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1.
Front Immunol ; 15: 1368275, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562943

RESUMO

Autoimmune encephalitis (AE) broadly refers to inflammation of the brain parenchyma mediated by autoimmune mechanisms. In most patients with AE, autoantibodies against neuronal cell surface antigens are produced by B-cells and induce neuronal dysfunction through various mechanisms, ultimately leading to disease progression. In recent years, B-cell targeted therapies, including monoclonal antibody (mAb) therapy and chimeric antigen receptor T-cell (CAR-T) therapy, have been widely used in autoimmune diseases. These therapies decrease autoantibody levels in patients and have shown favorable results. This review summarizes the mechanisms underlying these two B-cell targeted therapies and discusses their clinical applications and therapeutic potential in AE. Our research provides clinicians with more treatment options for AE patients whose conventional treatments are not effective.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Encefalite , Doença de Hashimoto , Humanos , Autoanticorpos , Anticorpos Monoclonais/uso terapêutico , Doenças Autoimunes do Sistema Nervoso/tratamento farmacológico
2.
STAR Protoc ; 5(2): 103019, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38635394

RESUMO

In vitro cell culture serves as an efficient system for studying animal cell behavior in a controlled setting. Here, we present a 3D culture model for forming ruminant adipose organoids using stromal vascular fraction cells. We describe steps for forming cell spheroids and growing them on a Matrigel-coated surface. We then detail procedures for inducing organoids to undergo angiogenesis and adipogenesis followed by capillary sprouting. This protocol can be utilized to study the interaction between blood vessels and adipocytes. For complete details on the use and execution of this protocol, please refer to Yu et al.1.

3.
Gen Physiol Biophys ; 43(2): 85-102, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38477602

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide. Chronic activation of endoplasmic reticulum stress (ERS) in hepatocytes may promote the development of NAFLD, yet endoplasmic reticulum stress-related genes (ERSGs) have not been studied in NAFLD. Our aim is to study the relationship between ERSGs and the immune microenvironment of NAFLD patients and to construct predictive models. We screened 48 endoplasmic reticulum stress-related differentially expressed genes (ERSR-DEGs) using data from two GEO datasets and the GeneCards database. Enrichment analysis revealed that ERSR-DEGs are closely associated with immune-related pathways and functions. The immune infiltration profile of NAFLD was obtained by single sample gene set enrichment analysis (ssGSEA). There were significant differences in immune cell infiltration and immune function between NAFLD group and control group. Using 113 NAFLD samples, we explored two molecular clusters based on ERSR-DEGs. A five-gene SVM model was selected as the best machine learning model, and a nomogram based on five-gene SVM model showed good predictive efficiency. The mRNA expression levels of POR, PPP1R15A, FOS and FAS were significantly different between NAFLD mice and healthy mice. In conclusion, ERS is closely associated with the development of NAFLD. We established a promising and SVM-based predictive model to assess the risk of disease in patients with ERS subtypes and NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse do Retículo Endoplasmático/genética , Hepatócitos
4.
Colloids Surf B Biointerfaces ; 235: 113774, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309154

RESUMO

This study presents the development of a sensitive and simple enhanced ratiometric fluorescence sensing platform in the consist of CdTe quantum dots (QDs), carbon dots (CDs), and hepatitis B core antibody labeled with horseradish peroxidase (HBcAb-HRP) for the visual analysis of H2O2 and glucose. The sulfur atoms in HBcAb-HRP have a strong affinity for Cd(II), which effectively enhances the fluorescence intensity of the CdTe QDs due to the generation of more radiative centers at the CdTe/Cd-SR complex. In the presence of H2O2, the Cd-S bonds are oxidized to form disulfide products and results in linear fluorescence quenching, while CDs maintain stable. Becasue glucose can be converted into H2O2 with the aid of glucose oxidase, this sensing platform can also be used for analyzing glucose. The detection limits for H2O2 and glucose are 2.9 µmol L-1 with RSD of 2.6% and 1.6 µmol L-1 with RSD of 2.4% respectively. In addition, under UV lamp irradiation, the orange-yellow CdTe QDs gradually quench with increasing H2O2 and glucose, while the blue CDs remain unchanged. A color change from orange-yellow to blue enables a visual semi-quantitative determination of H2O2 in commercial contact lens solution and glucose in human serum without any pretreatment. Thus, this CdTe QDs/CDs ratiometric sensing platform has significant potential for the rapid analysis of H2O2 and glucose in actual application.


