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1.
Psychiatry Res Neuroimaging ; 345: 111901, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39307122

ABSTRACT

RATIONALE AND OBJECTIVES: To explore the characteristics of brain structure in Chinese children with autism spectrum disorder (ASD) using artificial intelligence automatic brain segmentation technique, and to diagnose children with ASD using machine learning (ML) methods in combination with structural magnetic resonance imaging (sMRI) features. METHODS: A total of 60 ASD children and 48 age- and sex-matched typically developing (TD) children were prospectively enrolled from January 2023 to April 2024. All subjects were scanned using 3D-T1 sequences. Automated brain segmentation techniques were utilized to obtain the standardized volume of each brain structure (the ratio of the absolute volume of brain structure to the whole brain volume). The standardized volumes of each brain structure in the two groups were statistically compared, and the volume data of brain areas with significant differences were combined with ML methods to diagnose and predict ASD patients. RESULTS: Compared with the TD group, the volumes of the right lateral orbitofrontal cortex, right medial orbitofrontal cortex, right pars opercularis, right pars triangularis, left hippocampus, bilateral parahippocampal gyrus, left fusiform gyrus, right superior temporal gyrus, bilateral insula, bilateral inferior parietal cortex, right precuneus cortex, bilateral putamen, left pallidum, and right thalamus were significantly increased in the ASD group (P< 0.05). Among six ML algorithms, support vector machine (SVM) and adaboost (AB) had better performance in differentiating subjects with ASD from those TD children, with their average area under curve (AUC) reaching 0.91 and 0.92, respectively. CONCLUSION: Automatic brain segmentation technology based on artificial intelligence can rapidly and directly measure and display the volume of brain structures in children with autism spectrum disorder and typically developing children. Children with ASD show abnormalities in multiple brain structures, and when paired with sMRI features, ML algorithms perform well in the diagnosis of ASD.

2.
Radiat Prot Dosimetry ; 200(15): 1470-1476, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39270666

ABSTRACT

Our objective is to evaluate radiation dose and image quality in pediatric paranasal sinus computed tomography (CT) with automatic tube current modulation (ATCM) and sinogram-affirmed iterative reconstruction algorithm (SAFIRE). CT scans from 80 patients were divided into two groups: Group A [80 kVp, pitch 1.5, 40 mAs, the filtered back projection (FBP) algorithm] and Group B (70 kVp, pitch 3, ATCM with reference at 40 mAs, SAFIRE strengths 1-5). We have evaluated image quality and radiation dose. Group B demonstrated significantly lower volume computed tomography dose index, dose-length product, and effective dose than Group A (0.13 ± 0.03 vs. 1.57 ± 0.01 mGy, 2.27 ± 0.82 vs. 19.88 ± 2.01 mGy·cm, and 0.0081 ± 0.0017 vs. 0.079 ± 0.013 mSv, respectively; P < .001). Increasing SAFIRE strengths correlated with noise reduction and SNR enhancement. Group B's noise and SNRsoft at SAFIRE strength 5 were comparable with Group A. Images reconstructed with SAFIRE strength 5 in Group B exhibit comparable image quality with FBP in Group A.


Subject(s)
Algorithms , Paranasal Sinuses , Radiation Dosage , Radiographic Image Interpretation, Computer-Assisted , Tomography, X-Ray Computed , Humans , Child , Paranasal Sinuses/diagnostic imaging , Female , Male , Tomography, X-Ray Computed/methods , Radiographic Image Interpretation, Computer-Assisted/methods , Child, Preschool , Adolescent , Image Processing, Computer-Assisted/methods , Retrospective Studies , Infant
3.
J Med Chem ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39258312

