Developing a High-Umami, Low-Salt Soy Sauce through Accelerated Moromi Fermentation with Corynebacterium and Lactiplantibacillus Strains.

The traditional fermentation process of soy sauce employs a hyperhaline model and has a long fermentation period. A hyperhaline model can improve fermentation speed, but easily leads to the contamination of miscellaneous bacteria and fermentation failure. In this study, after the conventional koji and moromi fermentation, the fermentation broth was pasteurized and diluted, and then inoculated with three selected microorganisms including Corynebacterium glutamicum, Corynebacterium ammoniagenes, and Lactiplantibacillus plantarum for secondary fermentation. During this ten-day fermentation, the pH, free amino acids, organic acids, nucleotide acids, fatty acids, and volatile compounds were analyzed. The fermentation group inoculated with C. glutamicum accumulated the high content of amino acid nitrogen of 0.92 g/100 mL and glutamic acid of 509.4 mg/100 mL. The C. ammoniagenes group and L. plantarum group were rich in nucleotide and organic acid, respectively. The fermentation group inoculated with three microorganisms exhibited the best sensory attributes, showing the potential to develop a suitable fermentation method. The brewing speed of the proposed process in this study was faster than that of the traditional method, and the umami substances could be significantly accumulated in this low-salt fermented model (7% w/v NaCl). This study provides a reference for the low-salt and rapid fermentation of seasoning.

Seroprevalence and potential risk factors of brucellosis in sheep from America, Africa and Asia regions: A systematic review and meta-analysis.

BACKGROUND: Brucellosis, a neglected and global zoonotic disease, infect a variety of mammals, among which sheep are one of the main hosts. This disease results in huge economic losses and is a widespread concern around the world. RESULT: Based on the selection criteria, 40 articles from 2010 to 2021 of five databases (CNKI, Wanfang, VIP, PubMed and Science Direct) reported in America, Africa and Asia were included. The data showed that during this period, the overall seroprevalence of sheep brucellosis on these three continents was 6.2%. At the regional level, sheep brucellosis had the highest seroprevalence (8.5%) in Africa and the lowest seroprevalence (1.9%) in the Americas. With regard to the age of the sheep, the seroprevalence was significantly higher in adult sheep (15.5%) than in lambs (8.6%). Further, the seroprevalence was significantly higher in sheep that had abortion (44.3%) than in pregnant (13.0%) and non-pregnant sheep (9.5%). With regard to herd size, herds with >20 sheep (35.4%) had a significantly higher seroprevalence than herds with <20 sheep (16.8%). In terms of farming and grazing mode, free-range rearing (8.4%) was associated with a significantly higher seroprevalence than intensive farming (2.8%), and mixed grazing (37.0%) was associated with a significantly higher seroprevalence than single grazing (5.7%). CONCLUSION: Sheep brucellosis is widely distributed in sheep-rearing regions of America, Africa and Asia, and sheep are susceptible to brucellosis by themselves or from other infectious sources. Therefore, timely monitoring of ovine brucellosis and improving farming and grazing patterns are critical to reducing the prevalence of brucellosis.

Hierarchical Macroporous Agarose Materials with Polyethyleneimine-Assisted Multiple Boronate Affinity Binding Sites for the Separation of Neomycin.

Quantification of neomycin residues in food samples demands an efficient purification platform. Herein, hierarchical macroporous agarose monoliths with multiple boronate affinity sites were established for selective separation of neomycin. The silica core was synthesized by "one-step" Stöber procedures followed by modification with amino group and incorporation of polyethyleneimine. A versatile macroporous agarose monolith was prepared by emulsification strategies and functionalized with epoxy groups. After introducing polyethyleneimine-integrated silica nanoparticles onto the agarose monolith, fluorophenylboronic acids were immobilized. The physical and chemical characteristics of the composite monolith were analyzed systematically. After optimization, neomycin showed high binding ability of 23.69 mg/g, and the binding capacity can be manipulated by changing the pH and adding monosaccharides. The composite monolith was subsequently utilized to purify neomycin from the spiked model aquatic products followed by high-performance liquid chromatography analysis, which revealed a remarkable neomycin purification effect, indicating the great potential in the separation of neomycin from complicated aquatic products.

