Modulating Whey Proteins Antigenicity with Lactobacillus delbrueckii subsp. bulgaricus DLPU F-36 Metabolites: Insights from Spectroscopic and Molecular Docking Studies.

Numerous studies have highlighted the potential of Lactic acid bacteria (LAB) fermentation of whey proteins for alleviating allergies. Nonetheless, the impact of LAB-derived metabolites on whey proteins antigenicity during fermentation remains uncertain. Our objective was to elucidate the impact of small molecular metabolites on the antigenicity of α-lactalbumin (α-LA) and ß-lactoglobulin (ß-LG). Through metabolomic analysis, we picked 13 bioactive small molecule metabolites from Lactobacillus delbrueckii subsp. bulgaricus DLPU F-36 for coincubation with α-LA and ß-LG, respectively. The outcomes revealed that valine, arginine, benzoic acid, 2-keto butyric acid, and glutaric acid significantly diminished the sensitization potential of α-LA and ß-LG, respectively. Moreover, chromatographic analyses unveiled the varying influence of small molecular metabolites on the structure of α-LA and ß-LG, respectively. Notably, molecular docking underscored that the primary active sites of α-LA and ß-LG involved in protein binding to IgE antibodies aligned with the interaction sites of small molecular metabolites. In essence, LAB-produced metabolites wield a substantial influence on the antigenic properties of whey proteins.

Illuminating the Characteristics and Assembly of Prokaryotic Communities across a pH Gradient in Pit Muds for the Production of Chinese Strong-Flavor Baijiu.

Pit mud (PM), as an important source of microorganisms, is necessary for Chinese strong-flavor baijiu (CSFB) production. Although it has been revealed that the PM prokaryotic community diversities are influenced by its quality, product area, ages, etc., the characteristics and assembly process of the prokaryotic community in PMs across a pH gradient are still unclear. In this study, the regular changes of α- and ß-diversities of the prokaryotic community across a pH gradient in PMs were revealed, which could be divided into "stable", "relatively stable", and "drastically changed" periods. A total of 27 phyla, 53 classes, and 381 genera were observed in all given samples, dominated by Firmicutes, Bacteroidetes, Proteobacteria, Lactobacillus, Caproiciproducens, Proteiniphilum, etc. Meanwhile, the complexity of the network structure of the prokaryotic microbial communities is significantly influenced by pH. The community assembly was jointly shaped by deterministic and stochastic processes, with stochastic process contributing more. This study was a specialized report on elucidating the characteristics and assembly of PM prokaryotic communities across a pH gradient, and revealed that the diversity and structure of PM prokaryotic communities could be predictable, to some degree, which could contribute to expanding our understanding of prokaryotic communities in PM.

rTMS regulates homotopic functional connectivity in the SCD and MCI patients.

Objective: Impaired interhemispheric connectivity and corpus callosum atrophy have been linked to cognitive impairment in Alzheimer's disease (AD). Existing evidence indicates that repetitive transcranial magnetic stimulation (rTMS) targeting the bilateral precuneus may enhance cognitive function in AD. This study aims to investigate the effects of precuneus rTMS on cognitive function, as well as alterations in interhemispheric functional connectivity (FC) and its structural basis in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Methods: A total of 14 patients with SCD and 16 patients with MCI were enrolled in this study and received 10 Hz rTMS intervention on the bilateral precuneus for 2 weeks. Neurocognitive scales, structural and functional magnetic resonance imaging were collected at enrollment and after the rTMS intervention. Interhemispheric FC was assessed using mirror homotopic functional connectivity (VMHC), while the structural equation modeling (SEM) was employed to analyze the relationship between corpus callosum volume, interhemispheric connectivity, and cognitive function after rTMS intervention. Results: The precuneus rTMS not only enhanced episodic memory in SCD, but also improved multiple cognitive domains in MCI. Post-rTMS intervention, decreased VMHC values in the lingual cortex, middle occipital gyrus, putamen, and fusiform gyrus were observed in SCD, and an increased VMHC value in the postcentral gyrus along with reduced VMHC value in the cerebellum and putamen in MCI. After intervention, more brain regions show decreased FC in SCD and MCI patients, suggesting that precuneus rTMS may protect cerebral cortical plasticity by reducing excessive functional compensation, and thus improve cognitive function. The SEM indicated that the corpus callosum serves as the structural foundation for rTMS regulation of interhemispheric FC to further improve cognitive function. Conclusion: 10 Hz rTMS in the bilateral precuneus could be a promising strategy to improve cognitive function in patients with SCD and MCI. Our study implies that improvements in cognition brought about by precuneus rTMS may result from the remodeling of interhemispheric FC, with the corpus callosum possibly acting as the anatomical basis for functional modulation.

