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Mentha spicata is a popular herb used in foods, cosmetics, and medicines. In the present study, liquid chromatography-mass spectrometry-based metabolomics analysis and the zebrafish model were used to investigate the potential biomarkers of M. spicata growing in Shanghe County (Shandong Province, China) and their anti-inflammatory properties. Network pharmacology and molecular docking were performed to screen the main targets of the characteristic compounds to understand their mechanisms of action. Nine potential markers including sugars (1,2), polyphenolic acids (3-5), and flavonoids (6-9) were identified from the species. The inhibitory effects on leukocyte migration confirmed that compounds 1 and 3-9 played a positive role in the protective effect of Shanghe M. spicata (SM) extract against inflammation. Akt (protein kinase B), EGFR (epidermal growth factor receptor), and MMP9 (matrix metalloproteinase 9) were the core target proteins of the identified compounds in the anti-inflammatory process. The most significant Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment terms were response to abiotic stimulus (Biological Process), carbohydrate derivative binding (Molecular Function), and pathways in cancer. In docking simulations, 3-p-coumaroylquinic acid (3-PC, 4) and cirsimaritin (CN, 7) exhibited the highest potential affinity to the active sites of Akt and EGFR proteins, respectively; additionally, 5-demethylsinensetin (5-DS, 9) and luteolin (LN, 6) were considered the most suitable ligands for the MMP9 protein. The present study highlighted the use of SM resources as functional products with health benefits.
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BACKGROUND: The challenge of early and rapid diagnosis of periprosthetic joint infection (PJI) remains important. This study aimed to assess the efficacy of dual-energy computed tomography (CT) (DECT) iodine maps for diagnosing PJI in total hip arthroplasty. METHODS: We prospectively enrolled 68 patients who had postoperative joint pain after hip arthroplasty. All patients underwent preoperative DECT iodine imaging to quantify iodine concentration (IC) in periprosthetic tissues during arterial and venous phases. The diagnostic efficacy of DECT iodine maps was evaluated by constructing receiver operating characteristic (ROC) curves according to the Musculoskeletal Infection Society criteria. RESULTS: Compared with erythrocyte sedimentation rate (Area Under the Curve (AUC) = 0.837), polymorphonuclear cell percentage (AUC = 0.703), and C-reactive protein (AUC = 0.837), periprosthetic tissue venous-phase iodine concentration (IC) (AUC = 0.970) and arterial-phase IC (AUC = 0.964) exhibited outstanding discriminative capability between PJI and aseptic failure. The PJI cut-off point was venous IC = 1.225 mg/ml, with a sensitivity of 92.31% and specificity of 90.48%; for arterial IC = 1.065 mg/ml, the sensitivity was 96.15%, and a specificity was 90.70%. CONCLUSION: This study demonstrates the great potential of DECT iodine maps for the diagnosis of PJI around hip arthroplasty, which helps to differentiate between periprosthetic infection and aseptic failure after hip arthroplasty.
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Gossypol, a yellow polyphenolic compound found in the Gossypium genus, is toxic to animals that ingest cotton-derived feed materials. However, ruminants display a notable tolerance to gossypol, attributed to the pivotal role of ruminal microorganisms in its degradation. The mechanisms of how rumen microorganisms degrade and tolerate gossypol remain unclear. Therefore, in this study, Enterobacter sp. GD5 was isolated from rumen fluid, and the effects of gossypol on its metabolism and gene expression were investigated using liquid chromatography-mass spectrometry (LC-MS) and RNA analyses. The LC-MS results revealed that gossypol significantly altered the metabolic profiles of 15 metabolites (eight upregulated and seven downregulated). The Kyoto Encyclopedia of Genes and Genomes analysis results showed that significantly different metabolites were associated with glutathione metabolism in both positive and negative ion modes, where gossypol significantly affected the biosynthesis of amino acids in the negative ion mode. Transcriptomic analysis indicated that gossypol significantly affected 132 genes (104 upregulated and 28 downregulated), with significant changes observed in the expression of catalase peroxidase, glutaredoxin-1, glutathione reductase, thioredoxin 2, thioredoxin reductase, and alkyl hydroperoxide reductase subunit F, which are related to antioxidative stress. Furthermore, Gene Ontology analysis revealed significant changes in homeostatic processes following gossypol supplementation. Overall, these results indicate that gossypol induces oxidative stress, resulting in the increased expression of antioxidative stress-related genes in Enterobacter sp. GD5, which may partially explain its tolerance to gossypol.