Toward regulating biodegradation in stages of polyurethane copolymers with bicontinuous microphase separation.

For typical biodegradable polymers, their overall performance almost declines exponentially to the degradation degree, which inevitably leads to a dilemma between the requirements of service life and retention time in the environment (both in vitro and in vivo). It is a great challenge to develop a biodegradable polymeric device with relatively stable performance in service while rapidly degrading out of service. Herein, we demonstrate an effective strategy to control degradation of biodegradable polymers in stages by constructing separated bicontinuous microphases with very different microphase degradation rates. First, polyurethane copolymers (PCL-b-CrP-U) containing two blocks, i.e., semicrystalline poly(ε-caprolactone) (PCL) blocks and amorphous random copolymer blocks (CrP) based on ε-CL and p-dioxanone (PDO), were synthesized. The microscopic morphology of PCL-b-CrP-U is investigated by an alkali-accelerated degradation experiment, which also demonstrates that the chain cleavage-induced crystallization during degradation resulted in a self-reinforcement by forming degradation residues with a scaffold-like morphology. The tensile test shows that PCL-b-CrP-U has excellent mechanical properties (1500% of elongation at break, a tensile strength of about 7.5 MPa, and an elastic modulus of 40.0 MPa). The degradation experiments with artificial pancreatic juice as a working medium reveal that PCL-b-CrP-U samples containing relatively high PDO units exhibit a three-stage degradation, i.e. an induction stage, a steady degradation stage and an accelerated degradation stage. The CrP phase preferentially hydrolyzes to form some microchannels due to its amorphous nature and relatively high hydrophilicity, effectively accelerating the entry of water and enzymes into the inner parts of the sample. Meanwhile, at this stage, those originally amorphous PCL segments gradually crystalize owing to their enhanced chain mobility induced by the chain cleavage, forming a "scaffold"-like structure, which effectively reinforces the sample to resist the damage from external force and therefore guarantees a relatively stable mechanical performance of PCL-b-CrP-U during service. With the further depletion of the CrP phase, the intermediate "scaffold"-like structure is also very beneficial to accelerate the degradation of residues owing to its large specific surface area, which is expected to be beneficial for preventing long-term retention of the implantation devices.

Integrated Proteomics and Metabolomics Analyses of Serum in Chinese Patients with Severe and Active Graves' Orbitopathy: A Cross-sectional Study.

OBJECTIVE: The present study aims to investigate the alterations of serum proteomic and metabolomic profiles in Chinese patients with severe and active Graves' Orbitopathy (GO). MATERIALS AND METHODS: Thirty patients with GO and 30 healthy volunteers were enrolled. The serum concentrations of FT3, FT4, T3, T4, and thyroid-stimulating hormone (TSH) were analyzed, after which TMT labeling-based proteomics and untargeted metabolomics were performed. Metabo- Analyst and Ingenuity Pathway Analysis (IPA) was used for integrated network analysis. A nomogram was established based on the model to explore the disease prediction ability of the identified feature metabolites. RESULTS: One hundred thirteen proteins (19 up-regulated and 94 down-regulated) and 75 metabolites (20 increased and 55 decreased) were significantly altered in GO compared to the control group. By combining the lasso regression, IPA network, and protein-metabolite-disease sub-networks, we extracted feature proteins (CPS1, GP1BA, and COL6A1) and feature metabolites (glycine, glycerol 3-phosphate, and estrone sulfate). The logistic regression analysis revealed that the full model with the prediction factors and three identified feature metabolites had better prediction performance for GO compared to the baseline model. The ROC curve also indicated better prediction performance (AUC = 0.933 vs. 0.789). CONCLUSION: A new biomarker cluster combined with three blood metabolites with high statistical power can be used to discriminate patients with GO. These findings provide further insights into the pathogenesis, diagnosis, and potential therapeutic targets for this disease.