Corrigendum: Ethyl lauroyl arginate: an update on the antimicrobial potential and application in the food systems industry: a review.

[This corrects the article DOI: 10.3389/fmicb.2023.1125808.].

Machine learning prediction of motor function in chronic stroke patients: a systematic review and meta-analysis.

Background: Recent studies have reported that machine learning (ML), with a relatively strong capacity for processing non-linear data and adaptive ability, could improve the accuracy and efficiency of prediction. The article summarizes the published studies on ML models that predict motor function 3-6 months post-stroke. Methods: A systematic literature search was conducted in PubMed, Embase, Cochorane and Web of Science as of April 3, 2023 for studies on ML prediction of motor function in stroke patients. The quality of the literature was assessed using the Prediction model Risk Of Bias Assessment Tool (PROBAST). A random-effects model was preferred for meta-analysis using R4.2.0 because of the different variables and parameters. Results: A total of 44 studies were included in this meta-analysis, involving 72,368 patients and 136 models. Models were categorized into subgroups according to the predicted outcome Modified Rankin Scale cut-off value and whether they were constructed based on radiomics. C-statistics, sensitivity, and specificity were calculated. The random-effects model showed that the C-statistics of all models were 0.81 (95% CI: 0.79; 0.83) in the training set and 0.82 (95% CI: 0.80; 0.85) in the validation set. According to different Modified Rankin Scale cut-off values, C-statistics of ML models predicting Modified Rankin Scale>2(used most widely) in stroke patients were 0.81 (95% CI: 0.78; 0.84) in the training set, and 0.84 (95% CI: 0.81; 0.87) in the validation set. C-statistics of radiomics-based ML models in the training set and validation set were 0.81 (95% CI: 0.78; 0.84) and 0.87 (95% CI: 0.83; 0.90), respectively. Conclusion: ML can be used as an assessment tool for predicting the motor function in patients with 3-6 months of post-stroke. Additionally, the study found that ML models with radiomics as a predictive variable were also demonstrated to have good predictive capabilities. This systematic review provides valuable guidance for the future optimization of ML prediction systems that predict poor motor outcomes in stroke patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022335260, identifier: CRD42022335260.

Optimizing Primary Healthcare in Hong Kong: Strategies for the Successful Integration of Radiology Services.

The primary healthcare system in Hong Kong plays a crucial role in addressing the healthcare needs of its population. However, the integration of radiology services into primary care settings has not been fully realized, and there is significant potential for improvement. Incorporating radiology services into primary healthcare can enhance patient care, promote cost-effectiveness, and increase the overall efficiency of the healthcare system by enabling earlier diagnosis and intervention for various health conditions. To successfully integrate radiology services, key strategies include the establishment of public-private partnerships, the adoption of teleradiology and telemedicine services, the development of comprehensive regulatory and policy frameworks, and the exploration of innovative financial models and incentives. By embracing these strategies, Hong Kong can optimize its primary healthcare system and ensure more equitable, effective care for its population.

Lauric arginate ethyl ester: An update on the antimicrobial potential and application in the food systems.