Subject(s)
Enterobacter , Gossypol , Metabolomics , Gossypol/pharmacology , Gossypol/metabolism , Enterobacter/metabolism , Enterobacter/genetics , Enterobacter/drug effects , Animals , Transcriptome/drug effects , Gene Expression Regulation, Bacterial/drug effects , Metabolome/drug effects , Gene Expression Profiling , Rumen/microbiology , Rumen/metabolism , Rumen/drug effectsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Thrombosis is a common cause of morbidity and mortality worldwide. Lagopsis supina (Stephan ex Willd.) Ikonn.-Gal. ex Knorring is an ancient Chinese herbal medicine used for treating thrombotic diseases. Nevertheless, the antithrombotic mechanisms and effective constituents of this plant have not been clarified. AIM OF THE STUDY: This work aimed to elucidate the pharmacodynamics and mechanism of L. supina against thrombosis. MATERIALS AND METHODS: Systematic network pharmacology was used to explore candidate effective constituents and hub targets of L. supina against thrombosis. Subsequently, the binding affinities of major constituents with core targets were verified by molecular docking analysis. Afterward, the therapeutic effect and mechanism were evaluated in an arteriovenous bypass thrombosis rat model. In addition, the serum metabolomics analysis was conducted using ultra-high performance liquid chromatography coupled with Q-Exactive mass spectrometry. RESULTS: A total of 124 intersected targets of L. supina against thrombosis were predicted. Among them, 24 hub targets were obtained and their mainly associated with inflammation, angiogenesis, and thrombosis approaches. Furthermore, 9 candidate effective constituents, including (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3ß-ol, aurantiamide, (22E,24R)-5α,8α-epidioxyergosta-6,9 (11),22-trien-3ß-ol, lagopsinA, lagopsin C, 15-epi-lagopsin C, lagopsin D, 15-epi-lagopsin D, and lagopsin G in L. supina and 6 potential core targets (TLR-4, TNF-α, HIF-1α, VEGF-A, VEGFR-2, and CLEC1B) were acquired. Then, these 9 constituents demonstrated strong binding affinities with the 6 targets, with their lowest binding energies were all less than -5.0 kcal/mol. The antithrombotic effect and potential mechanisms of L. supina were verified, showing a positively associated with the inhibition of inflammation (TNF-α, IL-1ß, IL-6, IL-8, and IL-10) and coagulation cascade (TT, APTT, PT, FIB, AT-III), promotion of angiogenesis (VEGF), suppression of platelet activation (TXB2, 6-keto-PGF1α, and TXB2/6-keto-PGF1α), and prevention of fibrinolysis (t-PA, u-PA, PAI-1, PAI-1/t-PA, PAI-1/u-PA, and PLG). Finally, 14 endogenous differential metabolites from serum samples of rats were intervened by L. supina based on untargeted metabolomics analysis, which were closely related to amino acid metabolism, inflammatory and angiogenic pathways. CONCLUSION: Our integrated strategy based on network pharmacology, molecular docking, metabolomics, and in vivo experiments revealed for the first time that L. supina exerts a significant antithrombotic effect through the inhibition of inflammation and coagulation cascade, promotion of angiogenesis, and suppression of platelet activation. This paper provides novel insight into the potential of L. supina as a candidate agent to treat thrombosis.
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Sodium cyclamate in Baijiu is a key item in the China National Food Safety Supervision and Inspection Plan. A simple, economical, sensitive, and reliable method is urgently needed for routine analysis and internal quality control. A method based on high performance liquid chromatography with fluorescence detection (HPLC-FLD) was developed for the determination of sodium cyclamate in Baijiu by o-phthalaldehyde derivatization. First, the sodium cyclamate in the sample solution was converted into amino compounds using the desulfurization reaction under acidic conditions. Next, 400 g/L sodium hydroxide solution was added to the sample solution for neutralization. The amino compounds in the sample solution were then derivatized with o-phthalaldehyde to produce indole-substituted derivatives that are capable of producing fluorescence signals. Separation was carried out on a C18 column (250 mm×4.6 mm, 5 µm) in isocratic elution mode using a mobile phase consisting of acetonitrile and phosphate buffer. Finally, the eluate was monitored using a fluorescence detector, and an external standard method was used for quantification. A good linear relationship was obtained in the range of 0.1-2.0 mg/L, with correlation coefficients greater than 0.999. The average recoveries of sodium cyclamate spiked at levels of 0.1-1.0 mg/kg in Baijiu samples ranged from 90.7% to 100.9%, with relative standard deviations (RSDs) of 3.5%-5.6% (n=6). The limits of detection and quantification were 0.03 and 0.10 mg/kg, respectively. Nine Baijiu samples collected from the market were tested, and the results demonstrated that the contents of sodium cyclamate detected by the developed method were consistent with those obtained using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method described in GB 5009.97-2016 (the third method). The proposed method is economical, sensitive, specific, and accurate; thus, it provides a basic approach for the determination of sodium cyclamate in Baijiu samples and has great potential for routine analysis in foodstuffs.