ABSTRACT

The FLT3-ITD (internal tandem duplication) mutant has been a promising target for acute myeloid leukemia (AML) drug discovery but is now facing the challenge of resistance due to point mutations. Herein, we have discovered a type II FLT3 inhibitor, SILA-123. This inhibitor has shown highly potent inhibitory effects against FLT3-WT (IC50 = 2.1 nM) and FLT3-ITD (IC50 = 1.0 nM), tumor cells with the FLT3-ITD mutant such as MOLM-13 (IC50 = 0.98 nM) and MV4-11 (IC50 = 0.19 nM), as well as BaF3 cells associated with the FLT3-ITD mutant and point mutations like BaF3-FLT3-ITD-G697R (IC50 = 3.0 nM). Moreover, SILA-123 exhibited promising kinome selectivity against 310 kinases (S score (10) = 0.06). In in vivo studies, SILA-123 significantly suppressed the tumor growth in MV4-11 (50 mg/kg/d, TGI = 87.3%) and BaF3-FLT3-ITD-G697R (50 mg/kg/d, TGI = 60.0%) cell-inoculated allograft models. Our data suggested that SILA-123 might be a promising drug candidate for FLT3-ITD-positive AML.

4.
Food Funct ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39254213

ABSTRACT

Our previous studies have highlighted the potential of silver carp hydrolysate (SCH) in managing chronic diseases. Unfortunately, its fishy smell and bitter taste limited consumer acceptance. Prebiotic oligosaccharides are often used as dietary supplements, ignoring their role as carbonyl ligands in the Maillard reaction to enhance food's sensory and antioxidant properties. This study aimed to improve SCH's sensory attributes and investigate its physicochemical properties and antioxidant activities using prebiotic oligosaccharides via the Maillard reaction. The results showed that xylo-oligosaccharide (XOS) had the highest reactivity among the oligosaccharides tested, and it greatly enhanced the taste and flavor of SCH, as well as its antioxidant activities (0.45 to 16.5 times). Specifically, XOS effectively reduced the fishy smell and bitter taste, imparting a caramel-like flavor and overall acceptability to SCH. The improved flavor profile was attributed to the increased presence of sulfur-containing and nitrogen oxide volatile flavor compounds, such as benzothiazole, methional, and furans, which also contributed to antioxidant effects. Sensory evaluation results indicated that SCH obtained from papain exhibited a stronger bitter taste than that obtained from alcalase. Additionally, XOS imparted a reddish-brown color to SCH due to the higher browning intensity. This study is the first to demonstrate that XOS in the Maillard reaction can effectively improve the undesirable flavor and taste of SCH while enhancing its antioxidant activities, providing a theoretical basis for developing SCH as a market-acceptable functional food ingredient.

5.
Aquat Toxicol ; 275: 107070, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39217791

ABSTRACT

Discharged sewage is the dominant source of urban river pollution. Macrolide antibiotics have emerged as prominent contaminants, which are frequently detected in sewage and rivers and pose a threat to aquatic microbial community. As a typical primary producer, periphyton is crucial for maintaining the biodiversity and functions of aquatic ecosystem. However, effects of antibiotic exposure time as well as the recovery process of periphyton remain undetermined. In the present study, five exposure scenarios of two typical macrolides, erythromycin (ERY) and roxithromycin (ROX) were investigated at 50 µg/L, dose to evaluate their potential detrimental effects on the structure and function of periphyton and the subsequent recovery process in 14 days. Results revealed that the composition of periphytic community returned to normal over the recovery period, except for a few sensitive species. The antibiotics-caused significant photodamage to photosystem II, leading to continuous inhibition of the photosynthetic capacity of periphyton. Furthermore, no significant difference in carbon metabolism capacity was observed after direct antibiotic exposure, while the amine carbon utilization capacity of periphyton remarkably increased during the recovery process. These results indicated that periphyton community was capable of coping with the periodic exposure of antibiotic pollutants and recovering on its own. However, the ecological functions of periphyton can be permanently disturbed due to macrolide exposure. Overall, this study sheds light on the influence of macrolide exposure on the development, structure and function of the periphytic microbial community in rivers.