Assuntos
Compostos de Cádmio , Pontos Quânticos , Humanos , Peróxido de Hidrogênio/química , Pontos Quânticos/química , Glucose/química , Carbono , Compostos de Cádmio/química , Telúrio/química , Anticorpos Anti-Hepatite B , Peroxidase do Rábano Silvestre/química , Corantes Fluorescentes/química
5.
Bioresour Technol ; 395: 130325, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38228219

RESUMO

Herein, three enzymes (cellulase, ß-glucosidase, and pectinase) with synergistic effects were co-immobilized on the Eudragit L-100, and the recovery of co-immobilized enzymes from solid substrates were achieved through the reversible and soluble property of the carrier. The optimization of enzyme ratio overcomed the problem of inappropriate enzyme activity ratio caused by different immobilization efficiencies among enzymes during the preparation process of co-immobilized enzymes. The co-immobilized enzymes were utilized to catalytically hydrolyze cellulose from corn straw into glucose, achieving a cellulose conversion rate of 74.45% under conditions optimized for their enzymatic characteristics and hydrolytic reaction conditions. As a result of the reversibility and solubility of the carrier, the co-immobilized enzymes were recovered from the solid substrate after five cycles, retaining 54.67% of the enzyme activity. The aim of this study is to investigate the potential of co-immobilizing multiple enzymes onto the Eudragit L-100 carrier for the synergistic degradation of straw cellulose.


Assuntos
Celulase , Celulose , Celulose/metabolismo , Zea mays/metabolismo , Enzimas Imobilizadas/metabolismo , Ácidos Polimetacrílicos , Celulase/metabolismo , Hidrólise
6.
Int Immunopharmacol ; 128: 111552, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38280335

RESUMO

Colonic mucosal defect constitutes the major reason of recurrence and deterioration of ulcerative colitis (UC), and mucosal healing has become the therapeutic endpoint of UC. Unfortunately, specific promoter of mucosal healing is still absent. Our previous researches demonstrated that arctigenin could alleviate colitis symptoms in mice, but whether it has a positive impact on colonic mucosal healing remains unclear. This study explores whether and how arctigenin promotes mucosal healing. Orally administered arctigenin was shown to alleviate colitis in mice primarily by enhancing mucosal healing. In vitro, arctigenin was shown to promote the wound healing by accelerating colonic epithelial cell migration but not proliferation. Acceleration of the focal adhesion turnover, especially assembly, is crucial for arctigenin promoting the cell migration. Arctigenin was able to activate focal adhesion kinase (FAK) in colonic epithelial cells through directly binding with Tyr251 site of FAK, as evidenced by surface plasmon resonance assay and site-directed mutagenesis experiment. In the colonic epithelial cells of UC patients and colitis mice, FAK activation was significantly down-regulated compared with the controls. Arctigenin promoted colonic epithelial cell migration and mucosal healing in dextran sulphate sodium (DSS)-induced colitis mice dependent on activating FAK, as confirmed by combined use with FAK inhibitor. In summary, arctigenin can directly promote mucosal healing in colitis mice through facilitating focal adhesion turnover, especially assembly, and consequent migration of epithelial cells via targeting FAK. Arctigenin may be developed as a mucosal healing promoter, and FAK is a potential therapeutic target for UC and other mucosal defect-related diseases.


