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1.
Artigo em Inglês | MEDLINE | ID: mdl-38591127

RESUMO

Sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) is a widely expressed membrane glycoprotein that acts as an important modulator of lipid metabolism and inflammatory stress. N-glycosylation of SCAP has been suggested to modulate cancer development, but its role in NASH is poorly understood. In this study, the N-glycosylation of SCAP was analyzed by using sequential trypsin proteolysis and glycosidase treatment. The liver cell lines expressing wild-type and N-glycosylation sites mutated SCAP were constructed to investigate the N-glycosylation role of SCAP in regulating inflammation and lipid accumulation as well as the underlying mechanisms. The hepatic SCAP protein levels were significantly increased in C57BL/6J mice fed with western diet and sweet water (WD+SW) and diabetic db/db mice, which exhibited typical liver steatosis and inflammation. In vitro, the enhanced N-glycosylation increased the protein stability of SCAP and hence increased its total protein levels, while the ablation of N-glycosylation significantly decreased SCAP protein stability and alleviated lipid accumulation and inflammation in hepatic cell lines. Mechanistically, the presence of SCAP N-glycosylation increased not only the SREBP1-mediated acetyl-CoA synthetase 2 (ACSS2) transcription but also the AMPK-mediated S659 phosphorylation of ACCS2 protein, causing the enhanced ACSS2 levels in nucleus and hence increasing the histone H3K27 acetylation (H3K27ac), which is a key epigenetic modification associated with NASH. Modulating ACSS2 expression or its location in cytoplasm abolished the effects of SCAP N-glycosylation on H3K27ac and lipid accumulation and inflammation. In conclusion, SCAP N-glycosylation aggravates inflammation and lipid accumulation through enhancing ACSS2-mediated H3K27ac in hepatocytes.

2.
J Agric Food Chem ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557018

RESUMO

In this study, in silico analysis and peptidomics were performed to examine the generation mechanism of the umami taste of fermented broad bean paste (FBBP). Based on the information from peptidomics, a total of 470 free peptides were identified from FBBP, most of which were increased after fermentation. Additionally, the increase of the content of umami peptides, organic acids, and amino acids during fermentation contributed to the perception of umami taste in FBBP. Molecule docking results inferred that these umami molecules were easy to connect with Ser, Glu, His, and Gln in the T1R3 subunit through hydrogen bonds and electrostatic interaction force. The binding sites His145, Gln389, and Glu301 particularly contributed to the formation of the ligand-receptor complexes. The aromatic interaction, hydrogen bond, hydrophilicity, and solvent-accessible surface (SAS) played key roles in the receptor-peptide interaction. Sensory evaluation and electronic tongue results showed that EDEDE, DLSESV, SNGDDE, DETL, CDLSD, and TDEE screened from FBBP had umami characteristics and umami-enhancing effects (umami threshold values ranging from 0.131 to 0.394 mmol/L). This work provides new insight into the rapid and efficient screening of novel umami peptides and a deeper understanding of the taste mechanisms of umami molecules from FBBP.

3.
Medicine (Baltimore) ; 103(17): e37922, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669380

RESUMO

RATIONALE: Immunoglobulin G4-related disease (IgG4-RD) can involve various organs throughout the body, primarily manifesting as endocrine dysfunction, visual impairment, jaundice, and limited sexual function. IgG4-related autoimmune pancreatitis is triggered by autoimmune reactions and characterized by structural changes in the pancreas and pancreatic ducts. The disease mainly affects middle-aged and elderly males, typically presenting as progressive painless jaundice and misdiagnosed as cholangiocarcinoma or pancreatic cancer. PATIENT CONCERNS: This study reports a 54-year-old male who consulted with different institutions multiple times due to diabetes, pancreatitis, elevated liver enzymes, and jaundice. DIAGNOSES: Magnetic resonance imaging revealed swollen head of the pancreas and atrophic tail. Liver and pancreatic tissue pathology showed IgG4 plasma cell infiltration, while liver biopsy indicated interface hepatitis, liver fibrosis, and pseudolobule formation, with no evidence of bile duct damage. INTERVENTIONS: Following hormone therapy, the patient's serum IgG4 levels and liver enzyme levels returned to normal. OUTCOMES: The disease relapsed 2 years after maintaining hormone therapy, and the patient underwent additional hormone-induced remission therapy combined with azathioprine. LESSONS: The purpose of this research report is to enhance the awareness and understanding of IgG4-RD, emphasizing the necessity for personalized treatment strategies that take into account its recurrence, associations, and imaging features. This report provides valuable insights and guidance for clinicians in managing and diagnosing patients with IgG4-RD.