Subject(s)
Cyclamates , Fluorometry , Food Contamination , Chromatography, High Pressure Liquid/methods , Food Contamination/analysis , Cyclamates/analysis , Fluorometry/methodsABSTRACT
BACKGROUND: The selection of appropriate second-line therapy for liver cancer after first-line treatment failure poses a significant clinical challenge due to the lack of direct comparative studies and standard treatment protocols. A network meta-analysis (NMA) provides a robust method to systematically evaluate the clinical outcomes and adverse effects of various second-line treatments for hepatocellular carcinoma (HCC). METHODS: We systematically searched PubMed, Embase, Web of Science and the Cochrane Library to identify phase III/IV randomized controlled trials (RCTs) published up to March 11, 2024. The outcomes extracted were median overall survival (OS), median progression-free survival (PFS), time to disease progression (TTP), disease control rate (DCR), objective response rate (ORR), and adverse reactions. This study was registered in the Prospective Register of Systematic Reviews (CRD42023427843) to ensure transparency, novelty, and reliability. RESULTS: We included 16 RCTs involving 7,005 patients and 10 second-line treatments. For advanced HCC patients, regorafenib (HR = 0.62, 95%CI: 0.53-0.73) and cabozantinib (HR = 0.74, 95%CI: 0.63-0.85) provided the best OS benefits compared to placebo. Cabozantinib (HR = 0.42, 95%CI: 0.32-0.55) and regorafenib (HR = 0.46, 95% CI: 0.31-0.68) also offered the most significant PFS benefits. For TTP, apatinib (HR = 0.43, 95% CI: 0.33-0.57), ramucirumab (HR = 0.44, 95% CI: 0.34-0.57), and regorafenib (HR = 0.44, 95% CI: 0.38-0.51) showed significant benefits over placebo. Regarding ORR, ramucirumab (OR = 9.90, 95% CI: 3.40-42.98) and S-1 (OR = 8.68, 95% CI: 1.4-154.68) showed the most significant increases over placebo. Apatinib (OR = 3.88, 95% CI: 2.48-6.10) and cabozantinib (OR = 3.53, 95% CI: 2.54-4.90) provided the best DCR benefits compared to placebo. Tivantinib showed the most significant advantages in terms of three different safety outcome measures. CONCLUSIONS: Our findings suggest that, in terms of overall efficacy and safety, regorafenib and cabozantinib are the optimal second-line treatment options for patients with advanced HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Network Meta-Analysis , Pyridines , Randomized Controlled Trials as Topic , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/mortality , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/mortality , Pyridines/therapeutic use , Pyridines/adverse effects , Anilides/therapeutic use , Anilides/adverse effects , Phenylurea Compounds/therapeutic use , Phenylurea Compounds/adverse effects , Ramucirumab , Treatment Outcome , Progression-Free Survival , Antibodies, Monoclonal, Humanized/therapeutic useABSTRACT
The objective of this study was to evaluate the effects of pre-exercise L-citrulline supplementation on the athletic performance of Yili speed-racing horses during a high-intensity exercise. On the 20th day of the experiment, blood samples were collected at 3 h and 6 h post-supplementation to measure the amino acid and polyamine concentrations. On the 38th day of the experiment, the horses participated in a 2000 m speed race, and three distinct blood samples were gathered for assessing blood gases, hematological parameters, the plasma biochemistry, antioxidant parameters, and NO concentrations. The results indicate that the L-citrulline group showed a significant increase in the plasma citrulline and arginine concentrations. Conversely, the concentrations of alanine, serine, and threonine were significantly decreased. The glycine concentration decreased significantly, while there was a trend towards an increase in the glutamine concentration. Additionally, the levels of putrescine and spermidine in the plasma of the L-citrulline group were significantly increased. In terms of exercise performance, L-citrulline can improve the exercise performance of sport horses, significantly reduce the immediate post-race lactate levels in Yili horses, and accelerate the recovery of blood gas levels after an exercise. Furthermore, in the L-citrulline group of Yili horses, The levels of the total protein of plasma, superoxide dismutase, catalase, and lactate dehydrogenase were significantly increased both 2 h before and 2 h after the race. The total antioxidant capacity showed a highly significant increase, while the malondialdehyde content significantly decreased. In the immediate post-race period, the creatinine content in the L-citrulline group significantly increased. In conclusion, this study demonstrates that L-citrulline supplementation can influence the circulating concentrations of L-citrulline and arginine in Yili horses, enhance the antioxidant capacity, reduce lactate levels, and improve physiological and biochemical blood parameters, thereby having a beneficial effect on the exercise performance of athletic horses.