Assuntos
Colite Ulcerativa , Colite , Furanos , Lignanas , Humanos , Camundongos , Animais , Colite Ulcerativa/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/uso terapêutico , Adesões Focais/metabolismo , Colite/induzido quimicamente , Movimento Celular , Cicatrização , Células Epiteliais/metabolismo , Mucosa Intestinal/metabolismo , Sulfato de Dextrana , Camundongos Endogâmicos C57BL
7.
Sci Rep ; 14(1): 1104, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212603

RESUMO

The drilling pressure relief technology is an effective way to reduce the accumulation of elastic energy in the tunnel envelope, which can reduce the risk of regional ground pressure occurrence. However, there is a lack of theoretical guidance on which drilling parameter has the greatest degree of influence on the effectiveness of pressure relief. The uniaxial compression tests were conducted to study the relationships between drilling parameters (the diameter, depth, and spacing) and the mechanical properties and deformation modulus of specimens. The results show that: (1) The drilling diameter (DDR) and drilling depth (DDH) of single-hole specimens negatively correlate with the peak-failure strength and deformation modulus, while the drilling spacing (DS) of double-hole specimens positively correlates with the peak-failure strength and deformation modulus. It shows that the borehole diameter has a more significant effect on the decompression effect. (2) With the help of the Grey Relational Analysis, the factors affecting the peak-failure strength and deformation modulus of the drilled specimens were ranked in significance. From the largest to the smallest, they are DDR, followed by DDH and DS. (3) The role of the pressure relief mechanism is to transfer the high stress in the shallow part of the roadway to the deep part, reduce the peak strength of destruction and deformation modulus of the peripheral rock in the drilled section, so that the characteristics of the mechanical behavior of the rock are significantly weakened, and the range of the area of the drilled hole decompression is enlarged. During the loading of the borehole, the borehole stress field dominates in the early stage, and cracking starts near the borehole along the direction perpendicular to the direction of maximum principal stress (horizontal direction). In the later stage, the maximum principal stress field dominates and vertical cracks with large widths appear. During crack expansion, the plastic energy dissipation effect is enhanced and the deep impact conduction path is weakened, thus protecting the roadway. This study determined the significance of the pressure relief effect of different drilling parameters, which can guide reasonable modifications of drilling parameters in the field.

8.
J Cell Mol Med ; 28(3): e18091, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38169083

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a major chronic liver disease worldwide. Cuproptosis has recently been reported as a form of cell death that appears to drive the progression of a variety of diseases. This study aimed to explore cuproptosis-related molecular clusters and construct a prediction model. The gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. The associations between molecular clusters of cuproptosis-related genes and immune cell infiltration were investigated using 50 NAFLD samples. Furthermore, cluster-specific differentially expressed genes were identified by the WGCNA algorithm. External datasets were used to verify and screen feature genes, and nomograms, calibration curves and decision curve analysis (DCA) were performed to verify the performance of the prediction model. Finally, a NAFLD-diet mouse model was constructed to further verify the predictive analysis, thus providing new insights into the prediction of NAFLD clusters and risks. The role of cuproptosis in the development of non-alcoholic fatty liver disease and immune cell infiltration was explored. Non-alcoholic fatty liver disease was divided into two cuproptosis-related molecular clusters by unsupervised clustering. Three characteristic genes (ENO3, SLC16A1 and LEPR) were selected by machine learning and external data set validation. In addition, the accuracy of the nomogram, calibration curve and decision curve analysis in predicting NAFLD clusters was also verified. Further animal and cell experiments confirmed the difference in their expression in the NAFLD mouse model and Mouse hepatocyte cell line. The present study explored the relationship between non-alcoholic fatty liver disease and cuproptosis, providing new ideas and targets for individual treatment of the disease.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Algoritmos , Calibragem , Morte Celular , Linhagem Celular , Modelos Animais de Doenças , Apoptose
9.
Toxicology ; 502: 153719, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38181850

