Modification of velopharyngeal closure pressures during phonation by neuromuscular electrical stimulation in healthy individuals.

Introduction: Rhinophonia aperta may result from velopharyngeal insufficiency. Neuromuscular electrical stimulation (NMES) has been discussed in the context of muscle strengthening. The aim of this study was to evaluate in healthy subjects whether NMES can change the velopharyngeal closure pattern during phonation and increase muscle strength. Method: Eleven healthy adult volunteers (21-57 years) were included. Pressure profiles were measured by high resolution manometry (HRM): isolated sustained articulation of /a/ over 5 s (protocol 1), isolated NMES applied to soft palate above motor threshold (protocol 2) and combined articulation with NMES (protocol 3). Mean activation pressures (MeanAct), maximum pressures (Max), Area under curve (AUC) and type of velum reactions were compared. A statistical comparison of mean values of protocol 1 versus protocol 3 was carried out using the Wilcoxon signed rank test. Ordinally scaled parameters were analyzed by cross table. Results: MeanAct values measured: 17.15±20.69 mmHg (protocol 1), 34.59±25.75 mmHg (protocol 3) on average, Max: 37.86±49.17 mmHg (protocol 1), 87.24±59.53 mmHg (protocol 3) and AUC: 17.06±20.70 mmHg.s (protocol 1), 33.76±23.81 mmHg.s (protocol 3). Protocol 2 produced velum reactions on 32 occasions. These presented with MeanAct values of 13.58±12.40 mmHg, Max values of 56.14±53.14 mmHg and AUC values of 13.84±12.78 mmHg.s on average. Statistical analysis comparing protocol 1 and 3 showed more positive ranks for MeanAct, Max and AUC. This difference reached statistical significance (p=0.026) for maximum pressure values. Conclusions: NMES in combination with articulation results in a change of the velopharyngeal closure pattern with a pressure increase of around 200% in healthy individuals. This might be of therapeutic benefit for patients with velopharyngeal insufficiency.

High-Resolution Anorectal Manometry as a Screening Tool for Hirschsprung's Disease: A Comprehensive Retrospective Analysis.

Hirschsprung's disease (HD) is characterized by a congenital absence of enteric ganglion cells in the intestine, posing challenges in diagnosis, particularly in pediatric patients. The gold standard, rectal suction biopsy (RSB), carries risks, prompting an exploration of non-invasive alternatives such as high-resolution anorectal manometry (HR-ARM) for HD screening. We conducted a retrospective analysis of 136 patients suspected of HD between 2018 and 2022, which were stratified into three age groups: ≤12 months, ≤24 months, and >24 months. Criteria for suspicion included delayed meconium passage, unresponsive chronic constipation, and abnormal prior test results. HR-ARM, supplemented by additional tests, confirmed 16 HD cases. HR-ARM exhibited 93.75% sensitivity, 89.47% specificity, 99.03% negative predictive value (NPV), and 55.56% positive predictive value (PPV). Notably, HR-ARM consistently performed well in patients ≤ 2 years old but demonstrated reduced efficacy in older children, which was likely due to complications from chronic constipation. This study underscores HR-ARM's promise as a non-invasive HD screening tool, especially in younger patients. However, its limitations in older children warrant consideration. Establishing standardized protocols, particularly for assessing the recto-anal inhibitory reflex, is crucial. Further research is imperative to optimize HR-ARM's diagnostic role across varied age groups in HD assessment.

African Under-Utilized Medicinal Leafy Vegetables Studied by Microtiter Plate Assays and High-Performance Thin-Layer Chromatography-Planar Assays.

