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1.
Int J Biol Macromol ; : 133665, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38971294

ABSTRACT

Functional drugs nano delivery systems manufactured from natural active products are promising for the field of biomedicines. In this study, an anti-ulcerative colitis (UC) curcumin loaded biopolymeric nanocomposite (CZNH) was fabricated and investigated. CZNH nanocomposite was obtained using the anti-solvent precipitation method, wherein curcumin-loaded zein colloidal particles served as the core, while sodium casein (NaCas) and hyaluronic acid (HA) formed the outermost layer of CZNH nanocomposite. Fourier transform infrared (FT-IR) spectrum and transmission electron microscopy (TEM) findings demonstrated that CZNH nanocomposite was a double-layer spherical micelle (250 nm) resulting from the hydrogen bond interactions and electrostatic adsorptions between zein, NaCas, and HA. Furthermore, CZNH nanocomposite exhibited prominent resuspension and storage stability in aqueous solution, which can be stored at 4 °C for approximately 30 days. In vivo anti-UC studies showed that CZNH nanocomposite could effectively alleviate UC symptoms via mediating inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6], myeloperoxidase (MPO), and oxidative stress factor [malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)]. This study suggested that the CZNH nanocomposite showed great promise as an efficient curcumin nanocarrier for UC therapy.

2.
Elife ; 132024 Jun 21.
Article in English | MEDLINE | ID: mdl-38905121

ABSTRACT

Runs of homozygosity (ROH) segments, contiguous homozygous regions in a genome were traditionally linked to families and inbred populations. However, a growing literature suggests that ROHs are ubiquitous in outbred populations. Still, most existing genetic studies of ROH in populations are limited to aggregated ROH content across the genome, which does not offer the resolution for mapping causal loci. This limitation is mainly due to a lack of methods for the efficient identification of shared ROH diplotypes. Here, we present a new method, ROH-DICE, to find large ROH diplotype clusters, sufficiently long ROHs shared by a sufficient number of individuals, in large cohorts. ROH-DICE identified over 1 million ROH diplotypes that span over 100 SNPs and are shared by more than 100 UK Biobank participants. Moreover, we found significant associations of clustered ROH diplotypes across the genome with various self-reported diseases, with the strongest associations found between the extended HLA region and autoimmune disorders. We found an association between a diplotype covering the HFE gene and hemochromatosis, even though the well-known causal SNP was not directly genotyped or imputed. Using a genome-wide scan, we identified a putative association between carriers of an ROH diplotype in chromosome 4 and an increase in mortality among COVID-19 patients (P-value=1.82×10-11). In summary, our ROH-DICE method, by calling out large ROH diplotypes in a large outbred population, enables further population genetics into the demographic history of large populations. More importantly, our method enables a new genome-wide mapping approach for finding disease-causing loci with multi-marker recessive effects at a population scale.

3.
J Lipid Res ; 65(7): 100575, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38866327

ABSTRACT

Lipids are components of cytomembranes that are involved in various biochemical processes. High-altitude hypoxic environments not only affect the body's energy metabolism, but these environments can also cause abnormal lipid metabolism involved in the hypoxia-induced cognitive impairment. Thus, comprehensive lipidomic profiling of the brain tissue is an essential step toward understanding the mechanism of cognitive impairment induced by hypoxic exposure. In the present study, mice showed reduced new-object recognition and spatial memory when exposed to hypobaric hypoxia for 1 day. Histomorphological staining revealed significant morphological and structural damage to the hippocampal tissue, along with prolonged exposure to hypobaric hypoxia. Dynamic lipidomics of the mouse hippocampus showed a significant shift in both the type and distribution of phospholipids, as verified by spatial lipid mapping. Collectively, a diverse and dynamic lipid composition in mice hippocampus was uncovered, which deepens our understanding of biochemical changes during sustained hypoxic exposure and could provide new insights into the cognitive decline induced by high-altitude hypoxia exposure.