Effect of cognitive behavior therapy (CBT) on lowering of blood glucose levels in gestational diabetes mellitus (GDM) patients: study protocol for a prospective, open-label, randomized controlled trial.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common perinatal condition. Convincing evidence has shown that hyperglycemia and other chronic comorbidities of diabetes during the prenatal period increase maternal and fetal risk. Several guidelines have identified lifestyle management as the first-line therapy in GDM patients. To improve the efficacy of lifestyle intervention, cognitive behavior therapy (CBT) is proposed as a solution to improve clinical outcomes. The objective of this trial is to determine the efficacy in treating hyperglycemia of mobile-based CBT interventions in GDM patients, compared with conventional face-to-face interventions.  METHODS: This trial is designed as a prospective randomized controlled trial, which enrolled the patients diagnosed with GDM in First People's Hospital of Kunshan affiliated with Jiangsu University from September 2021 to March 2023 with a 3-month follow-up. The specific randomization method was established and implemented through the central randomization system of EDC clinical trials. The percentage of all blood glucose levels collected within the normal range between the two groups at baseline, during the intervention period, and postpartum infant and maternal outcomes will be measured. Summary statistics for continuous variables will include the number of subjects, mean, median, SD, or the standard error, minimum, and maximum. The chi-square test, t test, and paired-sample t test were used for statistical analysis of differences between groups. DISCUSSION: This trial investigates the effects of mobile-based CBT intervention on blood glucose levels in GDM patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100048527) [registered: 2021/07/09].

Population pharmacokinetics and pharmacogenetics of apatinib in adult cancer patients.

AIMS: Apatinib is widely used in Chinese cancer patients. As the in vivo drug disposition of apatinib has large individual differences, adverse events are prone to occur. Cytochrome P450 (CYP)3A5 and cancer types maybe the main factors affecting this individual differences. The objective of our study was to establish a population pharmacokinetics (PK) model of apatinib in adult cancer patients, and to explore optimal dosage regimens for individualized treatment. METHODS: Adult patients with various types of cancer treated with apatinib were enrolled. The concentration of apatinib in plasma was determined by high-performance liquid chromatography-tandem mass spectrometry. CYP3A5 genotype was determined using TaqMan allelic discrimination technique. The population PK model was developed by NONMEM V7.4. The dosing regimen was optimized based on Monte Carlo simulations. RESULTS: A population PK model of apatinib in adult cancer patient was established. CYP3A5 genotype and systemic cancer type (digestive system cancers, nondigestive system cancers) were the most significant covariates for PK parameters. Patients with CYP3A5*1 expressers (CYP3A5*1/*1 and CYP3A5*1/*3) had lower apparent clearance and apparent volume of distribution than patients who do not express CYP3A5*1 (CYP3A5*3/*3). Patients with nondigestive system cancer had higher apparent volume of distribution and absorption rate constant than digestive system cancer. The results of dose simulation suggest that the apatinib dose in patients who do not express CYP3A5*1 should be 33.33-50.00% higher than that in CYP3A5*1 expressers. CONCLUSIONS: A population PK model of apatinib in adult cancer patients was established. CYP3A5 genotype and systemic cancer type had concurrent effects on PK parameters. CYP3A5 patients who do not express CYP3A5*1 required higher doses.

Effect of mobile-based cognitive behavior therapy (CBT) on lowering of blood lipid levels in atherosclerotic cardiovascular disease (ASCVD) patients: study protocol for a multicenter, prospective, randomized controlled trial.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) remains a major source of mortality in China. Convincing evidence has demonstrated that the reduction of low-density lipoprotein cholesterol (LDL-C) is correlated with lowering ASCVD risk. The efficacy of lifestyle management in lipid levels reduction has been confirmed in numerous studies. However, considering that low compliance to lifestyle management has limited the benefits of lowering lipid levels, cognitive behavior therapy (CBT) is proposed as a solution to improve clinical outcomes. The objective of this trial is to compare the LDL-C outcome in ASCVD patients receiving mobile device-based CBT to a control group, with both groups under standard pharmacological treatments. METHODS: This trial is designed as a multicenter, prospective randomized controlled trial with a 6-month follow-up. Mean LDL-C level and the percentage of different LDL-C levels, coefficient of variation of LDL, General Self-Efficacy Scale (GSEs), quality of life index (QL-index), etc., between the two groups at baseline, 1, 3, and 6 months will be measured. DISCUSSION: This trial should demonstrate that the implementation of mobile-based CBT intervention will be potentially effective in lowering LDL-C levels in ASCVD patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( ChiCTR2100046775 ) [registered: 2021/5/28].

