lemeshow goodness-of-fit test was a good fit for both cohorts (P = .956 for the development cohort; P = .513 for the validation cohort). Decision curve analysis (DCA) demonstrated that the threshold probabilities for the 2 cohorts ranged from > 4% and 5-95%, respectively. Therefore, the prediction model had a good net benefit. The nomogram established in this study, incorporating 7 risk factors, demonstrated a good predictive ability. It could predict acupuncture failure in LDH patients and the risk of surgery within 6 months, enabling physicians to conduct individualized treatment measures.

Changes in the functional properties of casein conjugates prepared by Maillard reaction with pectin or arabinogalactan.

The aim of this study was to prepare conjugates of casein (CA) with pectin (CP) or arabinogalactan (AG) by the Maillard reaction (wet-heating) and to investigate the effects of CP or AG on the structural and functional properties of casein. The results indicated that the highest grafting degree of CA with CP or AG was observed at 90 °C for 1.5 h or 1 h, respectively. Secondary structure showed that grafting with CP or AG reduced the α-helix level and increased the random coil level of CA. Glycosylation treatment of CA-CP and CA-AG exhibited lower surface hydrophobicity and higher absolute ζ-potential values, further significantly improving the functional properties of CA (e.g., solubility, foaming property, emulsifying property, thermal stability, and antioxidant activity). Accordingly, our results indicated that it is feasible for CP or AG to improve the functional properties of CA by the Maillard reaction.

Combination of hyperthermia and intravesical chemotherapy for the treatment of pT1 stage bladder cancer: A retrospectively clinical study.

PURPOSE: To evaluate the efficiency and safety of combined local bladder hyperthermia and intravesical chemotherapy (IVC) for the treatment of patients with pT1 stage bladder cancer. METHOD: A total of 189 patients with pT1 who underwent transurethral resection of bladder cancer (TURBT) were retrospectively reviewed. After TURBT, the patients with low-grade urothelial carcinoma (UC) were treated with either an IVC with pirarubicin (THP) protocol or chemo-thermotherapy (CHT) with THP protocol, whereas patients with high-grade UC were treated with either an intravesical immunotherapy (IVI) with bacillus Calmette-Guerin (BCG) protocol or CHT protocol, patients' characteristics, tumor biological features, and follow-up data were analyzed and compared between CHT and IVC group in low-grade UC, CHT, and IVI group in high-grade UC, respectively. RESULTS: The median follow-up time was 24 months. In patients with low-grade UC, the median recurrence free survival (RFS) interval and costs of treatment in CHT group were significantly higher than those in IVC group (p = .01, p < .001, respectively), CHT was associated with higher RFS compared with IVC by Kaplan-Meier analysis, and three patients in IVC group upgraded to high grade when tumor recurred, whereas no cases were found upgraded in CHT group, p = .38. In patients with high-grade UC, tumor recurrence rates at 12 (p = .004) and 24 months (p = .004) after TURBT, rate of complications (p = .04)-especially for hematuresis (p = .03) and irritation symptoms (p = .04)-the median costs of treatment (p < .001) in CHT group were significantly lower than those in IVI group, RFS interval, health-related quality of life) at 12 and 24 months after TURBT in CHT group was significantly higher than those in IVI group (p < .001, p = .002, and p < .001, respectively), and CHT was associated with higher RFS compared with IVI by Kaplan-Meier analysis. The rate of patients upstaged to pT2 in CHT group seemed lower than that in IVI group, but there was no significantly statistical difference (14.3% vs. 24%, p = .58). CONCLUSION: CHT has a beneficial prophylactic effect in patients with pT1 bladder cancer, especially in patients with high-grade UC, which is much more effective and safer than BCG, meanwhile it costs less compared with BCG.

Deciphering the potential role of Maca compounds prescription influencing gut microbiota in the management of exercise-induced fatigue by integrative genomic analysis.