Assuntos
Pancreatite Autoimune , Colangite Esclerosante , Doença Relacionada a Imunoglobulina G4 , Humanos , Masculino , Pessoa de Meia-Idade , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/imunologia , Pancreatite Autoimune/diagnóstico , Pancreatite Autoimune/imunologia , Pancreatite Autoimune/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/complicações , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Pâncreas/patologia , Pâncreas/diagnóstico por imagem
4.
Nat Commun ; 15(1): 1263, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341471

RESUMO

Metallic 2M or 1T'-phase transition metal dichalcogenides (TMDs) attract increasing interests owing to their fascinating physicochemical properties, such as superconductivity, optical nonlinearity, and enhanced electrochemical activity. However, these TMDs are metastable and tend to transform to the thermodynamically stable 2H phase. In this study, through systematic investigation and theoretical simulation of phase change of 2M WS2, we demonstrate that ultrathin 2M WS2 has significantly higher intrinsic thermal stabilities than the bulk counterparts. The 2M-to-2H phase transition temperature increases from 120 °C to 210 °C in the air as thickness of WS2 is reduced from bulk to bilayer. Monolayered 1T' WS2 can withstand temperatures up to 350 °C in the air before being oxidized, and up to 450 °C in argon atmosphere before transforming to 1H phase. The higher stability of thinner 2M WS2 is attributed to stiffened intralayer bonds, enhanced thermal conductivity and higher average barrier per layer during the layer(s)-by-layer(s) phase transition process. The observed high intrinsic phase stability can expand the practical applications of ultrathin 2M TMDs.

5.
Food Res Int ; 177: 113880, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38225117

RESUMO

Pixian Douban (PXDB) is a popular Chinese condiment for its distinctive flavor. Broad bean fermentation (Meju) is the most important process in the formation of flavor substances. Key flavors were analyzed qualitatively and quantitatively, and metagenomic technology was applied to study the microbial diversity during broad bean fermentation. In addition, the main metabolic pathways of key flavors were explored. Results indicated that Staphylococcus_gallinarum was the main microorganism in the microbial community, accounting for 39.13%, followed by Lactobacillus_agilis, accounting for 13.76%. Aspergillus_flavus was the fungus with the highest species abundance, accounting for 3.02%. The KEGG Pathway enrichment analysis showed that carbohydrate metabolism and amino acid metabolism were the main metabolic pathways. Glycoside hydrolase and glycosyltransferase genes were the most abundant, accounting for more than 70% of the total number of active enzyme genes. A total of 113 enzymes related to key flavors and 39 microorganisms corresponding to enzymes were annotated. And Staphylococcus_gallinarum, Lactobacillus_agilis, Weissella_confusa, Pediococcus_acidilactici, Staphylococcus_kloosii, Aspergillus_oryzae, and Aspergillus_flavus played a key role in the metabolic pathway. This study reveals the formation mechanism of key flavors in fermented broad bean, it is important for guiding the industrial production of PXDB and improving product quality.


