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1.
J Cosmet Dermatol ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38923657

ABSTRACT

BACKGROUND: Natural herbs have been widely considered a reservoir for skin-lightening ingredients, but discovery of the effective ingredients from herbs remains a large challenge. AIM: This research aimed to rapidly identify compounds with skin-lightening activity in Chinese herbs. METHODS: The structure information of herbal compounds was collected and selected from the open-source data. High throughput virtual screening (HTVS) and Extra precision (XP) docking modes were used to screen for compounds that could bind to the mushroom tyrosinase involved in melanin synthesis. Furthermore, molecular dynamics (MD) simulations were introduced to assess the binding stability of those compounds with the key target protein. The candidate compounds found by this kind of multidimensional molecular screening were finally tested for their ability to inhibit pigmentation and potential toxicity using an in vivo zebrafish animal model. RESULTS: A Natural Compounds Database was established with 5616 natural compounds. Fourteen compounds with favorable binding capability were screened by the XP docking mode with mushroom tyrosinase and five compounds among them were found to have superior dynamic binding performance through MD simulations. Then the Zebrafish animal experiments revealed that two components, sennoside B (SB) and sennoside C (SC), could significantly inhibit melanogenesis rather than the other three compounds. Meanwhile, there were no obvious side effects observed in SB and SC about the morphology, heart rate, or body length of zebrafish. CONCLUSION: A strategy for rapid screening of compounds with whitening activity has been established, and two potent skin-lightening compounds, SB and SC, have been identified from a vast library of herbal compounds. This study revealed that SB and SC have potential for topical use in skin lightening for the first time. The findings of this study would provide an important theoretical basis for the application of these two compounds in the cosmetic field in the future.

2.
Nat Commun ; 15(1): 5264, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898065

ABSTRACT

Persistence reinforces continuous action, which benefits animals in many aspects. Diverse external or internal signals may trigger animals to start a persistent movement. However, it is unclear how the brain decides to persist with current actions by selecting specific information. Using single-unit extracellular recordings and opto-tagging in awake mice, we demonstrated that a group of dorsal mPFC (dmPFC) motor cortex projecting (MP) neurons initiate a persistent movement by selectively encoding contextual information rather than natural valence. Inactivation of dmPFC MP neurons impairs the initiation and reduces neuronal activity in the insular and motor cortex. After the persistent movement is initiated, the dmPFC MP neurons are not required to maintain it. Finally, a computational model suggests that a successive sensory stimulus acts as an input signal for the dmPFC MP neurons to initiate a persistent movement. These results reveal a neural initiation mechanism on the persistent movement.


Subject(s)
Motor Cortex , Movement , Neurons , Prefrontal Cortex , Animals , Motor Cortex/physiology , Prefrontal Cortex/physiology , Movement/physiology , Mice , Neurons/physiology , Male , Mice, Inbred C57BL , Models, Neurological
3.
Sci Rep ; 14(1): 12605, 2024 06 01.
Article in English | MEDLINE | ID: mdl-38824246

ABSTRACT

The diagnostic value of contrast-enhanced ultrasound combined with ultrasound elastography for benign and malignant thyroid nodules is still controversial, so we used meta-analysis to seek controversial answers. The PubMed, OVID, and CNKI databases were searched according to the inclusion and exclusion criteria. The literature was selected from the establishment of each database to February 2024. The QUADAS-2 tool assessed diagnostic test accuracy. SROC curves and Spearman's correlation coefficient were made by Review Manager 5.4 software to assess the presence of threshold effects in the literature. Meta-Disc1.4 software was used for Cochrane-Q and χ2 tests, which be used to evaluate heterogeneity, with P-values and I2 indicating heterogeneity levels. The appropriate effect model was selected based on the results of the heterogeneity test. Stata18.0 software was used to evaluate publication bias. The diagnostic accuracy of contrast-enhanced ultrasound combined with ultrasound elastography for benign and malignant thyroid nodules was evaluated by calculating the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, DOR, and area under the SROC curve. A total of 31 studies included 3811 patients with 4718 nodules were analyzed. There is no heterogeneity caused by the threshold effect, but there is significant non-threshold heterogeneity. Combined diagnostic metrics were: sensitivity = 0.93, specificity = 0.91, DOR = 168.41, positive likelihood ratio = 10.60, and negative likelihood ratio = 0.07. The SROC curve area was 0.97. Contrast-enhanced ultrasound and elastography show high diagnostic accuracy for thyroid nodules, offering a solid foundation for early diagnosis and treatment.Trial registration. CRD42024509462.