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Introduction: Although inguinal hernia (IH) is prevalent in elderly males, research on its specific diagnostic biomarkers is limited. Protein N-glycosylation is one of the most important and ubiquitous post-translational modifications and often results in a remarkable heterogeneity of protein glycoforms. Protein N-glycosylation often changes in a disease and holds great potential for discovering non-invasive biomarkers. This study aimed to gain insights into total serum protein N-glycosylation of IH to identify candidate non-invasive biomarkers for diagnosis and subtype classification of IH. Methods: Linkage-specific sialylation derivatization combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry detection was used to analyze serum protein N-glycosylation patterns in IH patients and healthy controls. Results: IH patients had abnormal glycan fucosylation and sialylation compared to healthy controls (HC), of which two glycan traits representing linkage-specific sialylation within monoantennary glycans showed high potential as diagnostic biomarkers for IH with an area under the curve (AUC) of 0.75. Additionally, serum N-glycans were different between indirect IH and direct IH in glycosylation features, namely complexity, fucosylation, galactosylation, sialylation, and α2,6-linked sialylation. Four distinctive glycans between the two subtypes showed good performance with AUC >0.8, suggesting that these glycan traits have potential as biomarkers for subtype classification. Conclusions: We first reported the serum N-glycomic features of IH patients. Furthermore, we identified several potential biomarkers for the diagnosis and subtype classification of IH. These findings can deepen the understanding of IH.
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Carbapenem-resistant Acinetobacter baumannii (CRAB) poses a significant threat to hospitalized patients as effective therapeutic options are scarce. Based on the genomic characteristics of the CRAB strain AB2877 harboring chromosome-borne blaOXA-23, which was isolated from the bronchoalveolar lavage fluid (BALF) of a patient in a respiratory intensive care unit (RICU), we systematically analyzed antibiotic resistance genes (ARGs) and the genetic context associated with ARGs carried by CRAB strains harboring chromosome-borne blaOXA-23 worldwide. Besides blaOXA-23, other ARGs were detected on the chromosome of the CRAB strain AB2877 belonging to ST208/1806 (Oxford MLST scheme). Several key genetic contexts associated with the ARGs were identified on the chromosome of the CRAB strain AB2877, including (1) the MDR region associated with blaOXA-23, tet(B)-tetR(B), aph(3'')-Ib, and aph(6)-Id (2); the resistance island AbGRI3 harboring armA and mph(E)-msr(E) (3); the Tn3-like composite transposon containing blaTEM-1D and aph(3')-Ia; and (4) the structure "ISAba1-blaADC-25." The first two genetic contexts were most common in ST195/1816, followed by ST208/1806. The last two genetic contexts were found most frequently in ST208/1806, followed by ST195/1816.IMPORTANCEThe blaOXA-23 gene can be carried by plasmid or chromosome, facilitating horizontal genetic transfer and increasing carbapenem resistance in healthcare settings. In this study, we focused on the genomic characteristics of CRAB strains harboring the chromosome-borne blaOXA-23 gene, and the important genetic contexts associated with blaOXA-23 and other ARGs were identified, and their prevalent clones worldwide were determined. Notably, although the predominant clonal CRAB lineages worldwide containing the MDR region associated with blaOXA-23, tet(B)-tetR(B), aph(3'')-Ib, and aph (6)-Id was ST195/1816, followed by ST208/1806, the CRAB strain AB2877 in our study belonged to ST208/1806. Our findings contribute to the knowledge regarding the dissemination of CRAB strains and the control of nosocomial infection.
Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Anti-Bacterial Agents , Carbapenems , Drug Resistance, Multiple, Bacterial , Whole Genome Sequencing , beta-Lactamases , Acinetobacter baumannii/genetics , Acinetobacter baumannii/drug effects , Carbapenems/pharmacology , Acinetobacter Infections/microbiology , Acinetobacter Infections/drug therapy , Drug Resistance, Multiple, Bacterial/genetics , Humans , beta-Lactamases/genetics , Anti-Bacterial Agents/pharmacology , Chromosomes, Bacterial/genetics , Microbial Sensitivity Tests , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Genome, Bacterial , Multilocus Sequence TypingABSTRACT
BACKGROUND: Intramedullary nail (IMN) and plate fixation are the most commonly used surgical modalities for distal tibia fractures. However, the superiority of their efficacy regarding functional outcomes and complications remains controversial. Here, we performed a systematic review and meta-analysis to compare the efficacy of these two modalities. METHODS: Randomized controlled trials (RCTs) comparing the efficacy of IMN and plate fixation in distal tibia fractures were searched in PubMed, Web of Science, EMBASE, ClinicalTrials.gov, and Cochrane Library up to January 31, 2024. Weighted mean difference (WMD) and odds ratio (OR) with corresponding 95% confidence interval (CI) were estimated using a random-effect model for continuous and categorical outcomes, respectively. RESULTS: A total of 20 RCTs comprising 1528 patients were included. Compared with plate fixation, IMN significantly shortened surgery time (WMD=-10.73 min, 95%CI: -15.93 to -5.52), union time (WMD=-1.56 weeks, 95%CI: -2.82 to -0.30), and partial (WMD=-1.71 weeks, 95%CI: -1.91 to -0.43) and full (WMD=-2.61 weeks, 95%CI: -3.53 to -1.70) weight-bearing time. IMN was associated with markedly reduced risk of wound infection (OR = 0.44, 95%CI: 0.31-0.63) and secondary procedures (OR = 0.72, 95%CI: 0.55-0.95), but increased the risk of malunion (OR = 1.53, 95%CI: 1.02-2.30) and anterior knee pain (OR = 3.94, 95%CI: 1.68-9.28). The rates of nonunion, delayed union, and functional assessment scores did not significantly differ between the two groups. The percentages of patients obtaining an excellent functional outcome or an excellent and good functional outcome post-operation were comparable. CONCLUSIONS: Both IMN and plate fixation are effective modalities for the surgical treatment of distal tibia fractures. IMN seems to be preferred since it confers more advantages, but the elevated rates of malunion and knee pain require attention. The decision on fixation modality should be tailored to the specific fracture, considering these pros and cons.
Subject(s)
Bone Plates , Fracture Fixation, Intramedullary , Randomized Controlled Trials as Topic , Tibial Fractures , Humans , Tibial Fractures/surgery , Fracture Fixation, Intramedullary/methods , Fracture Fixation, Intramedullary/instrumentation , Treatment Outcome , Bone Nails , Operative Time , Male , Female , Middle Aged , Adult , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Fracture Fixation, Internal/methods , Fracture Fixation, Internal/instrumentationABSTRACT
Metal vanadates as negative electrode materials for lithium-ion batteries have attracted widespread attention, attributed to their substantial capacity, broad availability, and exceptional safety. In this study, NiCo2V2O8@NC microspheres featuring a yolk-double shell structure were successfully synthesized via ion exchange reactions and surface deposition techniques, employing metal glycerolate as a template. Owing to the bimetallic cobalt-nickel synergistic effect and the N-doped carbon network, this configuration not only optimizes the pore structure but also enhances conductivity, thereby augmenting the stability of the overall structure. The unique yolk-double shell design significantly enhances the utilization of active components and reduces the ion transport distance, thereby achieving high capacity. Thanks to the synergistic effects of this bimetallic and intricate structure, the material demonstrates exceptional capacity and cycle stability in lithium storage. The initial discharge capacity possesses 1522 mAh g-1 at a current density of 0.2 A g-1, with the reversible capacity still maintained at 1197 mAh g-1 after 100 cycles. In addition, at a high current density of 0.5 A g-1, the initial discharge capacity is 1487 mAh g-1, with a reversible capacity of 747 mAh g-1 maintained after 500 cycles. This study offers a perspective and methodology for the design and fabrication of complex porous double shell nanostructures.