A growing number of nutraceuticals and cosmeceuticals have been utilized for millennia as anti-fatigue supplements in folk medicine. However, the anti-fatigue mechanism underlying is still far from being clearly explained. The aim of the study is to explore the underlying mechanism of the Maca compound preparation (MCP), a prescription for management of exercise-induced fatigue. In this study, mice weight-loaded swimming test was used to evaluate the anti-fatigue effect of MCP. MCP significantly improved the forelimb grip strength and Rota-rod test in behavioral tests via regulating energy metabolism. 16S rDNA sequencing results showed MCP can regulate the intestinal flora at the genus level by increasing several beneficial bacteria (i.e., Lactobacillus, Akkermansia and etc.), and decreasing the harmful bacteria (i.e., Candidatus_Planktophila and Candidatus_Arthromitus), where notable high relevance was observed between the fatigue-related biomarkers and fecal microbiota. The results of microbial function analysis suggested that MCP might improve exercise-induced fatigue by enhancing energy metabolism, carbohydrate and lipid metabolism and metabolism of terpenoids and polyketides and breakdown of amino acid metabolism. In addition, and H2O2-induced oxidative stress model on C2C12 cells was employed to further validate the regulation of MCP on energy metabolisms. MCP pre-treatment significantly reduced intracellular ROS accumulation, and increased glycogen content, ATP generation capacity and mitochondrial membrane potential of skeletal muscle cells, as well as conferred anti-cell necrosis ability. In conclusion, MCP plays a key role in regulating fatigue occurrence in exercising and gut microbiota balance, which may be of particular importance in the case of manual workers or sub-healthy populations.

Faecal incontinence is associated with an impaired rectosigmoid brake and improved by sacral neuromodulation.

BACKGROUND: The rectosigmoid brake, characterised by retrograde cyclic motor patterns on high-resolution colonic manometry, has been postulated as a contributor to the maintenance of bowel continence. Sacral neuromodulation (SNM) is an effective therapy for faecal incontinence, but its mechanism of action is unclear. This study aims to investigate the colonic motility patterns in the distal colon of patients with faecal incontinence, and how these are modulated by SNM. METHODS: A high-resolution fibreoptic colonic manometry catheter, containing 36 sensors spaced at 1-cm intervals, was positioned in patients with faecal incontinence undergoing stage 1 SNM. One hour of pre- and post meal recordings were obtained followed by pre- and post meal recordings with suprasensory SNM. A 700-kcal meal was given. Data were analysed to identify propagating contractions. RESULTS: Fifteen patients with faecal incontinence were analysed. Patients had an abnormal meal response (fewer retrograde propagating contractions compared to controls; p = 0.027) and failed to show a post meal increase in propagating contractions (mean 17 ± 6/h premeal vs. 22 ± 9/h post meal, p = 0.438). Compared to baseline, SNM significantly increased the number of retrograde propagating contractions in the distal colon (8 ± 3/h premeal vs. 14 ± 3/h premeal with SNM, p = 0.028). Consuming a meal did not further increase the number of propagating contractions beyond the baseline upregulating effect of SNM. CONCLUSION: The rectosigmoid brake was suppressed in this cohort of patients with faecal incontinence. SNM may exert a therapeutic effect by modulating this rectosigmoid brake.

Mechanism of Phellodendron and Anemarrhena Drug Pair on the Treatment of Liver Cancer Based on Network Pharmacology and Bioinformatics.