Subject(s)
Contrast Media , Elasticity Imaging Techniques , Thyroid Nodule , Ultrasonography , Humans , Thyroid Nodule/diagnostic imaging , Thyroid Nodule/pathology , Elasticity Imaging Techniques/methods , Ultrasonography/methods , Diagnosis, Differential , Sensitivity and Specificity , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/pathology , Thyroid Neoplasms/diagnosis
4.
Mol Biol Rep ; 51(1): 715, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824248

ABSTRACT

BACKGROUND: Camellia tachangensis F. C. Zhang is a five-compartment species in the ovary of tea group plants, which represents the original germline of early differentiation of some tea group plants. METHODS AND RESULTS: In this study, we analyzed single-nucleotide polymorphisms (SNPs) at the genome level, constructed a phylogenetic tree, analyzed the genetic diversity, and further investigated the population structure of 100 C. tachangensis accessions using the genotyping-by-sequencing (GBS) method. A total of 91,959 high-quality SNPs were obtained. Population structure analysis showed that the 100 C. tachangensis accessions clustered into three groups: YQ-1 (Village Group), YQ-2 (Forest Group) and YQ-3 (Transition Group), which was further consistent with the results of phylogenetic analysis and principal component analyses (PCA). In addition, a comparative analysis of the genetic diversity among the three populations (Forest, Village, and Transition Groups) detected the highest genetic diversity in the Transition Group and the highest differentiation between Forest and Village Groups. CONCLUSIONS: C. tachangensis plants growing in the forest had different genetic backgrounds from those growing in villages. This study provides a basis for the effective protection and utilization of C. tachangensis populations and lays a foundation for future C. tachangensis breeding.


Subject(s)
Camellia , Genetic Variation , Phylogeny , Polymorphism, Single Nucleotide , Camellia/genetics , Polymorphism, Single Nucleotide/genetics , China , Genetic Variation/genetics , Genetics, Population/methods , Genotype , Principal Component Analysis , Genome, Plant
5.
Eur Stroke J ; : 23969873241258058, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38859581

ABSTRACT

RATIONALE: To date, the benefit of intravenous thrombolysis for acute ischemic stroke (AIS) patients without advanced neuroimaging selection is confined to within 4.5 h of onset. Our phase II EXIT-BT (Extending the tIme window of Thrombolysis by ButylphThalide up to 6 h after onset) trial suggested the safety, feasibility, and potential benefit of intravenous tenecteplase (TNK) in AIS between 4.5 and 6 h of onset. The EXIT-BT2 trial is a pivotal study undertaken to confirm or refute this signal. AIM: To investigate the efficacy and safety of TNK for AIS between 4.5 and 6 h of onset with or without endovascular treatment. SAMPLE SIZE ESTIMATES: A maximum of 1440 patients are required to test the superiority hypothesis with 80% power according to a two-sided 0.05 level of significance, stratified by age, sex, history of diabetes, location of vessel occlusion, baseline National Institute of Health stroke scale score, stroke etiology, and plan for endovascular treatment. DESIGN: EXIT-BT2 is a prospective, randomized, open-label, blinded assessment of endpoint (PROBE), and multi-center study. Eligible AIS patients between 4.5 and 6 h of onset are randomly assigned 1:1 into a TNK group or control group. The TNK group will receive TNK (0.25 mg/kg, a single bolus over 5-10 s, maximum 25 mg). The control group will receive standard medical care in compliance with national guidelines for acute ischemic stroke. Both groups will receive standard stroke care from randomization to 90 days after stroke onset according to national guidelines. OUTCOME: The primary efficacy endpoint is excellent functional outcome, defined as a modified Rankin Scale score 0-1 at 90 days after randomization, while the primary safety endpoint is symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale score increase ⩾4 caused by intracranial hemorrhage within 24 (-6/+12) h after randomization. CONCLUSIONS: The results of EXIT-BT2 may determine whether intravenous TNK has a favorable risk/benefit profile in AIS between 4.5 and 6 h of onset.