4.
Mol Biol Evol ; 41(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38842255

ABSTRACT

The origins and extreme morphological evolution of the modern dog breeds are poorly studied because the founder populations are extinct. Here, we analyse eight 100 to 200 years old dog fur samples obtained from traditional North Swedish clothing, to explore the origin and artificial selection of the modern Nordic Lapphund and Elkhound dog breeds. Population genomic analysis confirmed the Lapphund and Elkhound breeds to originate from the local dog population, and showed a distinct decrease in genetic diversity in agreement with intense breeding. We identified eleven genes under positive selection during the breed development. In particular, the MSRB3 gene, associated with breed-related ear morphology, was selected in all Lapphund and Elkhound breeds, and functional assays showed that a SNP mutation in the 3'UTR region suppresses its expression through miRNA regulation. Our findings demonstrate analysis of near-modern dog artifacts as an effective tool for interpreting the origin and artificial selection of the modern dog breeds.


Subject(s)
Animal Fur , Selection, Genetic , Animals , Dogs/genetics , Polymorphism, Single Nucleotide , Breeding , Sweden , Genetic Variation , MicroRNAs/genetics
6.
Sensors (Basel) ; 24(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38894311

ABSTRACT

In recent years, there has been a considerable amount of research on visual evoked potential (VEP)-based brain-computer interfaces (BCIs). However, it remains a big challenge to detect VEPs elicited by small visual stimuli. To address this challenge, this study employed a 256-electrode high-density electroencephalogram (EEG) cap with 66 electrodes in the parietal and occipital lobes to record EEG signals. An online BCI system based on code-modulated VEP (C-VEP) was designed and implemented with thirty targets modulated by a time-shifted binary pseudo-random sequence. A task-discriminant component analysis (TDCA) algorithm was employed for feature extraction and classification. The offline and online experiments were designed to assess EEG responses and classification performance for comparison across four different stimulus sizes at visual angles of 0.5°, 1°, 2°, and 3°. By optimizing the data length for each subject in the online experiment, information transfer rates (ITRs) of 126.48 ± 14.14 bits/min, 221.73 ± 15.69 bits/min, 258.39 ± 9.28 bits/min, and 266.40 ± 6.52 bits/min were achieved for 0.5°, 1°, 2°, and 3°, respectively. This study further compared the EEG features and classification performance of the 66-electrode layout from the 256-electrode EEG cap, the 32-electrode layout from the 128-electrode EEG cap, and the 21-electrode layout from the 64-electrode EEG cap, elucidating the pivotal importance of a higher electrode density in enhancing the performance of C-VEP BCI systems using small stimuli.


Subject(s)
Algorithms , Brain-Computer Interfaces , Electroencephalography , Evoked Potentials, Visual , Humans , Evoked Potentials, Visual/physiology , Electroencephalography/methods , Male , Adult , Female , Young Adult , Photic Stimulation , Electrodes , Signal Processing, Computer-Assisted
7.
Article in Chinese | MEDLINE | ID: mdl-38858110

ABSTRACT

Objective:To investigate the differences in the therapeutic effects of endoscopic surgery combined with chemotherapy and endoscopic surgery combined with radiotherapy in the treatment of early nasopharyngeal carcinoma, and to select individualized treatment strategy for early nasopharyngeal carcinoma. Methods:The clinical data of 68 patients with early nasopharyngeal carcinoma(T1-2N0M0) who received surgical treatment in a high-incidence area were retrospectively analyzed. According to different treatment methods, they were divided into the surgery + chemotherapy group(n=34, treated with endoscopic surgery combined with chemotherapy) and the surgery + radiotherapy group(n=34, treated with endoscopic surgery combined with radiotherapy). Propensity score matching was used to match the patient data between the two groups at a 1∶1 ratio. Patients were followed up, and the survival rates and hematological toxicities were compared between the two groups. Results:Twenty-four cases in the surgery + chemotherapy group and 24 cases in the surgery + radiotherapy group were successfully matched. After matching, there was no statistically significant difference in T stage, and clinical stage between the two groups(all P>0.05). The 3-year OS and DFS in the surgery + chemotherapy group were 100.0% and 95.8%, respectively, while the 3-year OS and DFS in the surgery + radiotherapy group were 100.0% and 100.0%, respectively, with no significant difference in survival rates between the two groups(both P>0.05). After treatment, there was no statistically significant difference in bone marrow suppression between the surgery + chemotherapy group and the surgery + radiotherapy group (all P> 0.05) Conclusion:Endoscopic surgery combined with chemotherapy and surgery combined with radiotherapy have comparable clinical efficacy in the treatment of early nasopharyngeal carcinoma, but without radiotherapy-related complications, which is worth further investigation.