Lauric arginate ethyl ester (LAE), a cationic surfactant with low toxicity, displays excellent antimicrobial activity against a broad range of microorganisms. LAE has been approved as generally recognized as safe (GRAS) for widespread application in certain foods at a maximum concentration of 200 ppm. In this context, extensive research has been carried out on the application of LAE in food preservation for improving the microbiological safety and quality characteristics of various food products. This study aims to present a general review of recent research progress on the antimicrobial efficacy of LAE and its application in the food industry. It covers the physicochemical properties, antimicrobial efficacy of LAE, and the underlying mechanism of its action. This review also summarizes the application of LAE in various foods products as well as its influence on the nutritional and sensory properties of such foods. Additionally, the main factors influencing the antimicrobial efficacy of LAE are reviewed in this work, and combination strategies are provided to enhance the antimicrobial potency of LAE. Finally, the concluding remarks and possible recommendations for the future research are also presented in this review. In summary, LAE has the great potential application in the food industry. Overall, the present review intends to improve the application of LAE in food preservation.

[Research Progress of High-intensity Interval Training in Cardiac Rehabilitation of Patients with Acute Coronary Syndrome].

Acute coronary syndrome (ACS),with increasing mortality year by year,has become a major public health problem in China.Exercise rehabilitation as an important part of the out-of-hospital rehabilitation for the patients with heart diseases can further reduce the mortality of patients on the basis of drug treatment.The available studies have proved that high-intensity interval training (HIIT) is more effective and efficient than moderate-intensity continuous training (MICT) such as walking and jogging on chronic cardiovascular diseases such as heart failure,stable coronary heart disease,and hypertension and has high security.According to the latest research,HIIT can reduce the platelet response,mitigate myocardial ischemia-reperfusion injury,and increase the exercise compliance of ACS patients more significantly than MICT.Moreover,it does not increase the risk of thrombotic adverse events or malignant arrhythmia.Therefore,HIIT is expected to become an important part of exercise prescription in out-of-hospital cardiac rehabilitation strategy for the patients with ACS.

Spatial Pattern and Influencing Factors of Tourism Resources in Northwestern Ethnic Areas in China-A Case Study of Longde County.

With the in-depth development of the Western Development Strategy and Rural Revitalization, the tourism industry has become an important economic sector to drive local development in northwestern minority areas of China. This study established a database of tourism resources in Longde county and analyzed the spatial pattern of these tourism resources by using the scale index and kernel density. From the perspective of the natural and social environment, this paper quantitatively discusses the influencing factors of the spatial pattern of tourism resources in the county based on a multiple linear regression model. The results showed that: (1) There were 2049 tourism resources distributed in Longde County, and building and facility resources were the most prevalent. (2) The hierarchical structure of tourism resources in the county showed a "pyramid" distribution, where excellent tourism resources accounted for 22.60% of the total resources. (3) The spatial pattern showed an agglomeration distribution, and the spatial differences of all kinds of resources were significant. The resources were mainly distributed in Chengguan Town and Wenbao Township. (4) Topographic conditions, convenient transportation, population density and water system distribution were important factors that affected the spatial pattern of tourism resources. It was suggested that the government issue corresponding policies to optimize the spatial pattern of tourism resources; balance the relationship between the exploitation of tourism resources, tourism development and local economy, and the social and ecological environment; and promote the sustainable development of tourism in the northwestern ethnic areas in China.

Investigation of the Structure and Allergic Potential of Whey Protein by Both Heating Sterilization and Simulation with Molecular Dynamics.