6.
ACS Omega ; 9(24): 25812-25821, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38911804

ABSTRACT

Carbonized polydopamine (cPDA) exhibits a nitrogenous graphite-like structure with n-type semiconductor property. However, the low electrical conductivity and Seebeck coefficient of cPDA cannot meet the needs of flexible thermoelectric devices. In this study, a series of metal ions were coordinated with cPDA to enhance n-type thermoelectric properties. At 300 K, all metal-coordination cPDA (metal-cPDA) samples obtain lower thermal conductivity compared to cPDA. Mn-cPDA exhibits the greatest Seebeck coefficient of -25.94 µV K-1, which is almost six times higher than cPDA. Fe-cPDA shows the best electrical conductivity of 2.45 × 105 S m-1. An optimal power factor (PF) value of 11.93 µW m-1 K-2 is achieved in Ca-cPDA with the enhanced electrical conductivity of 9.5 × 104 S m-1 and Seebeck coefficient of -11.24 µV K-1. Using Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM), we revealed the structural characterization of metal-cPDA. Our results indictate that the different metal ions (Mn2+, Zn2+, Mg2+, Al3+, Ca2+, and Fe3+) exert varying influences on the growth of graphite-like structure within metal-cPDA, which lead to the evolution of electrical conductivity. We observe that the carrier density and carrier mobility depend on both the degree of graphitization and the metal-ion coordination, which work together on electrical conductivity and Seebeck coefficient. These findings and understanding of the thermoelectric properties of PDA-based materials will help to realize high-performance n-type thermoelectric materials for flexible electronic device applications.

7.
Chem Commun (Camb) ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38887875

ABSTRACT

Dearomative 1,3-dipolar cycloadditions of 1-Boc-pyrroles with in situ generated silver α-bromo alkylidenenitronates delivered a series of 3a,6a-dihydro-4-Boc-pyrrolo[2,3-d]isoxazole-2-oxides (17-91% yields) under very mild conditions. N-Deoxygenation of the cycloaddition product gave a dihydro-pyrrolo[2,3-d]isoxazole, elaborations of which produced various functionalized 2,3-dihydropyrroles and pyrrolidines, showcasing the potential utilities of our new strategy of pyrrole dearomatization.

8.
Plant Physiol Biochem ; 212: 108742, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38772166

ABSTRACT

Ginseng frequently encounters environmental stress during its growth and development. Late Embryogenesis Abundant (LEA) proteins play a crucial role in combating adversity stress, particularly against abiotic challenges In this study, 107 LEA genes from ginseng, spanning eight subfamilies, were identified, demonstrating significant evolutionary conservation, with the LEA2 subfamily being most prominent. Gene duplication events, primarily segmental duplications, have played a major role in the expansion of the LEA gene family, which has undergone strong purifying selection. PgLEAs were unevenly distributed across 22 chromosomes, with each subfamily featuring unique structural domains and conserved motifs. PgLEAs were expressed in various tissues, exhibiting distinct variations in abundance and tissue specificity. Numerous regulatory cis-elements, related to abiotic stress and hormones, were identified in the promoter region. Additionally, PgLEAs were regulated by a diverse array of abiotic stress-related transcription factors. A total of 35 PgLEAs were differentially expressed following treatments with ABA, GA, and IAA. Twenty-three PgLEAs showed significant but varied responses to drought, extreme temperatures, and salinity stress. The transformation of tobacco with the key gene PgLEA2-50 enhanced osmoregulation and antioxidant levels in transgenic lines, improving their resistance to abiotic stress. This study offers insights into functional gene analysis, focusing on LEA proteins, and establishes a foundational framework for research on ginseng's resilience to abiotic stress.