Biological activities of six under-utilized medicinal leafy vegetable plants indigenous to Africa, i.e., Basella alba, Crassocephalum rubens, Gnetum africanum, Launaea taraxacifolia, Solanecio biafrae, and Solanum macrocarpon, were investigated via two independent techniques. The total phenolic content (TPC) was determined, and six microtiter plate assays were applied after extraction and fractionation. Three were antioxidant in vitro assays, i.e., ferric reducing antioxidant power (FRAP), cupric reduction antioxidant capacity (CUPRAC), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, and the others were enzyme (acetylcholinesterase, butyrylcholinesterase, and tyrosinase) inhibition assays. The highest TPC and antioxidant activity from all the methods were obtained from polar and medium polar fractions of C. rubens, S. biafrae, and S. macrocarpon. The highest acetyl- and butyrylcholinesterase inhibition was exhibited by polar fractions of S. biafrae, C. rubens, and L. taraxacifolia, the latter comparable to galantamine. The highest tyrosinase inhibition was observed in the n-butanol fraction of C. rubens and ethyl acetate fraction of S. biafrae. In vitro assay results of the different extracts and fractions were mostly in agreement with the bioactivity profiling via high-performance thin-layer chromatography-multi-imaging-effect-directed analysis, exploiting nine different planar assays. Several separated compounds of the plant extracts showed antioxidant, α-glucosidase, α-amylase, acetyl- and butyrylcholinesterase-inhibiting, Gram-positive/-negative antimicrobial, cytotoxic, and genotoxic activities. A prominent apolar bioactive compound zone was tentatively assigned to fatty acids, in particular linolenic acid, via electrospray ionization high-resolution mass spectrometry. The detected antioxidant, antimicrobial, antidiabetic, anticholinesterase, cytotoxic, and genotoxic potentials of these vegetable plants, in particular C. rubens, S. biafrae, and S. macrocarpon, may validate some of their ethnomedicinal uses.

Investigating the molecular mechanism of Qizhu anticancer prescription in inhibiting hepatocellular carcinoma based on high-resolution mass spectrometry and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Of all primary liver cancer cases, hepatocellular carcinoma (HCC) accounts for about 90%. Most patients with HCC receive a diagnosis in the medium-to-late stages or with chronic liver disease, have lost the opportunity for radical treatment, such as surgical resection, and their 5-year survival rate is low. Qizhu Anticancer Prescription (QZACP) is an empirical formula composed of traditional Chinese herbs that can clinically relieve HCC symptoms, inhibit the progression of HCC, reduce recurrence rate, and prolong survival; however, its exact mode of action remains unknown. AIM OF THE STUDY: This study's purpose was to investigate the mode of action of QZACP in the prevention and treatment of HCC. MATERIALS AND METHODS: Initially, drug components in the QZACP decoction were analyzed using high-resolution mass spectrometry. A subcutaneous tumor xenograft model in nude mice was constructed to further analyze the active components of QZACP that had entered tumor tissues through oral administration. Potential targets of QZACP in the prevention and treatment of HCC were identified and then confirmed in vivo via network pharmacology and molecular docking. In addition, regulatory effects of QZACP on HCC cell proliferation and the cell cycle were detected using a CCK-8 assay and flow cytometry. RESULTS: High-resolution mass spectrometry revealed that the QZACP decoction contained deacetyl asperulosidic acid methyl ester (DAAME), paeoniflorin, calycosin-7-glucoside, liquiritin, glycyrrhizic acid, astragaloside IV, saikosaponin A, curdione, and atractylenolide II. In nude mice, QZACP could effectively inhibit the growth of subcutaneous tumors, where DAAME, paeoniflorin, liquiritin, and glycyrrhizic acid could enter liver cancer tissues after oral administration. Among these, DAAME was the most highly expressed in HCC tissues and may be an important active component of QZACP for inhibiting HCC. Utilizing network pharmacology, the targets of action of these four drug components were identified. After verification using western blotting, STAT3, VEGFA, JUN, FGF2, BCL2L1, AR, TERT, MMP7, MMP1, ABCB1, CA9, and ESR2 were identified as targets of QZACP inhibition in HCC. In vitro experiments revealed that QZACP inhibited the proliferation of HCC cells while inducing G0/G1 phase cell cycle arrest. In vivo experiments demonstrated that DAAME significantly inhibited HCC growth. After intersection of the 24 DAAME targets predicted using network pharmacology with the 435 HCC disease targets, only CA9 was identified as a DAAME-HCC crossover target. Molecular docking results revealed that the binding site of DAAME and CA9 had good stereo-complementarity with a docking score of -8.1 kcal/mol. Western blotting and immunohistochemical results also confirmed that DAAME significantly decreased CA9 protein expression in HCC. CONCLUSIONS: QZACP inhibits HCC by reducing the expression of STAT3, VEGFA, JUN, FGF2, BCL2L1, AR, TERT, MMP7, MMP1, ABCB1, CA9, and ESR2. DAAME may be an important active component of QZACP for the prevention and treatment of HCC, inhibiting it by targeting the expression of CA9.