Subject(s)
Anti-Bacterial Agents , Macrolides , Periphyton , Rivers , Water Pollutants, Chemical , Rivers/chemistry , Water Pollutants, Chemical/toxicity , Anti-Bacterial Agents/toxicity , Macrolides/toxicity , Periphyton/drug effects , Roxithromycin/toxicity , Erythromycin/toxicity , Photosynthesis/drug effects
6.
Int J Paediatr Dent ; 2024 Sep 08.
Article in English | MEDLINE | ID: mdl-39245892

ABSTRACT

BACKGROUND: Regenerative endodontic procedures (REPs) is effective for treating young permanent teeth with pulp necrosis. However, its efficacy on delayed replanted avulsed teeth is unclear. AIM: This retrospective study aimed to assess the efficacy of REPs in treating delayed replanted immature permanent teeth with apical periodontitis. DESIGN: Avulsed teeth receiving REPs were systematically screened based on predetermined criteria. This study assessed the REP outcomes, postoperative periodontal healing, and overall treatment efficacy. Samples were grouped by REP outcomes and root development stage, with Fisher's exact tests used to compare outcomes among different groups. RESULTS: Among the included 17 teeth, 47.1% exhibited successful REPs and periodontal healing. Another 47.1%, due to replacement resorption or REP failure, were categorized as tooth survival. Healing of periapical lesions was observed in 88.2% of the cases, but only 41.2% demonstrated continued root development. Although differences were not significant (p = 0.05), teeth with continued root development had a higher rate of functional healing (85.7%) compared to those without (30%). CONCLUSION: Within the limitations of this study, REPs presented reliable outcomes for treating delayed replanted immature permanent teeth with apical periodontitis mainly in periapical lesion healing. Teeth with continued root development after REPs exhibited a higher rate of functional healing. Further investigation is required to explore potential synergies between REP outcomes and periodontal healing.

7.
Article in English | MEDLINE | ID: mdl-39232998

ABSTRACT

Seminal plasma extracellular vesicles (SPEVs) play an important role in regulating sperm motility by delivering various cargoes, such as miRNAs, mRNAs, proteins and metabolites. However, information on the lipid compositions of SPEVs and their roles in semen quality is limited. Here, we performed high-throughput transcriptomic and lipidomic analysis on SPEVs isolated from 20 boars with high or low sperm motility. Then, we evaluated the lipid composition and gene expression characteristics of SPEVs and identified the specific lipids and genes related to sperm motility. As a result, a total of 26 lipid classes were identified in SPEVs, and five subclasses, CerG2, CerG3, LPE, LPS and TG, were significantly different in boars with high and low sperm motility. In addition, 195 important lipids and 334 important genes were identified by weighted gene coexpression analysis (WGCNA) and differential expression analysis. We observed that several important genes and lipids in SPEVs potentially influence sperm motility via glycerophospholipid metabolism, glycerolipid metabolism, the sphingolipid signaling pathway and the ferroptosis pathway. Furthermore, we found a significant correlation between the content of 22 lipids and the expression levels of 67 genes (|cor| > 0.8, P < 0.05). Moreover, we observed that three important gene-lipid linkages (CerG1 (d22:0/24:0) - RCAN3, Cer (d18:1/24:0) - SCFD2 and CerG1 (d18:0/24:1) - SCFD2) were strongly correlated with sperm motility. Based on the results, some genes and lipids in SPEVs may play important roles in sperm motility by interacting with sperm through important pathways.