RESUMO

Per- and polyfluoroalkyl substances (PFASs), a group of synthetic chemicals that were once widely used for industrial purposes and in consumer products, are widely found in the environment and in human blood due to their extraordinary resistance to degradation. Once inside the body, PFASs can activate nuclear receptors such as PPARα and CAR. The present study aimed to investigate the impact of perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) on liver structure and functions, as well as bile acid homeostasis in mice. A single administration of 0.1 mmole/kg of PFDA, not PFOA, elevated serum ALT and bilirubin levels and caused cholestasis in WT mice. PFDA increased total and various bile acid species in serum but decreased them in the liver. Furthermore, in mouse livers, PFDA, not PFOA, down-regulated mRNA expression of uptake transporters (Ntcp, Oatp1a1, 1a4, 1b2, and 2b1) but induced efflux transporters (Bcrp, Mdr2, and Mrp2-4). In addition, PFDA, not PFOA, decreased Cyp7a1, 7b1, 8b1, and 27a1 mRNA expression in mouse livers with concomitant hepatic accumulation of cholesterol. In contrast, in PPARα-null mice, PFDA did not increase serum ALT, bilirubin, or total bile acids, but produced prominent hepatosteatosis; and the observed PFDA-induced expression changes of transporters and Cyps in WT mice were largely attenuated or abolished. In CAR-null mice, the observed PFDA-induced bile acid alterations in WT mice were mostly sustained. These results indicate that, at the dose employed, PFDA has more negative effects than PFOA on liver function. PPARα appears to play a major role in mediating most of PFDA-induced effects, which were absent or attenuated in PPARα-null mice. Lack of PPARα, however, exacerbated hepatic steatosis. Our findings indicate separated roles of PPARα in mediating the adaptive responses to PFDA: protective against hepatosteatosis but exacerbating cholestasis.


Assuntos
Caprilatos , Colestase , Ácidos Decanoicos , Fluorocarbonos , Humanos , Camundongos , Animais , Ácidos e Sais Biliares/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Proteínas de Neoplasias , Fígado , Fluorocarbonos/metabolismo , Camundongos Knockout , Bilirrubina/toxicidade , Bilirrubina/metabolismo , RNA Mensageiro/metabolismo
10.
Sci Rep ; 13(1): 18676, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907527

RESUMO

To study the effect of mining dynamic response characteristics on the footwall working face of the normal fault under the influence of the gob area, theoretical research, indoor experiment, and numerical simulation are adopted to analyze the stress manifestation characteristics, overburden movement, and energy evolution characteristics during the process of mining. The results show that: (1) In the process of mining toward the fault, the working face shows the change characteristics of "stable-activation mutation-final stability". At 20 m from the fault, the arch structure of the working face was damaged, fissures appeared near the high fault fracture zone, and the displacement of the overburden rock increased significantly; (2) the maximum value was reached at 4-8 m from the coal wall, and the superposition of tectonic stress and mining stress led to the concentration of the stress and energy accumulating on the top plate near the fault, and the data close to the gob area were even larger; (3) If the plastic damage zone of the high-level rock layer on the hanging wall and footwall of the fault appears to have a wide range of penetration, and the area formed between the shear displacement curve of the fault plane and the X-axis appears to have a significant enhancement, it is considered that the fault has been activated; (4) The size of the coal pillar of the fault is determined to be 40 m, and combined with the pressure unloading technique of the variable-diameter drilling hole, the validation is carried out through the micro-vibration monitoring, and the results of which can be used as a reference for the safety of the working face under similar conditions.