Existing status and future advancements of adulteration detection techniques in herbal products.

BACKGROUND: Herbal products have been commonly used all over the world for centuries. Its products have gained remarkable acceptance as therapeutic agents for a variety of disorders. However, following recent research disclosing discrepancies between labeling and actual components of herbal products, there is growing concern about the efficacy, quality and safety of the products. The admixture and adulteration of herbal medicinal products pose a risk of serious health compromise and the well-being of the consumers. To prevent adulteration in raw ingredients and final herbal products, it is necessary to use approaches to assess both genomes as well as metabolomics of the products; this offers quality assurance in terms of product identification and purity. The combinations of molecular and analytical methods are inevitable for thorough verification and quality control of herbal medicine. METHODS AND RESULTS: This review discusses the combination of DNA barcoding, DNA metabarcoding, mass spectroscopy as well as HPLC for the authentication of herbal medicine and determination of the level of adulteration. It also discusses the roles of PCR and real-time PCR techniques in validating and ensuring the quality, purity and identity of the herbal products. CONCLUSIONS: In conclusion, each technique has its own pros and cons, but the cumulative of both the chemical and molecular methods is proven to be the best strategy for adulteration detection. Moreover, CRISPR diagnosis tools equipped with multiplexing techniques may be implemented for screening adulteration from herbal drugs, this will play a crucial role in herbal product authentication in the future.

Discovery of antitussive material basis and mechanisms in Citri Sarcodactylis Fructus by coupling UHPLC-Q/Orbitrap HRMS combined spectrum-effect relationship and metabolomics analyses.

Citri Sarcodactylis Fructus (CSF) is widely used as food raw material and traditional Chinese medicine. Fingerprints of different fractions of CSF were established for spectrum-effect relationship analysis, and the main compounds were identified by UHPLC Quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS). The antitussive effect was evaluated using a classical mouse model of cough induced by ammonia water. One-way ANOVA was used to determine differences in efficacy. The potential active compounds were screened by spectrum-effect relationship with grey relational degree analysis (GRA), Pearson bivariate correlation analysis (Pearson's), and partial least squares analysis (PLS) analyses. Differential metabolites associated with cough in serum were screened and identified using orthogonal partial least squares-discriminant analysis, HMDB database, and UHPLC-Q/Orbitrap HRMS. Metabolic pathway analysis was performed using MetaboAnalyst 5.0. Results indicate that 70 % ethanol elution fraction (70 % EF) is the major active fraction, and 8 components were identified to possess antitussive effects. Metabolomic analysis showed that 19 metabolites are potential biomarkers related to cough, and 70 % EF can remarkable restore 13 of them to normal levels (P < 0.05). These biomarkers are mainly involved in glycerophospholipid metabolism and sphingolipid metabolism. This study aims to reveal the main pharmacodynamic active sites and potential active ingredients of CSF's antitussive effect. In addition, metabolomics was used to preliminarily elucidate the in-vivo regulatory mechanism of the antitussive effect of the 70 % EF of CSF.

Effects of processing technology on tea quality analyzed using high-resolution mass spectrometry-based metabolomics.

Fixation is a crucial step in green tea processing that can impact quality. In this study, we explored the differences in the chemical components of steamed and fried green teas made from the same batch of fresh tea leaves using different fixing methods. Results showed that concentrations of sucrose and free amino acids were significantly higher in steamed green tea. Abundances of 12 compounds including purine nucleoside, pyrimidine nucleoside derivatives, and catechins were higher in fried green tea, while 34 compounds such as amino acids and their derivatives, benzofurans and flavonoids were higher in steamed green tea. Thus, steaming retained more compounds associated with sweet and fresh tastes, such as free amino acids, while frying produced more compounds with bitter tastes, such as catechin. This might explain why steamed green tea is mellower than fried tea.