Prevalence of bovine viral diarrhea virus in cattle between 2010 and 2021: A global systematic review and meta-analysis.

Background: Bovine viral diarrhea is one of the diseases that cause huge economic losses in animal husbandry. Many countries or regions have successively introduced eradication plans, but BVDV still has a high prevalence in the world. This meta-analysis aims to investigate the prevalence and risk factors of BVDV in the world in recent 10 years, and is expected to provide some reference and theoretical basis for BVDV control plans in different regions. Method: Relevant articles published from 2010 to 2021 were mainly retrieved from NCBI, ScienceDirect, Chongqing VIP, Chinese web of knowledge (CNKI), web of science and Wanfang databases. Results: 128 data were used to analyze the prevalence of BVDV from 2010 to 2021. BVDV antigen prevalence rate is 15.74% (95% CI: 11.35-20.68), antibody prevalence rate is 42.77% (95% CI: 37.01-48.63). In the two databases of antigen and antibody, regions, sampling time, samples, detection methods, species, health status, age, sex, breeding mode, and seasonal subgroups were discussed and analyzed, respectively. In the antigen database, the prevalence of dairy cows in the breed subgroup, ELISA in the detection method subgroup, ear tissue in the sample subgroup, and extensive breeding in the breeding mode were the lowest, with significant differences. In the antibody database, the prevalence rate of dairy cows in the breed subgroup and intensive farming was the highest, with a significant difference. The subgroups in the remaining two databases were not significantly different. Conclusion: This meta-analysis determined the prevalence of BVDV in global cattle herds from 2010 to 2021. The prevalence of BVDV varies from region to region, and the situation is still not optimistic. In daily feeding, we should pay attention to the rigorous and comprehensive management to minimize the spread of virus. The government should enforce BVDV prevention and control, implement control or eradication policies according to local conditions, and adjust the policies in time.

Mutant Allele Frequency-Based Intra-Tumoral Genetic Heterogeneity Related to the Tumor Shrinkage Mode After Neoadjuvant Chemotherapy in Breast Cancer Patients.

The shrinkage mode of tumor extent after neoadjuvant chemotherapy (NAC) is an important index to evaluate the odds of breast-conserving surgery. However, there is no sufficient measurement to predict the shrinkage mode after NAC. In this study, we analyzed 24 patients' formalin-fixed, paraffin-embedded samples before and after treatment and analyzed 456 cancer-related genes panel by using target next-generation sequencing. Meanwhile, the pathological shrinkage mode was reconstructed in three dimensions after surgery, and the genetic heterogeneity level was estimated by mutant-allele tumor heterogeneity (MATH). We measured the genetic intra-tumor heterogeneity and explored its correlation with the shrinkage mode after NAC. A total of 17 matched pair samples of primary tumor tissue and residual tumor tissue were successfully accessed. It was found that the most common mutated genes were TP53 and PIK3CA in both samples before and after NAC, and no recurrent mutations were significantly associated with the shrinkage mode. Besides, the MATH value of formalin-fixed, paraffin-embedded samples before and after NAC was analyzed by the area under the curve of the receiver operating characteristic, and it is feasible to classify patients into concentric shrinkage mode and non-concentric shrinkage mode in NAC based on the MATH threshold of 58. Our findings indicate that the MATH value was associated with the shrinkage mode of breast cancer in a non-linear model. Patients with the MATH value below the threshold of 58 before and after NAC displayed a concentric shrinkage mode. The area under the curve was 0.89, with a sensitivity of 0.69 and specificity of 1. Our study might provide a promising application of intra-tumor heterogeneity that is measured by MATH to make a choice of surgery.

Development and application of SYBR Green â real-time quantitative reverse transcription PCR assay for detection of swine Getah virus.

