ABSTRACT
Clove (Syzygium aromaticum) is one of the most commonly used spices in stewed beef to enrich and improve its aroma during the stewing process. Gas chromatography ion mobility spectroscopy (GC-IMS), Q Exactive GC-Orbitrap-MS-O (QE-GC-MS/O), combined with sensory evaluation were employed to analyze the flavor endowment of aroma-active compounds in cloves to stewed beef. A total of 173 volatiles were identified in the clove powder (CP), stewed beef with clove (SBC), and stewed beef with salt (SBS), of which 21 volatiles were considered as aroma-active compounds. The concept of flavor endowment of aroma-active compounds in cloves was defined innovatively, and the endowment rate values (ERVs) of stewed beef were calculated. Nine aroma-active compounds in cloves were found to have a flavor endowment effect on stewed beef, while the terpenoids exhibited high ERVs. Despite the low ERV of eugenol, it still significantly impacted the aroma profile of SBC due to its high odor activity value (OAV) and flavor dilution (FD) factor. These volatiles offered mainly the clove, herbal, anise, and floral odor to stewed beef, which was also confirmed by sensory evaluation. These findings indicated that the terpenoids, phenolics and ethers in cloves had a significant influence on the overall aroma of stewed beef through the flavor endowment, which contributed to the precise use of cloves and improved the aroma of stewed beef.
ABSTRACT
Atherosclerosis is the pathological cause of atherosclerotic cardiovascular disease (ASCVD), which rapidly progresses during the cellular senescence. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce major cardiovascular events in patients with ASCVD and have potential antisenescence effects. Here, we investigate the effects of the SGLT2 inhibitor dapagliflozin on cellular senescence in atherosclerotic mice. Compared with ApoE-/- control mice treated with normal saline, those in the ApoE-/- dapagliflozin group, receiving intragastric dapagliflozin (0.1 mg kg-1 d-1) for 14 weeks, exhibited the reduction in the total aortic plaque area (48.8%±6.6% vs. 74.6%±8.0%, P<0.05), the decrease in the lipid core area ((0.019±0.0037) mm2vs. (0.032±0.0062) mm2, P<0.05) and in the percentage of senescent cells within the plaques (16.4%±3.7% vs. 30.7%±2.0%, P<0.01), while the increase in the thickness of the fibrous cap ((21.6±2.1) µm vs. (14.6±1.5) µm, P<0.01). Transcriptome sequencing of the aortic arch in the mice revealed the involvement of the PPARα and the fatty acid metabolic signaling pathways in dapagliflozin's mechanism of ameliorating cellular aging and plaque progression. In vitro, dapagliflozin inhibited the expression of PPARα and its downstream signal FABP4, by which the accumulation of senescent cells in human aortic smooth muscle cells (HASMCs) was reduced under high-fat conditions. This effect was accompanied by a reduction in the intracellular lipid content and alleviation of oxidative stress. However, these beneficial effects of dapagliflozin could be reversed by the PPARα overexpression. Bioinformatics analysis and molecular docking simulations revealed that dapagliflozin might exert its effects by directly interacting with the RXRA protein, thereby influencing the expression of the PPARα signaling pathway. In conclusion, the cellular senescence of aortic smooth muscle cells is potentially altered by dapagliflozin through the suppression of the RXRA-PPARα-FABP4 signaling pathway, resulting in a deceleration of atherosclerotic progression.
ABSTRACT
Scoparodane C (1), a diterpenoid with a rare 3,4-seco-3-nor-2,11-epoxy-ent-clerodane scaffold, was obtained from the aerial parts of Isodon scoparius, along with isocopariusines A-E (2-6), five ent-clerodanoids featuring a 5/6-fused ring system, and isocopariusines F-H (7-9), three common ent-clerodanoids. The structures of these previously undescribed compounds were established by a combination of spectroscopic analysis, X-ray diffraction, chemical derivatization, and quantum chemical calculation. Remarkably, isocopariusine B (3) showed strong resistance reversal activity against fluconazole-resistant Candida albicans.