Subject(s)
Carcinoma , Endoscopy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/radiotherapy , Retrospective Studies , Male , Prognosis , Female , Combined Modality Therapy , Carcinoma/therapy , Survival Rate , Middle Aged , Neoplasm Staging , Incidence , Treatment Outcome , Adult
8.
ACS Nano ; 18(22): 14764-14778, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38776362

ABSTRACT

High-energy-density lithium-metal batteries (LMBs) coupling lithium-metal anodes and high-voltage cathodes are hindered by unstable electrode/electrolyte interphases (EEIs), which calls for the rational design of efficient additives. Herein, we analyze the effect of electron structure on the coordination ability and energy levels of the additive, from the aspects of intramolecular electron cloud density and electron delocalization, to reveal its mechanism on solvation structure, redox stability, as-formed EEI chemistry, and electrochemical performances. Furthermore, we propose an electron reconfiguration strategy for molecular engineering of additives, by taking sorbide nitrate (SN) additive as an example. The lone pair electron-rich group enables strong interaction with the Li ion to regulate solvation structure, and intramolecular electron delocalization yields further positive synergistic effects. The strong electron-withdrawing nitrate moiety decreases the electron cloud density of the ether-based backbone, improving the overall oxidation stability and cathode compatibility, anchoring it as a reliable cathode/electrolyte interface (CEI) framework for cathode integrity. In turn, the electron-donating bicyclic-ring-ether backbone breaks the inherent resonance structure of nitrate, facilitating its reducibility to form a N-contained and inorganic Li2O-rich solid electrolyte interface (SEI) for uniform Li deposition. Optimized physicochemical properties and interfacial biaffinity enable significantly improved electrochemical performance. High rate (10 C), low temperature (-25 °C), and long-term stability (2700 h) are achieved, and a 4.5 Ah level Li||NCM811 multilayer pouch cell under harsh conditions is realized with high energy density (462 W h/kg). The proof of concept of this work highlights that the rational ingenious molecular design based on electron structure regulation represents an energetic strategy to modulate the electrolyte and interphase stability, providing a realistic reference for electrolyte innovations and practical LMBs.

9.
Molecules ; 29(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38731456

ABSTRACT

The construction of high-performance n-type semiconductors is crucial for the advancement of organic electronics. As an attractive n-type semiconductor, molecular systems based on perylene diimide derivatives (PDIs) have been extensively investigated over recent years. Owing to the fascinating aggregated structure and high performance, S-heterocyclic annulated PDIs (SPDIs) are receiving increasing attention. However, the relationship between the structure and the electrical properties of SPDIs has not been deeply revealed, restricting the progress of PDI-based organic electronics. Here, we developed two novel SPDIs with linear and dendronized substituents in the imide position, named linear SPDI and dendronized SPDI, respectively. A series of structural and property characterizations indicated that linear SPDI formed a long-range-ordered crystalline structure based on helical supramolecular columns, while dendronized SPDI, with longer alkyl side chains, formed a 3D-ordered crystalline structure at a low temperature, which transformed into a hexagonal columnar liquid crystal structure at a high temperature. Moreover, no significant charge carrier transport signal was examined for linear SPDI, while dendronized SPDI had a charge carrier mobility of 3.5 × 10-3 cm2 V-1 s-1 and 2.1 × 10-3 cm2 V-1 s-1 in the crystalline and liquid crystalline state, respectively. These findings highlight the importance of the structure-function relationship in PDIs, and also offer useful roadmaps for the design of high-performance organic electronics for down-to-earth applications.