Background: This study aims to explore the key targets and signaling pathways of the traditional Chinese medicine Phellodendron and Anemarrhena drug pair (PADP) for the treatment of liver cancer. Methods: Firstly, bioinformatics technology was used to analyze GSE62232 gene chip to obtain the differential genes of liver cancer. A network pharmacology technology was used to find the active components of PADP and their targets. Secondly, the differential genes were imported into STRING database to draw a PPI network, and network topology structure map combined with Cytoscape software. And the R language was used to identify differential gene targets and pathways through GO and KEGG pathway enrichment analysis. In addition, AutoDock Vina was used for molecular docking of core targets and core compounds. Moreover, GEPIA online analysis tool was used to perform survival analysis of the core target genes. Finally, RT-PCR was used to verify the changes of key target genes. CCK-8 assay was performed to detect cell proliferation. Flow cytometry was performed to detect the cell cycle and apoptotic. Transwell invasion assay was performed to detect cell invasion. Results: Firstly, a total of 21,654 genes were obtained. After screening, 1019 differential genes were obtained, including 614 down-regulated genes and 405 up-regulated genes. Furthermore, after screening by ADME standards, 52 active ingredients were obtained, of which 37 were Phellodendron and 15 were Anemarrhena. And a total of 36 differential genes have been identified, including 13 up-regulated genes and 23 down-regulated genes. Moreover, through enrichment analysis, we found that PADP may treat liver cancer through multiple channels and multiple pathways including the p53 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway and so on. Secondly, the molecular docking results showed that there was certain affinity between the core compounds and core target genes. In addition, GEPIA online analysis showed that ESR1, AR, CCNB1, CDK1, AKR1C3 and CCNA2 might become potential target genes for the survival and prognosis of PADP for the treatment of liver cancer. Finally, it was found that PADP could up regulate genes ESR1 and AR, down regulate genes CCNB1, CDK1, AKR1C3, and CCNA2. PADP could promote the apoptosis of liver cancer cells, shorten the cell cycle, and inhibit the proliferation and invasion of liver cancer cells. Conclusion: PADP may treat liver cancer through multiple targets, multiple channels, and multiple pathways, thereby suppressing cancer cells and improving the living quality of patients.

Network Pharmacology Exploration Reveals Gut Microbiota Modulation as a Common Therapeutic Mechanism for Anti-Fatigue Effect Treated with Maca Compounds Prescription.

Maca compounds prescription (MCP) is a common botanical used in dietary supplements, primarily to treat exercise-induced fatigue. The aim of this study is to elucidate the multi-target mechanism of MCP on fatigue management via network pharmacology and gut microbiota analysis. Databases and literature were used to screen the chemical compounds and targets of MCP. Subsequently, 120 active ingredients and 116 fatigue-related targets played a cooperative role in managing fatigue, where several intestine-specific targets indicated the anti-fatigue mechanism of MCP might be closely related to its prebiotics of intestinal bacteria. Thus, forced swimming tests (FSTs) were carried and mice fecal samples were collected and analyzed by 16S rRNA sequencing. Gut microbiota were beneficially regulated in the MCP-treated group in phylum, genus and OTU levels, respectively, and that with a critical correlation included Lactobacillus and Candidatus Planktophila. The results systematically reveal that MCP acts against fatigue on multi-targets with different ingredients and reshapes the gut microbial ecosystem.

18[Formula: see text]-Glycyrrhetinic Acid Inhibits TGF-[Formula: see text]-Induced Epithelial-to-Mesenchymal Transition and Metastasis of Hepatocellular Carcinoma by Targeting STAT3.

18[Formula: see text]-glycyrrhetinic acid (GA) is the active ingredient of the traditional Chinese medicinal herb Glycyrrhizae radix et rhizoma. We previously demonstrated that GA inhibited tumor growth in hepatocellular carcinoma (HCC). However, the effect of GA on transforming growth factor-[Formula: see text] (TGF-[Formula: see text]-induced epithelial-mesenchymal transition (EMT) and metastasis were still unclear. In this study, in vitro transwell assays and immunofluorescence (IF) demonstrated that GA inhibited TGF-[Formula: see text]-induced migration, invasion and EMT of HCC cells. However, it had little effect on the inhibition of proliferation by TGF-[Formula: see text]. Moreover, we confirmed that GA suppressed the metastasis of HCC cells in vivousing an ectopic lung metastasis model. Furthermore, we found that GA inhibited TGF-[Formula: see text]-induced EMT mainly by reducing the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which played an essential role in TGF-[Formula: see text]-induced EMT and cell mobility. Mechanistically, GA inhibited the phosphorylation of STAT3 by increasing the expression of Src homology 2 domain-containing protein tyrosine phosphatases 1 and 2 (SHP1 and SHP2). Therefore, we concluded that GA inhibited TGF-[Formula: see text]-induced EMT and metastasis via the SHP1&SHP2/STAT3/Snail pathway. Our data provide an attractive therapeutic target for future multimodal management of HCC.

