Ginkgo biloba extract protects against diabetic cardiomyopathy by restoring autophagy via adenosine monophosphate-activated protein kinase/mammalian target of the rapamycin pathway modulation.

Studies demonstrated that Ginkgo biloba extract (GBE) played a cardioprotective role in diabetic conditions. Impaired autophagy is one of the mechanisms underlying diabetic cardiomyopathy (DCM). The effect of GBE on autophagy has been observed in several diseases; however, whether GBE can ameliorate DCM by regulating autophagy remains unclear. Here, we investigated the effect of GBE on DCM and the potential mechanisms regarding autophagy using a streptozotocin (STZ)-induced diabetic rat model and a high-glucose (HG)-stimulated H9C2 cell model. We demonstrated that GBE attenuated metabolic disturbances, improved cardiac function, and reduced myocardial pathological changes in diabetic rats. Impaired autophagy as well as dysregulation of the adenosine monophosphate-activated protein kinase/ mammalian target of the rapamycin (AMPK/mTOR) signaling pathway were observed in diabetic hearts, as evidenced by the reduced conversion of LC3B-I to LC3B-II along with excessive p62 accumulation, decreased AMPK phosphorylation, and increased mTOR phosphorylation, which could be reversed by GBE treatment. In vitro, GBE reduced the apoptosis induced by HG in H9C2 cells by activating AMPK and inhibiting mTOR to restore autophagy. However, this effect was inhibited by the AMPK inhibitor Compound C. In conclusion, the ameliorative effect of GBE on DCM might be dependent on the restoration of autophagy through modulation of the AMPK/mTOR pathway.

Inclusion of quantitative high-density plaque in coronary computed tomographic score system to predict the time of guidewire crossing chronic total occlusion.

OBJECTIVE: This study aimed to establish a new scoring system that includes histological quantitative features derived from coronary computed tomographic angiography (CCTA) to predict the efficiency of chronic total occlusion percutaneous coronary intervention (CTO-PCI). METHODS: This study analyzed clinical, morphological, and histological characteristics of 207 CTO lesions in 201 patients (mean age 60.0 [52.0-65.0] years, 85% male), which were recruited from two centers. The primary endpoint was a guidewire successfully crossing the lesions within 30 m. The new predictive model was generated by factors that were determined by multivariate analysis. The CCTA plaque (CTAP) score that included a quantitative plaque characteristic was developed by assigning an appropriate integer score to each independent predictor, then summing all points. In addition, the CTAP score was compared with other predictive scores based on CCTA. RESULTS: The endpoint was achieved in 63% of the lesions. The independent predictors included previous CTO-PCI failure, the proximal blunt stump, proximal side branch, distal side branch, occluded segment bending > 45°, and high-density plaque volume (fibrous volume + calcified volume) ≥ 19.9 mm3. As the score increased from 0 to 5, the success rate of the guidewire crossing within 30 m decreased from 96 to 0%. Comparing the CTAP score with other predictive scores, the CTAP score showed the highest discriminant power (c-statistic = 0.81 versus 0.73-0.77, p value 0.02-0.07). The CTAP score showed similar results for procedural success. CONCLUSION: The CTAP score efficiently predicted the guidewire crossing efficiency and procedural success. KEY POINTS: • An increase in high-density plaque volume (fibrous + dense calcium) was more probable to reduce the efficiency of crossing and lead to procedural failure. • The new prediction scoring system with the addition of the quantitative characteristics of plaques had an improved predictive ability compared with the traditional prediction scoring system.

Insight into Isomeric Diversity of Glycated Amino Acids in Maillard Reaction Mixtures.