As the main allergens in milk, whey proteins are heat-sensitive proteins and are widespread in dairy products and items in which milk proteins are involved as food additives. The present work sought to investigate the effect of heating sterilization on the allergenicity of α-lactalbumin (α-LA) and ß-lactoglobulin (ß-LG), the main composite and allergen in whey protein isolate (WPI), by combining molecular dynamics with experimental techniques for detecting the spatial structure and IgE binding capacity. The structure of WPI was basically destroyed at heat sterilization conditions of 95 °C for 5 min and 65 °C for 30 min by SDS-PAGE analysis and spectroscopic analysis. In addition, α-lactalbumin (α-LA) may be more sensitive to temperature, resulting in exposure to allergic epitopes and increasing the allergic potential, while the binding capacity of ß-lactoglobulin (ß-LG) to IgE was reduced under 65 °C for 30 min. By the radius of gyration (Rg) and root-mean-square deviation (RMSD) plots calculated in molecular dynamics simulations, α-LA was less structurally stable at 368 K, while ß-LG remained stable at higher temperatures, indicating that α-LA was more thermally sensitive. In addition, we observed that the regions significantly affected by temperatures were associated with the capacity of allergic epitopes (α-LA 80-101 and ß-LG 82-93, 105-121) to bind IgE through root-mean-standard fluctuation (RMSF) plots, which may influence the two major allergens. We inferred that these regions are susceptible to structural changes after sterilization, thus affecting the allergenicity of allergens.

Dietary Stevia Residue Extract Supplementation Improves Antioxidant Capacity and Intestinal Microbial Composition of Weaned Piglets.

This study aimed to investigate the effects of diet supplementation with stevia residue extract (SRE) on growth performance, intestinal health, and antioxidant capacity of weaned piglets. A total of 144 weaned piglets (body weight 6.8 ± 0.5 kg) were randomly selected and allocated into four treatment groups with six replicates of six pigs/pen. The treatments consisted of a basal diet without SRE or basal diet supplemented with 100, 200, or 400 mg/kg SRE. The results showed that the addition of 200 mg/kg SRE to the diet significantly reduced (p < 0.05) the diarrhea rate of piglets compared with the control group. The supplementation of 400 mg/kg SRE in the diet significantly reduced the piglets' serum MDA content and significantly increased (p < 0.05) the T-AOC, T-SOD, and GSH-PX activity in the serum. The dietary supplementation with 400 mg/kg SRE significantly increased (p < 0.05) the CAT and GSH-PX activity in the liver. Moreover, the supplementation of 400 mg/kg SRE in the diet significantly increased (p < 0.05) the relative abundance of Prevotellaceae (genus) and Roseburia (genus) beneficial bacteria compared to the control group. Spearman's correlation analysis showed that Prevotella (genus) abundance was positively correlated with liver GSH-PX activity and acetic acid content of colon contents. In conclusion, the supplementation of 400 mg/kg SRE to the diet can improve piglet health by regulating antioxidant reduction homeostasis, which may also be associated with an increase in the relative numbers of potentially beneficial bacteria.

N-Acetyl-L-Cysteine Protects Airway Epithelial Cells during Respiratory Syncytial Virus Infection against Mucin Synthesis, Oxidative Stress, and Inflammatory Response and Inhibits HSPA6 Expression.

Objective. Respiratory syncytial virus (RSV) infection is an important cause of hospitalization of children worldwide, leading to significant morbidity and mortality. RSV infection leads to increasing inflammatory and apoptosis events in the airway epithelium through mechanisms involving ROS generation. The antioxidant N-acetyl-L-cysteine (NAC) has been shown to inhibit influenza virus replication and to reduce the secretion of inflammatory and apoptotic mediators during virus infection. The study aims to investigate the effects of NAC on human bronchial epithelial cells BEAS-2B and HSPA6 expression during RSV infection. Methods. CCK-8 assays were performed to evaluate cell survival. The production of proinflammatory factors, TNF-α, IL-6, IL-1ß, IL-18, and MUC5AC was examined by quantitative real-time PCR and ELISA. Oxidative stress was determined by reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH)/glutathione disulfide (GSSG) ratio. Immunoblotting analysis of epidermal growth factor receptor (EGFR) and its phosphorylation was performed. The antiviral effect of NAC was assessed by determining viral titers using plaque assay. Results. RSV infection reduced cell survival, promoted the release of proinflammatory factors, increased the ROS production and MDA concentration, and diminished the SOD activity and GSH/GSSG ratio, all which were attenuated by NAC treatment. Accordingly, NAC treatment inhibited the activation of EGFR and MUC5AC in BEAS-2B cells with RSV infection. Furthermore, NAC administration resulted in a marked decrease in RSV-induced HSPA6 expression in BEAS-2B cells. Concomitantly, EPB treatment led to an evident inhibition of RSV fusion gene and viral replication in RSV-infected BEAS-2B cells. Conclusion. This work supports the use of NAC to exert antimucin synthesis, anti-inflammatory, antioxidant, and antiviral effects on airway epithelium during RSV infection.

