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1.
Int J Biol Macromol ; : 123500, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36736520

RESUMO

Lycium barbarum polysaccharide (LBP) is the main active component of Lycium barbarum (L. barbarum), which has important medicinal and nutritional value. However, the effect of LBP treatment on Luciobarbus capito (L. capito) still remains unknown. Given this, the current work aims to probe the underlying effect of different levels of LBP treatment (i.e. 0.10, 0.50 and 1.00 g/L) on L. capito in the context of enzymatic activity analysis, histological observations and gut microbiota analysis. Compared with control group, the activities of hepatic antioxidant enzymes, intestinal digestive enzymes and hepatic immune enzyme were found to be significantly increased after 0.10 g/L LBP and 0.50 g/L LBP treatment (P < 0.05). This result indicated that moderate levels of LBP treatment could dramatically enhance the immunity and antioxidant capacity of L. capito. Furthermore, the compositional structures of the gut microbiota in L. capito were found to be greatly shaped after LBP treatment, whereas the diversity and abundance of the gut microbiota were only found to be slightly changed (P > 0.05). No significant changes were screened in the morphologic structures of gut constructions. This work would provide theoretical and experimental basis for future application of LBP as supplement in the culture process of the farmed fish.

2.
Food Res Int ; 164: 112443, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36738008

RESUMO

Starch-stabilized Pickering emulsions were employed as a novel particulate filler in myofibrillar protein (MP)-based gels for improving the gelling characteristics. The role of emulsions prepared by native starches (NS) with distinctive crystalline types (i.e., A-type waxy corn starch, B-type potato starch, and C-type pea starch) and their OSA-modified counterparts (A-OS, B-OS, C-OS) in the gelling performance was evaluated and compared with MP-stabilized-emulsion. Compared with MP-emulsion, starch-emulsion caused substantial increases in the gelling properties, notably for OSA-starch emulsions. Herein, A-OS exhibited up to 1.26-, 5.3-, and 2.9-fold increments in storage modulus, gel strength, and water holding capacity relative to pure MP gel, respectively, higher than B-OS and C-OS. Moreover, light microscopy evinced a more compact gel network filled with smaller and uniform oil droplets when A-OS emulsions were incorporated into the gels. The addition of OSA-starch emulsions, especially A-OS emulsion, facilitated the protein conformational conversion from α-helix to ß-sheet and caused a marked reduction of free sulfhydryls in the gels; yet, the chemical forces that stabilized the gels altered, where remarkable reinforcements in hydrogen bond and hydrophobic interaction were detected, in support of the construction of splendid MP gels. Hence, OSA-starch emulsions show promise as functional components in meat products.

3.
ACS Nano ; 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36735721

RESUMO

Outer membrane vesicles (OMVs) are crucial for bacterial intercellular communication and the crosstalk between the gut microbiota and its host. Methods capable of visualizing gut microbiota derived OMVs would be of great significance but have been rarely reported. Here, nanoprobes carrying a fluorescence-activating and absorption-shifting tag are prepared by combining genetic engineering and antibiotic-boosted vesicle formation and release. Benefiting from their natural structure and molecular oxygen-independent emission, the resulting nanovesicles can be applied as endogenous fluorescence probes to anaerobically track gut microbiota associated OMVs. These nanoprobes show flexibility in on-demand fluorescence turn-on/off and reversibly switchable emission bands for intelligent and dual-color imaging. With these special characteristics, the behaviors of microbiota OMVs to not only inhibit specific pathogenic strains through membrane fusion but also repair the intestinal barrier via entering intestinal epithelia and promoting the expressions of tight junctions are tracked and identified in the gut. Based on these discoveries, OMVs are disclosed to be able to remit inflammation in a murine model of colitis following transplantation to the intestine by oral delivery. This work provides an approach to visualize the dynamics of the gut microbiota and disclose potential targets for disease intervention.