Maillard reactions generate a wide array of amino acid- and sugar-derived intermediates; the isomeric mixtures of glycated amino acids are of particular interest. Excluding stereoisomers, regioisomers, and various anomers, most amino acids can form two monoglycated and three N,N-diglycated isomers when reacted with sugars during the Maillard reaction. Using synthetic Schiff bases and Amadori compounds as standards, we have demonstrated that diagnostic ions obtained from MS/MS fragmentations in negative ionization mode can be used effectively for the discrimination between glucose-derived Schiff bases and their corresponding Amadori compounds in both mono- and diglycated forms. The utilization of these diagnostic ions and isotopic labeling in the glycine/glucose model system revealed that milling glucose/glycine mixtures for 30 min/30 Hz at ambient temperature produced monoglycated glycine in equal proportions of Amadori and Schiff base forms, whereas diglycated glycine was a mixture of the three isomers: Schiff-Schiff, Schiff-Amadori, or Amadori-Amadori in approximately equal molar proportions. The above results were further corroborated using a synthetic histidine Amadori product, N,N-difructosyl-ß-alanine, dipeptides, and ribose. Using mechanochemistry as a convenient synthetic tool in combination with MS/MS diagnostic ions, the isomeric diversity of the early stages of the Maillard reaction can be revealed.

Metagenomic assembly and binning analyses the prevalence and spread of antibiotic resistome in water and fish gut microbiomes along an environmental gradient.

The pristine river and urban river show an environmental gradient caused by anthropogenic impacts such as wastewater treatment plants and domestic wastewater discharges. Here, metagenomic and binning analyses unveiled antibiotic resistance genes (ARGs) profiles, their co-occurrence with metal resistance genes (MRGs) and mobile genetic elements (MGEs), and their host bacteria in water and Hemiculter leucisculus samples of the river. Results showed that the decrease of ARG abundances from pristine to anthropogenic regions was attributed to the reduction of the relative abundance of multidrug resistance genes in water microbiomes along the environmental gradient. Whereas anthropogenic impact contributed to the enrichment of ARGs in fish gut microbiomes. From pristine to anthropogenic water samples, the dominant host bacteria shifted from Pseudomonas to Actinobacteria. Potential pathogens Vibrio parahaemolyticus, Enterobacter kobei, Aeromonas veronii and Microcystis aeruginosa_C with multiple ARGs were retrieved from fish gut microbes in lower reach of Ba River. The increasing trends in the proportion of the contigs carrying ARGs (ARCs) concomitant with plasmids along environmental gradient indicated that plasmids act as efficient mobility vehicles to enhance the spread of ARGs under anthropogenic pressures. Moreover, the higher co-occurrence of ARGs and MRGs on plasmids revealed that anthropogenic impacts accelerated the co-transfer potential of ARGs and MRGs and the enrichment of ARGs. Partial least squares path modeling revealed anthropogenic contamination could shape fish gut antibiotic resistome mainly via affecting ARG host bacteria in water microbiomes, following by ARGs co-occurrence with MGEs and MRGs in gut microbiomes. This study enhanced our understanding of the mechanism of the anthropogenic activities on the transmission of antibiotic resistome in river ecosystem and emphasized the risk of ARGs and pathogens transferring from an aquatic environment to fish guts.

Phenotype profiles and adaptive preference of Acinetobacter johnsonii isolated from Ba River with different environmental backgrounds.

Acinetobacter johnsonii is a potentially opportunistic pathogen widely distributed in nosocomial and natural environments, but little attention has been paid to this bacillus. Here A. johnsonii strains from Ba River with different pollution levels were isolated. In this study, we found that the increasing anthropogenic contaminants accounted for the emergence of multidrug-resistant (MDR) A. johnsonii strains. Correlation analysis results showed that the resistance phenotype of strains could be generated by co-selection of heavy metals or non-corresponding antibiotics. The whole genome sequence analysis showed that the relative heavy pollution of water selects strains containing more survival-relevant genes. We found that only some genes like blaOXA-24 were responsible for its corresponding resistance profile. Additionally, the tolerance profiles toward heavy metals also attribute to the expression of efflux pumps rather than corresponding resistance genes. In summary, our finding revealed that the resistance profiles of A. johnsonii could be generated by cross or co-selection of anthropogenic contaminants and mediated by efflux pumps instead of corresponding resistance determinants. Our study also has deep-sight into the adaptive preference of bacteria in natural environments, and contributes to surveillance studies and MDR- A. johnsonii monitoring worldwide.

Experimental and Density Functional Theory Studies on 1,1,1,4,4,4-Hexafluoro-2-Butene Pyrolysis.