10.
Small ; : e2401204, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38801305

ABSTRACT

The demand for state-of-the-art high-energy-density lithium-ion batteries is increasing. However, the low specific capacity of electrode materials in conventional full-cell systems cannot meet the requirements. Ni-rich layered oxide cathodes such as Li(Ni0.8Co0.1Mn0.1)O2 (NCM811) have a high theoretical specific capacity of 200 mAh g-1, but it is always accompanied by side reactions on the electrode/electrolyte interface. Phosphorus anode possesses a high theoretical specific capacity of 2596 mAh g-1, but it has a huge volume expansion (≈300%). Herein, a highly compatible and secure electrolyte is reported via introducing an additive with a narrow electrochemical window, Lithium difluoro(oxalato)borate (LiDFOB), into 1 m LiPF6 EC/DMC with tris (2,2,2-trifluoroethyl) phosphate (TFEP) as a cosolvent. LiDFOB participates in the formation of organic/inorganic hybrid electrode/electrolyte interface layers at both the cathode and anode sides. The side reactions on the surface of the NCM811 cathode and the volume expansion of the phosphorus anode are effectively alleviated. The NCM811//RP full cell in this electrolyte shows high capacity retention of 82% after 150 cycles at a 0.5C rate. Meanwhile, the electrolyte shows non-flammability. This work highlights the importance of manipulating the electrode/electrolyte interface layers for the design of lithium-ion batteries with high energy density.

11.
Peptides ; 175: 171177, 2024 May.
Article in English | MEDLINE | ID: mdl-38354953

ABSTRACT

Trichophyton mentagrophytes is a zoophilic dermatophyte that can cause dermatophytosis in humans and animals. Antimicrobial peptides (AMPs) are considered as a promising agent to overcome the drug-resistance of T. mentagrophytes. Our findings suggest that cationic antimicrobial peptide (ACP5) not only possesses stronger activity against T. mentagrophytes than fluconazole, but also shows lower toxicity to L929 mouse fibroblast cells than terbinafine. Notably, its resistance development rate after resistance induction was lower than terbinafine. The present study aimed to evaluate the fungicidal mechanism of ACP5 in vitro and its potential to treat dermatophyte infections in vivo. ACP5 at 1 ×MIC completely inhibited T. mentagrophytes spore germination in vitro. ACP5 severely disrupts the mycelial morphology, leading to mycelial rupture. Mechanistically, ACP5 induces excessive ROS production, damaging the integrity of the cell membrane and decreasing the mitochondrial membrane potential, causing irreversible damage in T. mentagrophytes. Furthermore, 1% ACP5 showed similar efficacy to the commercially available drug 1% terbinafine in a guinea pig dermatophytosis model, and the complete eradication of T. mentagrophytes from the skin by ACP5 was verified by tissue section observation. These results indicate that ACP5 is a promising candidate for the development of new agent to combat dermatophyte resistance.


Subject(s)
Arthrodermataceae , Tinea , Humans , Mice , Animals , Guinea Pigs , Terbinafine/pharmacology , Terbinafine/therapeutic use , Trichophyton , Tinea/drug therapy , Antimicrobial Peptides , Antifungal Agents/pharmacology , Tartrate-Resistant Acid Phosphatase/pharmacology
12.
Interdiscip Sci ; 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38416364