Assuntos
Fabaceae , Lactobacillus , Microbiota , Vicia faba , Fabaceae/genética , Microbiota/genética , Metagenoma , Fermentação , Aspergillus flavus/genética
6.
AAPS J ; 26(1): 22, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291293

RESUMO

It is generally believed that bioavailability (F) calculated based on systemic concentration area under the curve (AUC) measurements cannot exceed 1.0, yet some published studies report this inconsistency. We teach and believe, based on differential equation derivations, that rate of absorption has no influence on measured systemic clearance following an oral dose, i.e., determined as available dose divided by AUC. Previously, it was thought that any difference in calculating F from urine data versus that from systemic concentration AUC data was due to the inability to accurately measure urine data. A PubMed literature search for drugs exhibiting F > 1.0 and studies for which F was measured using both AUC and urinary excretion dose-corrected analyses yielded data for 35 drugs. We show and explain, using Kirchhoff's Laws, that these universally held concepts concerning bioavailability may not be valid in all situations. Bioavailability, determined using systemic concentration measurements, for many drugs may be overestimated since AUC reflects not only systemic elimination but also absorption rate characteristics, which is most easily seen for renal clearance measures. Clearance of drug from the absorption site must be significantly greater than clearance following an iv bolus dose for F(AUC) to correctly correspond with F(urine). The primary purpose of this paper is to demonstrate that studies resulting in F > 1.0 and/or greater systemic vs urine bioavailability predictions may be accurate. Importantly, these explications have no significant impact on current regulatory guidance for bioequivalence testing, nor on the use of exposure (AUC) measures in making drug dosing decisions.


Assuntos
Preparações Farmacêuticas , Disponibilidade Biológica , Injeções Intravenosas , Área Sob a Curva , Administração Oral
7.
Sci China Life Sci ; 67(5): 1027-1034, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38280143

RESUMO

Protein-mediated chromatin interactions can be revealed by coupling proximity-based ligation with chromatin immunoprecipitation. However, these techniques require complex experimental procedures and millions of cells per experiment, which limits their widespread application in life science research. Here, we develop a novel method, Hi-Tag, that identifies high-resolution, long-range chromatin interactions through transposase tagmentation and chromatin proximity ligation (with a phosphorothioate-modified linker). Hi-Tag can be implemented using as few as 100,000 cells, involving simple experimental procedures that can be completed within 1.5 days. Meanwhile, Hi-Tag is capable of using its own data to identify the binding sites of specific proteins, based on which, it can acquire accurate interaction information. Our results suggest that Hi-Tag has great potential for advancing chromatin interaction studies, particularly in the context of limited cell availability.


Assuntos
Cromatina , Cromatina/metabolismo , Cromatina/genética , Humanos , Sítios de Ligação , Ligação Proteica , Transposases/metabolismo , Transposases/genética , Imunoprecipitação da Cromatina/métodos , Animais
8.
Cancer Sci ; 115(2): 477-489, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38081591

RESUMO

Inhibition of cholesterol de novo synthesis (DNS) by statins has controversial effects on the treatment of hepatocellular carcinoma (HCC). High fatty acid conditions have been reported to limit the effect of statins on metabolism diseases. Whether high fatty acid conditions interfere with the effect of statins on HCC remains unclear. Here, we reported that inhibiting cholesterol DNS with atorvastatin promoted the oncogenic capabilities of diethylnitrosamine (DEN) in mice fed high fatty acid diets (HFD). The combined analysis of metabolomics and transcriptomics revealed that arachidonic acid (AA) metabolism was the most significant changed pathway between mice with and without atorvastatin treatment. In vitro, in the presence of AA precursor linoleic acid (LA), atorvastatin promoted the proliferation and migration ability of HCC cell lines. However, in the absence of LA, these phenomena disappeared. TCGA and tissue microarray examination revealed that prostaglandin e synthase 2 (PTGES2), a key enzyme in AA metabolism, was associated with the poor outcome of HCC patients. Overexpression of PTGES2 promoted the proliferation and migration of HCC cell lines, and knockdown of PTGES2 inhibited the proliferation and migration of cells. Additionally, atorvastatin upregulated PTGES2 expression by enhancing Sterol-regulatory element binding protein 2 (SREBP2)-mediated transcription. Knockdown of PTGES2 reversed the proliferation and migration ability enhanced by atorvastatin. Overall, our study reveals that a high fatty acid background is one of the possible conditions limiting the application of statins in HCC, under which statins promote the progression of HCC by enhancing SREBP2-mediated PTGES2 transcription.