Application of Wearable Sensors in the Treatment of Cervical Spondylosis Radiculopathy with Acupuncture.

Research shows that cervical spondylosis radiculopathy (CSR) is the most common type of cervical spondylosis in clinic, and Chinese medicine treatment has obvious advantages, among which acupuncture therapy has received increasing attention. CSR has the characteristics of high incidence, long treatment time, and easy recurrence after treatment. In order to meet the different needs of different patients, this paper uses wearable sensors to collect patient dynamic data, extracts the action features of cervical spondylosis to design a scoring system, analyzes the input feature scores through a convolutional neural network (CNN) model, and then outputs personalized acupuncture treatment plan. The development status of wearable sensors at home and abroad is introduced, and the modules and functions of the wearable sensors are designed. The CNN network is used as the network model for classification and recognition. The experimental results show that the CNN model used in this paper has a high classification accuracy, achieving an accuracy of up to 97%, and can help produce an effective treatment plan. In order to determine whether the treatment plan output by the model is effective, each group of data is handed over to two cervical spondylosis experts for scoring, and then the final treatment plan is determined from 10 acupuncture plans. In our experiments, 9 out of 10 plans generated by the CNN model were the same as generated by the experts, which shows the effectiveness of the model.

Sintering Nano-Silver Paste by Resistive Joule Heating Process for 2G HTS Tape Joints.

Developing a joining technology for 2G HTS tapes without significantly reducing their superconducting property is crucial for numerous applications (MRI, motor/generator, power transmission, etc.). In this study, low sintering temperature (~230 °C) nano-silver paste was used as solder to join two 2G HTS tapes. In addition, two heating methods, i.e., furnace heating (heat flux outside-in) and resistive Joule heating (heat flux inside-out), were studied. This study indicates that the heat flux from internal by resistive Joule heating method shows less deteriorating impact to the 2G RE-Ba-Cu-O tape (RE: rare earth element) during the sintering process with the best specific resistance of 0.074 µΩ∙cm2 and Ic retention percentage of 99% (i.e., Ic reduced from 100 A before joining to 99 A after joining). This study indicates that nano-silver paste together with resistive Joule heating can possibly be used as soldering materials to join 2G HTS tapes.

Dietary stevia residue extract supplementation improves the performance and antioxidative capacity of growing-finishing pigs.