Rapid identification of the compounds of Bushen Huoxue Prescription based on offline two-dimensional liquid chromatography with high-resolution mass spectrometry and molecular network technology.

The comprehensive and efficient characterization of components in traditional Chinese medicine is crucial for elucidating its active constituents and uncovering its mechanism. Identifying the compounds of the Bushen Huoxue Prescription (BHP) is difficult because of its complex composition and the large difference in concentration among its compounds. In this study, a hydrophilic interaction liquid chromatography coupled with reversed-phase LC (HILIC × RPLC) offline 2D-LC tandem high-resolution mass spectrometry method was established to analyze the total compounds of the BHP. Database screening and molecular networking were performed to identify the compounds. In contrast to conventional 1D chromatography, 2D chromatography increased peak capacity, enriched trace ingredients, and prevented the masking of high-abundance compounds. A total of 165 compounds were identified, and 14 potential compounds needed to be further identified. This study provided an effective method for comprehensively analyzing the complex system of traditional Chinese medicine compounds.

Platelet hyperactivity: a comparison of water-soluble, bioactive compound levels in commercial tomato products and water-soluble tomato concentrate, a supplement with an approved EFSA antiplatelet health effect.

The aim of this study was to evaluate and compare the concentration of water-soluble bioactive compounds in tomato products (polyphenols profile, water-soluble vitamins and nucleophilic substances) with the concentration of the same bioactive molecules existing in a water-soluble patented tomato extract, water-soluble tomato extract (WSTC), commercially available as FruitFlow®. This patented tomato extract has been recognised by EFSA (European Food Safety Authority) in a specific Health Claim declaration as having an "Antiplatelet health effect". More than 100 commercial tomato samples, coming from 18 different processing tomato companies worldwide, were analysed and compared with the FruitFlow® supplement. According to the multivariate statistical analyses applied to the data matrix, it is possible to conclude that the commercial tomato products measured (pastes, purees, others) show a significantly higher concentration of water-soluble bioactive molecules (nucleosides/nucleotides and polyphenols) responsible for an anti-platelet aggregation effect than the FruitFlow® dietary supplement.

Effects of hyperthermia and acidosis on mitochondrial production of reactive oxygen species.

Exercise is associated with the development of oxidative stress, but the specific source and mechanism of production of pro-oxidant chemicals during exercise has not been confirmed. We used equine skeletal muscle mitochondria to test the hypothesis that hyperthermia and acidosis affect mitochondrial oxygen consumption and production of reactive oxygen species (ROS). Skeletal muscle biopsies were obtained at rest, after an acute episode of fatiguing exercise, and after a 9-wk conditioning program to increase aerobic fitness. Mitochondrial oxygen consumption and ROS production were measured simultaneously using high-resolution respirometry. Both hyperthermia and acidosis increased nonphosphorylating (LEAK) respiration (5.8× and 3.0×, respectively, P < 0.001) and decreased efficiency of oxidative phosphorylation. The combined effects of hyperthermia and acidosis resulted in large decreases in phosphorylating respiration, further decreasing oxidative phosphorylation efficiency from 97% to 86% (P < 0.01). Increased aerobic fitness reduced the effects of acidosis on LEAK respiration. Hyperthermia increased and acidosis decreased ROS production (2× and 0.23×, respectively, P < 0.001). There was no effect of acute exercise, but an aerobic conditioning program was associated with increased ROS production during both nonphosphorylating and phosphorylating respiration. Hyperthermia increased the ratio of ROS production to O2 consumption during phosphorylating respiration, suggesting that high-temperature impaired transfer of energy through the electron transfer system despite relatively low mitochondrial membrane potential. These data support the role of skeletal muscle mitochondria in the development of exercise-induced oxidative stress, particularly during forms of exercise that result in prolonged hyperthermia without acidosis.NEW & NOTEWORTHY The results of this study provide evidence for the role of mitochondria-derived ROS in the development of systemic oxidative stress during exercise as well as skeletal muscle diseases such as exertional rhabdomyolysis.