[L-carnitine-astaxanthin compound nutrients for the treatment of idiopathic oligospermia and asthenozoospermia: A multicenter clinical observation].

OBJECTIVE: To investigate the clinical effects of the L-carnitine-astaxanthin compound nutrients Menglankang (MLK) on idiopathic oligospermia (OS) and asthenospermia (AS). METHODS: This study included 73 cases of OS and 220 cases of AS treated with MLK once a bag, bid, for 3 successive months. Before and at 1, 2 and 3 months after treatment, we obtained and analyzed the semen parameters and sperm DNA fragmentation index (DFI) of the patients. RESULTS: Compared with the baseline, the OS patients showed remarkable increases after 1 and 2 months of treatment in the semen volume (ï¼»3.07 ± 1.47ï¼½ vs ï¼»3.26 ± 1.26ï¼½ and ï¼»3.30 ± 1.28ï¼½ ml), sperm concentration (ï¼»10.96 ± 6.09ï¼½ vs ï¼»16.74 ± 11.15ï¼½ and ï¼»17.56 ± 9.92ï¼½ ×106/ml, P < 0.05), total sperm count (ï¼»29.78 ± 17.48ï¼½ vs ï¼»52.98 ± 32.07ï¼½ and ï¼»57.67 ± 36.98ï¼½ ×106, P < 0.05) and the percentages of progressively motile sperm (PMS) (ï¼»39.8 ± 11.66ï¼½% vs ï¼»45.3 ± 14.03ï¼½% and ï¼»46.42 ± 10.69ï¼½%, P < 0.05) and morphologically normal sperm (MNS) (ï¼»1.71 ± 1.07ï¼½% vs ï¼»1.79 ± 0.91ï¼½% and ï¼»1.84 ± 0.96ï¼½%), and so did the AS patients in PMS (ï¼»19.23 ± 8.32ï¼½% vs ï¼»25.46 ± 13.86ï¼½% and ï¼»27.33 ± 12.88ï¼½%, P < 0.05). After 3 months of medication, the OS patients exhibited even more significant increases in the semen volume (ï¼»3.63 ± 1.39ï¼½ ml) (P < 0.05), sperm concentration (ï¼»20.56 ± 14.7ï¼½ ×106/ml) (P < 0.05), total sperm count (ï¼»66.35 ± 55.91ï¼½ ×106) (P < 0.05), PMS (ï¼»49.24 ± 13.45ï¼½%) (P < 0.05) and MNS (ï¼»2.59 ± 0.93ï¼½%) (P < 0.05), and so did the AS patients in the semen volume (ï¼»3.27 ± 1.42ï¼½ vs ï¼»3.85 ± 1.59ï¼½ ml, P < 0.05), PMS (ï¼»29.11 ± 13.58ï¼½%) (P < 0.05) and NMS (ï¼»2.01 ± 1.14ï¼½% vs ï¼»2.57 ± 1.15ï¼½%, P < 0.05). In comparison with the baseline, the sperm DFI was not significantly improved at 1 month after treatment, but remarkably decreased at 2 and 3 months in the OS patients (ï¼»25.87 ± 13.76ï¼½% vs ï¼»18.66 ± 10.83ï¼½% and ï¼»16.48 ± 11.46ï¼½%, P < 0.05) and the AS patients as well (ï¼»26.40 ± 12.28ï¼½% vs ï¼»19.35 ± 11.54ï¼½% and ï¼»15.32 ± 10.89ï¼½%, P < 0.05). CONCLUSIONS: The L-carnitine-astaxanthin compound nutrients Menglankang can significantly improve the semen quality of the patients with idiopathic oligospermia or asthenospermia.