BACKGROUND: Improper disposal of stevia residue causes environmental pollution and waste of resources. The extract of stevia residue is rich in chlorogenic acid and isochlorogenic acids, and has a great potential in livestock and poultry breeding. Therefore, this study aimed to investigate the effects of dietary stevia residue extract (SRE) supplementation on the performance, meat quality, antioxidative capacity and gut microbiota in growing-finishing pigs. RESULTS: The results showed that increasing the concentration of SRE supplementation linearly increased (P < 0.05) body weight from day 1 to 35. Supplementation with SRE significantly increased (P < 0.05) average daily gain (ADG) from day 1 to 75. 100 mg kg-1 SRE supplementation significantly increased (P < 0.05) hot carcass weight and gastric index. Moreover, increasing the concentration of SRE linearly increased (P < 0.05) the score of appearance of longissimus thoracis, as well as serum albumin, triglyceride and high-density lipoprotein cholesterol content. Further study found that increasing the concentration of SRE linearly increased (P < 0.05) serum total superoxide dismutase activity, and showed a significant quadratic relationship (P < 0.05) with activity of serum catalase, while linearly decreasing (P < 0.05) muscle malondialdehyde (MDA) content. Furthermore, supplementation with 100 mg kg-1 SRE significantly decreased (P < 0.05) serum MDA content, while 600 and 800 mg kg-1 SRE supplementation significantly decreased (P < 0.05) muscle MDA content. However, SRE supplementation had no significant effect on gut microbiota (P > 0.05). CONCLUSION: These data indicated that dietary SRE supplementation improves the performance and antioxidative capacity of growing-finishing pigs. We recommend that the optimal supplemental level of SRE in the diet of growing-finishing pigs is 100 mg kg-1 . © 2022 Society of Chemical Industry.

Suboptimal adherence to daily growth hormone in a US real-world study: an unmet need in the treatment of pediatric growth hormone deficiency.

OBJECTIVE: To evaluate adherence to, and discontinuation of, somatropin treatment over 4 years in a US population-based study of children with pediatric growth hormone deficiency (pGHD). METHODS: A retrospective cohort analysis of commercially insured patients ≥3 and <16 years, diagnosed with pGHD, newly treated with somatropin was conducted using Optum De-identified Clinformatics Data Mart. Index date was defined as the first prescription for somatropin between 01 July 2002 and 30 September 2019. Five non-exclusive patient cohorts were identified (>3, 12, 24, 36, and 48 months of post-index continuous enrollment). Suboptimal adherence was defined as medication possession ratio <80%. Discontinuation was defined as the date at which a gap of >60 days between somatropin fills first occurred. Cox proportional hazards regression was used to evaluate time to discontinuation. RESULTS: In the 12-month cohort (n = 3091), mean age was 11.3 ± 2.9 years, 75.9% were male, 70.9% white, 9.4% Hispanic, 3.6% Asian, and 3.1% black. The proportion with suboptimal adherence at months 12 and 48 was 19.6% and 35.9%, respectively. Discontinuation occurred in 42.2% of patients. The rate of discontinuation (HR [95% CI]) was higher for age ≥10 (1.74 [1.53-1.98]), females (1.35 [1.21-1.50]), black and Hispanic race/ethnicity (1.50 [1.18-1.90] and 1.27 [1.09-1.49] compared to White) and obesity (1.69 [1.19-2.40]). CONCLUSION: Suboptimal adherence increases with treatment duration, and risk of discontinuation is associated with age, female gender, black or Hispanic race/ethnicity, and obesity. Strategies that facilitate adherence among children at risk of discontinuation may improve clinical outcomes.

[Liquid chromatography-mass spectrometry-based metabolomics study of the efficacy of Chinese medicine asthma-relieving decoction on respiratory syncytial virus infection].