Getah virus (GETV), a mosquito-borne virus belonging to the Alphavirus genus of family Togaviridae, has become increasingly problematic, which poses a huge threat to the safety of animals and public health. In order to detect GETV quickly and accurately, we have developed a SYBR Green I real-time quantitative reverse transcription PCR (RT-qPCR) assay for GETV with the detection limit of 66 copies/µL, excellent correlation coefficient (R2) of 0.9975, and amplification efficiency (E) of 98.90%, the target selected was the non-structural protein 3 of GETV. The sensitivity of it was higher than that of ordinary RT-PCR by 1000 folds, and the inter-assay and intra-assay CV values were all less than 0.99%. The newly developed RT-qPCR assay exhibited good sensitivity and reproducibility, which will provide technical support for the reliable and specific rapid diagnosis, and quantitative analysis of GETV infection.

Development of a Copper-Based Metal Organic Electrode for Nitrite Sensing.

BACKGROUND: Nitrite is naturally present in vegetables and added to processed meats to enhance their color and prolong their shelf life. It is of concern because it reacts to form nitrosamines, which have been linked to cancer. OBJECTIVE: To develop a quick, reliable, and inexpensive method for quantifying nitrite in foods. METHOD: A copper-based metal organic framework (Cu-MOF)/gold-platinum alloy nanoparticle(Au@Pt)-modified glassy carbon electrode (GCE) was developed via a simple wet chemical synthesis followed by electrochemical deposition of gold-platinum alloy nanoparticles onto the surface of a GCE. Morphological characterization and component analysis of the prepared nanomaterials were carried out by Fourier transform infrared spectroscopy and scanning electron microscopy. Cyclic voltammetry and electrochemical impedance spectroscopy were used to study the electrochemical behavior of the fabricated electrodes. RESULTS: The quantitative and specific detection of nitrite was obtained by the amperometric i-t method. At a pH of 7, temperature of 25°C, and ionic strength of 0.4 M, the electrode exhibited a linear range of 0.001-12.2 mM nitrite with a low detection limit of 72 nM (S/N = 3). CONCLUSIONS: The Cu-MOF/Au@Pt/GCE exhibited good repeatability, reproducibility, stability, and selectivity to provide a capable analysis method for food samples. HIGHLIGHTS: A Cu-MOF with a large surface area and high porosity was developed to provide an electrode with many active sites. The Au@Pt alloy nanoparticle improved the electrocatalytic activity toward nitrite. The synergistic action between the Cu-MOF and Au@Pt alloy nanoparticle enhanced the electrochemical performance of the sensor.

The role of GtxA during Gallibacterium anatis infection of primary chicken oviduct epithelial cells.

Gallibacterium anatis (G. anatis), one of the major pathogens causing reproductive tract disorders in laying hens, leads to a reduction in egg production and increased mortality, caused by either single or mixed infections with other pathogens. As a specific virulence factor of G. anatis, the role of GtxA in layers' salpingitis remains unclear. In this study, we explored the effect of GtxA on G. anatis infection by comparing wild strain Yu-PDS-RZ-1-SLG (RZ) and its GtxA deleted counterpart RZΔgtxA in primary chicken oviduct epithelial cells (COEC). Their adherence, invasion, cytoxicity, and ability to induce apoptosis and and cytokine secretion were evaluated and the cytotoxicity and cytokine secretion of the recombinant GtxA protein and its N-terminal adenylate cyclase and C-terminal RTX hemolysin domain were also analyzed. We found that the adhesion ability of RZΔgtxA was significantly lower than that of parental strain RZ, and its toxicity to COEC was weakened; Meanwhile, apoptosis was inhibited and the expression of IL-6, IL-2, TNF-α and IFN-γ were dramatically reduced in COEC infected by RZΔgtxA. In contrast, the recombinant protein GtxA inhibited the proliferation of oviduct cells and induced obvious cytotoxicity, and the expression of IL-6, TNF-α and IFN-γ were up-regulated in COEC interacted with recombinant proteins. Our study indicates that GtxA promotes G. anatis adherence to cells, changes cells permeability and expression of inflammatory factors, resulting in cell damage and apoptosis.

Protective Effects of Salvianolate on Myocardial Injury or Myocardial Infarction after Elective Percutaneous Coronary Intervention in NSTE-ACS Patients: A Randomized Placebo-Controlled Trial.