Subject(s)
Gene Expression Regulation, Plant , Multigene Family , Panax , Plant Proteins , Stress, Physiological , Panax/genetics , Panax/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Stress, Physiological/genetics , Genome, Plant/genetics , Phylogeny , Plants, Genetically Modified , Nicotiana/genetics , Nicotiana/metabolism
9.
Phys Chem Chem Phys ; 26(20): 14832-14838, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38721813

ABSTRACT

Magnetic molecules are promising candidates for quantum information processing (QIP) due to their tunable electron structures and quantum properties. A high spin Co(II) complex, CoH2dota, is studied for its potential to be used as a quantum bit (qubit) utilizing continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopy at low temperature. On the X-band microwave energy scale, the system can be treated as an effective spin 1/2 with a strongly anisotropic g-tensor resulting from the significant spin-orbital coupling. An experimental and theoretical study is conducted to investigate the anisotropic Rabi oscillations of the two magnetically equivalent spin centres with different orientations in a single crystal sample, which aims to verify the relationship between the Rabi frequency and the orientation of the g-tensor. The findings of this study show that an effective quantum manipulation method is developed for orthorhombic spin systems.

10.
Front Psychol ; 15: 1379652, 2024.
Article in English | MEDLINE | ID: mdl-38725946

ABSTRACT

The development of facial expression recognition ability in children is crucial for their emotional cognition and social interactions. In this study, 510 children aged between 6 and 15 participated in a two forced-choice task of facial expression recognition. The findings supported that recognition of the six basic facial expressions reached a relatively stable mature level around 8-9 years old. Additionally, model fitting results indicated that children showed the most significant improvement in recognizing expressions of disgust, closely followed by fear. Conversely, recognition of expressions of happiness and sadness showed slower improvement across different age groups. Regarding gender differences, girls exhibited a more pronounced advantage. Further model fitting revealed that boys showed more pronounced improvements in recognizing expressions of disgust, fear, and anger, while girls showed more pronounced improvements in recognizing expressions of surprise, sadness, and happiness. These clear findings suggested the synchronous developmental trajectory of facial expression recognition from childhood to adolescence, likely influenced by socialization processes and interactions related to brain maturation.

11.
Adv Sci (Weinh) ; : e2401436, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38749008

ABSTRACT

Yarn-woven triboelectric nanogenerators (TENGs) have greatly advanced wearable sensor technology, but their limited sensitivity and stability hinder broad adoption. To address these limitations, Poly(VDF-TrFE) and P(olyadiohexylenediamine (PA66)-based nanofibers coaxial yarns (NCYs) combining coaxial conjugated electrospinning and online conductive adhesive coating are developed. The integration of these NCYs led to enhanced TENGs (NCY-TENGs), notable for their flexibility, stretchability, and improved sensitivity, which is ideal for capturing body motion signals. One significant application of this technology is the fabrication of smart insoles from NCY-TENG plain-woven fabrics. These insoles are highly sensitive and possess antibacterial, breathable, and washable properties, making them ideal for real-time gait monitoring in patients with diabetic foot conditions. The NCY-TENGs and their derivatives show immense potential for a variety of wearable electronic devices, representing a considerable advancement in the field of wearable sensors.

12.
Plant Physiol ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38753307

ABSTRACT

Sweet osmanthus (Osmanthus fragrans) is famous in China for its flowers and contains four groups: Albus, Luteus, Aurantiacus, and Asiaticus. Understanding the relationships among these groups and the genetic mechanisms of flower color and aroma biosynthesis are of tremendous interest. In this study, we sequenced representative varieties from two of the four sweet osmanthus groups. Multi-omic and phylogenetic analyses of varieties from each of the four groups showed that Asiaticus split first within the species, followed by Aurantiacus and the sister groups Albus and Luteus. We show that the difference in flower color between Aurantiacus and the other three groups was caused by a 4-bp deletion in the promoter region of carotenoid cleavage dioxygenase 4 (OfCCD4) that leads to expression decrease. In addition, we identified 44 gene pairs exhibiting significant structural differences between the multi-seasonal flowering variety 'Rixianggui' in the Asiaticus group and other autumn flowering varieties. Through correlation analysis between intermediate products of aromatic components and gene expression, we identified eight genes associated with the linalool, α- and ß-ionone biosynthesis pathways. Overall, our study offers valuable genetic resources for sweet osmanthus, while also providing genetic clues for improving the flower color and multi-season flowering of osmanthus and other flowers.