A series of thermal decomposition experiments were conducted over a temperature range of 873-1073 K to evaluate the thermal stability of 1,1,1,4,4,4-hexafluoro-2-butene (HFO-1336mzz(Z)) and the production of hydrogen fluoride (HF). According to the detected products and experimental phenomena, the thermal decomposition of HFO-1336mzz(Z) could be divided into three stages. Our experimental results showed that HF concentration gradually increased with the elevation of thermal decomposition temperature. In this present study, a total of seven chemical reaction pathways of HFO-1336mzz(Z) pyrolysis were proposed to explore the generated mechanism on products through density functional theory (DFT) with M06-2X/6-311++(d,p) level theory. The thermal decomposition mechanism of pure HFO-1336mzz(Z) was discussed and the possible formation pathways of HF and other main products were proposed.

Mechanochemistry of Strecker degradation: Interaction of glyoxal with amino acids.

Mechanochemistry is rapidly evolving into a versatile and green method for chemical synthesis. Due to its unique reaction conditions, ball milling of sugars and amino acids mainly leads to the formation of Amadori products with minimum degradation. In this study, we milled glyoxal trimer dihydrate with twenty proteogenic amino acids to demonstrate the formation of Strecker degradation products. HS-GC/MS studies indicated that Strecker degradation proceeded to selectively generate Strecker aldehyde and unsubstituted pyrazine as the major volatiles. Moreover, ESI/qToF/MS studies demonstrated for the first time the formation of the proposed key Strecker degradation intermediates, such as the condensation products and their decarboxylated products, indicating the similarity of the mechanism of Strecker reaction under ball milling to that proposed under hydrothermal reaction conditions. These studies provided supporting evidence that ball milling at ambient temperatures could be used as a novel synthetic approach to prepare precursors of aroma-active volatiles through Strecker degradation.

Mechanochemistry in Glycation Research.

Mechanochemistry by milling has recently attracted considerable interest for its ability to drive solvent-free chemical transformations exclusively through mechanical energy and at ambient temperatures. Despite its popularity and expanding applications in different fields of chemistry, its impact on Food Science remains limited. This review aims to demonstrate the specific benefits that mechanochemistry can provide in performing controlled glycation, and in "activating" sugar and amino acid mixtures, thereby allowing for continued generation of colors and aromas even after termination of milling. The generated mechanical energy can be tuned under specific conditions either to form only the corresponding Schiff bases and Amadori compounds or to generate their degradation products, as a function of the frequency of the oscillations in combination with the reactivity of the selected substrates. Similarly, its ability to initiate the Strecker degradation and generate pyrazines and Strecker aldehydes was also demonstrated when proteogenic amino acids were milled with glyoxal.

Species distribution modeling combined with environmental DNA analysis to explore distribution of invasive alien mosquitofish (Gambusia affinis) in China.

China has become one of the most serious countries suffering from biological invasions in the world. In the context of global climate change, invasive alien species (IAS) are likely to invade a wider area, posing greater ecological and economic threats in China. Western mosquitofish (Gambusia affinis), which is known as one of the 100 most invasive alien species, has distributed widely in southern China and is gradually spreading to the north, causing serious ecological damage and economic losses. However, its distribution in China is still unclear. Hence, there is an urgent need for a more convenient way to detect and monitor the distribution of G. affinis to put forward specific management. Therefore, we detected the distribution of G. affinis in China under current and future climate change by combing Maxent modeling prediction and eDNA verification, which is a more time-saving and reliable method to estimate the distribution of species. The Maxent modeling showed that G. affinis has a broad habitat suitability in China (especially in southern China) and would continue to spread in the future with ongoing climate change. However, eDNA monitoring showed that occurrences can already be detected in regions that Maxent still categorized as unsuitable. Besides temperature, precipitation and human influence were the most important environmental factors affecting the distribution of G. affinis in China. In addition, by environmental DNA analysis, we verified the presence of G. affinis predicted by Maxent in the Qinling Mountains where the presence of G. affinis had not been previously recorded.

Radiomics Analysis of CTO Plaques for Predicting Successful Guidewire Crossing Within 30 Minutes of PCI.