OBJECTIVE: To evaluate the protective effects of salvianolate on percutaneous coronary intervention (PCI) related myocardial injury or myocardial infarction after elective PCI in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients. METHODS: A total of 149 patients with NSTE-ACS who underwent elective PCI were enrolled. The patients were randomly allocated in a 1:1 ratio to the salvianolate group (74 cases) or the control group (75 cases). After exclusion criteria of coronary angiography, 60 patients with PCI therapy remained in the salvianolate group and 68 in the control group. The incidence and the severity of PCI related myocardial injury or myocardial infarction, in addition to major adverse cardiac events (MACEs) during 1 year follow-up after PCI were studied between the two groups. Multivariate logistic regression analysis was used to determine the independent factors for PCI related myocardial injury or myocardial infarction after elective PCI. RESULTS: Compared with the control group, salvianolate treatment reduced the incidence of PCI related severe myocardial injury or myocardial infarction (11.7% vs. 26.5%, P=0.035). The rate of MACEs or all-cause death within 1 month or 1 year after the procedure was not significantly different between the two groups. CONCLUSIONS: Periprocedural treatment with salvianolate reduces the incidence of PCI related severe myocardial injury or myocardial infarction, although it does not influence clinical prognosis. [Chinese clinical trial registry: ChiCTR1800016992].

Oral microbiome and pancreatic cancer.

BACKGROUND: Microbiota profiles differ between patients with pancreatic cancer and healthy people, and understanding these differences may help in early detection of pancreatic cancer. Saliva sampling is an easy and cost-effective way to determine microbiota profiles compared to fecal and tissue sample collection. AIM: To investigate the saliva microbiome distribution in patients with pancreatic adenocarcinoma (PDAC) and the role of oral microbiota profiles in detection and risk prediction of pancreatic cancer. METHODS: We conducted a prospective study of patients with pancreatic cancer (n = 41) and healthy individuals (n = 69). Bacterial taxa were identified by 16S ribosomal ribonucleic acid gene sequencing, and a linear discriminant analysis effect size algorithm was used to identify differences in taxa. Operational taxonomic unit values of all selected taxa were converted into a normalized Z-score, and logistic regressions were used to calculate risk prediction of pancreatic cancer. RESULTS: Compared with the healthy control group, carriage of Streptococcus and Leptotrichina (z-score) was associated with a higher risk of PDAC [odds ratio (OR) = 5.344, 95% confidence interval (CI): 1.282-22.282, P = 0.021 and OR = 6.886, 95%CI: 1.423-33.337, P = 0.016, respectively]. Veillonella and Neisseria (z-score) were considered a protective microbe that decreased the risk of PDAC (OR = 0.187, 95%CI: 0.055-0.631, P = 0.007 and OR = 0.309, 95%CI: 0.100-0.952, P = 0.041, respectively). Among the patients with PDAC, patients reporting bloating have a higher abundance of Porphyromonas (P = 0.039), Fusobacterium (P = 0.024), and Alloprevotella (P = 0.041); while patients reporting jaundice had a higher amount of Prevotella (P = 0.008); patients reporting dark brown urine had a higher amount of Veillonella (P = 0.035). Patients reporting diarrhea had a lower amount of Neisseria and Campylobacter (P = 0.024 and P = 0.034), and patients reporting vomiting had decreased Alloprevotella (P = 0.036). CONCLUSION: Saliva microbiome was able to distinguish patients with pancreatic cancer and healthy individuals. Leptotrichia may be specific for patients living in Sichuan Province, southwest China. Symptomatic patients had different bacteria profiles than asymptomatic patients. Combined symptom and microbiome evaluation may help in the early detection of pancreatic cancer.

A Prospective Randomized Multicenter Controlled Trial on Salvianolate for Treatment of Unstable Angina Pectoris in A Chinese Elderly Population.