ABSTRACT

Efficient and precise design of antimicrobial peptides (AMPs) is of great importance in the field of AMP development. Computing provides opportunities for peptide de novo design. In the present investigation, a new machine learning-based AMP prediction model, AP_Sin, was trained using 1160 AMP sequences and 1160 non-AMP sequences. The results showed that AP_Sin correctly classified 94.61% of AMPs on a comprehensive dataset, outperforming the mainstream and open-source models (Antimicrobial Peptide Scanner vr.2, iAMPpred and AMPlify) and being effective in identifying AMPs. In addition, a peptide sequence generator, AP_Gen, was devised based on the concept of recombining dominant amino acids and dipeptide compositions. After inputting the parameters of the 71 tridecapeptides from antimicrobial peptides database (APD3) into AP_Gen, a tridecapeptide bank consisting of de novo designed 17,496 tridecapeptide sequences were randomly generated, from which 2675 candidate AMP sequences were identified by AP_Sin. Chemical synthesis was performed on 180 randomly selected candidate AMP sequences, of which 18 showed high antimicrobial activities against a wide range of the tested pathogenic microorganisms, and 16 of which had a minimal inhibitory concentration of less than 10 µg/mL against at least one of the tested pathogenic microorganisms. The method established in this research accelerates the discovery of valuable candidate AMPs and provides a novel approach for de novo design of antimicrobial peptides.

13.
Chem Biodivers ; 21(3): e202302070, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38302826

ABSTRACT

Ultrasound-assisted extraction (UAE) method proves to be more effective compared to traditional extraction methods. In the present study, response surface methodology (RSM) was used to determine the optimal process parameters for extracting polysaccharides (U-MCP) from jaboticaba fruit using UAE. The optimum extraction conditions were ultrasonic time 70 min, extraction temperature 60 °C, and power 350 W. Under these conditions, the sugar content of U-MCP was 52.8 %. The molecular weights of the ultrasound-assisted extracted U-MCP ranged from 9.52×102 to 3.27×103  Da, and consisted of five monosaccharides including mannose, galacturonic acid, glucose, galactose, and arabinose. Moreover, in vitro antioxidant and hypoglycaemic assay revealed that U-MCP has prominent anti-oxidant activities (1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals, hydroxyl radicals and 2,2'-Azinobis (3-ethylbenzothiazoline-6-sulfonic Acid Ammonium Salt) (ABTS) radicals scavenging activities) and hypoglycemic activities (α-amylase and α-glucosidase inhibition activities).


Subject(s)
Antioxidants , Hypoglycemic Agents , Antioxidants/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Fruit/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemistry , Monosaccharides/analysis
14.
Vis Comput Ind Biomed Art ; 6(1): 24, 2023 Dec 11.
Article in English | MEDLINE | ID: mdl-38072844

ABSTRACT

The traditional feature-extraction method of oriented FAST and rotated BRIEF (ORB) detects image features based on a fixed threshold; however, ORB descriptors do not distinguish features well in capsule endoscopy images. Therefore, a new feature detector that uses a new method for setting thresholds, called the adaptive threshold FAST and FREAK in capsule endoscopy images (AFFCEI), is proposed. This method, first constructs an image pyramid and then calculates the thresholds of pixels based on the gray value contrast of all pixels in the local neighborhood of the image, to achieve adaptive image feature extraction in each layer of the pyramid. Subsequently, the features are expressed by the FREAK descriptor, which can enhance the discrimination of the features extracted from the stomach image. Finally, a refined matching is obtained by applying the grid-based motion statistics algorithm to the result of Hamming distance, whereby mismatches are rejected using the RANSAC algorithm. Compared with the ASIFT method, which previously had the best performance, the average running time of AFFCEI was 4/5 that of ASIFT, and the average matching score improved by 5% when tracking features in a moving capsule endoscope.