Assuntos
Carcinoma Hepatocelular , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Hepáticas , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ácidos Graxos/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Ácido Araquidônico/farmacologia , Prostaglandina-E Sintases/genética , Atorvastatina/farmacologia , Linhagem Celular Tumoral , Colesterol , Proliferação de Células
9.
Clin Cancer Res ; 30(2): 269-273, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-37676259

RESUMO

On October 21, 2022, the FDA approved tremelimumab (Imjudo) in combination with durvalumab for adult patients with unresectable hepatocellular carcinoma. The approval was based on the results from the HIMALAYA study, in which patients with unresectable hepatocellular carcinoma who were naïve to previous systemic treatment were randomly assigned to receive one of three study arms: tremelimumab in combination with durvalumab (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The primary objective of improvement in overall survival (OS) for tremelimumab in combination with durvalumab compared with sorafenib met statistical significance with a stratified HR of 0.78 [95% confidence interval (CI), 0.66-0.92; P = 0.0035]. The median OS was 16.4 months (95% CI, 14.2-19.6) with tremelimumab in combination with durvalumab and 13.8 months (95% CI, 12.3-16.1) with sorafenib. Adverse reactions occurring in ≥20% of patients receiving tremelimumab in combination with durvalumab were rash, fatigue, diarrhea, pruritus, musculoskeletal pain, and abdominal pain. The recommended tremelimumab dose for patients weighing 30 kg or more is 300 mg, i.v., as a single dose in combination with durvalumab 1,500 mg at cycle 1/day 1, followed by durvalumab 1,500 mg, i.v., every 4 weeks. For those weighing less than 30 kg, the recommended tremelimumab dose is 4 mg/kg, i.v., as a single dose in combination with durvalumab 20 mg/kg, i.v., followed by durvalumab 20 mg/kg, i.v., every 4 weeks.


Assuntos
Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/etiologia , Sorafenibe , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/etiologia
10.
Int J Mol Sci ; 24(23)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38068940

RESUMO

The principal difference between hydroponics and other substrate cultivation methods is the flowing liquid hydroponic cultivation substrate. Our previous studies have revealed that a suitable flowing environment of nutrient solution promoted root development and plant growth, while an excess flow environment was unfavorable for plants. To explain the thigmomorphogenetic response of excess flow-induced metabolic changes, six groups of lettuce (Lactuca sativa L.), including two flow conditions and three time periods, were grown. Compared with the plants without flow, the plants with flow showed decreased root fresh weight, total root length, root surface area, and root volume but increased average root diameter and root density. The roots with flow had more upregulated metabolites than those without flow, suggesting that the flow may trigger metabolic synthesis and activity. Seventy-nine common differential metabolites among six groups were screened, and enrichment analysis showed the most significant enrichment in the arginine biosynthesis pathway. Arginine was present in all the groups and exhibited greater concentrations in roots with flow than without flow. It can be speculated from the results that a high-flowing environment of nutrient solution promotes arginine synthesis, resulting in changes in root morphology. The findings provide insights on root thigmomorphogenesis affected by its growing conditions and help understand how plants respond to environmental mechanical forces.


Assuntos
Plantas , Hidroponia/métodos , Nutrientes , Arginina
11.
Nanomicro Lett ; 16(1): 51, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38099969

RESUMO

With the rapid development of portable electronics and electric road vehicles, high-energy-density batteries have been becoming front-burner issues. Traditionally, homogeneous electrolyte cannot simultaneously meet diametrically opposed demands of high-potential cathode and low-potential anode, which are essential for high-voltage batteries. Meanwhile, homogeneous electrolyte is difficult to achieve bi- or multi-functions to meet different requirements of electrodes. In comparison, the asymmetric electrolyte with bi- or multi-layer disparate components can satisfy distinct requirements by playing different roles of each electrolyte layer and meanwhile compensates weakness of individual electrolyte. Consequently, the asymmetric electrolyte can not only suppress by-product sedimentation and continuous electrolyte decomposition at the anode while preserving active substances at the cathode for high-voltage batteries with long cyclic lifespan. In this review, we comprehensively divide asymmetric electrolytes into three categories: decoupled liquid-state electrolytes, bi-phase solid/liquid electrolytes and decoupled asymmetric solid-state electrolytes. The design principles, reaction mechanism and mutual compatibility are also studied, respectively. Finally, we provide a comprehensive vision for the simplification of structure to reduce costs and increase device energy density, and the optimization of solvation structure at anolyte/catholyte interface to realize fast ion transport kinetics.