11.
Blood Sci ; 5(4): 221-236, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37941914

RESUMO

Multiple myeloma (MM) is a malignant neoplasm characterized by clonal proliferation of abnormal plasma cells. In many countries, it ranks as the second most prevalent malignant neoplasm of the hematopoietic system. Although treatment methods for MM have been continuously improved and the survival of patients has been dramatically prolonged, MM remains an incurable disease with a high probability of recurrence. As such, there are still many challenges to be addressed. One promising approach is single-cell RNA sequencing (scRNA-seq), which can elucidate the transcriptome heterogeneity of individual cells and reveal previously unknown cell types or states in complex tissues. In this review, we outlined the experimental workflow of scRNA-seq in MM, listed some commonly used scRNA-seq platforms and analytical tools. In addition, with the advent of scRNA-seq, many studies have made new progress in the key molecular mechanisms during MM clonal evolution, cell interactions and molecular regulation in the microenvironment, and drug resistance mechanisms in target therapy. We summarized the main findings and sequencing platforms for applying scRNA-seq to MM research and proposed broad directions for targeted therapies based on these findings.

12.
Pediatrics ; 152(6)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38018230

RESUMO

OBJECTIVE: To investigate the potential association between preterm birth and infantile appendicitis. METHODS: We conducted a retrospective, multicenter, matched case-control study. This study included consecutive patients <1 year of age with surgery- or autopsy-confirmed appendicitis, admitted between December 2007 and May 2023. For each case, 10 healthy infants were randomly selected and matched by age. Infants were categorized as neonates (0 to 28 days) or older infants (>28 days and <1 year). RESULTS: The study included 106 infants diagnosed with appendicitis (median age 2.4 months) and 1060 age-matched healthy controls. In the univariate analysis, preterm birth was significantly associated with the development of appendicitis within the first year of life (odds ratio [OR], 4.23; 95% confidence interval [CI], 2.67-6.70). Other factors associated with a higher risk of infantile appendicitis included being male (OR, 1.91; 95%CI, 1.25-2.94), weight-for-age z-score (OR, 0.72; 95%CI, 0.64-0.81), and exclusively fed on formula (OR, 2.95; 95%CI, 1.77-4.91). In multivariable analyses, preterm remained significantly associated with appendicitis (adjusted OR, 3.32; 95%CI, 1.76-6.24). Subgroup analysis revealed that a preterm birth history increased the risk of appendicitis in both neonates (adjusted OR, 4.56; 95%CI, 2.14-9.71) and older infants (adjusted OR, 3.63; 95%CI, 1.72-7.65). However, preterm did not significantly influence the incidence of appendiceal perforation. CONCLUSIONS: Preterm infants have an increased risk of appendicitis during the first year of life. A preterm birth history may help improve the timely diagnosis of infantile appendicitis.


Assuntos
Apendicite , Nascimento Prematuro , Lactente , Feminino , Recém-Nascido , Humanos , Masculino , Recém-Nascido Prematuro , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Apendicite/diagnóstico , Apendicite/epidemiologia , Apendicite/cirurgia , Estudos de Casos e Controles
13.
Heliyon ; 9(11): e22083, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38034714

RESUMO

Background: The increasing evidence suggests that necroptosis mediates many behaviors of tumors, as well as the regulation of the tumor microenvironment. Long non-coding RNAs (lncRNAs) are involved in a variety of regulatory processes during tumor development and are significantly associated with patient prognosis. It suggests that necroptosis-related lncRNAs (NRlncRNAs) may serve as biomarkers for the prognosis of hepatocellular carcinoma (HCC). Methods: lncRNA expression profiles of HCC were obtained from TCGA database. LncRNAs associated with necroptosis were extracted using correlation analysis. Prognostic models were constructed based on least absolute shrinkage and selection operator algorithm (LASSO) and multivariate Cox regression analysis. The differences of tumor microenvironment between high-risk and low-risk groups were further analyzed. Single-cell RNA sequencing data of HCC was performed to assess the enrichment of necroptosis-related genes in immune cell subsets. Finally, real-time RT-PCR was used to detect the prognosis-related lncRNAs expression in different HCC cell lines. Results: We constructed a prognostic signature based on 8 NRlncRNAs, which also showed good predictive accuracy. The model showed that the prognosis of patients with high-risk score was significantly worse than that of patients with low-risk score (P < 0.05). Combined with the clinical characteristics and risk score of HCC, Nomogram was drawn for reference in clinical practice. In addition, immune cell infiltration analysis and single cell RNA sequencing analysis showed that a low level of immune infiltration was observed in patients at high risk and that there was a significant correlation between NRlncRNAs and macrophages. The results of RT-qPCR also showed that 8 necroptosis-related lncRNAs were highly expressed in HCC cell lines and human liver cancer tissues. Conclusion: This prognostic signature based on the necroptosis-related lncRNAs may provide meaningful clinical insights for the prognosis and immunotherapy responses in patients with HCC.