4.
Biomed Pharmacother ; 160: 114304, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36724638

RESUMO

Ovarian cancer is the second cause of death among gynecological malignancies. In this study, we designed a novel estrogen-targeted PEGylated liposome loaded with oxaliplatin and paclitaxel (ES-SSL-OXA/PTX) which could target estrogen receptor (ER) highly expressed on the surface of SKOV-3 cells to enhance therapeutic efficacy and reduce the side effects for SKOV-3 tumor therapy. ES-SSL-OXA/PTX was prepared by thin film hydration method and exhibited a uniform spherical morphology. Encapsulation efficiency (EE) were determined by HPLC method with the results of 44.10% for OXA and 65.85% for PTX. The mean particle size and polydispersity index (PDI) were 168.46 nm and 0.145, respectively. In vivo and in vitro targeting study confirmed that ES-SSL-OXA/PTX has optimum specific targeting ability. Meanwhile, In vitro and in vivo antitumor results of ES-SSL-OXA/PTX exhibited a superior antiproliferative effect on SKOV-3 cells and a stronger anti-tumor efficacy with the tumor inhibition rate of 85.24%. The pharmacokinetics results of ES-SSL-OXA/PTX showed a prolonged half-life time and a slowed clearance rate. The preliminary safety study of acute toxicity and long-term toxicity demonstrated ES-SSL-OXA/PTX exhibited a reduced toxicity profile. Based on the above results, ES-SSL-OXA/PTX could be a promising novel formulation for the treatment of ovarian cancer in future clinic.

5.
Psychiatry Investig ; 20(1): 69-74, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36721888

RESUMO

A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.

6.
Pest Manag Sci ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36722434

RESUMO

BACKGROUND: In order to promote the green development of agriculture, it is important to study the enantioselective effect of chiral pesticides. The bioactivity of the chiral fungicide penthiopyrad (PEN) racemate and enantiomers against phytopathogens, toxicity to non-target organisms, effect on tomato fruit growth and maturation, and environmental fate in tomato cultivation were evaluated at enantioselective level in this study. RESULTS: The results indicated that at the same efficacy, the optically pure S-(+)-PEN could lower the dosage of racemate by 20%-96%. The S-enantiomer had low toxicity to earthworms. Besides, the S-(+)-PEN did not cause significant abiotic stress to the tomato and increased fruit fresh weight and size via modulating the contents of plant hormones. However, the content of H2 O2 , O2 - and malondialdehyde in the R-enantiomer treatment group was significantly higher than the control group. The effect of the racemate on tomato fruit was between the enantiomers. Furthermore, compared to R-(-)-PEN and racemate, the S-enantiomer degraded more quickly in tomato fruit, leaves, and soil, reducing the danger of human exposure. CONCLUSION: The S-enantiomer is highly effective and less toxic. The development of enantiomer pure S-(+)-PEN products might be an efficient and low-risk strategy. The results lay the foundation for comprehensive evaluation and proper application of the PEN. This article is protected by copyright. All rights reserved.

7.
Molecules ; 28(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36677626

RESUMO

Five novel bis-tridentate Ir(III) complexes (Ir-1-Ir-5) incorporating versatile N^N^C ligands and a N^C^N ligand (1,3-di(2-pyridyl)-4,6-dimethylbenzene) were synthesized. With the combination of experimental and theoretical methods, their steady and transient state characteristics were researched scientifically. The UV-visible absorption spectra show that the broadband charge transfer absorbance of those bis-tridentate Ir(III) complexes can reach 550 nm, all of these complexes reveal the long-lasting phosphorescent emission. Because the excited-state absorption is more powerful than the ground-state absorption, a sturdy reverse saturable absorption (RSA) process can ensue in the visible and near-infrared regions when the complexes are exposed to a 532 nm laser. Therefore, the optical power limiting (OPL) effect follows the trend: Ir-5 > Ir-4 ≈ Ir-3 > Ir-2 > Ir-1. Generally speaking, the expansion of π-conjugation and the introduction of electron donating/withdrawing groups on the N^N^C ligand could effectively elevate the OPL effect. Therefore, these octahedral bis-tridentate Ir(III) complexes might be exploited as potential OPL materials.

8.
Adv Sci (Weinh) ; : e2206253, 2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36683217

RESUMO

Due to their intrinsic anti-inflammatory and immunomodulatory properties, adipose-derived stem cells (ADSCs) are explored as a promising alternative in treating rheumatoid arthritis (RA). To address the poor survival and function loss of directly injected stem cells, efforts in this area are focus on the generation of efficient cell delivery vehicles. Herein, a novel extracellular matrix (ECM)-inspired injectable hydrogel for ADSCs encapsulation and RA treatment is proposed. The hydrogel with dendritic polylysine and polysaccharide components is formed through the reversible Schiff base crosslinking. It possesses self-healing capability, superior mechanical properties, minimal toxicity, and immunomodulatory ability. When encapsulated with ADSCs, the hydrogel could recover chronic inflammation by directly reversing the dominant macrophage phenotype from M1 to M2 and inhibiting the migration of fibroblast-like synoviocytes. Through a collagen-induced arthritis rat model, the tremendous therapeutic outcomes of this ADSCs-laden hydrogel, including inflammation attenuation, cartilage protection, and bone mineral density promotion are demonstrated. These results make the ECM-inspired hydrogel laden with ADSCs an ideal candidate for treating RA and other autoimmune disorders.