ABSTRACT
Background: We aimed to elucidate the quantitative relationship between the neuromuscular blockade depth and intraoperative motor-evoked potential amplitudes. Methods: This prospective, single-arm, open-label, observational study was conducted at a single university hospital in Seoul, Korea, and included 100 adult patients aged ≥19 years undergoing brain tumor removal surgery under general anesthesia. We measured the neuromuscular blockade degree and motor-evoked potential amplitude in the deltoid, abductor pollicis brevis, tibialis anterior, and abductor hallucis muscles until dural opening. Results: The pharmacokinetic-pharmacodynamic model revealed the exposure-response relationship between the rocuronium effect-site concentration and motor-evoked potential amplitudes. The mean motor-evoked potential amplitudes decreased proportionally with increasing neuromuscular blockade depth. As the mean amplitude increased, the coefficient of variation decreased bi-exponentially. The critical ratio of the first evoked response to the train-of-four stimulation (T1)/control response (Tc) thresholds beyond which the coefficient of variation exhibited minimal change were found to be 0.63, 0.65, 0.68, and 0.63 for the deltoid, abductor pollicis brevis, tibialis anterior, and abductor hallucis muscles, respectively. Conclusions: Our results reveal that the motor-evoked potential amplitude exhibits deterioration proportional to the degree of neuromuscular blockade. In light of the observed bi-exponential decline of the coefficient of variation with the motor-evoked potential amplitude, we recommend maintaining a T1/Tc ratio higher than 0.6 for partial neuromuscular blockade.
ABSTRACT
The key odorants contributing to the warmed-over flavor (WOF) of reheated precooked stewed beef were characterized using a sensomics approach. Overall, 36 odorants were identified, and based on flavor dilution factors, odor activity values, aroma recombination, and omission test, 11 compounds mainly derived from lipid oxidation were characterized as the key odorants contributing to the formation of WOF. In particular, 3-(methylthio)propanal, which was positively correlated with meaty aroma, was implicated in an overall increase in WOF. Thus, these odorants were elected as potential markers of WOF in the reheated precooked stewed beef. In summary, the WOF of the precooked stewed beef could be attributed to an overall increase in lipid oxidation products and a decrease in the odorants with desirable aromas. The characterization of WOF in precooked stewed beef will aid in the flavor quality control of precooked stewed beef dishes.
ABSTRACT
What is already known on this topic?: A new conceptual term, small and vulnerable newborns (SVN), bringing preterm birth, small for gestational age (SGA), or low birth weight (LBW) together is being advocated for assessing whether a child is at high risk. What is added by this report?: According to the new conceptual term, the increasing incidence of high-risk newborns (from 9.82% to 10.96%) has been observed among 2,005,408 newborns over the period from 2013 to 2022, which is higher than using any of the three definitions of SVN. Maternal age ≥35, primiparity, and multiple births are high risks for SVN. What are the implications for public health practice?: The new conceptual framework should be used to better assess the number of high-risk newborns. Attention should be paid to multiple births to prevent preterm-related SVN. To reduce term newborns who are SGA, we need to be concerned not only with multiple pregnancies but also with first-time mothers.
ABSTRACT
Developing flexible energy storage devices with good deformation resistance under extreme operating conditions is highly desirable yet remains very challenging. Super-elastic MXene-enhanced polyvinyl alcohol/polyaniline (AMPH) hydrogel electrodes are designed and synthesized through vertical gradient ice templating-induced polymerization. This approach allows for the unidirectional growth of polyaniline (PANI) and 2D MXene layers along the elongated arrayed ice crystals in a controlled manner. The resulting 3D unidirectional AMPH hydrogel exhibits inherent stretchability and electronic conductivity, with the ability to completely recover its shape even under extreme conditions, such as 500% tensile strain, 50% compressive strain. The presence of MXene in the hydrogel electrode enhances its resilience to mechanical compression and stretching, resulting in less variation in resistance. AMPH has a specific capacitance of 130.68 and 88.02 mF cm-2 at a current density of 0.2 and 2 mA cm-2, respectively, and retains 90% and 70% of its original capacitance at elongation of 100% and 200%, respectively. AMPH-based supercapacitors demonstrate exceptional performance in high salinity environments and wide temperature ranges (-30-80 °C). The high electrochemical activity, temperature tolerance, and mechanical robustness of AMPH-based supercapacitor endow it promising as the power supply for flexible and wearable electronic devices.