14.
Anal Chim Acta ; 1279: 341846, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37827657

RESUMO

BACKGROUND: Silver nanoparticles (Ag NPs) are extensively used in various applications, but their reactivity leads to oxidative dissolution into Ag(I). When dealing with real samples involving Ag NPs, it is inevitable to encounter situations where both Ag NPs and Ag(I) coexist. Single particle-inductively coupled plasma mass spectrometry (SP-ICP-MS) is a valuable technique for nanoparticle size characterization. However, the presence of coexisting dissolved ions strongly interferes with the accuracy of particle size analysis using SP-ICP-MS. Therefore, it is crucial to develop a reliable separation analysis method to accurately measure both Ag NPs and Ag(I). RESULTS: In this study, we synthesized a silver ion-imprinted magnetic adsorbent with high adsorption capacity (149 mg g-1) and rapid adsorption kinetics (30 min) at both µg L-1 and mg L-1 concentration. The adsorbent selectively adsorbs Ag(I) at pH 7 while hardly adsorbing Ag NPs. It is reusable for more than 5 cycles after regeneration. Using this magnetic adsorbent prior to SP-ICP-MS, we accurately determined the sizes of standard Ag NPs in agreement with the size determined by transmission electron microscopy. The detection limit of particle size and number concentrations of Ag NPs was 12.6 nm and 6.3 × 105 particles L-1. Moreover, we successfully applied the developed method to analyze Ag(I) and Ag NPs in antibacterial gel extracts and validated its accuracy through acid digestion-ICP-MS, TEM, and spiking experiments. SIGNIFICANCE AND NOVELTY: Direct SP-ICP-MS analysis in the presence of Ag(I) led to a high baseline, obscuring signals from smaller Ag NPs. Our method of selectively removing Ag(I) substantially improves the accuracy of Ag NPs detection via SP-ICP-MS in the antibacterial gel extracts (e.g. from 48.26 to 35.67 nm). Compared to other approaches used in SP-ICP-MS, our method has a higher adsorption capacity, allowing for better tolerance of coexisting Ag(I).


Assuntos
Nanopartículas Metálicas , Prata , Prata/química , Nanopartículas Metálicas/química , Análise Espectral , Íons , Tamanho da Partícula , Fenômenos Magnéticos
15.
Front Genet ; 14: 1251999, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37745847