13.
Clin Epigenetics ; 16(1): 72, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38812044

ABSTRACT

Lactic acid, traditionally considered as a metabolic waste product arising from glycolysis, has undergone a resurgence in scientific interest since the discovery of the Warburg effect in tumor cells. Numerous studies have proved that lactic acid could promote angiogenesis and impair the function of immune cells within tumor microenvironments. Nevertheless, the precise molecular mechanisms governing these biological functions remain inadequately understood. Recently, lactic acid has been found to induce a posttranslational modification, lactylation, that may offer insight into lactic acid's non-metabolic functions. Notably, the posttranslational modification of proteins by lactylation has emerged as a crucial mechanism by which lactate regulates cellular processes. This article provides an overview of the discovery of lactate acidification, outlines the potential "writers" and "erasers" responsible for protein lactylation, presents an overview of protein lactylation patterns across different organisms, and discusses the diverse physiological roles of lactylation. Besides, the article highlights the latest research progress concerning the regulatory functions of protein lactylation in pathological processes and underscores its scientific significance for future investigations.


Subject(s)
Protein Processing, Post-Translational , Humans , Lactic Acid/metabolism , Animals , Histones/metabolism , Histones/genetics , Histone Code/genetics , Neoplasms/genetics , Neoplasms/metabolism , Epigenesis, Genetic/genetics
14.
RSC Adv ; 14(24): 17032-17040, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38808236

ABSTRACT

Nanopore technology, re-fueled by two-dimensional (2D) materials such as graphene and MoS2, controls mass transport by allowing certain species while denying others at the nanoscale and has a wide application range in DNA sequencing, nano-power generation, and others. With their low transmembrane transport resistance and high permeability stemming from their ultrathin nature, crystalline 2D materials do not possess nanoscale holes naturally, thus requiring additional fabrication to create nanopores. Herein, we demonstrate that nanopores exist in amorphous monolayer carbon (AMC) grown at low temperatures. The size and density of nanopores can be tuned by the growth temperature, which was experimentally verified by atomic images and further corroborated by kinetic Monte Carlo simulation. Furthermore, AMC films with varied degrees of disorder (DOD) exhibit tunable transmembrane ionic conductance over two orders of magnitude when serving as nanopore membranes. This work demonstrates the DOD-tuned property in amorphous monolayer carbon and provides a new candidate for modern membrane science and technology.

15.
Molecules ; 29(10)2024 May 07.
Article in English | MEDLINE | ID: mdl-38792045

ABSTRACT

Efficient and thorough treatment of dye wastewater is essential to achieve ecological harmony. In this study, a new type of calcium-based modified coal gangue (Ca-CG) was prepared by using solid waste coal gangue as raw material and a CaCl2 modifier, which was used for the removal of malachite green, methylene blue, crystal violet, methyl violet and other dyes in water. When the dosage of Ca-CG was 1-5 g/L, the dosage of Ca-CG was the main factor affecting the dye adsorption effect. The adsorption effects of Ca-CG on four dyes were as follows: malachite green > crystal violet > methylene blue > methyl violet. Kinetics, isotherms and thermodynamic analysis showed that the adsorption of malachite green, methyl blue, crystal violet and methyl violet by Ca-CG fitted the second-order kinetic model, and adsorption with chemical reaction is the main process. The adsorption of four dyes by Ca-CG conformed to the Freundlich model, which is dominated by multi-molecular layer adsorption, and the adsorption was easy to carry out. The adsorption process of Ca-CG on the four dyes was spontaneous. The results of FTIR, XRD and SEM showed that the calcium-based materials such as lipscombite and dolomite were the key to the adsorption of malachite green by Ca-CG, and the main mechanisms for the adsorption of malachite green by Ca-CG are surface precipitation, electrostatic action, and chelation reaction. Ca-CG adsorption has great potential for the removal of dye wastewater.