Design of Hepatic Targeted Drug Delivery Systems for Natural Products: Insights into Nomenclature Revision of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-dysfunction-associated fatty liver disease (MAFLD), affects a quarter of the worldwide population. Natural products have been extensively utilized in treating NAFLD because of their distinctive advantages over chemotherapeutic drugs, despite the fact that there are no approved drugs for therapy. Notably, the limitations of many natural products, such as poor water solubility, low bioavailability in vivo, low hepatic distribution, and lack of targeted effects, have severely restricted their clinical application. These issues could be resolved via hepatic targeted drug delivery systems (HTDDS) that boost clinical efficacy in treating NAFLD and decrease the adverse effects on other organs. Herein an overview of natural products comprising formulas, single medicinal plants, and their crude extracts has been presented to treat NAFLD. Also, the clinical efficacy and molecular mechanism of active monomer compounds against NAFLD are systematically discussed. The targeted delivery of natural products via HTDDS has been explored to provide a different nanotechnology-based NAFLD treatment strategy and to make suggestions for natural-product-based targeted nanocarrier design. Finally, the challenges and opportunities put forth by the nomenclature update of NAFLD are outlined along with insights into how to improve the NAFLD therapy and how to design more rigorous nanocarriers for the HTDDS. In brief, we summarize the up-to-date developments of the NAFLD-HTDDS based on natural products and provide viewpoints for the establishment of more stringent anti-NAFLD natural-product-targeted nanoformulations.

Anti-fatigue effect of Lepidium meyenii Walp. (Maca) on preventing mitochondria-mediated muscle damage and oxidative stress in vivo and vitro.

Maca (Lepidium meyenii Walp.) has emerged as a popular functional plant food due to its various pharmacological properties, including anti-oxidation, anti-inflammation and anti-fatigue activity. In this study, we investigated the role of Maca aqueous extract (ME) on muscle during exercise-induced fatigue both in vivo and in vitro. As a result, ME significantly enhanced mouse leg grip-strength and increased exercise endurance in the rota-rod test. ME could clear the accumulation of metabolites - blood lactic acid (BLA), blood urea nitrogen (BUN) and reactive oxygen species (ROS) levels after weight-loaded forced swimming. Focusing on muscle, we found that the administration of ME strengthened mouse muscle structures so that exercise-induced metabolic stress was alleviated by upregulating NAD+/NADH. Furthermore, ME inhibited the reduction of the viability and accumulation of ROS by treatment with H2O2 in C2C12 skeletal muscle cells. ME-induced activation of energy metabolism in skeletal muscle might up-regulate mitochondrial biogenesis and function, thereby protecting against oxidative stress-induced damage. We concluded that the effects of Maca played a crucial role in the regulation of exercise-induced fatigue in mouse muscle, which could be expected to serve as a functional food supplement for improving exercise performance and alleviating physical fatigue.

Protective effects of tryptophan-catabolizing Lactobacillus plantarum KLDS 1.0386 against dextran sodium sulfate-induced colitis in mice.

Tryptophan is an essential amino acid for the human body, whose intake is through the diet. Several studies support the theory that microbiota-derived tryptophan metabolite played a crucial role in maintaining the balance between gut microbiota and the mucosal immune system. Previously, we selected the Lactobacillus plantarum KLDS 1.0386 strain with high tryptophan-metabolic activity after the screening of 16 Lactobacillus strains. The current study aimed to assess the effects of L. plantarum KLDS 1.0386 combination with tryptophan in improving ulcerative colitis (UC) induced by dextran sodium sulfate (DSS) and the potential mechanisms involved. Our results showed that L. plantarum KLDS 1.0386 combined with tryptophan (LAB + Trp) decreased DAI score, MPO level, and pro-inflammatory cytokine (TNF-α, IL-1ß, and IL-6) concentration. It also increased anti-inflammatory cytokine (IL-10) production, tight junction proteins (claudin-1, occludin, and ZO-1), and mucin (MUC1 and MUC2) mRNA expressions. The level of indole-3-acetic acid (IAA), an important tryptophan metabolite in the liver, serum, and colon, was elevated after LAB + Trp treatment, which further upregulated aryl hydrocarbon receptor (AHR) mRNA expression to activate the IL-22/STAT3 signaling pathway. Moreover, the supplementation with LAB + Trp modulated gut microbiota composition. The present study provided novel insights that can be used to reduce the number of UC patients by employing a method utilizing tryptophan-catabolizing Lactobacillus strains.