RESUMO

Objective: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the world, and its pathogenesis is not fully understood. Disulfidptosis is the most recently reported form of cell death and may be associated with NAFLD progression. Our study aimed to explore the molecular clusters associated with disulfidptosis in NAFLD and to construct a predictive model. Methods: First, we analyzed the expression profile of the disulfidptosis regulators and immune characteristics in NAFLD. Using 104 NAFLD samples, we investigated molecular clusters based on differentially expressed disulfidptosis-related genes, along with the related immune cell infiltration. Cluster-specific differentially expressed genes were then identified by using the WGCNA method. We also evaluated the performance of four machine learning models before choosing the optimal machine model for diagnosis. Nomogram, calibration curves, decision curve analysis, and external datasets were used to confirm the prediction effectiveness. Finally, the expression levels of the biomarkers were assessed in a mouse model of a high-fat diet. Results: Two differentially expressed DRGs were identified between healthy and NAFLD patients. We revealed the expression profile of DRGs in NAFLD and the correlation with 22 immune cells. In NAFLD, two clusters of molecules connected to disulfidptosis were defined. Significant immunological heterogeneity was shown by immune infiltration analysis among the various clusters. A significant amount of immunological infiltration was seen in Cluster 1. Functional analysis revealed that Cluster 1 differentially expressed genes were strongly linked to energy metabolism and immune control. The highest discriminatory performance was demonstrated by the SVM model, which had a higher area under the curve, relatively small residual and root mean square errors. Nomograms, calibration curves, and decision curve analyses were used to show how accurate the prediction of NAFLD was. Further analysis revealed that the expression of three model-related genes was significantly associated with the level of multiple immune cells. In animal experiments, the expression trends of DDO, FRK and TMEM19 were consistent with the results of bioinformatics analysis. Conclusion: This study systematically elucidated the complex relationship between disulfidptosis and NAFLD and developed a promising predictive model to assess the risk of disease in patients with disulfidptosis subtypes and NAFLD.

16.
Int J Biol Macromol ; 253(Pt 4): 127025, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37769783

RESUMO

CRISPR/Cas-mediated genome-editing technology has accelerated the development of the life sciences. Prime editing has raised genome editing to a new level because it allows for all 12 types of base substitutions, targeted insertions and deletions, large DNA fragment integration, and even combinations of these edits without generating DNA double-strand breaks. This versatile and game-changing technology has successfully been applied to human cells and plants, and it currently plays important roles in basic research, gene therapy, and crop breeding. Although prime editing has substantially expanded the range of possibilities for genome editing, its efficiency requires improvement. In this review, we briefly introduce prime editing and highlight recent optimizations that have improved the efficiency of prime editors. We also describe how the dual-pegRNA strategy has expanded current editing capabilities, and we summarize the potential of prime editing in treating mammalian diseases and improving crop breeding. Finally, we discuss the limitations of current prime editors and future prospects for optimizing these editors.


Assuntos
Sistemas CRISPR-Cas , Melhoramento Vegetal , Animais , Humanos , Sistemas CRISPR-Cas/genética , Edição de Genes , Plantas/genética , DNA , Mamíferos/genética
17.
ACS Nano ; 17(12): 11583-11592, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37317992

RESUMO

Using graphene as a tunable optical material enables a series of optical devices such as switchable radar absorbers, variable infrared emissivity surfaces, or visible electrochromic devices. These devices rely on controlling the charge density on graphene with electrostatic gating or intercalation. In this paper, we studied the effect of ionic liquid intercalation on the long-term performance of optoelectronic devices operating within a broad infrared wavelength range. Our spectroscopic and thermal characterization results reveal the key limiting factors for the intercalation process and the performance of the infrared devices, such as the electrolyte ion-size asymmetry and charge distribution scheme and the effects of oxygen. Our results provide insight for the limiting mechanism for graphene applications in infrared thermal management and tunable heat signature control.

18.
Proc Natl Acad Sci U S A ; 120(20): e2220725120, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37155857

RESUMO

Dissimilatory sulfate reduction (DSR) mediated by sulfate-reducing microorganisms (SRMs) plays a pivotal role in global sulfur, carbon, oxygen, and iron cycles since at least 3.5 billion y ago. The canonical DSR pathway is believed to be sulfate reduction to sulfide. Herein, we report a DSR pathway in phylogenetically diverse SRMs through which zero-valent sulfur (ZVS) is directly generated. We identified that approximately 9% of sulfate reduction was directed toward ZVS with S8 as a predominant product, and the ratio of sulfate-to-ZVS could be changed with SRMs' growth conditions, particularly the medium salinity. Further coculturing experiments and metadata analyses revealed that DSR-derived ZVS supported the growth of various ZVS-metabolizing microorganisms, highlighting this pathway as an essential component of the sulfur biogeochemical cycle.