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The nutritional benefits of mare milk are attracting increasing consumer interest. Limited availability due to low yield poses a challenge for widespread adoption. Although lysine and threonine are often used to enhance protein synthesis and muscle mass in horses, their impact on mare milk yield and nutrient composition remains underexplored. This study investigated the effects of lysine and threonine supplementation on 24 healthy Yili mares, mares at day 30 of lactation, over a 120-day period. The mares were divided into control and three experimental groups (six mares each) under pure grazing conditions. The control group received no amino acid supplementation, while experimental groups received varying daily doses of lysine and threonine: Group I (40 g lysine + 20 g threonine), Group II (60 g lysine + 40 g threonine), and Group III (80 g lysine + 60 g threonine). Supplementation in Group II notably increased milk yield, while Groups I and II showed higher milk fat percentages, and all experimental groups exhibited improved milk protein percentages. Additionally, blood levels of total protein, albumin, triglycerides, and glucose were reduced. Detailed analyses from Group II at peak lactation (day 60) included targeted metabolomics and microbial sequencing of milk, blood, and fecal samples. Amino acid metabolomics assessed amino acid content in mare milk and serum, while 16S rRNA gene sequencing evaluated rectal microbial composition. The results indicated that lysine and threonine supplementation significantly increased levels of threonine and creatine in the blood, and lysine, threonine, glutamine, and alanine in mare milk. Microbial analysis revealed a higher prevalence of certain bacterial families and genera, including Prevotellaceae, p_251_o5, and Rikenellaceae at the family level, and unclassified_p_251_o5, Prevotellaceae_UCG_001, and Rikenellaceae_RC9_gut_group at the genus level. Multi-omics analysis showed positive correlations between specific fecal genera and amino acids in mare milk. For instance, Prevotellaceae_UCG_003, unclassified Bacteroidetes_BS11_gut_group, and Corynebacterium were positively correlated with lysine, while unclassified Prevotellaceae was positively correlated with alanine and threonine, and Unclassified_Bacteroidales_BS11_gut_group was positively correlated with glutamine. In summary, lysine and threonine supplementation in grazing lactating mares enhanced milk production and improved milk protein and fat quality. It is recommended that herders, veterinarians, and technicians consider amino acid content in the diet of lactating mares. The optimal supplementation levels under grazing conditions for Yili horses were determined to be 60 g lysine and 40 g threonine per day. Future research should explore the molecular mechanisms by which these amino acids influence milk protein and lipid synthesis in mare mammary epithelial cells.
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Panax notoginseng has the effect of stimulating circulation to end stasis. Our study was designed to evaluate the anti-thrombotic effect of protoparaxotriol saponins (PTS) from Panax notoginseng and the involved mechanisms. A thrombosis model was constructed, and the anti-thrombotic activity of PTS was determined by erythrocyte staining, heart rate, and blood flow velocity. In addition, quantitative real-time polymerase chain reaction (qPCR) was used to identify changes in the expression of genes related to coagulation, inflammation, and apoptosis. PTS alleviated arachidonic acid (AA)-induced caudal vein thrombosis, restored blood flow, and increased the area of cardiac erythrocyte staining, heart rate and blood flow velocity. It reduced the ponatinib-induced cerebral thrombus area and decreased the intensity of erythrocyte staining. The qPCR data showed that the anti-thrombotic effect of PTS was mediated by suppression of genes related to coagulation, inflammation and apoptosis, and also involved inhibition of NF-κB and PI3K/Akt pathways.
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Abscisic acid (ABA) is one of the many naturally occurring phytohormones widely found in plants. This study focused on refining APAn, a series of previously developed agonism/antagonism switching probes. Twelve novel APAn analogues were synthesized by introducing varied branched or oxygen-containing chains at the C-6' position, and these were screened. Through germination assays conducted on A. thaliana, colza, and rice seeds, as well as investigations into stomatal movement, several highly active ABA receptor antagonists were identified. Microscale thermophoresis (MST) assays, molecular docking, and molecular dynamics simulation showed that they had stronger receptor affinity than ABA, while PP2C phosphatase assays indicated that the C-6'-tail chain extending from the 3' channel effectively prevented the ligand-receptor binary complex from binding to PP2C phosphatase, demonstrating strong antagonistic activity. These antagonists showed effective potential in promoting seed germination and stomatal opening of plants exposed to abiotic stress, particularly cold and salt stress, offering advantages for cultivating crops under adverse conditions. Moreover, their combined application with fluridone and gibberellic acid could provide more practical agricultural solutions, presenting new insights and tools for overcoming agricultural challenges.