Respiratory syncytial virus (RSV) can cause lower respiratory tract infections, such as bronchiolitis in infants. In China, traditional asthma-relieving medicine has numerous clinical applications in the treatment of RSV infections. However, due to the complexity of the traditional Chinese medicine system, its therapeutic mechanism and main pharmacological components remain unclear. Metabolomics can be used to analyze the efficacy of traditional Chinese medicine to provide modern scientific evidence for such treatments. In this study, an animal model experiment was performed with seven groups of three-week-old rats. The model group and five intervention groups were inoculated nasally with RSV for three consecutive days, and the normal group was treated with the same amount of saline for three consecutive days under the same conditions. In parallel, the five intervention groups were treated separately with the following via intragastric administration for seven consecutive days: asthma-relieving traditional Chinese medicine decoction, its three constituent agents (ascending (xuan) therapy, descending (jiang) therapy, pyretic clearing (qing) therapy), and ribavirin. Both normal group and RSV model group were administered with normal saline via intragastric administration as controls for seven consecutive days. The fundus plasma of rats in each group was collected on day 0, day 3, and day 7. Liquid chromatography-mass spectrometry-based untargeted metabolomics analysis was performed to investigate the changes in the metabolome after RSV infection, the effects of the asthma-relieving decoction on the regulation of metabolites related to RSV infection, and the primary source of efficacy. The detected metabolite ions were corrected using internal standards. Multivariate analysis of ions with an RSD value of less than 30% in quality control (QC) samples was used to construct principal component analysis models to monitor the overall metabolic changes of each group. The results showed that, during RSV infection and treatment, the asthma-relieving decoction and the positive control ribavirin had similar effects on the overall metabolic regulation of RSV-infected rats. Among the three asthma-relieving decoction constituent agents, the ascending (xuan) therapy agents which was composed of ephedra and ginkgo had a closer metabolic regulation effect with asthma-relieving decoction, and might be the main source of pharmacological efficacy. Based on the retention time, m/z value and tandem mass spectra in the database established by our laboratory, a total of 150 metabolites were identified. Paired t-tests were performed using data of the identified metabolites before and after RSV infection in each group, and it was found that 83 metabolite levels significantly changed after RSV infection, indicating that RSV infection could lead to disorders of multiple metabolic pathways in rats. The altered pathways included aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, primary bile acid biosynthesis, phenylalanine metabolism and sphingomyelin metabolism. On the third day, the asthma-relieving decoction had regulatory effects on several metabolites such as bile acids, amino acids, organic acids, lipids, etc. Among the three asthma-relieving decoction constituent agents, the ascending (xuan) therapy agents had more similar effects on the regulation of metabolites with the asthma-relieving decoction. On the other hand, the descending (jiang) therapy agents and pyretic clearing (qing) therapy agents down-regulated the abnormal increase in acylcarnitine caused by the RSV infection. Additionally, both asthma-relieving decoction and its constituent agents could maintain the stability of the immune system and metabolism of the intestinal flora in rats. This study used metabolomics to evaluate the efficacy of an asthma-relieving decoction and demonstrate the metabolites and the corresponding changes after asthma-relieving decoction-based treatment. It provides theoretical support for research on the therapeutic mechanism and active ingredients of asthma-relieving decoction.

Inhibitory Effect of pH-Responsive Nanogel Encapsulating Ginsenoside CK against Lung Cancer.

Ginsenoside CK is one of the intestinal bacterial metabolites of ginsenoside prototype saponins, such as ginsenoside Rb1, Rb2, Rc, and Rd. Poor water solubility and low bioavailability have limited its application. The nanogel carriers could specifically deliver hydrophobic drugs to cancer cells. Therefore, in this study, a nanogel was constructed by the formation of Schiff base bonds between hydrazide-modified carboxymethyl cellulose (CMC-NH2) and aldehyde-modified ß-cyclodextrin (ß-CD-CHO). A water-in-oil reverse microemulsion method was utilized to encapsulate ginsenoside CK via the hydrophobic cavity of ß-CD. ß-CD-CHO with a unique hydrophobic cavity carried out efficient encapsulation of CK, and the drug loading and encapsulation efficiency were 16.4% and 70.9%, respectively. The drug release of CK-loaded nanogels (CK-Ngs) in vitro was investigated in different pH environments, and the results showed that the cumulative release rate at pH 5.8 was 85.5% after 140 h. The methylthiazolyldiphenyl-tetrazolium bromide (MTT) toxicity analysis indicated that the survival rates of A549 cells in CK-Ngs at 96 h was 2.98% compared to that of CK (11.34%). In vivo animal experiments exhibited that the inhibitory rates of CK-Ngs against tumor volume was 73.8%, which was higher than that of CK (66.1%). Collectively, the pH-responsive nanogel prepared herein could be considered as a potential nanocarrier for CK to improve its antitumor effects against lung cancer.