Long-term trends in water quality and influence of water recharge and climate on the water quality of brackish-water lakes: A case study of Shahu Lake.

This study aimed to assess the long-term fluctuations in water quality and the influence of Yellow River water recharge and climatic condition on the water environmental index of a typical brackish-water lake. This study investigated several surface water quality parameters and their relationships with the water quality index (WQI) and trophic status index (TSI) of Shahu Lake from 2011 to 2018. A health risk assessment was conducted, and the correlations among water recharge, climatic conditions, and the aforementioned elements were determined. Results show that the water quality in this lake went from good to moderate and back to good as reflected in the changes in its WQI values from 2011 to 2018. The relative water quality inferiority of this lake in 2015 and 2016 was attributed to the significant increase in its CODMn, TP, TN, NH3-N, and fluoride (F-) concentrations during these years. A combination of these parameters could rapidly predict water quality through a stepwise multiple linear regression. During the study period (except in the frozen season), Shahu Lake maintained a eutrophic status every month (especially in July) irrespective of the spatial changes resulting from low secchi depth and high TP. The limiting nutrient of Shahu Lake changed from phosphorus to both nitrogen and phosphorus, especially during summer, due to seasonal variations and exogenous inputs. The lake had an acceptable health risk level, and water recharge both had positive and negative effects on this lake as reflected in the significant decrease or increase in the concentrations of its principal parameters. This condition was also attributed to temperature and precipitation, which resulted in significant TSI variations. The findings of this study provide ways of estimating and forecasting water quality and trophic status and a basis for managing and improving similar brackish-water lakes.

Mechanism of Selenium Nanoparticles Inhibiting Advanced Glycation End Products.

Selenium nanoparticles (SeNPs) have been applied in fields of nanobiosensors, environment, nanomedicine, etc. as a result of their excellent characteristics. Early studies had shown that SeNPs have certain inhibition ability against glycation, but the inhibition mechanism, especially for the influence of SeNPs on the reaction activity of glycation sites, remains unclear. The aim of the presented research was to reveal the effects of SeNPs on the ß-lactoglobulin (ß-Lg)/d-ribose glycation system at the molecular level and explore the possible inhibitory mechanism of SeNPs on the formation of advanced glycation end products (AGEs) by analyzing the glycation sites via high-performance liquid chromatography (HPLC)-Orbitrap-tandem mass spectrometry (MS/MS). Changes in contents of AGE formation and free amino acid contents had indicated that SeNPs could significantly slow the glycation process, thus attenuating the formation of AGEs. HPLC-Orbitrap-MS/MS analysis revealed that, at 6, 12, and 24 h, the number of glycation sites of glycated ß-Lg decreased from 7, 7, and 9 to 5, 5, and 6 after the intervention of SeNPs, respectively. The glycation extent of each glycation site was controlled, and the dual-glycation ability of K8, K14, K47, K91, and K101 was changed. All of these results confirmed that SeNPs could indeed slow the process of protein glycation at the molecular level. This may be the reason for SeNPs reducing the formation of AGEs during glycation. Therefore, this study shed light on the insight of how SeNPs reduce the formation of AGEs.

Mechanism of Dayuanyin in the treatment of coronavirus disease 2019 based on network pharmacology and molecular docking.