Subject(s)
Abscisic Acid , Germination , Molecular Docking Simulation , Abscisic Acid/chemistry , Germination/drug effects , Arabidopsis/drug effects , Arabidopsis/metabolism , Plant Growth Regulators/chemistry , Plant Growth Regulators/pharmacology , Seeds/drug effects , Seeds/chemistry , Seeds/growth & development , Oryza/drug effects , Oryza/metabolism , Oryza/growth & development , Arabidopsis Proteins/antagonists & inhibitors , Arabidopsis Proteins/metabolism , Molecular Dynamics Simulation , Agriculture/methods , Gibberellins/chemistry , Gibberellins/metabolism , PyridonesABSTRACT
Fourteen undescribed nitrogenous merosesquiterpenoids, purpurols A-D (1-4) and puraminones A-J (5-14), along with three known related compounds (15-17) were isolated from the sponge Pseudoceratina purpurea collected in the South China Sea. Their structures and absolute configurations were unambiguously elucidated by a combination of spectroscopic data, X-ray diffraction analysis, electronic circular dichroism calculations, and chemical derivatization. Purpurols A-D (1-4) incorporated nitrogenous heterocycles, compounds 1 and 2 feature an unusual benzothiazole ring, while 3 and 4 feature benzoxazole ring. Puraminones A-J (5-14) represent sesquiterpenoid aminoquinones with different amine and amino acid side chains at C-20. Additionally, twenty unreported sesquiterpenoid aminoquinone analogues were obtained through chemical derivatization. It is worth noting that all compounds are featured with unusual rearranged 4,9-friedodrimane subunit. In the bioassays, purpurols A and B showed weak anti-inflammation in zebrafish, as well as some compounds showed activities against tumor cells, therefore, preliminary structure-cytotoxicity relationships are also discussed.
Subject(s)
Porifera , Sesquiterpenes , Zebrafish , Animals , Porifera/chemistry , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/isolation & purification , Humans , Molecular Structure , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Drug Screening Assays, Antitumor , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Structure-Activity RelationshipABSTRACT
Exploring the bacterial community in the S. glauca rhizosphere was of great value for understanding how this species adapted to the saline-alkali environment and for the rational development and use of saline-alkali soils. In this study, high-throughput sequencing technology was used to investigate the diversity characteristics and distribution patterns of soil bacterial communities in the rhizosphere of S.glauca-dominated communities in the Hetao Irrigation Distract, Inner Mongolia, China. The relationships among bacterial characteristics, soil physicochemical properties and vegetation in four sampling sites were analyzed. The soil bacterial communities in the rhizosphere of S. glauca-dominated communities were mainly composed of 16 phyla (i.e., Proteobacteria, Actinobacteria, Bacteroidetes, Gemmatimonadetes, Chloroflexi, Acidobacteria, Firmicutes, Planctomycetes, Deinococcus-Thermus, Verrucomicrobia, Saccharibacteria, Cyanobacteria, Nitrospirae, JL-ETNP-Z39, Parcubacteria and Chlorobi), and these populations accounted for more than 99% of the total bacterial community. At the genus level, the main bacterial communities comprised Halomonas, Nitriliruptor, Euzebya and Pelagibius, which accounted for 15.70% of the total bacterial community. An alpha diversity analysis indicated that the richness and diversity of rhizosphere soil bacteria differed significantly among the sampling sites, and the bacterial richness and diversity indices of severe saline-alkali land were higher than those of light and moderate saline-alkali land. The principal component analysis (PCA) and linear discriminant analysis effect size (LEfSe) showed significant differences in the species composition of the rhizosphere soil bacterial community among different sampling sites. A correlation analysis showed that the number of bacterial species exhibited the highest correlation with the soil water content (SWC). The richness and evenness indices were significantly correlated with the SWC and SO4 2-, K+ and Mg2+ concentrations. The electrical conductivity (EC), soluble ions (Na+, CO3 2- + HCO3 -, K+, Ca2+, Mg2+, and SO4 2+), SWC and vegetation coverage (VC) were the main drivers affecting the changes in its community structure. The bacterial community in the rhizosphere of S. glauca enhanced the adaptability of S. glauca to saline-alkali environment by participating in the cycling process of nutrient elements, the decomposition of organic matter and the production of plant growth regulating substances. These results provided a theoretical reference for further study on the relationship among rhizosphere soil microorganisms and salt tolerance in halophytes.
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Recent research in computational imaging largely focuses on developing machine learning (ML) techniques for image recognition in the medical field, which requires large-scale and high-quality training datasets consisting of raw images and annotated images. However, suitable experimental datasets for cervical spine X-ray are scarce. We fill the gap by providing an open-access Cervical Spine X-ray Atlas (CSXA), which includes 4963 raw PNG images and 4963 annotated images with JSON format (JavaScript Object Notation). Every image in the CSXA is enriched with gender, age, pixel equivalent, asymptomatic and symptomatic classifications, cervical curvature categorization and 118 quantitative parameters. Subsequently, an efficient algorithm has developed to transform 23 keypoints in images into 77 quantitative parameters for cervical spine disease diagnosis and treatment. The algorithm's development is intended to assist future researchers in repurposing annotated images for the advancement of machine learning techniques across various image recognition tasks. The CSXA and algorithm are open-access with the intention of aiding the research communities in experiment replication and advancing the field of medical imaging in cervical spine.