ABSTRACT
BACKGROUND: Determining the impact of somatic mutations requires understanding the functional relationship of genes acquiring mutations; however, it is largely unknown how mutations in functionally related genes influence each other. METHODS: We employed non-synonymous-to-synonymous or dNdS ratios to evaluate the evolutionary dependency (ED) of gene pairs, assuming a mutation in one gene of a gene pair can affect the evolutionary fitness of mutations in its partner genes as mutation context. We employed PanCancer- and tumor type-specific mutational profiles to infer the ED of gene pairs and evaluated their biological relevance with respect to gene dependency and drug sensitivity. RESULTS: We propose that dNdS ratios of gene pairs and their derived cdNS (context-dependent dNdS) scores as measure of ED distinguishing gene pairs either as synergistic (SYN) or antagonistic (ANT). Mutation contexts can induce substantial changes in the evolutionary fitness of mutations in the paired genes, e.g., IDH1 and IDH2 mutation contexts lead to substantial increase and decrease of dNdS ratios of ATRX indels and IDH1 missense mutations corresponding to SYN and ANT relationship with positive and negative cdNS scores, respectively. The impact of gene silencing or knock-outs on cell viability (genetic dependencies) often depends on ED, suggesting that ED can guide the selection of candidates for synthetic lethality such as TCF7L2-KRAS mutations. Using cell line-based drug sensitivity data, the effects of targeted agents on cell lines are often associated with mutations of genes exhibiting ED with the target genes, informing drug sensitizing or resistant mutations for targeted inhibitors, e.g., PRSS1 and CTCF mutations as resistant mutations to EGFR and BRAF inhibitors for lung adenocarcinomas and melanomas, respectively. CONCLUSIONS: We propose that the ED of gene pairs evaluated by dNdS ratios can advance our understanding of the functional relationship of genes with potential biological and clinical implications.
Subject(s)
Evolution, Molecular , Mutation , Neoplasms , Humans , Neoplasms/genetics , Silent MutationABSTRACT
Regenerative therapy, a key area of tissue engineering, holds promise for restoring damaged organs, especially in bone regeneration. Bone healing is natural to the body but becomes complex under stress and disease. Large bone deformities pose significant challenges in tissue engineering. Among various methods, scaffolds are attractive as they provide structural support and essential nutrients for cell adhesion and growth. Collagen and hydroxyapatite (HA) are widely used due to their biocompatibility and biodegradability. Collagen and nano-scale HA enhance cell adhesion and development. Thus, nano HA/collagen scaffolds offer potential solutions for bone regeneration. This review focuses on the use and production of nano-sized HA/collagen composites in bone regeneration.
[Box: see text].
ABSTRACT
In fermented foods, acetic acid bacteria (AAB), kinds of bacteria with a long history of utilization, contribute to safety, nutritional, and sensory properties primarily through acetic acid fermentation. AAB are commonly found in various fermented foods such as vinegar, sour beer, fermented cocoa and coffee beans, kefir beverages, kombucha, and sourdough. They interact and cooperate with a variety of microorganisms, resulting in the formation of diverse metabolites and the production of fermented foods with distinct flavors. Understanding the interactions between AAB and other microbes is crucial for effectively controlling and utilizing AAB in fermentation processes. However, these microbial interactions are influenced by factors such as strain type, nutritional conditions, ecological niches, and fermentation duration. In this review, we examine the relationships and research methodologies of microbial interactions and interaction studies between AAB and yeasts, lactic acid bacteria (LAB), and bacilli in different food fermentation processes involving these microorganisms. The objective of this review is to identify key interaction models involving AAB and other microorganisms. The insights gained will provide scientific guidance for the effective utilization of AAB as functional microorganisms in food fermentation processes.