BACKGROUND: At present, coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, is spreading all over the world, with disastrous consequences for people of all countries. The traditional Chinese medicine prescription Dayuanyin (DYY), a classic prescription for the treatment of plague, has shown significant effects in the treatment of COVID-19. However, its specific mechanism of action has not yet been clarified. This study aims to explore the mechanism of action of DYY in the treatment of COVID-19 with the hope of providing a theoretical basis for its clinical application. METHODS: First, the TCMSP database was searched to screen the active ingredients and corresponding target genes of the DYY prescription and to further identify the core compounds in the active ingredient. Simultaneously, the Genecards database was searched to identify targets related to COVID-19. Then, the STRING database was applied to analyse protein-protein interaction, and Cytoscape software was used to draw a network diagram. The R language and DAVID database were used to analyse GO biological processes and KEGG pathway enrichment. Second, AutoDock Vina and other software were used for molecular docking of core targets and core compounds. Finally, before and after application of DYY, the core target gene IL6 of COVID-19 patients was detected by ELISA to validate the clinical effects. RESULTS: First, 174 compounds, 7053 target genes of DYY and 251 genes related to COVID-19 were selected, among which there were 45 target genes of DYY associated with treatment of COVID-19. This study demonstrated that the use of DYY in the treatment of COVID-19 involved a variety of biological processes, and DYY acted on key targets such as IL6, ILIB, and CCL2 through signaling pathways such as the IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and cytokine-cytokine receptor interaction. DYY might play a vital role in treating COVID-19 by suppressing the inflammatory storm and regulating immune function. Second, the molecular docking results showed that there was a certain affinity between the core compounds (kaempferol, quercetin, 7-Methoxy-2-methyl isoflavone, naringenin, formononetin) and core target genes (IL6, IL1B, CCL2). Finally, clinical studies showed that the level of IL6 was elevated in COVID-19 patients, and DYY can reduce its levels. CONCLUSIONS: DYY may treat COVID-19 through multiple targets, multiple channels, and multiple pathways and is worthy of clinical application and promotion.

The effects of low-and high-frequency non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) on gastric slow waves evaluated using in vivo high-resolution mapping in porcine.

BACKGROUNDS: Gastric motility is regulated by an electrophysiological activity called slow-wave and neuronal innervations by the vagus nerve. Transcutaneous auricular vagal nerve stimulation (taVNS) has been demonstrated to have therapeutic potential for a wide range of medical conditions, including the management of gastric dysfunctions. The main objective of this study was to gain a better understanding of how non-invasive neuromodulation influences gastric slow wave under in vivo conditions. METHODS: TaVNS protocols were applied in conjunction with 192-channel gastric bioelectrical mapping in porcine subjects under general anesthesia. The spatiotemporal profiles of gastric slow wave were assessed under two different taVNS protocols at 10 and 80 Hz. KEY RESULTS: The taVNS protocols effectively altered the interval and amplitude of gastric slow waves, but not the velocity or the percentage of spatial dysrhythmias. In the subjects that responded to the protocols, the 10 Hz protocol was shown to normalize slow-wave propagation pattern in 90% of the subjects, whereas the 80 Hz protocol was shown to inhibit slow waves in 60% of the subjects. CONCLUSIONS AND INFERENCES: Chronic responses of gastric motility and slow waves in response to taVNS should be investigated using non-invasive means in conscious subjects in future.

Ag@TiO2 Nanoprisms with Highly Efficient Near-Infrared Photothermal Conversion for Melanoma Therapy.

Melanoma is a primary reason of death from skin cancer and associated with high lethality. Photothermal therapy (PTT) has been developed into a powerful cancer treatment technique in recent years. Here, we created a low-cost and high-performance PTT agent, Ag@TiO2 NPs, which possesses a high photothermal conversion efficiency of ≈65 % and strong near-infrared (NIR) absorption about 808 nm. Ag NPs were synthesized using a two-step method and coated with TiO2 to obtain Ag@TiO2 NPs by a facile sol-gel method. Because of the oxide, Ag@TiO2 NPs exhibit remarkable high photothermal conversion efficiencies and biocompatibility in vivo and in vitro. Cytotoxicity and therapeutic efficiency of photothermal cytotoxicity of Ag@TiO2 NPs were tested in B16-F10 cells and C57BL/6J mice. Under light irradiation, the elevated temperature causes cell death in Ag NPs-treated (100 µg mL-1 ) cells in vitro (both p<0.01). In the case of subcutaneous melanoma tumor model, Ag@TiO2 NPs (100 µg mL-1 ) were injected into the tumor and irradiated with a 808 nm laser of 2 W cm-2 for 1 minute. As a consequence, the tumor volume gradually decreased by NIR laser irradiation with only a single treatment. The results demonstrate that Ag@TiO2 NPs are biocompatible and an attractive photothermal agent for cutaneous melanoma by local delivery.