Subject(s)
Algorithms , Cervical Vertebrae , Machine Learning , Humans , Cervical Vertebrae/diagnostic imaging , Radiography , Male , FemaleABSTRACT
This study conducted experimental analyses on a 280 Ah single lithium iron phosphate battery using an independently constructed experimental platform to assess the efficacy of compressed nitrogen foam in extinguishing lithium-ion battery fires. Based on theoretical analysis, the fire-extinguishing effects of compressed nitrogen foam at different outlet pressures from foam mixture tanks were analyzed, examining factors such as battery surface temperature, flame temperature, and thermal weight loss. The results indicate that the compressed nitrogen foam can extinguish the open flame of the battery in 14 s at 0.7 MPa, with the battery's surface temperature dropping by approximately 11 % before and after the application of the extinguishing agent. Compared with other commonly used extinguishing agents, the compressed nitrogen foam demonstrates superior extinguishing efficiency, but its cooling efficiency is somewhat lower. At pressures ranging from 0.4 to 0.6 MPa, the foam displays prolonged drainage time and sustained cooling effects, rendering it more suitable for lithium-ion battery fire scenarios. To address the issue of reduced cooling performance during later stages of fire suppression by compressed nitrogen foam, an intermittent injection approach has been proposed to effectively preserve its cooling efficacy.
ABSTRACT
BACKGROUND: Hemolytic disease of the newborn (HDN) is a common condition that can have a severe impact on the health of newborns due to the hemolytic reactions it triggers. Although numerous studies have focused on understanding the pathogenesis of HDN, there are still many unanswered questions. METHODS: In this retrospective study, serum samples were collected from 15 healthy newborns and 8 infants diagnosed with hemolytic disease. The relationship between different metabolites and various IgG subtypes in Healthy, HDN and BLI groups was studied by biochemical technique and enzyme-linked immunosorbent assay (ELISA). Metabolomics analysis was conducted to identify the differential metabolites associated with HDN. Subsequently, Pearson's correlation analysis was used to determine the relation of these differential metabolites with IgG isoforms. The relationship between the metabolites and IgG subtypes was observed after treatment. RESULTS: The study results revealed that infants with hemolytic disease exhibited abnormal elevations in TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4 levels when compared to healthy newborns. Additionally, differences in metabolite contents were also observed. N, N-DIMETHYLARGININE showed negative correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4, while 2-HYDROXYBUTYRATE, AMINOISOBUTANOATE, Inosine, and ALLYL ISOTHIOCYANATE exhibited positive correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4. Through metabolomics-based research, we have discovered associations between differential metabolites and different IgG isoforms during the onset of HDN. CONCLUSION: These findings suggest that changes in metabolite and IgG isoform levels are linked to HDN. Understanding the involvement of IgG isoforms and metabolites can provide valuable guidance for the diagnosis and treatment of HDN.
Subject(s)
Immunoglobulin G , Metabolomics , Protein Isoforms , Humans , Immunoglobulin G/blood , Infant, Newborn , Metabolomics/methods , Female , Male , Retrospective Studies , Erythroblastosis, Fetal/blood , Erythroblastosis, Fetal/metabolism , Erythroblastosis, Fetal/diagnosisABSTRACT
Hyperlipidemia has been a huge challenge to global health, leading to the cardiovascular disease, hypertension, and diabetes. Atorvastatin calcium (AC), a widely prescribed drug for hyperlipidemia, faces huge challenges with oral administration due to poor water solubility and hepatic first-pass effects, resulting in low therapeutic efficacy. In this work, we designed and developed a hybrid microneedle (MN) patch system constructed with soluble poly(vinyl alcohol) (PVA) and AC-loaded polymeric micelles (AC@PMs) for transdermal delivery of AC to enhance the hyperlipidemia therapy. We first prepared various AC@PM formulations self-assembled from mPEG-PLA and mPEG-PLA-PEG block copolymers using a dialysis method and evaluated the physicochemical properties in combination with experiment skills and dissipative particle dynamics (DPD) simulations. Then, we encapsulated the AC@PMs into the PVA MN patch using a micromold filling method, followed by characterizing the performances, especially the structural stability, mechanical performance, and biosafety. After conducting in vivo experiments using a hyperlipidemic rat model, our findings revealed that the hybrid microneedle-mediated administration exhibited superior therapeutic efficacy when compared to oral delivery methods. In summary, we have successfully developed a hybrid microneedle (MN) patch system that holds promising potential for the efficient transdermal delivery of hydrophobic drugs.