Lack of improvement in anorectal manometry parameters after implementation of a pelvic floor/anal sphincter biofeedback in persons with motor-incomplete spinal cord injury.

BACKGROUND: Effect of biofeedback on improving anorectal manometric parameters in incomplete spinal cord injury is unknown. A short-term biofeedback program investigated any effect on anorectal manometric parameters without correlation to bowel symptoms. METHODS: This prospective uncontrolled interventional study comprised three study subject groups, Group 1: sensory/motor-complete American Spinal Injury Association Impairment Scale (AIS) A SCI (n = 13); Group 2 (biofeedback group): sensory incomplete AIS B SCI (n = 17) (n = 3), and motor-incomplete AIS C SCI (n = 8), and AIS D SCI (n = 6); and Group 3: able-bodied (AB) controls (n = 12). High-resolution anorectal manometry (HR-ARM) was applied to establish baseline characteristics in all subjects for anorectal pressure, volume, length of pressure zones, and duration of sphincter squeeze pressure. SCI participants with motor-incomplete SCI were enrolled in pelvic floor/anal sphincter bowel biofeedback training (2 × 6-week training periods comprised of two training sessions per week for 30-45 min per session). HR-ARM was also performed after each of the 6-week periods of biofeedback training. RESULTS: Compared to motor-complete or motor-incomplete SCI participants, AB subjects had higher mean intra-rectal pressure, maximal sphincteric pressure, residual anal pressure, recto-anal pressure gradient, and duration of squeeze (p < 0.05 for each of the endpoints). No significant difference was evident at baseline between the motor-complete and motor-incomplete SCI groups. In motor-incomplete SCI subjects, the pelvic floor/anal sphincter biofeedback protocol failed to improve HR-ARM parameters. CONCLUSION: Biofeedback training program did not improve anal manometric parameters in subjects with motor-incomplete or sensory-incomplete SCI. Biofeedback did not change physiology, and its effects on symptoms are unknown. INFERENCES: Utility of biofeedback is limited in patients with incomplete spinal cord injury in terms of improving HR-ARM parameters.

Untargeted cannabinomics reveals the chemical differentiation of industrial hemp based on the cultivar and the geographical field location.

Cannabis sativa has long been harvested for industrial applications related to its fibers. Industrial hemp cultivars, a botanical class of Cannabis sativa with a low expression of intoxicating Δ9-tetrahydrocannabinol (Δ9-THC) have been selected for these purposes and scarcely investigated in terms of their content in bioactive compounds. Following the global relaxation in the market of industrial hemp-derived products, research in industrial hemp for pharmaceutical and nutraceutical purposes has surged. In this context, metabolomics-based approaches have proven to fulfill the aim of obtaining comprehensive information on the phytocompound profile of cannabis samples, going beyond the targeted evaluation of the major phytocannabinoids. In the present paper, an HRMS-based metabolomics study was addressed to seven distinct industrial hemp cultivars grown in four experimental fields in Northern, Southern, and Insular Italy. Since the role of minor phytocannabinoids as well as other phytocompounds was found to be critical in discriminating cannabis chemovars and in determining its biological activities, a comprehensive characterization of phytocannabinoids, flavonoids, and phenolic acids was carried out by LC-HRMS and a dedicated data processing workflow following the guidelines of the metabolomics Quality Assurance and Quality Control Consortium. A total of 54 phytocannabinoids, 134 flavonoids, and 77 phenolic acids were annotated, and their role in distinguishing hemp samples based on the geographical field location and cultivar was evaluated by ANOVA-simultaneous component analysis. Finally, a low-level fused model demonstrated the key role of untargeted cannabinomics extended to lesser-studied phytocompound classes for the discrimination of hemp samples.

A Proteomic Study of the Bioactivity of Annona muricata Leaf Extracts in HT-1080 Fibrosarcoma Cells.