In vitro and in vivo evaluation of an exopolysaccharide produced by Lactobacillus helveticus KLDS1.8701 for the alleviative effect on oxidative stress.

Correlations between oxidative stress and degenerative diseases have been gaining increasing attention. A number of studies affirm that exopolysaccharide (EPS) produced by lactic acid bacteria (LAB) can alleviate oxidative stress and further prevent the related diseases. In our previous study, Lactobacillus helveticus KLDS1.8701 has been shown to possess high antioxidant capacity in vitro. The aim of this study was to evaluate the ameliorative effects of EPS produced by L. helveticus KLDS1.8701 on oxidative stress. Firstly, EPS was isolated from the culture of L. helveticus KLDS1.8701 and purified using DEAE-Sepharose Fast Flow chromatography. Secondly, the antioxidant capacities of EPS fractions were evaluated using in vitro methods. Thirdly, an in vivo study was performed to investigate the possible protective effects of EPS on d-galactose (d-gal)-induced liver damage and gut microbiota disorder. In vitro antioxidant activity results suggested that EPS-1 exhibited strong scavenging properties on 2,2-diphenyl-1-picrylhydrazyl radical, superoxide radical, hydroxyl radical, and chelating activity on ferrous ion. In vivo, EPS-1 supplementation significantly attenuated oxidative status such as decreased organic index, liver injury and liver oxidative stress. EPS-1 supplementation shifted the gut microbiota composition to that of the control group. In addition, the analysis of Spearman's rank correlation suggested that the protective effects of EPS correlated with manipulating the gut microbiota composition in d-gal-induced mice. These results implied that EPS-1 supplementation could mitigate hepatic oxidative stress via manipulating the gut microbiota composition and be used as a potential candidate to attenuate oxidative damage.

The Effect of Gastric Electrical Stimulation on Small Bowel Motility in Patients With Gastroparesis and Concomitant Pancreatic and Small Bowel Dysfunction: From Animal Model to Human Application.

BACKGROUND/AIMS: Patients with gastroparesis often have biliary/pancreatic and small bowel symptoms but the effects of gastric electrical stimulation on small bowel electrical activity of the mid-gut have not been studied. Animal model aim: Establish gastric and upper small bowel/biliary slow wave activity relationships with electrical stimulation. Human study aim: Demonstrate improvement in symptoms associated with proximal small bowel dysmotility in gastric stimulated patients. MATERIALS AND METHODS: Animal model: In vivo evoked responses of duodenal and Sphincter of Oddi measures recorded during gastric electrical stimulation in a nonsurvival swine model (N = 3). High-resolution electrical slow wave mapping of frequency, amplitude, and their ratio, for duodenal and Sphincter of Oddi electrical activity were recorded. Human study: Patients (N = 8) underwent temporary gastric stimulation with small bowel electrodes. Subjective and objective data was collected before and after temporary gastric stimulation. Symptom scores, gastric emptying times, and mucosal electrograms via low-resolution mapping were recorded. RESULTS: Animal gastric stimulation resulted in some changes in electrical activity parameters, especially with the highest energies delivered but the changes were not statistically significant. Human study revealed improvement in symptom and illness severity scores, and changes in small bowel mucosal slow wave activity. CONCLUSIONS: Gastric electrical stimulation in an animal model seems to show nonsignificant effects small bowel slow wave activity and myoelectric signaling, suggesting the existence of intrinsic neural connections. Human data shows more significance, with possible potential for therapeutic use of electrical stimulation in patients with gastroparesis and pancreato-biliary and small bowel symptoms of the mid-gut. This study was limited by the nonsurvival pig model, small sample size, and open label human study.