OBJECTIVE: To evaluate the efficacy and safety of salvianolate in elderly patients with unstable angina pectoris (UAP). METHODS: A prospective double-blind randomized placebo-controlled multicenter trial in elderly patients with UAP from 13 third-grade class-A hospitals in China was performed. A total of 318 patients were randomly allocated in a 1:1 ratio to an experimental group (160 patients) and a control group (158 patients). The experimental group was treated with salvianolate for 14 days on the basis of conventional medicine, and the control group was given a placebo for 14 days with the same criteria. Follow-up was lasted 28 days in both groups. The primary endpoint was biweekly frequency of angina pectoris attacks. The secondary endpoints included biweekly dosage of nitroglycerin, the Seattle Angina Questionnaire, angina pectoris severity and duration, myocardial injury markers, high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as major adverse cardiovascular events (MACEs). Safety was assessed according to adverse events and serious adverse events. RESULTS: Baseline characteristics were similar between treatment groups. Compared with those in the control group, the frequency of biweekly angina attacks (2.92 vs . 4.08, P=0.025), the biweekly dosage of nitroglycerin, as well as the severity and duration of angina attacks (P<0.01) were reduced by salvianolate. The Seattle Angina Questionnaire score was also significantly improved in the experimental group than in the control group (P<0.05). No significant differences were observed between the two groups with respect to the incidence of MACEs. Salvianolate was well tolerated. CONCLUSIONS: Salvianolate appear to have efficacy and well tolerated for elderly patients with UAP. [ClinicalTrials.gov identifier: NCT03037047].

miR-15b-5p targeting amyloid precursor protein is involved in the anti-amyloid eflect of curcumin in swAPP695-HEK293 cells.

Curcumin exerts a neuroprotective effect on Alzheimer's disease; however, it is not known whether microRNAs are involved in this protective effect. This study was conducted using swAPP695-HEK293 cells as an Alzheimer's disease cell model. swAPP695-HEK293 cells were treated with 0, 0.5, 1, 2, 5, and 10 µM curcumin for 24 hours. The changes in miR-15b-5p, miR-19a-3p, miR-195-5p, miR-101-3p, miR-216b-5p, miR-16-5p and miR-185-5p expression were assessed by real-time quantitative polymerase chain reaction. The mRNA and protein levels of amyloid precursor protein, amyloid-ß40 and amyloid-ß42 were evaluated by quantitative real-time polymerase chain reaction, western blot assays and enzyme-linked immunosorbent assays. swAPP695-HEK293 cells were transfected with miR-15b-5p mimic, or treated with 1 µM curcumin 24 hours before miR-15b-5p inhibitor transfection. The effects of curcumin on amyloid precursor protein, amyloid-ß40 and amyloid-ß42 levels were evaluated by western blot assays and enzyme-linked immunosorbent assay. Luciferase assays were used to analyze the interaction between miR-15b-5p and the 3'-untranslated region of amyloid precursor protein. The results show that amyloid precursor protein and amyloid-ß expression were enhanced in swAPP695-HEK293 cells compared with HEK293 parental cells. Curcumin suppressed the expression of amyloid precursor protein and amyloid-ß and up-regulated the expression of miR-15b-5p in swAPP695-HEK293 cells. In addition, we found a negative association of miR-15b-5p expression with amyloid precursor protein and amyloid-ß levels in the curcumin-treated cells. Luciferase assays revealed that miR-15b-5p impaired the luciferase activity of the plasmid harboring the 3'-untranslated region of amyloid precursor protein. These findings indicate that curcumin down-regulates the expression of amyloid precursor protein and amyloid-ß in swAPP695-HEK293 cells, which was partially mediated by miR-15b-5p via targeting of the 3'-untranslated region of amyloid precursor protein.

[Epigenetic mechanism of obesity-induced male infertility].

Epigenetic changes induced by obesity can lead to male infertility phenotype. As for the relationship between obesity and male infertility, early studies mostly focused on the endocrine aspect. Recent studies have found that obesity can cause epigenetic changes, such as DNA methylation, residual histone modification, small RNA, etc, affecting sperm maturation and development. DNA methylation is a regulatory marker on cytosine residue of cytosine-phosphate-guanine dinucleotide. Obesity leads to abnormal DNA methylation, changes mRNA expression abundance, affects imprinted gene expression induses imprinted gene diseases. The modification methods of residual histones include methylation, acetylation, etc. They can interact or cooperate to ensure the normal growth and development of sperm. Obesity changes methylase and acetylase activities and directly affects methylation and acetylation of residual histones, and the expression of micro-RNAs in sperm as well, consequently causing sperm defects. This article reviews epigenetic changes caused by obesity and the mechanism of male infertility.