ABSTRACT
We propose a state-of-the-art deep learning approach for accurate electrocardiogram (ECG) signal analysis, addressing both waveform delineation and beat type classification tasks. For beat type classification, we integrated two novel schemes into the deep learning model, significantly enhancing its performance. The first scheme is an adaptive beat segmentation method that determines the optimal duration for each heartbeat based on RR-intervals, mitigating segmenting errors from conventional fixed-period segmentation. The second scheme incorporates relative heart rate information of the target beat compared to neighboring beats, improving the model's ability to accurately detect premature atrial contractions (PACs) that are easily confused with normal beats due to similar morphology. Extensive evaluations on the PhysioNet QT Database, MIT-BIH Arrhythmia Database, and real-world wearable device data demonstrated the proposed approach's superior capabilities over existing methods in both tasks. The proposed approach achieved sensitivities of 99.81% for normal beats, 99.08% for premature ventricular contractions, and 97.83% for PACs in beat type classification. For waveform delineation, we achieved F1-scores of 0.9842 for non-waveform, 0.9798 for P-waves, 0.9749 for QRS complexes, and 0.9848 for T-waves. It significantly outperforms existing methods in PAC detection while maintaining high performance across both tasks. The integration of aforementioned two schemes into the deep learning model improved the accuracy of normal sinus rhythms and arrhythmia detection.
ABSTRACT
The tumor microenvironment (TME) promotes metabolic reprogramming and dysfunction in immune cells. Here, we examined the impact of the TME on phospholipid metabolism in CD8+ T cells. In lung cancer, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were lower in intratumoral CD8+ T cells than in circulating CD8+ T cells. Intratumoral CD8+ T cells exhibited decreased expression of phospholipid phosphatase 1 (PLPP1), which catalyzes PE and PC synthesis. T cell-specific deletion of Plpp1 impaired antitumor immunity and promoted T cell death by ferroptosis. Unsaturated fatty acids in the TME stimulated ferroptosis of Plpp1-/- CD8+ T cells. Mechanistically, programmed death-1 (PD-1) signaling in CD8+ T cells induced GATA1 binding to the promoter region Plpp1 and thereby suppressed Plpp1 expression. PD-1 blockade increased Plpp1 expression and restored CD8+ T cell antitumor function but did not rescue dysfunction of Plpp1-/- CD8+ T cells. Thus, PD-1 signaling regulates phospholipid metabolism in CD8+ T cells, with therapeutic implications for immunotherapy.
ABSTRACT
Fulvic acids (FAs) have been commercially used in cosmetics and agronomy due to their unique biological activities, such as plant stimulation and anti-inflammatory effects. However, the extraction sources of FAs, such as peat, are currently limited. Consequently, new extraction methods using renewable resources need to be developed, while reproducing the biological functions. Here, ionic liquids (ILs) effectively extracted fulvic-like substances (FLSs) from wood sawdust. The overall molecular weight distributions of FLSs were similar to those of commercial FAs, and key organic groups (e.g., aromatic, phenolic, and methoxy groups) were also found to be shared between commercial FAs and FLSs. Detailed compositional analysis revealed by high-resolution mass spectrometry showed that the extracts contain both lignin-like and lipid-like molecules, while commercial FAs are biased toward lignin-like and carbohydrate-like molecules. FLSs generally showed better and similar performance in radical scavenging activity against ABTS+· and H2O2. Fibroblast proliferation and lettuce growth enhancements were also observed with the extract containing 1-ethyl-3-methylimidazolium acetate and triethylammonium hydrogen sulfate, respectively, which performed better than commercial FAs. Immunofluorescence staining of in vitro human follicle dermal papilla cells supports that coexpression of hair growth-related proteins can be accelerated with FLSs, and this effect was further evidenced by in vivo mouse model experiments. Finally, the reusability of ILs in the extraction process was confirmed by analyzing the structural features of FLSs from each recycling. Our findings indicate that ILs are useful for obtaining biologically functional fulvic analogs from renewable plant sources.