Graviola (Annona muricata) is a tropical plant with many traditional ethnobotanic uses and pharmacologic applications. A metabolomic study of both aqueous and DMSO extracts from Annona muricata leaves recently allowed us to identify dozens of bioactive compounds. In the present study, we use a proteomic approach to detect altered patterns in proteins on both conditioned media and extracts of HT-1080 fibrosarcoma cells under treatment conditions, revealing new potential bioactivities of Annona muricata extracts. Our results reveal the complete sets of deregulated proteins after treatment with aqueous and DMSO extracts from Annona muricata leaves. Functional enrichment analysis of proteomic data suggests deregulation of cell cycle and iron metabolism, which are experimentally validated in vitro. Additional experimental data reveal that DMSO extracts protect HT-1080 fibrosarcoma cells and HMEC-1 endothelial cells from ferroptosis. Data from our proteomic study are available via ProteomeXchange with identifier PXD042354.

Atrial extrasystoles enhance low-voltage fractionation electrograms in patients with atrial fibrillation.

BACKGROUND AND AIMS: Atrial extrasystoles (AES) provoke conduction disorders and may trigger episodes of atrial fibrillation (AF). However, the direction- and rate-dependency of electrophysiological tissue properties on epicardial unipolar electrogram (EGM) morphology is unknown. Therefore, this study examined the impact of spontaneous AES on potential amplitude, -fractionation, -duration, and low-voltage areas (LVAs), and correlated these differences with various degrees of prematurity and aberrancy. METHODS AND RESULTS: Intra-operative high-resolution epicardial mapping of the right and left atrium, Bachmann's Bundle, and pulmonary vein area was performed during sinus rhythm (SR) in 287 patients (60 with AF). AES were categorized according to their prematurity index (>25% shortening) and degree of aberrancy (none, mild/opposite, moderate and severe). In total, 837 unique AES (457 premature; 58 mild/opposite, 355 moderate, and 154 severe aberrant) were included. The average prematurity index was 28% [12-45]. Comparing SR and AES, average voltage decreased (-1.1 [-1.2, -0.9] mV, P < 0.001) at all atrial regions, whereas the amount of LVAs and fractionation increased (respectively, +3.4 [2.7, 4.1] % and +3.2 [2.6, 3.7] %, P < 0.001). Only weak or moderate correlations were found between EGM morphology parameters and prematurity indices (R2 < 0.299, P < 0.001). All parameters were, however, most severely affected by either mild/opposite or severely aberrant AES, in which the effect was more pronounced in AF patients. Also, there were considerable regional differences in effects provoked by AES. CONCLUSION: Unipolar EGM characteristics during spontaneous AES are mainly directional-dependent and not rate-dependent. AF patients have more direction-dependent conduction disorders, indicating enhanced non-uniform anisotropy that is uncovered by spontaneous AES.

Cyanobacterial blooms increase the release of vanadium through iron reduction and dissolved organic matter complexation in the sediment of eutrophic lakes.

Vanadium (V), a hazardous environmental contaminant, can be highly toxic to aquatic or even human life. Nonetheless, knowledge of its redox geochemistry and mobility in sediments, especially those of eutrophic lakes, remains limited. In this study, we combined in situ high-resolution sampling and laboratory simulation experiments for monitoring soluble and labile V to reveal the mobilization mechanism of V in the sediment of Lake Taihu. The results showed that the concentration of soluble V (1.18-5.22 µg L-1) exceeded the long-term ecotoxicology limitation proposed by the government of the Netherlands. The highest value appeared in summer (July to September), with an average concentration of 3.87 µg L-1, which exceeded the short-term exposure limit. The remobilization of V in summer was caused by the combined effect of the reduction of Fe(hydr)oxides and dissolved organic matter (DOM) complexation, which accelerated the release of associated Fe-bound V and increased the solubility of DOM-V. Additionally, V showed high mobility in winter, owing to the species of V(Ⅲ)/V(Ⅳ) being oxidized to V(Ⅴ) with higher solubility. It is noteworthy that the elevated remobilization of V in sediments increases the risk of V release from sediments, which poses the threat of water V pollution in Lake Taihu.

Detailed analysis of tachycardia cycle length aids diagnosis of the mechanism and location of atrial tachycardias.