BACKGROUND: Coronary computed tomography angiography provides valuable information for evaluating the difficulty of chronic total occlusion (CTO) percutaneous coronary intervention. This study aimed to investigate the value of CTO plaque characteristics derived from radiomics analysis for predicting the difficulty of percutaneous coronary intervention. METHODS: Patients with CTO were retrospectively enrolled from a hospital as training and internal test sets and from the other 2 territory hospitals as external test sets. Radiomics characteristics were extracted from the CTO segment on coronary computed tomography angiography. Radiomics and combined models were developed to predict successful guidewire crossing within 30 minutes (guidewire success) of CTO percutaneous coronary intervention. Subgroup analysis was conducted to investigate the influence of potential risk factors on the radiomics model performance. RESULTS: A total of 551 patients (median, 60; interquartile range, 52.00-66.00 years, 460 men) with 565 CTO lesions were finally enrolled. In the training, internal test, and external test sets, 203 of 357, 85 of 149, and 38 of 59 CTO lesions achieved guidewire success, respectively. Six radiomics features were selected for constructing the radiomics model. In the external test set, the area under the receiver operating characteristic curve of the radiomics model was significantly higher than prior prediction models (P<0.05 for all) with the area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity of 0.86, 74.58%, 81.58%, and 61.90%, respectively. The performance of the radiomics model was dependent on calcification, CTO location, adjacent branch(es), and operator caseload. CONCLUSIONS: CTO characteristics revealed by radiomics analysis can be used as effective imaging biomarkers for predicting guidewire success. However, the performance of the radiomics model depends on anatomic and operator factors.

Mechanochemical generation of N,N-diglycated glycine and MS/MS characterization of its isomeric composition.

The formation of Schiff bases and Amadori rearrangement products (ARP) during the Maillard reaction in solutions is well documented, but their studies in solid-state are limited. Here we report mass-spectrometric characterization of N,N-diglycated Schiff bases and Amadori products obtained during ball milling of amino acids and glucose. Signal intensities of the diglycated adducts in mass-spectra depended on type of the amino acid and the MS ionization mode. Glycine provided for the highest yields of N,N-diglycation, followed by lysine, when the reaction was analyzed under negative ionization mode. Using diagnostic MS/MS fragmentation, we were able to distinguish between Schiff-Schiff, Schiff-Amadori, or Amadori-Amadori isomers. Milling glucose/glycine model for 30 min at ambient temperature produced diglycated glycine as a mixture of the three possible isomers in approximately equal molar proportions. Milling of synthetic Schiff base or ARP of glycine with [U-13C]-glucose generated the same but partially labelled isomers, with respective predominance of N,N-diglucosyl-glycine or N,N-difructosyl-glycine.

Molecular Basis for the Simultaneous Enhancement of the Aroma-Generating Capacity and Bioactivity of Maillard Reaction Precursors through Mechanochemistry.

Ball milling at ambient temperatures can accelerate the formation and accumulation of early-stage Maillard reaction intermediates considered important precursors of aromas and antioxidants. In this study, using chemical and biological assays, we explored the potential of sequential milling and heating to enhance the antioxidant and aroma-generating capacity of Maillard model systems. Milling (30 Hz/30 min) followed by dry heating (90 °C/30 min) of glycine or lysine with glucose significantly increased not only the intensity of their aroma-active compounds as analyzed by headspace-gas chromatography/mass spectrometry (HS-GC/MS) but also their free radical scavenging capacity as assessed by 2,2'-azino-bis-(3-ethylbenzothiazoneline-6-sulfonic acid) (ABTS) and oxygen radical absorbance capacity (ORAC) assays. This was attributed to the increased formation of redox-active endiol moieties and precursors of N,N-dialkyl-pyrazinium radical cation in the lysine system assessed by electrospray ionization-quadrupole time-of-flight/tandem mass spectrometry (ESI-QqTOF/MS/MS) analysis. The test samples also inhibited NO generation and cellular oxidative stress in RAW 264.7 murine macrophage cells, indicating size reduction induced by milling promoted paracellular absorption.

Quantitative coronary computed tomography angiography assessment of chronic total occlusion percutaneous coronary intervention.