9.
Am J Chin Med ; : 1-20, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36611142

RESUMO

For centuries, Sophora alopecuroides L. has been used both as a food and an herbal medicine in northern China. A new cytisine-type alkaloid, N-methylene-(5,7,4[Formula: see text]-trihydroxy)-isoflavone (LY01), was found in the fruits of Sophora alopecuroides L. and shows neuroprotective effects against Parkinson's disease (PD). PD is a frequently occurring, irreversible neurodegenerative disease that seriously threatens the health of the elderly population. There is no cure for PD. The available treatments help manage the symptoms, but their use is limited by multiple side effects. Therefore, more pharmacological treatments addressing this pathology are urgently required. This study aimed to evaluate the neuroprotective effects of LY01 against PD, as well as their underlying mechanisms, using both in vitro and in vivo experimental models. A 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride (MPTP)-induced mouse model of PD was used to assess the effects of LY01 on the motor coordination deficit, progression of the pathology, and molecular characteristics. 1-Methyl-4-phenylpyridinium (MPP[Formula: see text])-activated SH-SY5Y cells and lipopolysaccharide (LPS)-activated BV-2 cells were used to evaluate LY01 effects on oxidative damage and neuroinflammation. In the rotarod test, LY01 alleviated the impaired motor coordination in PD mice. Furthermore, LY01 treatment prevented the loss of dopaminergic neurons in the substantia nigra and striatum of the PD mice, reduced neuroinflammation in the mice with MPTP-induced PD and the LPS-activated BV-2 cells, and diminished oxidative stress in the PD mice and the MPP[Formula: see text]-induced SH-SY5Y cells. In conclusion, these results suggest the potential of LY01 as a therapeutic agent for treating PD.

10.
J Transl Med ; 21(1): 45, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698183

RESUMO

BACKGROUND: Deterioration of normal intestinal epithelial cells is crucial for colorectal tumorigenesis. However, the process of epithelial cell deterioration and molecular networks that contribute to this process remain unclear. METHODS: Single-cell data and clinical information were downloaded from the Gene Expression Omnibus (GEO) database. We used the recently proposed dynamic network biomarker (DNB) method to identify the critical stage of epithelial cell deterioration. Data analysis and visualization were performed using R and Cytoscape software. In addition, Single-Cell rEgulatory Network Inference and Clustering (SCENIC) analysis was used to identify potential transcription factors, and CellChat analysis was conducted to evaluate possible interactions among cell populations. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set variation analysis (GSVA) analyses were also performed. RESULTS: The trajectory of epithelial cell deterioration in adenoma to carcinoma progression was delineated, and the subpopulation of pre-deteriorated epithelial cells during colorectal cancer (CRC) initialization was identified at the single-cell level. Additionally, FOS/JUN were identified as biomarkers for pre-deteriorated epithelial cell subpopulations in CRC. Notably, FOS/JUN triggered low expression of P53-regulated downstream pro-apoptotic genes and high expression of anti-apoptotic genes through suppression of P53 expression, which in turn inhibited P53-induced apoptosis. Furthermore, malignant epithelial cells contributed to the progression of pre-deteriorated epithelial cells through the GDF signaling pathway. CONCLUSIONS: We demonstrated the trajectory of epithelial cell deterioration and used DNB to characterize pre-deteriorated epithelial cells at the single-cell level. The expression of DNB-neighboring genes and cellular communication were triggered by DNB genes, which may be involved in epithelial cell deterioration. The DNB genes FOS/JUN provide new insights into early intervention in CRC.