Antigenicity and Safety Evaluation of Lactiplantibacillus plantarum 7-2 Screened to Reduce α-Casein Antigen.

α-Casein (α-CN) is considered the main allergen in bovine milk. Lactic acid bacteria (LAB) fermentation can hydrolyze milk protein and therefore reduce the antigenicity. In this paper, a LAB reducing the antigenicity of casein, identified as LactiplantibacillusPlantarum 7-2 (L. plantarum 7-2), was primarily identified by screening for protein hydrolysis ability using a method involving the determination of released free amino acid with further selection for the ideal antigenicity-reducing capability by enzyme-linked immunosorbent assay (ELISA). In order to verify the capability of L. plantarum 7-2 in inhibiting antigenicity, the standard milk proteins α-LA, ß-LG, α-CN, ß-CN and κ-CN were cultured with L. plantarum 7-2 for 18 h; The results of SDS-PAGE show that all the bands corresponding to the full length tested proteins became unclear or completely disappeared indicating that these proteins were hydrolyzed by L. plantarum 7-2. Correspondingly, the antigenicities of α-CN and ß-LG were significantly reduced. L. plantarum 7-2 demonstrated negative hemolysis and nitrate reductase capabilities and was sensitive to the commonly used antibiotics ampicillin clindamycin tetracycline chloramphenicol, and erythromycin, demonstrating that L. plantarum 7-2 could be used in dairy product fermentation to reduce the antigenicity of milk protein.

Pro-pigmentary action of 5-fluorouracil through the stimulated secretion of CXCL12 by dermal fibroblasts / 中华医学杂志(英文版)

BACKGROUND@#There is growing evidence that 5-fluorouracil (5-FU) combined with therapeutic trauma can effectively induce skin repigmentation in vitiligo patients who are unresponsive to conventional treatments. Previous studies have mainly focused on identifying the antimitotic activity of 5-FU for the treatment of skin cancer, but few studies have investigated its extra-genotoxic actions favoring melanocyte recruitment.@*METHODS@#We utilized the full thickness excisional skin wound model in Dct-LacZ transgenic mice to dynamically assess the migration of melanocytes in the margins of wounds treated with or without 5-FU. The in-situ expression of CXCL12 was examined in the wound beds using immunofluorescence staining. Quantitative real-time polymerase chain reaction and Western blotting analyses were performed to detect the expression levels of CXCL12 mRNA and protein in primary mouse dermal fibroblasts treated with or without 5-FU. Transwell assays and fluorescein isothiocyanate (FITC)-phalloidin staining were used to observe cell migration and filamentous actin (F-actin) changes of melan-a murine melanocytes.@*RESULTS@#Whole mount and cryosection X-gal staining showed that the cell numbers of LacZ-positive melanocytes were much higher in the margins of dorsal and tail skin wounds treated with 5-FU compared with the controls. Meanwhile, CXCL12 immunostaining was significantly increased in the dermal compartment of wounds treated with 5-FU (control vs. 5-FU, 22.47 ± 8.85 vs. 44.69 ± 5.97, P < 0.05). Moreover, 5-FU significantly upregulated the expression levels of CXCL12 mRNA (control vs. 5-FU, 1.00 ± 0.08 vs. 1.54 ± 0.06, P < 0.05) and protein (control vs. 5-FU, 1.00 ± 0.06 vs. 2.93 ± 0.10, P < 0.05) in cultured fibroblasts. Inhibition of the CXCL12/CXCR4 axis suppressed melanocyte migration in vitro using a CXCL12 small interfering RNA (siRNA) or a CXCR4 antagonist (AMD3100).@*CONCLUSION@#5-FU possesses a pro-pigmentary activity through activation of the CXCL12/CXCR4 axis to drive the chemotactic migration of melanocytes.