8.
Mater Today Bio ; 28: 101167, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39205871

ABSTRACT

In confronting the global prevalence of bone-related disorders, bone tissue engineering (BTE) has developed into a critical discipline, seeking innovative materials to revolutionize treatment paradigms. Quantum dots (QDs), nanoscale semiconductor particles with tunable optical properties, are at the cutting edge of improving bone regeneration. This comprehensive review delves into the multifaceted roles that QDs play within the realm of BTE, emphasizing their potential to not only revolutionize imaging but also to osteogenesis, drug delivery, antimicrobial strategies and phototherapy. The customizable nature of QDs, attributed to their size-dependent optical and electronic properties, has been leveraged to develop precise imaging modalities, enabling the visualization of bone growth and scaffold integration at an unprecedented resolution. Their nanoscopic scale facilitates targeted drug delivery systems, ensuring the localized release of therapeutics. QDs also possess the potential to combat infections at bone defect sites, preventing and improving bacterial infections. Additionally, they can be used in phototherapy to stimulate important bone repair processes and work well with the immune system to improve the overall healing environment. In combination with current trendy artificial intelligence (AI) technology, the development of bone organoids can also be combined with QDs. While QDs demonstrate considerable promise in BTE, the transition from laboratory research to clinical application is fraught with challenges. Concerns regarding the biocompatibility, long-term stability of QDs within the biological environment, and the cost-effectiveness of their production pose significant hurdles to their clinical adoption. This review summarizes the potential of QDs in BTE and highlights the challenges that lie ahead. By overcoming these obstacles, more effective, efficient, and personalized bone regeneration strategies will emerge, offering new hope for patients suffering from debilitating bone diseases.

9.
Adv Sci (Weinh) ; : e2407931, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39206752

ABSTRACT

In the context of the growing importance of heterocyclic compounds across various disciplines, numerous strategies for their construction have emerged. Exploiting the distinctive properties of cyclopropenes, this study introduces an innovative approach for the synthesis of benzo-fused five-membered oxa- and aza-heterocycles through a formal [4+1] cyclization and subsequent acid-catalyzed intramolecular O- to N- rearrangement. These transformations exhibit mild reaction conditions and a wide substrate scope. The applications in the late-stage modification of complex molecules and in the synthesis of a potential PD-L1 gene down-regulator, make this method highly appealing in related fields. Combined experimental mechanistic studies and DFT calculations demonstrate Rh(III)-mediated sequential C─H coupling/π-allylation/dynamically favorable O-attack route.

10.
Talanta ; 279: 126653, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39098239

ABSTRACT

Patulin (PAT) is a mycotoxin-produced secondary metabolite that can contaminate foods, causing toxic effects on animal and human health. Therefore, for the first time, we have constructed a "turn-on" dual-mode aptamer sensor for PAT using oleic acid-coated upconversion nanomaterials (OA-UCNPs) and G-Quadruplex-hemin DNAzyme (G4-DNAzyme) as fluorescent and colorimetry probes. The sensor employs aptamers binding to PAT as recognition elements for specific molecule detection. Mxene-Au can be used as a biological inducer to assist OA-UCNPs in controlling fluorescence intensity. In addition, colorimetric signal amplification was performed using the trivalent G4-DNAzyme to increase detection sensitivity and reduce false positives. Under optimal conditions, the dual-mode aptasensor has a detection limit of 5.3 pg mL-1 in fluorescence and 2.4 pg mL-1 in colorimetric methods, respectively, with the wider linear range and limit of detection (LOD) of the colorimetric assay. The combination aptasensor can detect PAT with high sensitivity and high specificity and has broad application prospects in the field of food safety detection.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , DNA, Catalytic , G-Quadruplexes , Hemin , Patulin , Patulin/analysis , Aptamers, Nucleotide/chemistry , DNA, Catalytic/chemistry , Biosensing Techniques/methods , Hemin/chemistry , Colorimetry/methods , Limit of Detection , Nanostructures/chemistry
11.
Plant Physiol Biochem ; 215: 108964, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39094477