Background: Morphological and clinical characteristics are widely used to predict the success of percutaneous coronary intervention (PCI) in patients with chronic total occlusion (CTO). However, the impact of quantitative characteristics derived from coronary computed tomography angiography (CCTA) on guidewire crossing and PCI success is still unclear. This study aimed to explore the association between these quantitative characteristics and the difficulty of PCI for CTO. Methods: A total of 207 CTO lesions from 201 patients (84.6% male; mean age 58.9 years) with pre-procedural CCTA scans who had undergone PCI for CTO were retrospectively enrolled in this case-control study. A semi-automated CCTA plaque-analysis software was adopted to obtain the total plaque volume and volume of each component according to the Hounsfield Unit (HU) value, including dense calcium (>351 HU), fibrous (131-350 HU), fibrofatty (76-130 HU), and necrotic core (-30-75 HU) tissue. Differences in the quantitative characteristics of the CTO lesions were compared between: (I) the group of lesions with successful guidewire crossing (≤30 min) and the group with failed guidewire crossing (≤30 min); (II) the group of lesions with procedural success [defined as achieving residual stenosis of <30% and a grade 3 thrombolysis in myocardial infarction (TIMI) flow] and the group with procedural failure. Logistic regression was used to explore the association of quantitative characteristics with successful guidewire crossing in ≤30 min and procedural success. Results: A total of 131 (63.3%) lesions of 126 patients achieved successful guidewire crossing in ≤30 min and 157 (75.8%) lesions of 152 (75.6%) patients achieved procedural success. Quantitative characteristics such as occlusion length, plaque volume, volume of dense calcium, and fibrous and fibrofatty tissue showed significant differences between the groups of lesions with successful guidewire crossing in ≤30 min and with failed guidewire crossing in ≤30 min, as well as the groups of lesions with procedural success and with procedural failure. According to the results of logistic regression analysis, lower percentages of dense calcium [odds ratio (OR) =0.970, 95% confidence interval (CI): 0.950 to 0.991; P=0.004] and fibrous (OR =0.970, 95% CI: 0.949 to 0.992; P=0.007) tissue and higher percentage of necrotic core tissue (OR =1.018, 95% CI: 1.005 to 1.030; P=0.005) were significantly associated with successful guidewire crossing in ≤30 min. Decreased percentages of dense calcium (OR =0.969; 95% CI: 0.949 to 0.989; P=0.002) and fibrous tissue (OR =0.966, 95% CI: 0.944 to 0.990; P=0.005) and higher percentage of necrotic core tissue (OR =1.022, 95% CI: 1.008 to 1.036; P=0.002) were associated with procedural success. After adjusting for cardiovascular risk factors, the percentages of dense calcium, fibrous, and necrotic core tissue were still associated with successful guidewire crossing in ≤30 min, and the quantitative parameters showed consistent association with procedural success. Conclusions: Quantitative characteristics derived from CCTA for CTO are associated with successful guidewire crossing and procedural success of PCI.

Pathophysiology and molecular mechanism of caveolin involved in myocardial protection strategies in ischemic conditioning.

Multiple pathophysiological pathways are activated during the process of myocardial injury. Various cardioprotective strategies protect the myocardium from ischemia, infarction, and ischemia/reperfusion (I/R) injury through different targets, yet the clinical translation remains limited. Caveolae and its structure protein, caveolins, have been suggested as a bridge to transmit damage-preventing signals and mediate the protection of ultrastructure in cardiomyocytes under pathological conditions. In this review, we first briefly introduce caveolae and caveolins. Then we review the cardioprotective strategies mediated by caveolins through various pathophysiological pathways. Finally, some possible research directions are proposed to provide future experiments and clinical translation perspectives targeting caveolin based on the investigative evidence.

A Novel Classification for Predicting Chronic Total Occlusion Percutaneous Coronary Intervention.