15.
Article in English | MEDLINE | ID: mdl-37971454

ABSTRACT

Objective: Our aim was to explore the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-related quantitative parameters for benign and malignant nasal cavity and sinus tumors. Methods: A total of 78 patients with nasal sinus tumors admitted to People's Hospital of Qingdao Chengyang District in China were enrolled in our study, Of the patients, 41 were diagnosed as having benign tumors and 37 as having malignant tumors by pathological diagnosis. All patients received DCE-MRI scans before surgery to derive time-intensity curves (TICs) and related quantitative parameters (flux rate constant [Kep], transfer constant [Ktrans], extravascular volume fraction [Ve]). The diagnostic surgical pathology results were used as the gold standard to analyze the diagnostic effect of TIC and related quantitative parameters of DCE-MRI, and the receiver operating characteristic (ROC) curves were plotted to determine the values of each parameter in predicting nasal sinus tumors. Results: The percentage of class I in the benign group was significantly higher than in the malignant group (P < .05); the percentage of class III in the benign group was significantly lower than in the malignant group (P < .05); the percentage of class II in the 2 groups was comparable (P > .05). Kep, Ktrans and Ve in the benign group were 0.338±0.124, 0.061±0.035 and 0.532±0.138, respectively; Kep, Ktrans and Ve in the malignant group were 0.785±0.211, 0.441±0.125 and 0.327±0.048, respectively. The levels of Kep and Ktrans were significantly lower in the benign group than in the malignant group (all P < .05); the levels of Ve were significantly higher in the benign group than in the malignant group (P < .05). The optimal Kep cut-off value for predicting malignant nasal sinus tumors was 0.510 min-1, with a sensitivity of 81.4% and specificity of 89.5%; the optimal Ktrans cut-off value for predicting malignant nasal sinus tumors was 0.206 min-1, with a sensitivity of 84.3% and specificity of 89.7%; the optimal Ve cut-off value for predicting malignant nasal sinus tumors was 0.384 min-1, with a sensitivity of 71.8% and specificity of 82.4%. Conclusion: DCE-MRI-related quantitative parameters are ideal for the diagnosis of benign and malignant nasal sinus tumors. This modality provides more data for the identification of the nature of the tumor, and thus merits clinical promotion and application.

16.
ACS Nano ; 17(22): 22632-22641, 2023 Nov 28.
Article in English | MEDLINE | ID: mdl-37933557

ABSTRACT

Lithium-sulfur batteries (LSBs) are one of the most promising candidates for next-generation energy storage systems. To develop long-life LSBs, there is an urgent need to develop functional materials with higher catalytic activity toward polysulfides and reduced dendritic lithium growth. Herein, an electrostatic field electrocatalyst is designed in a zwitterionic covalent organic framework (COF) with a "two birds with one stone" ability for simultaneously overcoming obstacles in the lithium metal anode and sulfur cathode. The synergism between cationic and anionic moieties in the zwitterionic COF creates an electrostatic field for bidirectionally catalyzing S cathode conversion. Besides, the rational design of zwitterionic COF as a separator modification layer allows lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) dissociation and fast lithium-ion conduction, which alleviates lithium dendrite growth and thus improves the cycling life of LSBs. This contribution not only pioneers the application of zwitterionic COF in the field of LSBs but also highlights the potential of electrostatic field electrocatalysts.

17.
Angew Chem Int Ed Engl ; 62(50): e202315834, 2023 Dec 11.
Article in English | MEDLINE | ID: mdl-37933998

ABSTRACT

Aqueous zinc metal batteries hold great promise for large-scale energy storage because of their high safety, rich material resources and low cost. However, the freeze of aqueous electrolytes hinders low-temperature operation of the batteries. Here, aqueous localized anion-cation aggregated electrolytes composed of Zn(BF4 )2 as the salt and tetrahydrofuran (THF) as the diluent, are developed to improve the low-temperature performance of the Zn anode. THF promotes the inclusion of BF4 - in the solvation sheath of Zn2+ , facilitating the formation of ZnF2 -rich solid-electrolyte-interphase. THF also affects the hydrogen bonding between neighboring H2 O molecules, effectively lowering the freezing point. Therefore, the full cells of Zn||polyaniline (PANI) exhibit an ultralong cycle life of 8000 cycles with an average Coulombic efficiency of 99.99 % at -40 °C. Impressively, the pouch cells display a high capacity retention of 86.2 % after 500 cycles at -40 °C, which demonstrates the great prospect of such electrolytes in cold regions. This work provides new insights for the design of low-temperature aqueous electrolytes.