ABSTRACT

Rehmannia piasezkii is a kind of medicinal plants, of the Orobanchaceae family, and well known for its large pink or purple corolla. However, no research on the molecular mechanism of flower color formation in R. piasezkii has been conducted so far. In this study, we investigated the transcriptome of root, stem, leaf and corollas of R. piasezkii using transcriptome sequencing technology and assembled 144,582 unigenes. A total of 58 anthocyanin biosynthetic genes were identified in the R. piasezkii transcriptome, fourteen of which were highly correlated with anthocyanin content, especially RpF3H2, RpDFR2, RpANS1, RpANS2 and RpUFGT. Totally, 35 MYB genes with FPKM values greater than 5 were identified in the R. piasezkii transcriptome, including an R2R3 MYB transcriptional factor RpMYB1, which belongs to subgroup 6 of the R2R3 MYB family. Agrobacterium-mediated transient expression of Nicotiana benthamiana revealed that overexpression of RpMYB1 could activate the expression of structural genes in anthocyanin synthesis pathway and promote the accumulation of anthocyanins in N. benthamiana leaves, indicating that RpMYB1 is a positive regulator of anthocyanin synthesis. Furthermore, combined transient overexpression of RpMYB1 with RpANS1, RpMYB1+RpANS1 with other structural genes all could further enhance the accumulation of anthocyanins in N. benthamiana leaves. Permanent overexpression of RpMYB1 in R. glutinosa promoted anthocyanin accumulation and expression levels of RgCHS, RgF3H, RgDFR and RgANS. Further evidence from dual-luciferase assay suggested that RpMYB1 could bind to the promoter of RpDFR2 and hence activating its expression. These findings provide insight into the molecular regulation in anthocyanin biosynthesis in R. piasezkii and provide valuable genetic resources for the genetic improvement of flower color.


Subject(s)
Anthocyanins , Gene Expression Regulation, Plant , Plant Proteins , Rehmannia , Anthocyanins/biosynthesis , Anthocyanins/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Rehmannia/genetics , Rehmannia/metabolism , Gene Expression Profiling , Transcriptome , Transcription Factors/genetics , Transcription Factors/metabolism , Flowers/genetics , Flowers/metabolism , Plants, Genetically Modified
12.
Sci Rep ; 14(1): 17853, 2024 08 01.
Article in English | MEDLINE | ID: mdl-39090217

ABSTRACT

Acute respiratory distress syndrome (ARDS) is a devastating critical care syndrome with significant morbidity and mortality. The objective of this study was to evaluate the predictive values of dynamic clinical indices by developing machine-learning (ML) models for early and accurate clinical assessment of the disease prognosis of ARDS. We conducted a retrospective observational study by applying dynamic clinical data collected in the ARDSNet FACTT Trial (n = 1000) to ML-based algorithms for predicting mortality. In order to compare the significance of clinical features dynamically, we further applied the random forest (RF) model to nine selected clinical parameters acquired at baseline and day 3 independently. An RF model trained using clinical data collected at day 3 showed improved performance and prognostication efficacy (area under the curve [AUC]: 0.84, 95% CI: 0.78-0.89) compared to baseline with an AUC value of 0.72 (95% CI: 0.65-0.78). Mean airway pressure (MAP), bicarbonate, age, platelet count, albumin, heart rate, and glucose were the most significant clinical indicators associated with mortality at day 3. Thus, clinical features collected early (day 3) improved performance of integrative ML models with better prognostication for mortality. Among these, MAP represented the most important feature for ARDS patients' early risk stratification.


Subject(s)
Machine Learning , Respiratory Distress Syndrome , Humans , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/diagnosis , Male , Female , Retrospective Studies , Middle Aged , Prognosis , Aged , Algorithms , Adult , Predictive Value of Tests , ROC Curve
13.
Eur J Med Chem ; 277: 116733, 2024 Nov 05.
Article in English | MEDLINE | ID: mdl-39098132

ABSTRACT

Macrocyclic compounds have emerged as potent tools in the field of drug design, offering unique advantages for enhancing molecular recognition, improving pharmacokinetic properties, and expanding the chemical space accessible to medicinal chemists. This review delves into the evolutionary trajectory of macrocyclic-based strategies, tracing their journey from laboratory innovations to clinical applications. Beginning with an exploration of the defining structural features of macrocycles and their impact on drug-like characteristics, this discussion progresses to highlight key design principles that have facilitated the development of diverse macrocyclic drug candidates. Through a series of illustrative representative case studies from approved macrocyclic drugs and candidates spanning various therapeutic areas, particular emphasis is placed on their efficacy in targeting challenging protein-protein interactions, enzymes, and receptors. Additionally, this review thoroughly examines how macrocycles effectively address critical issues such as metabolic stability, oral bioavailability and selectivity. Valuable insights into optimization strategies employed during both approved and clinical phases underscore successful translation of promising leads into efficacious therapies while providing valuable perspectives on harnessing the full potential of macrocycles in drug discovery and development endeavors.