Assuntos
Adenoma , Carcinoma , Neoplasias Colorretais , Humanos , Proteína Supressora de Tumor p53/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Células Epiteliais/metabolismo , Adenoma/genética , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica
11.
RSC Adv ; 13(3): 1765-1778, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36712618

RESUMO

Flexible fiber membranes for pollutant removal have received increasing attention due to their high adsorption performance and easy recycling characteristics. However, due to the lack of environmentally friendly regeneration, some adsorption membranes have low regeneration efficiency, especially in terms of chemical adsorption, so they lack reusability. This study prepares a series of conducting polymer [PAn (polyaniline) or PPy (polypyrrole) or PTh (polythiophene)] graphene quantum dots (GQDs, the size of GQDs is about 20 nm)/TiO2 ternary fiber membranes via a facile electrospinning method with chemical deposition. Remarkably, this creates an anatase TiO2 and π-conjugated system. The combination is beneficial to the photocatalytic degradation of organic pollutants, showing synergistic promotion in both the degradation rate and the degree of decomposition. The UV-vis test shows that the combination of GQDs broadens the optical response threshold of TiO2, from near ultraviolet region excitation to visible region excitation. At the same time, the conductive polymer load further reduces the energy required for photogenerated electron transfer, which theoretically improves the degradation effect. Photocatalytic degradation tests showed that the PTh/GQDs/TiO2 fiber membrane exhibited significant high photocatalytic activity of visible-light in the methylene blue (MB) and TC degradation. The degradation rate level is 92.90% and 80.58%, respectively and the MB removal is more than 4 times that of bare TiO2 membrane. After photocatalytic regeneration four times, the regeneration efficiency can be maintained above 95%. Notably, various experimental results show that the interface charge transfer mechanism between GQDs/TiO2 and PTh follows the Z-scheme heterojunction, which maximizes the retention of strong reducing electrons and oxidation holes. In the degradation, the active species of ·O2 - and ·OH, make different contributions in the photocatalysts, which oxidize and break down the pollutant molecules into small molecules and then to harmless substances. According to the electronegativity difference of the material itself, PTh acts as electron acceptor in the degradation system, and TiO2 fiber membrane doped with GQDs acts as electron donor. The present research, not only offers feasibility of the PTh/GQDs/TiO2 flexible fiber membrane as an environment-friendly catalyst, but also motivates researchers to develop flexible fiber materials for future photocatalytic technology.

12.
Biosens Bioelectron ; 225: 115098, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36701949

RESUMO

In this work, PtPd nanoparticles functionalized porphyrin metal-organic framework nanoenzymes (PtPd@PCN-224 nanoenzymes) are exploited as signal amplification tags to fabricate a rapid and ultrasensitive sensitive CRISPR/Cas14a-based electrochemical biosensor for Burkholderia pseudomallei (B. pseudomallei) specific DNA sequences detection. The prepared PtPd@PCN-224 nanoenzymes not only catalyze the reduction peak current of H2O2 to obtain a strong electrochemical signal output, but also provide massive active sites for the assembly of nucleic acids by Zr-O-P bonds. Besides, the designed target-activated CRISPR/Cas14a is able to recognize the target DNA sequences and further trigger the trans-cleavage of ssDNA for signal amplification. Benefiting from the target-activated CRISPR/Cas14a and PtPd@PCN-224 nanoenzymes, the developed electrochemical biosensor for B. pseudomallei DNA detection exhibits high sensitivity with detection of limit down to 12.8 aM and excellent specificity for distinguishing non-targeted bacteria. Moreover, the CRISPR/Cas14a-based electrochemical detection platform can also apply for other pathogenic bacteria diagnostic by well-designing sgRNA for target sequence recognition, possessing high flexibility and versatility in clinical diagnosis.

13.
Artigo em Inglês | MEDLINE | ID: mdl-36705239

RESUMO

BACKGROUND: Xinfeng capsule (XFC) is a well-known drug against rheumatoid arthritis (RA). However, the combination mechanisms of XFC on RA remain unclear. OBJECTIVE: The purpose of this study is to explore the mechanisms of XFC against RA in terms of compounds, targets, and signaling pathways via network pharmacology. METHODS: The bioactive compounds and potential targets of XFC were extracted from TCMSP and BATMAN-TCM database, and the putative RA-related targets were determined from the DisGeNET, PHGKB, PharmGKB, and CTD database. The approach of protein-protein interaction, gene ontology analysis, and kyoto encyclopedia of genes and genomes pathway enrichment analysis were constructed, respectively. In animal experiments, we evaluated the expression of core targets. RESULTS: We found that XFC handled 30 active compounds and 131 common target genes. Among them, mairin, folic acid, cholesterol, and triptolide in XFC were selected as the central active compounds against RA. The mechanisms of XFC on RA which concerned critical targets were protein kinase B (AKT1) and tumor necrosis factor (TNF). In vivo, we found that the expression levels of AKT1 and TNF in the modeling group were significantly increased but reversed by XFC. CONCLUSION: The combination mechanisms of XFC were elucidated in terms of components and targets and signaling pathways, which may be related to inhibiting the proliferation of synovial cells and inflammation.