AIMS: Although the mechanism of an atrial tachycardia (AT) can usually be elucidated using modern high-resolution mapping systems, it would be helpful if the AT mechanism and circuit could be predicted before initiating mapping. OBJECTIVE: We examined if the information gathered from the cycle length (CL) of the tachycardia can help predict the AT-mechanism and its localization. METHODS: One hundred and thirty-eight activation maps of ATs including eight focal-ATs, 94 macroreentrant-ATs, and 36 localized-ATs in 95 patients were retrospectively reviewed. Maximal CL (MCL) and minimal CL (mCL) over a minute period were measured via a decapolar catheter in the coronary sinus. CL-variation and beat-by-beat CL-alternation were examined. Additionally, the CL-respiration correlation was analysed by the RhythmiaTM system. : Both MCL and mCL were significantly shorter in macroreentrant-ATs [MCL = 288 (253-348) ms, P = 0.0001; mCL = 283 (243-341) ms, P = 0.0012], and also shorter in localized-ATs [MCL = 314 (261-349) ms, P = 0.0016; mCL = 295 (248-340) ms, P = 0.0047] compared to focal-ATs [MCL = 506 (421-555) ms, mCL = 427 (347-508) ms]. An absolute CL-variation (MCL-mCL) < 24 ms significantly differentiated re-entrant ATs from focal-ATs with a sensitivity = 96.9%, specificity = 100%, positive predictive value (PPV) = 100%, and negative predictive value (NPV) = 66.7%. The beat-by-beat CL-alternation was observed in 10/138 (7.2%), all of which showed the re-entrant mechanism, meaning that beat-by-beat CL-alternation was the strong sign of re-entrant mechanism (PPV = 100%). Although the CL-respiration correlation was observed in 28/138 (20.3%) of ATs, this was predominantly in right-atrium (RA)-ATs (24/41, 85.7%), rather than left atrium (LA)-ATs (4/97, 4.1%). A positive CL-respiration correlation highly predicted RA-ATs (PPV = 85.7%), and negative CL-respiration correlation probably suggested LA-ATs (NPV = 84.5%). CONCLUSION: Detailed analysis of the tachycardia CL helps predict the AT-mechanism and the active AT chamber before an initial mapping.

Hazelnut (Corylus avellana L.) shells as a potential source of dietary fibre: impact of hydrothermal treatment temperature on fibre structure and degradation compounds.

BACKGROUND: Hemicellulose extraction from lignocellulosic biomasses has gained interest over the years, and hydrothermal treatment is one of the most common methods employed for this purpose. This work aimed to deeply study hazelnut (Corylus avellana L.) shells as a new source of dietary fibre, evaluating the effect of hydrothermal treatment temperatures on the type and structure of fibre extracted, but also on the formation of side-products derived from lignocellulose degradation. RESULTS: Different process temperatures led to diverse polysaccharides in the hydrothermal extract. Pectin was identified for the first time in hazelnut shells when experimenting with extraction at 125 °C, whereas at 150 °C a heterogeneous mixture of pectin, xylan, and xylo-oligosaccharides was present. The highest yield in terms of total fibre was gained at 150 and 175 °C, and then decreased again at 200 °C. Finally, more than 500 compounds from different chemical classes were putatively identified and they appeared to be present in the extracted fibre with a different distribution and relative amount, depending on the heat treatment severity. A generally high content of phenols, phenyls, oligosaccharides, dehydro-sugars, and furans was observed. CONCLUSIONS: Modulation of the hydrothermal treatment temperature allows fibre extracts with very different compositions, and therefore different potential end uses, to be obtained from hazelnut shells. A sequential temperature-based fractionation approach, as a function of the severity of the extraction parameters, can also be considered. Nevertheless, the study of the side-compounds formed from lignocellulosic matrix degradation, as a function of the applied temperature, needs to be fully addressed for a safe introduction of the fibre extract within the food chain. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Identification of new PTP1B-inhibiting decipiene diterpenoid esters from Eremophila clarkei by high-resolution PTP1B inhibition profiling, enzyme kinetics analysis, and molecular docking.