16.
Viruses ; 16(5)2024 04 29.
Article in English | MEDLINE | ID: mdl-38793585

ABSTRACT

Influenza A virus (IAV) continues to pose serious threats to the global animal industry and public health security. Identification of critical host factors engaged in the life cycle of IAV and elucidation of the underlying mechanisms of their action are particularly important for the discovery of potential new targets for the development of anti-influenza drugs. Herein, we identified Hydroxyacyl-CoA Dehydratase 3 (HACD3) as a new host factor that supports the replication of IAV. Downregulating the expression of HACD3 reduced the level of viral PB1 protein in IAV-infected cells and in cells that were transiently transfected to express PB1. Silencing HACD3 expression had no effect on the level of PB1 mRNA but could promote the lysosome-mediated autophagic degradation of PB1 protein. Further investigation revealed that HACD3 interacted with PB1 and selective autophagic receptor SQSTM1/p62, and HACD3 competed with SQSTM1/p62 for the interaction with PB1, which prevented PB1 from SQSTM1/p62-mediated autophagic degradation. Collectively, these findings establish that HACD3 plays a positive regulatory role in IAV replication by stabilizing the viral PB1 protein.


Subject(s)
Autophagy , Influenza A virus , Viral Proteins , Virus Replication , Humans , Viral Proteins/metabolism , Viral Proteins/genetics , Influenza A virus/physiology , Influenza A virus/genetics , HEK293 Cells , Host-Pathogen Interactions , Animals , A549 Cells , Dogs , Influenza, Human/virology , Influenza, Human/metabolism , Sequestosome-1 Protein/metabolism , Sequestosome-1 Protein/genetics , Proteolysis
17.
J Org Chem ; 89(10): 7148-7155, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38718346

ABSTRACT

Alkyl- and arylpyridines and 2,2'-bipyridines are conventionally prepared by Minisci reactions of pyridines and transition metal-catalyzed coupling reactions of halopyridines. Herein, purple light-promoted radical coupling reactions of 2- or 4-bromopyridines with Grignard reagents in Et2O or a mixture of Et2O and tetrahydrofuran in regular glassware without the need for a transition metal catalyst were disclosed for the first time. Methyl, primary and secondary alkyl, cycloalkyl, aryl, heteroaryl, pyridyl, and alkynyl Grignard reagents were compatible with the protocol. As a result, alkyl- and arylpyridines and 2,2'-bipyridines were easily prepared. Single electron transfer from the Grignard reagent to bromopyridine was stimulated by purple light. An electron extruded from the dimerization of the Grignard reagent worked as the catalyst. Light on/off experiments indicated that constant irradiation was required for product formation. Studies of radical clock substrates verified the involvement of a pyridyl radical from bromopyridine and the noninvolvement of an alkyl or aryl radical from the Grignard reagent. The available proof supports a photoinduced SRN mechanism for the new coupling reactions.