14.
Brief Bioinform ; 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36705581

RESUMO

Complex biological systems do not always develop smoothly but occasionally undergo a sharp transition; i.e. there exists a critical transition or tipping point at which a drastic qualitative shift occurs. Hunting for such a critical transition is important to prevent or delay the occurrence of catastrophic consequences, such as disease deterioration. However, the identification of the critical state for complex biological systems is still a challenging problem when using high-dimensional small sample data, especially where only a certain sample is available, which often leads to the failure of most traditional statistical approaches. In this study, a novel quantitative method, sample-perturbed network entropy (SPNE), is developed based on the sample-perturbed directed network to reveal the critical state of complex biological systems at the single-sample level. Specifically, the SPNE approach effectively quantifies the perturbation effect caused by a specific sample on the directed network in terms of network entropy and thus captures the criticality of biological systems. This model-free method was applied to both bulk and single-cell expression data. Our approach was validated by successfully detecting the early warning signals of the critical states for six real datasets, including four tumor datasets from The Cancer Genome Atlas (TCGA) and two single-cell datasets of cell differentiation. In addition, the functional analyses of signaling biomarkers demonstrated the effectiveness of the analytical and computational results.

15.
Int J Biol Macromol ; 231: 123232, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36681217

RESUMO

Bone augmentation has an enormous demand in oral clinical treatment. Although there are various options available for clinical management to address it, these approaches could increase patient suffering due to surgical trauma and even cause psychological trauma to the patients. Moreover, presently, there is still a lack of well-considered microinvasive bone augmentation systems to deal with this challenge. Herein, we newly developed a subperiosteal injectable and osteogenesis-promoting hydroxylapatite/laponite/alginate nanocomposite hydrogels to address the insufficient microinvasive bone augmentation strategies. The physical performances (like swelling profiles, degradation behaviors, mechanical properties, and surface morphologies) of the gels were determined, and can be slightly tuned through altering concentrations of laponite. The cytocompatibility test results show outstanding biocompatibility of the hydrogels. Furthermore, the in vitro testing for bone-inducing activity and in vivo determination of bone-augmentation in the rat cranial subperiosteum exhibit that the hydrogels significantly promoted rat periosteum-derived mesenchymal stromal cells (P-MSCs) osteogenic differentiation in vitro and bone augmentation in vivo. Therefore, the research reveals that the nanocomposite hydrogels possessing subperiosteal microinvasive injectability, osteogenesis-enhancing capability, and clinical applicability have extremely great potential application in subperiosteal microinvasive bone augmentation.

16.
Int J Biol Macromol ; 230: 123150, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36621730

RESUMO

Naringenin is a natural flavonoid that is widely distributed in citrus fruits and pharmacologically demonstrated to licit lipid-lowering activity. However, the clinical relevance of naringenin is limited due to its poor water solubility and inefficient absorption. In this study, we designed and developed naringenin-zein-sodium caseinate-galactosylated chitosan nanoparticles (GC-NPs) for hepatocyte-specific targeting, with naringenin-zein-sodium caseinate-chitosan nanoparticles (CS-NPs) as a control. Electrostatic adsorption was the primary binding mode in the GC-NPs and CS-NPs. Moreover, the particle size and zeta potential of GC-NPs were larger than those of CS-NPs and both types of nanoparticles had similar encapsulation rates. In vitro study experiments demonstrated that GC-NPs aggregated inside and outside of the cell membrane and significantly inhibited total triglyceride and cholesterol levels in oleic acid-induced HepG2 cells (p < 0.05). In high-fat diet-fed C57BL/6J mice, GC-NPs administration visibly improved the body weight, total cholesterol, and triglyceride content in the serum and liver, and high-density lipoprotein cholesterol levels improved, which corresponded to liver histological results. Additionally, in vitro and in vivo assays demonstrated that GC-NPs exhibited higher lipid-lowering activity than CS-NPs and naringenin monomers. These results suggest that GC-NPs are effective for oral delivery of naringenin in lipid-lowering therapies.