Aims: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is characterized by a low success rate and an increase in complications. This study aimed to explore a new and simple classification method based on plaque composition to predict guidewire (GW) crossing within 30 min of CTO lesions. Methods: This study consecutively enrolled individuals undergoing attempted PCI of CTO who underwent coronary computed tomographic angiography (CCTA) within 2 months. Lesions were divided into soft and hard CTO groups according to the necrotic core proportion. Results: In this study, 207 lesions were divided into soft (20.3%) and hard CTO (79.7%) groups according to a necrotic core percentage cutoff value of 72.7%. The rate of successful GW crossing within 30 min (57.6 vs. 85.7%, p = 0.004) and final success (73.3 vs. 95.2%, p = 0.001) were much lower in the hard CTO group. For patients with hard CTO, previous failed attempt, proximal side branch, bending > 45 degrees calcium ≥ 50% cross-sectional area (CSA), and distal reference diameter ≤ 2.5 mm were demonstrated to be associated with GW failure within 30 min. For patients with soft CTO, only blunt entry was proved to be an independent predictive factor of GW failure within 30 min. Conclusions: Grouping CTO lesions according to the proportion of necrotic core is reasonable and necessary in predicting GW crossing within 30 min. A soft CTO with a necrotic core is more likely to be recanalized compared with a hard CTO with fibrous and/or dense calcium. Different plaque types have variable predictive factors.

Characteristics of phytoplankton-zooplankton communities and the roles in the transmission of antibiotic resistance genes under the pressure of river contamination.

Insight into the distribution of antibiotic resistance genes (ARGs) in phytoplankton-zooplankton communities (PZCs) is essential for the management and control of antibiotic resistance in aquatic ecosystems. This study characterized the profiles of PZCs and their carried ARGs in a typical urban river and ranked the factors (water physicochemical parameters, PZCs, bacterial abundance, and mobile genetic elements) influencing the dynamic of ARG profiles by the partial least squares path modeling. Results showed Cyanobacteria, Bacillariophyta and Chlorophyta were dominant phyla of phytoplankton, and Rotifera was with the highest abundance in zooplankton. River contamination markedly altered the structure of PZCs, increasing the abundance of phytoplankton and zooplankton, decreasing the diversity of phytoplankton while elevating in zooplankton. PZCs harbored large amounts of ARGs with average relative abundance of 2.35 × 10-2/copies nearly an order magnitude higher than the living water and most ARGs exhibited significant accumulation in PZCs with the aggravated environmental pollution. The partial least squares path modeling predicted the water parameters as the most important factor mainly playing indirect effects on ARGs via PZCs and bacterial communities, followed by mobile genetic elements as the most essential direct factor for ARGs profiles. Besides, PZCs were also important drivers for the carried ARGs via direct effects on the ARGs' composition and indirect effects on host bacterial communities of ARGs and their mobile genetic elements. The present study fills the gaps in knowledge about the distribution of ARGs in PZCs and provided a new perspective to decipher the key roles of PZCs in the maintenance and dissemination of ARGs in urban river ecosystems.

Optimal treatment strategies for coronary artery disease in patients with advanced kidney disease: a meta-analysis.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of death in advanced kidney disease. However, its best treatment has not been determined. METHODS: We searched PubMed and Cochrane databases and scanned references to related articles. Studies comparing the different treatments for patients with CAD and advanced CKD (estimated glomerular filtration rate <30 ml/min/1.73 m2 or dialysis) were selected. The primary result was all-cause death, classified according to the follow-up time: short-term (<1 month), medium-term (1 month-1 year), and long-term (>1 year). RESULTS: A total of 32 studies were selected to enroll 84,498 patients with advanced kidney disease. Compared with medical therapy (MT) alone, percutaneous coronary intervention (PCI) was associated with low risk of short-, medium-term and long-term all-cause death (more than 3 years). For AMI patients, compared with MT, PCI was not associated with low risk of short- and medium-term all-cause death. For non-AMI patients, compared with MT, PCI was associated with low risk of long-term mortality (more than 3 years). Compared with MT, coronary artery bypass surgery (CABG) had no significant advantages in each follow-up period of all-cause death. Compared with PCI, CABG was associated with a high risk of short-term death, but low risk of long-term death: 1-3 years; more than 3 years. CABG could also reduce the risk of long-term risk of cardiac death, major adverse cardiovascular events (MACEs), myocardial infarction (MI), and repeat revascularization. CONCLUSIONS: In patients with advanced kidney disease and CAD, PCI reduced the risk of short-, medium- and long- term (more than 3 years) all-cause death compared with MT. Compared with PCI, CABG was associated with a high risk of short-term death and a low risk of long-term death and adverse events.

Mechanochemical generation of Schiff bases and Amadori products and utilization of diagnostic MS/MS fragmentation patterns in negative ionization mode for their analysis.