18.
Front Neurol ; 15: 1343654, 2024.
Article in English | MEDLINE | ID: mdl-38751887

ABSTRACT

Objective: This study aimed to develop a nomogram tool to predict cerebral white matter lesions (WMLs) in elderly men. Methods: Based on a retrospective cohort from January 2017 to December 2019, a multivariate logistic analysis was performed to construct a nomogram for predicting WMLs. The nomogram was further validated using a follow-up cohort between January 2020 and December 2022. The calibration curve, receiver operating characteristics (ROC) curves, and the decision curves analysis (DCA) were used to evaluate discrimination and calibration of this nomogram. Result: A total of 436 male patients were enrolled in this study, and all 436 patients were used as the training cohort and 163 follow-up patients as the validation cohort. A multivariate logistic analysis showed that age, cystatin C, uric acid, total cholesterol, platelet, and the use of antiplatelet drugs were independently associated with WMLs. Based on these variables, a nomogram was developed. The nomogram displayed excellent predictive power with the area under the ROC curve of 0.951 [95% confidence interval (CI), 0.929-0.972] in the training cohort and 0.915 (95% CI, 0.864-0.966) in the validation cohort. The calibration of the nomogram was also good, as indicated by the Hosmer-Lemeshow test with p-value of 0.594 in the training cohort and 0.178 in the validation cohort. The DCA showed that the nomogram holds good clinical application value. Conclusion: We have developed and validated a novel nomogram tool for identifying elderly men at high risk of WMLs, which exhibits excellent predictive power, discrimination, and calibration.

19.
Comput Biol Chem ; 110: 108072, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38636391

ABSTRACT

The methylation and demethylation of lysine and arginine side chains are fundamental processes in gene regulation and disease development. Histone lysine methylation, controlled by histone lysine methyltransferases (KMTs) and histone lysine demethylases (KDMs), plays a vital role in maintaining cellular homeostasis and has been implicated in diseases such as cancer and aging. This study focuses on two members of the lysine demethylase (KDM) family, KDM4E and KDM6B, which are significant in gene regulation and disease pathogenesis. KDM4E demonstrates selectivity for gene regulation, particularly concerning cancer, while KDM6B is implicated in inflammation and cancer. The study utilizes specific inhibitors, DA-24905 and GSK-J1, showcasing their exceptional selectivity for KDM4E and KDM6B, respectively. Employing an array of computational simulations, including sequence alignment, molecular docking, dynamics simulations, and free energy calculations, we conclude that although the binding cavities of KDM4E and KDM6B has high similarity, there are still some different crucial amino acid residues, indicating diverse binding forms between protein and ligands. Various interaction predominates when proteins are bound to different ligands, which also has significant effect on selective inhibition. These findings provide insights into potential therapeutic strategies for diseases by selectively targeting these KDM members.


Subject(s)
Enzyme Inhibitors , Jumonji Domain-Containing Histone Demethylases , Jumonji Domain-Containing Histone Demethylases/antagonists & inhibitors , Jumonji Domain-Containing Histone Demethylases/metabolism , Jumonji Domain-Containing Histone Demethylases/chemistry , Humans , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Molecular Dynamics Simulation , Drug Discovery , Molecular Docking Simulation , Molecular Structure , Histone Demethylases/antagonists & inhibitors , Histone Demethylases/metabolism , Histone Demethylases/chemistry , Structure-Activity Relationship
20.
J Sci Food Agric ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38619112

ABSTRACT

BACKGROUND: The adhesion of probiotics to the intestine is crucial for their probiotic function. In previous studies, Tremella polysaccharides (TPS) (with sodium casein) have shown the potential to encapsulate probiotics and protect them in a simulated gastrointestinal tract. This study explored the effect of TPS (with sodium casein) on the adhesion of probiotics. RESULTS: Lactobacillus plantarum was coated with TPS and sodium casein in different proportions, and was freeze-dried. The rheological properties of the mixture of probiotics powder and mucin solution were determined by static and dynamic rheological analysis. Aqueous solutions of probiotic powder and mucin mixture exhibited pseudoplastic fluid rheological properties. The higher the proportion of TPS content, the higher the apparent viscosity and yield stress. The mixed bacterial powder and mucin fluid displayed thixotropy and was in accordance with the Herschel-Bulkley model. The TPS increased the bio-adhesive force of the probiotic powder and mucin. When using TPS as the only carbon source, the adhesion of L. plantarum to Caco-2 cells increased by 228% in comparison with glucose in vitro. Twelve adhesive proteins were also detected in the whole-cell proteome of L. plantarum. Among them, ten adhesive proteins occurred abundantly when grown with TPS as a carbon source. CONCLUSION: Tremella polysaccharides therefore possess probiotic properties and can promote the intestinal adhesion of L. plantarum. © 2024 Society of Chemical Industry.

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