17.
Cancer Med ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36606571

RESUMO

BACKGROUND AND AIMS: Distinguishing pancreatic cancer from nonneoplastic masses is critical and remains a clinical challenge. The study aims to construct a deep learning-based artificial intelligence system to facilitate pancreatic mass diagnosis, and to guide EUS-guided fine-needle aspiration (EUS-FNA) in real time. METHODS: This is a prospective study. The CH-EUS MASTER system is composed of Model 1 (real-time capture and segmentation) and Model 2 (benign and malignant identification). It was developed using deep convolutional neural networks and Random Forest algorithm. Patients with pancreatic masses undergoing CH-EUS examinations followed by EUS-FNA were recruited. All patients underwent CH-EUS and were diagnosed both by endoscopists and CH-EUS MASTER. After diagnosis, they were randomly assigned to undergo EUS-FNA with or without CH-EUS MASTER guidance. RESULTS: Compared with manual labeling by experts, the average overlap rate of Model 1 was 0.708. In the independent CH-EUS video testing set, Model 2 generated an accuracy of 88.9% in identifying malignant tumors. In clinical trial, the accuracy, sensitivity, and specificity for diagnosing pancreatic masses by CH-EUS MASTER were significantly better than that of endoscopists. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were respectively 93.8%, 90.9%, 100%, 100%, and 83.3% by CH-EUS MASTER guided EUS-FNA, and were not significantly different compared to the control group. CH-EUS MASTER-guided EUS-FNA significantly improved the first-pass diagnostic yield. CONCLUSION: CH-EUS MASTER is a promising artificial intelligence system diagnosing malignant and benign pancreatic masses and may guide FNA in real time. TRIAL REGISTRATION NUMBER: NCT04607720.

18.
Cereb Cortex ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627245

RESUMO

Studies have shown that protein phosphorylation plays an important role in morphine abuse. However, the neurobiological mechanism of protein phosphatase 2A (PP2A) underlying the morphine-priming process is still unclear. Here we constructed T29-2-Cre; PP2Afl/fl conditional knockout mice (KO) and investigated the role of hippocampal PP2A in morphine priming. We observed that the deficit of PP2A inhibited the priming behavior of morphine and blocked the priming-induced long-term potentiation (LTP) in the hippocampus of KO mice. Moreover, the expression levels of Rack1 and the membrane GluN2B were significantly reduced in the nucleus accumbens of KO mice compared with those in the control mice, which may be attributed to the decreased HDAC4 in the hippocampus of KO mice. Consistent with it, the similar inhibited priming effects were also observed in the wild-type mice treated with sodium butyrate (NaB)-a nonspecific inhibitor of histone deacetylases-3 h after morphine administration. Taken together, our results suggest that hippocampal PP2A may be involved in morphine priming through the PP2A/HDAC4/Rack1 pathway.

20.
Anal Chim Acta ; 1239: 340699, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36628767

RESUMO

Antibodies against small molecules with high titer and high affinity are always pursued in the field of vaccines for drugs of abuse, antidotes to toxins and immunoassays in medical, environmental, and food safety. The exposure degree of the target molecule to the immune system is critical to induce a strongly specific antibody response, thus, the spacer arm length between the target molecule and carrier protein plays an important role. However, the influence of spacer arm length on antibody titer, affinity, and assay performance is not yet clear and highly demanded to be addressed. In the present study, we proposed a model study to answer the question by using two typical small molecules, melamine and p-nitroaniline, which were introduced by varied spacer arms with increasing alkane linear length from 2 to 12 carbon atoms brick by brick. The spacer arm lengths of the haptens were obtained by computational chemistry. The titer and affinity of mouse antisera were analyzed and compared, showing that all haptens with spacer arms of 6-8 carbon atoms, i.e. 6.3-8.8 Å in length, induced strong antibodies represented by the highest titer and affinity without exception, while the haptens with spacer arms of 2-4 carbon atoms and 10-12 carbon atoms, i.e. 1.5-3.9 Å and 11.3-13.9 Å in length, failed to induce high-quality antibody response. Moreover, the titer and sensitivity of the subsequently developed immunoassays were significantly affected by using coating haptens with different spacer arm lengths, and coating haptens with a spacer arm of 6.3-8.8 Å in length delivered the optimum detection performance. The antibody recognition mechanism study further confirmed that the hapten spacer arm length had a critical effect on the recognition properties of the induced antibody, which should be interactive with the spacer arm each other. This study showed that the hapten with appropriate spacer arm length is important to antibody response and immunoassay development, providing a valuable and general clue for the rational design of hapten.


Assuntos
Formação de Anticorpos , Haptenos , Animais , Camundongos , Haptenos/química , Anticorpos , Imunoensaio , Ensaio de Imunoadsorção Enzimática
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