The use of tandem mass spectrometry under positive ionization mode was previously developed as a tool for distinguishing isomeric Schiff bases and Amadori products. In this paper, similar diagnostic MS/MS fragmentation patterns were identified under negative ionization mode and was utilized to study the composition of mechanochemically generated Maillard reaction mixtures. The major diagnostic ion of the Schiff base was found to be a diose attached to the amino acid residue, while that of the Amadori compound was a triose. The structures of the diagnostic ions were confirmed through isotope labeling technique and elemental composition. Furthermore, application of this technique showed that ball milling of glucose with different amino acids almost exclusively results in the formation of a mixture of Schiff bases and Amadori compounds, and that amino acids with basic side chains generated more Schiff bases and those with acidic side chains generated more Amadori products.

Diagnostic MS/MS fragmentation patterns for the discrimination between Schiff bases and their Amadori or Heyns rearrangement products.

Schiff bases, the Amadori and Heyns rearrangement products are the most important isomeric intermediates involved in the early Maillard reaction; distinguishing between them by analytical mass spectroscopic techniques remains a challenge. Here we demonstrate that MS/MS fragmentation patterns can be used for the discrimination between glucose derived Schiff bases, Amadori, and Heyns compounds with glycine. An ESI-qTOF-MS system operated in the positive mode under both acidic and neutral conditions was employed to generate unique MS/MS fragmentation patterns of the molecules. Analysis of the MS data has indicated that acidic medium is suitable for generating characteristic and diagnostic ions. At high collision energy (20 eV), the spectrum of Schiff base was largely uninformative, whereas both Amadori and Heyns compounds undergo characteristic fragmentations with high diagnostic value. At low collision energy values (10eV), we observed formation of prominent diagnostic ions from the Schiff base precursor, as well as extensive dehydration reactions of all three molecules. Under acidic conditions, the diagnostic fragmentation pattern of the Amadori compound featured consecutive dehydration reactions. At higher values (20 eV) it underwent the α-fission at the carbonyl group and produced a prominent diagnostic ion [AA + H + CH2]+ at m/z 88. The Schiff base was found to preferentially undergo the retro-aldol degradation and produce diagnostic ions at m/z 118 [AA + H + diose]+ and m/z 140 [AA + Na + diose]+, together with their sugar complements at m/z 85 [tetrose + H-2H2O]+ and m/z 143 [tetrose + Na]+. In the case of Heyns compound, several diagnostic ions were also detected, including the ions at m/z 154 [M + H-2H2O-C2H4O2]+, m/z 170 [AA + Na + triose]+ and m/z 142 [AA + H + Furan]+.

Effects of Oral Drugs on Coronary Microvascular Function in Patients Without Significant Stenosis of Epicardial Coronary Arteries: A Systematic Review and Meta-Analysis of Coronary Flow Reserve.

Objective: This study aims to investigate the impact of cardiovascular medications on the coronary flow reserve (CFR) in patients without obstructive coronary artery disease (CAD). Methods: We searched PubMed, EMBASE, and Cochrane databases from inception to 15 November 2019. Studies were included if they reported CFR from baseline to follow-up after oral drug therapy of patients without obstructive CAD. Data was pooled using random-effects modeling. The primary outcome was change in CFR from baseline to follow-up after oral drug therapy. Results: A total of 46 studies including 845 subjects were included in this study. Relative to baseline, the CFR was improved by angiotensin-converting enzymes (ACEIs), aldosterone receptor antagonists (ARBs) [standard mean difference (SMD): 1.12; 95% CI: 0.77-1.47], and statins treatments (SMD: 0.61; 95%CI: 0.36-0.85). Six to 12 months of calcium channel blocker (CCB) treatments improved CFR (SMD: 1.04; 95% CI: 0.51-1.58). Beta-blocker (SMD: 0.24; 95% CI: -0.39-0.88) and ranolazine treatment (SMD: 0.31; 95% CI: -0.39-1.01) were not associated with improved CFR. Conclusions: Therapy with ACEIs, ARBs, and statins was associated with improved CFR in patients with confirmed or suspicious CMD. CCBs also improved CFR among patients followed for 6-12 months. Beta-blocker and ranolazine had no impact on CFR.