ABSTRACT
Background: Douzhi, a traditional Chinese fermented beverage, features microbial communities primarily composed of lactic acid bacteria (LAB). As fermented foods continue to gain recognition and popularity, douzhi is attracting growing interest. However, investigation of the critical aspects of douzhi's fermentation processes, including fermentation characteristics and microbial community dynamics, remains vital for enhancing food safety and quality for douzhi, as well as for similar fermented food products. Method: In this study, we collected douzhi microbial communities from four chain stores, using them as fermentation starter cultures. The microbial dynamics of the fermentation were analyzed, focusing on the inoculation of LAB strains and the transition from a mung bean-based matrix to skimmed milk. The metabolomic profiles of the fermented mung bean matrices were also studied. Results: Douzhi samples obtained from representative chain stores were found to be overwhelmingly dominated by LAB. When inoculated along with the douzhi community, both LAB strains exhibited notable and substantial reductions in the pH value of the designated mung bean matrices compared to those inoculated indigenous microbiota. Specifically, Lactiplantibacillus plantarum CGMCC 1.1856 retained its population, whereas Pediococcus pentosaceus CGMCC 1.2695 exhibited a decrease in relative abundance. Using skimmed milk as a fermentation substrate instead of the mung bean matrix resulted in significant shifts in microbial communities, particularly leading to an increase in Escherichia sp. The metagenomic analyses and functional predictions illustrated that various metabolic functions were enhanced during the fermentation process due to LAB inoculation. The liquid chromatography-mass spectrometry based metabolomic analysis revealed that the inoculation of Lactiplantibacillus plantarum and Pediococcus pentosaceus in mung bean matrix did not introduce new metabolites but significantly altered the concentration and profile of existing metabolites, especially increased low molecular carbohydrates, which may enhance the nutritional potential of the fermented product. Discussion: This study examines the microbial dynamics of douzhi microbiota fermentation, emphasizing the role of lactic acid bacteria in enhancing fermentation activity and metabolite profiles. These insights contribute to improving manufacturing processes and ensuring the safety and quality of douzhi and similar fermented foods.
ABSTRACT
Fermentative features of doenjang-meju, a traditional Korean soybean brick, were investigated over 45 days via genome-centered metatranscriptomics. The pH value rapidly decreased within 10 days and successively increased after 20 days, along with an initial bacterial growth, including lactic acid bacteria, and subsequent fungal growth, suggesting their association. Polysaccharides and lipids underwent degradation, and amino acids, free sugars, and organic acids increased during the early stage. Metagenome analysis identified Aspergillus, Bacillus, Enterococcus, Staphylococcus, and Leuconostoc as major microbes, which were isolated and genome-sequenced. Metatranscriptomic analysis revealed the major roles of Bacillus and Enterococcus during the early period, shifting to Aspergillus dominance after 10 days. Metabolic pathway reconstruction and transcriptional analysis reveal that Aspergillus primarily decomposed polysaccharides to free sugars; Aspergillus and Bacillus metabolized lipids, free sugars, and organic acids generated by Enterococcus; and Aspergillus and Bacillus were instrumental in amino acid metabolism: their contributions varied by compounds and pathways.
ABSTRACT
Three new ent-kaurane diterpenoids, silvaticusins A-C (1-3), along with a new ent-kaurane dimer silvaticusin D (4) were isolated from the aerial parts of Isodon silvaticus. The structures of these new compounds were established mainly by comprehensive analysis of their NMR and MS data. The absolute configuration of compounds 1 and 4 were determined using a single-crystal X-ray diffraction and computational methods, respectively. Compounds 2 and 3 were found to exhibit remarkable cytotoxic effects against five human tumor cell lines (HL-60, A-549, SMMC-7721, MDA-MB-231, and SW-480), with IC50 values spanning from 1.27 ± 0.08 to 7.52 ± 0.33 µM.
ABSTRACT
Induction of resistin-like molecule ß (Relm-ß) and mitofusin 2 (MFN2) mediated aberrant mitochondrial fission have been found to be involved in the pathogenesis of pulmonary arterial hypertension (PAH). However, the molecular mechanisms underlying Relm-ß regulation of MFN2 therefore mitochondrial fission remain unclear. This study aims to address these issues. Primary cultured PASMCs and monocrotaline (MCT)-induced PAH rats were applied in this study. The results showed that Relm-ß promoted cells proliferation in PASMCs, this was accompanied with the upregulation of USP18, Twist1 and miR-214, and downregulation of MFN2. We found that Relm-ß increased USP18 expression which in turn raised Twist1 by suppressing its proteasome degradation. Elevation of Twist1 increased miR-214 expression and then reduced MFN2 expression and mitochondrial fragmentation leading to PASMCs proliferation. In vivo study, we confirmed that Relm-ß was elevated in MCT-induced PAH rat model, and USP18/Twist1/miR-214/MFN2 axis was altered similar as in vitro. Targeting this cascade by Relm-ß receptor inhibitor Calhex231, proteasome inhibitor MG-132, Twist1 inhibitor Harmine or miR-214 antagomiR prevented the development of pulmonary vascular remodeling and therefore PAH in MCT-treated rats. In conclusion, we demonstrate that Relm-ß promotes PASMCs proliferation and vascular remodeling by activating USP18/Twist1/miR-214 dependent MFN2 reduction and mitochondrial fission, suggesting that this signaling pathway might be a promising target for management of PAH.