Assuntos
Sulfatos , Enxofre , Sulfatos/metabolismo , Oxirredução , Enxofre/metabolismo , Sulfetos/metabolismo , Óxidos de Enxofre
19.
Nanomicro Lett ; 15(1): 64, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36899127

RESUMO

Solar-driven interfacial evaporation is an emerging technology for water desalination. Generally, double-layered structure with separate surface wettability properties is usually employed for evaporator construction. However, creating materials with tunable properties is a great challenge because the wettability of existing materials is usually monotonous. Herein, we report vinyltrimethoxysilane as a single molecular unit to hybrid with bacterial cellulose (BC) fibrous network, which can be built into robust aerogel with entirely distinct wettability through controlling assembly pathways. Siloxane groups or carbon atoms are exposed on the surface of BC nanofibers, resulting in either superhydrophilic or superhydrophobic aerogels. With this special property, single component-modified aerogels could be integrated into a double-layered evaporator for water desalination. Under 1 sun, our evaporator achieves high water evaporation rates of 1.91 and 4.20 kg m-2 h-1 under laboratory and outdoor solar conditions, respectively. Moreover, this aerogel evaporator shows unprecedented lightweight, structural robustness, long-term stability under extreme conditions, and excellent salt-resistance, highlighting the advantages in synthesis of aerogel materials from the single molecular unit.

20.
Anim Nutr ; 12: 128-137, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36683879

RESUMO

The current study investigated the effects of intermittent feeding (IF) and fasting strategies at different times post-hatch on muscle growth and white striping (WS) breast development. In the first trial, 32 one-day-old Abor Acre broilers were fed ad libitum (AL) for 3 d post-hatch and then randomly allotted into 4 feeding strategies including AL, 1h-IF group (1 h IF, 4 times feeding/d, 1 h each time), 1.5h-IF (1.5 h IF, 4 times feeding/d, 1.5 h each time), and fasting (1d acute fasting, 6 d free access to feed) groups and fed for 7 d. Although angiogenic genes including VEGFA, VEGFR1, and VEGFR2, and myogenic genes including MYOG and MYOD were upregulated (P < 0.05), the breast muscle satellite cell (SC) number and PAX7, MYF5 expression were decreased by the IF strategies (P < 0.05). One-day fasting at 6 d of age also upregulated angiogenic genes and MYOD expression (P < 0.05), downregulated MYF5 expression (P < 0.05), but did not change SC number (P > 0.05). In the second trial, 384 one-day-old birds were fed AL for 1 wk and then randomly allotted to the above 4 feeding strategies starting at 8 d of age until 42 d of age. Similarly, IF and fasting strategies upregulated the expression of angiogenic and myogenic genes (P < 0.05). Both 1h-IF and 1.5h-IF increased breast muscle SC number (P < 0.05). At slaughter, breast muscle fiber diameter of 1.5h-IF was smaller but the SC number was larger than that of the birds fed AL (P < 0.05). The IF and fasting strategies prevented WS development, and reduced breast WS scores and triglyceride content (P < 0.05) without changing the body weight (P > 0.05). Fasting and 1h-IF reduced the expression of adipogenic genes ZNF423 and PDGFRα (P < 0.05). Moreover, IF and fasting strategies reduced fibrosis in breast muscle and reduced skeletal muscle-specific E3 ubiquitin ligases (TRIM63 and MAFBX) (P < 0.05). Fasting significantly reduced CASPASE-3 in breast muscle (P < 0.05). In conclusion, IF starting in the first week decreases SC number. Compared to AL, IF or fasting promotes muscular angiogenesis, increases SC number, prevents muscle degeneration, and prevents the development of WS without impairing the growth performance of broiler chickens.

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