Subject(s)
Drug Design , Macrocyclic Compounds , Macrocyclic Compounds/chemistry , Macrocyclic Compounds/pharmacology , Macrocyclic Compounds/chemical synthesis , Humans , Molecular Structure , Animals
14.
Sci Rep ; 14(1): 19045, 2024 08 16.
Article in English | MEDLINE | ID: mdl-39152147

ABSTRACT

Ardisia crispa(Myrsinaceae) is an ethnomedicine with horticultural and important medicinal values. Its morphology is complex, and its identification is difficult. We analyse the chloroplast genome characteristics and phylogenetic position of A. crispa to provide basic research data for the identification of A. crispa species and resource conservation. This study assemble and annotate the chloroplast genome of A. crispa and to compare it with the chloroplast genome within Ardisia. The A. crispa chloroplast genome is 156,785 bp in length, with a typical quadripartite structure containing 131 genes, including 86 protein-coding genes, 37 tRNA genes, and 8 rRNA genes; a total of 59 SSRs sites were identified, and the codon preference of this chloroplast genome is greater in A/U than in G/C, and leucine is the amino acid with the highest frequency of use. The chloroplast genomes of the nine Ardisia species are conserved in gene content and number, with more stable boundaries and less variation. In the phylogenetic tree, A. crispa is clustered on a branch with A. crispa var dielsii, and is closely related to A. mamillata and A. pedalis. In this study, we constructed and analyzed the chloroplast genome structure of A. crispa, and conducted phylogenetic analysis using the whole chloroplast genome sequence data of Ardisia plants, which is of great significance in understanding the genetic basis of A. crispa and adaptive evolution in Ardisia plants, and this will lay the foundation for the future research on A. crispa resource conservation and species identification.


Subject(s)
Ardisia , Genome, Chloroplast , Phylogeny , Plants, Medicinal , Plants, Medicinal/genetics , Plants, Medicinal/classification , Ardisia/genetics , RNA, Transfer/genetics , Codon/genetics
15.
Front Pharmacol ; 15: 1430400, 2024.
Article in English | MEDLINE | ID: mdl-39130639

ABSTRACT

Objectives: Fibroleukin (FGA) and NOTCH3 are vital in both exercise-induced muscle adaptation and colon adenocarcinoma (COAD) progression. This study aims to elucidate the roles of FGA and NOTCH3 in phenotypic variations of striated muscle induced by exercise and in COAD development. Additionally, it seeks to evaluate the prognostic significance of these proteins. Methods: Gene Set Variation Analysis (GSVA) and protein-protein interaction (PPI) network analysis were employed to identify differentially expressed genes (DEGs). Molecular docking studies were conducted to assess the binding affinities of 39 compounds to the NOTCH3 protein. In vitro assays, including mobileular viability, gene expression, and apoptosis assays, were performed to evaluate the effects of glycerophosphoinositol on FGA and NOTCH3 expression. Additionally, copy number variation (CNV), methylation status, and survival analyses were conducted across multiple cancers types. Results: The NOTCH signaling pathway was consistently upregulated in exercise-induced muscle samples. High NOTCH3 expression was associated with poor prognosis in COAD, extracellular matrix organization, immune infiltration, and activation of the PI3K-Akt pathway. Molecular docking identified gamma-Glu-Trp, gamma-Glutamyltyrosine, and 17-Deoxycortisol as strong binders to NOTCH3. Glycerophosphoinositol treatment modulated FGA and NOTCH3 expression, influencing cell proliferation and apoptosis. CNV and methylation analyses revealed specific changes in FGA and NOTCH3 across 20 cancers types. Survival analyses showed strong associations between FGA/NOTCH3 expression and survival metrics, with negative correlations for FGA and positive correlations for NOTCH3. Conclusion: FGA and NOTCH3 play significant roles in exercise-induced muscle adaptation and colon cancer progression. The expression profiles and interactions of these proteins provide promising prognostic markers and therapeutic targets. These findings offer valuable insights into the post-translational modifications (PTMs) in human cancer, highlighting novel pharmacological and therapeutic opportunities.