Subject(s)
Cell Proliferation , GTP Phosphohydrolases , MicroRNAs , Mitochondria , Rats, Sprague-Dawley , Signal Transduction , Twist-Related Protein 1 , Ubiquitin Thiolesterase , Animals , Male , Rats , Cell Proliferation/drug effects , GTP Phosphohydrolases/metabolism , Hypertension, Pulmonary/chemically induced , Hypertension, Pulmonary/metabolism , Hypertension, Pulmonary/pathology , Hypertension, Pulmonary/physiopathology , Intercellular Signaling Peptides and Proteins/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Mitochondria/metabolism , Mitochondria/drug effects , Mitochondrial Dynamics/drug effects , Mitochondrial Proteins , Monocrotaline/toxicity , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Pulmonary Arterial Hypertension/metabolism , Pulmonary Arterial Hypertension/chemically induced , Pulmonary Arterial Hypertension/pathology , Pulmonary Arterial Hypertension/physiopathology , Pulmonary Artery/drug effects , Pulmonary Artery/pathology , Pulmonary Artery/metabolism , Signal Transduction/drug effects , Twist-Related Protein 1/metabolism , Twist-Related Protein 1/genetics , Ubiquitin Thiolesterase/metabolism , Ubiquitin Thiolesterase/geneticsABSTRACT
The clinical consequences of perioperative albumin extravasation accompanying major abdominal surgery remain underexplored. We retrospectively reviewed the data of patients who underwent cytoreductive surgery (CRS) and hyperthermic intraoperative peritoneal chemotherapy (HIPEC). Parameters of albumin kinetics, including serum albumin concentration decrease (∆Alb) and extravasated albumin level (Albshift), were assessed from surgery until postoperative day (POD) 3. Logistic regression analysis identified factors associated with major complications. The association of albumin kinetics with major complications was evaluated using receiver operating characteristic (ROC) curve analysis. Serum albumin levels decreased during surgery and subsequently increased. Of the 121 analyzed patients, 25 (21%) developed major complications. The ∆Alb and Albshift during surgery and on POD 3 were greater in patients who developed major complications than in those who did not (12 ± 12 vs. 6 ± 14, p = 0.032, and 127.5 (71.9) vs. 48.5 (44.9), p < 0.001, respectively). Perioperative ∆Alb and Albshift were associated with major complications. The areas under the ROC curve of Albshift during the 3 days post-surgery and Albshift on POD 3 were 0.843 and 0.910, respectively. Albshift during the 3 days post-surgery and Albshift on POD 3 were correlated with complications (p < 0.05). In conclusion, perioperative albumin loss was associated with major complications in patients undergoing CRS and HIPEC. Albshift was associated with serious complications.
ABSTRACT
Multiple dynamic impact signals are widely used in a variety of engineering scenarios and are difficult to identify accurately and quickly due to the signal adhesion phenomenon caused by nonlinear interference. To address this problem, an intelligent algorithm combining wavelet transforms with lightweight neural networks is proposed. First, the features of multiple impact signals are analyzed by establishing a transfer model for multiple impacts in multibody dynamical systems, and interference is suppressed using wavelet transformation. Second, a lightweight neural network, i.e., fast-activated minimal gated unit (FMGU), is elaborated for multiple impact signals, which can reduce computational complexity and improve real-time performance. Third, the experimental results show that the proposed method maintains excellent feature recognition results compared to gate recurrent unit (GRU) and long short-term memory (LSTM) networks under all test datasets with varying impact speeds, while its metrics for computational complexity are 50% lower than those of the GRU and LSTM. Therefore, the proposed method is of great practical value for weak hardware application platforms that require the accurate identification of multiple dynamic impact signals in real time.