In this study, an extract of the leaves of Eremophila clarkei Oldfield & F.Muell. showed protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with an IC50 value of 33.0 µg/mL. The extract was therefore investigated by high-resolution PTP1B inhibition profiling to pinpoint the constituents responsible for the activity. Subsequent isolation and purification using analytical-scale HPLC led to identification of eight previously undescribed decipiene diterpenoids, eremoclarkanes A-H, as well as eremoclarkic acid, a biogenetically related new phenolic acid. In addition, one known decipiene diterpenoid and ten known O-methylated flavonoids were isolated. The structures of the isolated compounds were elucidated by extensive analysis of their HRMS and 1D and 2D NMR spectra. The absolute configuration of decipiene diterpenoids was determined by comparison of experimental and calculated ECD spectra. The flavonoid hispidulin (2b) and the four decipiene diterpenoids 13a, 13b, 13f, and 14b exhibited PTP1B inhibitory activity with IC50 values ranging from 22.8 to 33.6 µM. This is the first report of PTP1B inhibitory activity of decipienes, and enzyme kinetics revealed that 13a and 13b are competitive inhibitors of PTP1B, whereas 13f and 14b displayed mixed-type-mode inhibition of PTP1B. Finally, molecular docking indicated that 13a, 13b, 13f, and 14b showed comparable binding affinity towards the active and/or allosteric site of PTP1B enzyme. Structure-activity relationship (SAR) of the identified O-methylated flavonoids and decipiene diterpenoids towards PTP1B is discussed. Plausible enzymatic and photochemically driven routes for the formation of the decipienes and conversion products thereof are presented and discussed.

Simultaneous determination of multiple constituents, serum composition, and tissue distribution of Qingshen granule using ultra-high performance liquid chromatography-quadrupole-orbitrap high-resolution mass spectrometry.

Qingshen granule, composed of 14 herbal drugs, is primarily used as the assistant therapy for chronic kidney disease. Qingshen granule chemical composition was complex, but its chemical constituents and the pharmacodynamic material basis remain unreported. Ultra-high-performance liquid chromatography (UHPLC)-quadrupole-orbitrap high-resolution mass spectrometry was applied to recognize the chemical constituents of Qingshen granule. The analysis was performed using the ACQUITY UHPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) with acetonitrile-0.1% formic acid as the mobile phase for gradient elution. The data were collected using heated electrospray ionization in positive and negative ion modes. This study successfully applied the UPHLC-quadrupole-orbitrap high-resolution mass spectrometry technique with the Compound Discoverer 3.3 platform to analyze Qingshen granule chemical composition. A total of 127 and 42 chemical components were identified in Qingshen granule in vitro and in vivo, respectively. In the tissue distribution of Qingshen granule, 9, 10, 11, 10, and 18 prototype components were detected in the heart, liver, spleen, lungs, and kidneys, respectively. Qingshen granule chemical constituents were characterized rapidly for the first time in this study, laying a foundation for further research on the substance basis and quality control of Qingshen granule in treating chronic kidney disease.

The colonic metabolism differences of main alkaloids in normal and colitis mice treated with Coptis chinensis Franch. and Sophora flavescens Ait. herbal pair using liquid chromatography-high resolution mass spectrometry method combined with chemometrics.

Coptis chinensis Franch. and Sophora flavescens Ait. is a herbal pair frequently used in treating ulcerative colitis. However, the bio-disposition profile of the major components in the inflamed gut remains unclear, which is essential to understand the pharmacological material basis of this herb pair. Here we established an integral quantitative and chemometric method to deduce the colonic metabolism differences of this herbal pair in normal and colitis mice. With this LC-MS method, a total of 41 components have been found in the Coptis chinensis Franch. and Sophora flavescens Ait. extract, and 28 metabolites were found in the colon after oral administration. Alkaloid and its phase I metabolites were the main components in the colon of normal and colitis mice. The results of principal component analysis at 6 h after oral administration showed significant colonic metabolism differences between normal and colitis mice. Heamap results showed that colitis induced significant changes in the colonic bio-disposition of this herbal pair extract. In particular, in the context of colitis, the phase I metabolism of berberine, coptisine, jatrorrhizine, palmatine,and epiberberine has been inhibited. These results may provide a basis for understanding the pharmacological material basis of Coptis chinensis Franch. and Sophora flavescens Ait. in treating ulcerative colitis.