16.
Molecules ; 29(15)2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39124956

ABSTRACT

Eupatorium lindleyanum DC. (EL) is a traditional Chinese herb known for its phlegm-reducing, cough-relieving and asthma-calming properties. It is widely used for treating cough and bronchitis. However, preliminary experiments have revealed wide variations in the composition of its different medicinal parts (flowers, leaves and stems), and the composition and efficacy of its different medicinal parts remain largely underexplored at present. In this study, non-targeted rapid resolution liquid chromatography coupled with a quadruple time-of-flight mass spectrometry (RRLC-Q-TOF-MS)-based metabolomics approach was developed to investigate the differences in the chemical composition of different medicinal parts of EL. We identified or tentatively identified 9 alkaloids, 11 flavonoids, 14 sesquiterpene lactones, 3 diterpenoids and 24 phenolic acids. In addition, heatmap visualization, quantitative analysis by high-performance liquid chromatography (HPLC-PDA) and ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-MS/MS) showed particularly high levels of sesquiterpene lactones, flavonoids and phenolic acids in the flowers, such as eupalinolide A and B and chlorogenic acid, among others. The leaves also contained some flavonoid sesquiterpene lactones and phenolic acids, while the stems were almost absent. The findings of in vitro activity studies indicated that the flowers exhibited a notable inhibitory effect on the release of the inflammatory factors TNF-α and IL-6, surpassing the anti-inflammatory efficacy observed in the leaves. Conversely, the stems demonstrated negligible anti-inflammatory activity. The variations in anti-inflammatory activity among the flowers, leaves and stems of EL can primarily be attributed to the presence of flavonoids, phenolic acids and sesquiterpene lactones in both the flowers and leaves. Additionally, the flowers contain a higher concentration of these active components compared to the leaves. These compounds mediate their anti-inflammatory effects through distinct biochemical pathways. The results of this study are anticipated to provide a scientific basis for the rational and effective utilization of EL resources.


Subject(s)
Anti-Inflammatory Agents , Eupatorium , Tandem Mass Spectrometry , Eupatorium/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Plant Leaves/chemistry , Animals , Flavonoids/chemistry , Flavonoids/pharmacology , Flavonoids/analysis , Metabolome , Metabolomics/methods , Mice , Plant Extracts/chemistry , Plant Extracts/pharmacology , RAW 264.7 Cells , Flowers/chemistry , Plant Stems/chemistry , Plants, Medicinal/chemistry
17.
J Vis Exp ; (210)2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39158307

ABSTRACT

Real-time approaches are typically needed in studies of learning and memory, and in vivo calcium imaging provides the possibility to investigate neuronal activity in awake animals during behavior tasks. Since the hippocampus is closely associated with episodic and spatial memory, it has become an essential brain region in this field's research. In recent research, engram cells and place cells were studied by recording the neural activities in the hippocampal CA1 region using the miniature microscope in mice while performing behavioral tasks including open-field and linear track. Although the dentate gyrus is another important region in the hippocampus, it has rarely been studied with in vivo imaging due to its greater depth and difficulty for imaging. In this protocol, we present in detail a calcium imaging process, including how to inject the virus, implant a GRIN (Gradient-index) lens, and attach a base plate for imaging the dentate gyrus of the hippocampus. We further describe how to preprocess the calcium imaging data using MATLAB. Additionally, studies of other deep brain regions that require imaging may benefit from this method.