18.
Biomed Pharmacother ; 169: 115941, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-38006619

ABSTRACT

Chaenomeles sinensis fruit polysaccharide (CSP) and carboxymethylated CSP (CSP-M) were prepared using ultrasound extraction and the sodium hydroxide-chloroacetic acid method. Structural analysis revealed that both CSP and CSP-M mainly consisted of glucose, arabinose, rhamnose, glucuronic acid, galactose, and xylose, and the introduction of carboxymethyl did not damage the polymer chain of CSP. In vivo studies verified that both CSP and CSP-M could remarkably alleviate the symptoms of ulcerative colitis (UC) mice and reduce intestinal epithelial cell depletion, along with the infiltration of inflammatory cells in colon tissue, by mediating the expression of myeloperoxidase (MPO), inflammatory factors [tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6], and oxidative stress factors [malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and nitric oxide (NO)]. Most importantly, the introduction of carboxymethyl significantly enhanced the anti-UC activity of CSP, confirming the efficacy of carboxymethylation as a method to enhance the biological activities of CSP, thereby suggesting the potential of CSP-M as a therapeutic option for UC.


Subject(s)
Colitis, Ulcerative , Colitis , Rosaceae , Mice , Animals , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/metabolism , Dextran Sulfate/adverse effects , Inflammation/metabolism , Colon/metabolism , Oxidative Stress , Tumor Necrosis Factor-alpha/metabolism , Glutathione/metabolism , Polysaccharides/adverse effects , Disease Models, Animal , Colitis/metabolism
19.
bioRxiv ; 2023 Nov 19.
Article in English | MEDLINE | ID: mdl-38014185

ABSTRACT

The availability of large genotyped cohorts brings new opportunities for revealing high-resolution genetic structure of admixed populations, via local ancestry inference (LAI), the process of identifying the ancestry of each segment of an individual haplotype. Though current methods achieve high accuracy in standard cases, LAI is still challenging when reference populations are more similar (e.g., intra-continental), when the number of reference populations is too numerous, or when the admixture events are deep in time, all of which are increasingly unavoidable in large biobanks. Here, we present a new LAI method, Recomb-Mix. Adopting the commonly used site-based formulation based on the classic Li and Stephens' model, Recomb-Mix integrates the elements of existing methods and introduces a new graph collapsing to simplify counting paths with the same ancestry label readout. Through comprehensive benchmarking on various simulated datasets, we show that Recomb-Mix is more accurate than existing methods in diverse sets of scenarios while being competitive in terms of resource efficiency. We expect that Recomb-Mix will be a useful method for advancing genetics studies of admixed populations.

20.
Int J Biol Macromol ; 249: 126017, 2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37517752

ABSTRACT

Anemarrhena asphodeloides polysaccharide (AAP70-1) was reported to have immunomodulatory effects in our previous report. To further improve the immunomodulatory effects of AAP70-1, an A. asphodeloides polysaccharide-zinc complex (AAP-Zn) was synthesized using a ZnCl2 modification method, and the potential mechanisms by which AAP-Zn activates macrophages were investigated. The results showed that the structural features of AAP-Zn were similar to those of AAP70-1 with a Zn content of 0.2 %, confirming that Zn mainly interacted with AAP70-1 by forming ZnO coordination bonds and Zn…OH bonds. In addition, the administration of AAP70-1 and AAP-Zn effectively improved the immunomodulatory effects by enhancing phagocytosis and upregulating the mRNA expression of cytokines (TNF-α, IL-6, IL-1ß, and IL-18), as well as increasing the production levels of nitric oxide (NO) and reactive oxygen species (ROS) in zebrafish embryos. The intracellular mechanism by which AAP-Zn activates macrophages was found to involve activation of the NF-κB and MAPK signaling pathways. Our findings suggested that AAP-Zn may be a potential immunopotentiator in the field of biomedicine or functional foods.


Subject(s)
Anemarrhena , NF-kappa B , Animals , NF-kappa B/metabolism , Anemarrhena/chemistry , Zinc/pharmacology , Zebrafish/metabolism , Polysaccharides/pharmacology , MAP Kinase Signaling System
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