Subject(s)
Calcium , Dentate Gyrus , Neurons , Animals , Dentate Gyrus/cytology , Dentate Gyrus/diagnostic imaging , Mice , Calcium/metabolism , Calcium/analysis , Neurons/cytology
18.
J Pharm Anal ; 14(7): 100947, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39149142

ABSTRACT

Cancer genomics has led to the discovery of numerous oncogenes and tumor suppressor genes that play critical roles in cancer development and progression. Oncogenes promote cell growth and proliferation, whereas tumor suppressor genes inhibit cell growth and division. The dysregulation of these genes can lead to the development of cancer. Recent studies have focused on non-coding RNAs (ncRNAs), including circular RNA (circRNA), long non-coding RNA (lncRNA), and microRNA (miRNA), as therapeutic targets for cancer. In this article, we discuss the oncogenes and tumor suppressor genes of ncRNAs associated with different types of cancer and their potential as therapeutic targets. Here, we highlight the mechanisms of action of these genes and their clinical applications in cancer treatment. Understanding the molecular mechanisms underlying cancer development and identifying specific therapeutic targets are essential steps towards the development of effective cancer treatments.

19.
iScience ; 27(8): 110403, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39091462

ABSTRACT

Constipation and frailty are associated with intestinal dysbiosis. This study aims to identify intestinal microbial signatures that can differentiate between constipated elders accompanied by frailty and those without frailty. We collected stool samples from 61 participants and conducted 16S rRNA gene sequencing. Constipated patients with frailty (Constipation_F) exhibited reduced gut microbial diversities compared to constipated patients without frailty (Constipation_NF) and healthy individuals (C). From differential genera, random forest models identified 14, 8, and 5 biomarkers for distinguishing Constipation_F from Constipation_NF, Constipation_F from C, and Constipation_NF from C, respectively. Functional analysis revealed that pathways (P381-PWY and PWY-5507) related to vitamin B12 synthesis were reduced in Constipation_F, which aligns with the decreased abundances of vitamin-B12-producing Actinomyces and Akkermansia in this group. Our study unveils substantial differences in gut microbiota between constipated elders with frailty and those without, underscoring the diagnostic and therapeutic potential of genera involved in vitamin B12 synthesis.

20.
BMC Pediatr ; 24(1): 498, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095721

ABSTRACT

OBJECTIVE: To determine the prevalence of and risk factors for overweight and obese among Chinese children and adolescents. METHODS: This analytical cross-sectional study included 16,640 children and adolescents aged 6-18 years across four provinces of China in 2016. Physical characteristics and responses to questionnaires were analyzed. Body Mass Index (BMI) and the prevalence of overweight and obesity were calculated. RESULTS: Among children and adolescents, the overall prevalence of overweight and obesity in 2016 in four regions of China was 27.2% and 29.6%, respectively. Among different stages and sexes, the highest prevalence of obesity (15.8%) was observed in adolescent boys. From childhood to adolescence, the obesity rate among boys increased by 0.7% (from 15.1% to 15.8%), while the obesity rate among girls decreased by 0.9% (from 10.8% to 9.9%). Children and adolescents who were overweight or obese had significantly higher systolic blood pressures, larger waist circumferences and larger hip sizes than those with a normal BMI. Logistic regression analyses identified thirteen factors associated with overweight or obesity in children and adolescents. CONCLUSIONS: Our results indicate that the prevalence of overweight and obesity is high among children and adolescents, especially among male adolescents in four regions of China. A suitable intervention program should not only help parents understand the serious risk of childhood obesity but also, more importantly, help to encourage a healthy lifestyle among children and adolescents.


Subject(s)
Body Mass Index , Pediatric Obesity , Humans , Adolescent , China/epidemiology , Cross-Sectional Studies , Male , Female , Child , Pediatric Obesity/epidemiology , Prevalence , Risk Factors , Overweight/epidemiology , Sex Distribution
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