12.
Biochem Biophys Rep ; 35: 101533, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37664524

RESUMO

This study investigated the expression pattern of retinoblastoma binding protein 4 (RBBP4) gene in glioma and explored its associations with clinicopathologic characteristics and prognosis of patients. Data retrieved from the GEPIA, CGGA, HPA and TIMER databases were processed to analyze RBBP4 expression in glioma and investigate its relationship with clinicopathologic characteristics, tumor immune infiltration and prognosis in glioma patients. Immunohistochemistry was applied to determine the expression of RBBP4 protein in glioma tissue. Additionally, the Coexpedia database was visited to identify co-expressed genes for RBBP4 gene, while the Cytoscape software was run to visualize the enriched GO entries and KEGG pathways of these co-expressed genes. The expression levels of RBBP4 in lower-grade glioma (LGG) and glioblastoma (GBM) tissues were markedly elevated when compared to normal tissues (both p < 0.05). The up-regulation of RBBP4 expression was associated with an increase in WHO grade (II-IV), wild-type IDH, and 1p/19q non-codeletion (all p < 0.05). Multi-variate Cox regression analysis showed that both increased abundance of infiltrating macrophages and up-regulated RBBP4 expression independently predicted poor survival outcomes in LGG patients (both p < 0.05). Furthermore, RBBP4 expression exhibited significant positive correlations with the abundance of infiltrating B cell, CD8+ T cell, CD4+ T cell, macrophage, neutrophil, and dendritic cell in LGG (all p < 0.05). Functional enrichment analyses indicated that the co-expressed genes associated with RBBP4 were highly involved in pathways such as the p53 signaling pathway, cell cycle, DNA replication, glutathione metabolism, as well as biological processes including cell cycle process, DNA replication, and DNA repair. High levels of RBBP4 are predictive for the poor survival outcome of LGG patients. RBBP4 gene, therefore, is expected to be a potential biomarker for prognosis of LGG and a target for immunotherapy.

13.
Int J Mol Sci ; 24(17)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37686137

RESUMO

The Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes viral encephalitis in humans, pigs and other mammals across Asia and the Western Pacific. Genetic screening tools such as CRISPR screening, DNA sequencing and RNA interference have greatly improved our understanding of JEV replication and its potential antiviral approaches. However, information on exon and intron mutations associated with JEV replication is still scanty. CRISPR-Cas9-mediated cytosine base editing can efficiently generate C: G-to-T: A conversion in the genome of living cells. One intriguing application of base editing is to screen pivotal variants for gene function that is yet to be achieved in pigs. Here, we illustrate that CRISPR-Cas9-mediated cytosine base editor, known as AncBE4max, can be used for the functional analysis of calreticulin (CALR) variants. We conducted a CRISPR-Cas9-mediated cytosine base editing screen using 457 single guide RNAs (sgRNAs) against all exons and introns of CALR to identify loss-of-function variants involved in JEV replication. We unexpectedly uncovered that two enriched sgRNAs targeted the same site in intron-2 of the CALR gene. We found that mutating four consecutive G bases in the intron-2 of the CALR gene to four A bases significantly inhibited JEV replication. Thus, we established a CRISPR-Cas9-mediated cytosine-base-editing point mutation screening technique in pigs. Our results suggest that CRISPR-mediated base editing is a powerful tool for identifying the antiviral functions of variants in the coding and noncoding regions of the CALR gene.


Assuntos
Calreticulina , Vírus da Encefalite Japonesa (Espécie) , Vírus da Encefalite Japonesa (Subgrupo) , Animais , Humanos , Antivirais , Calreticulina/genética , Sistemas CRISPR-Cas/genética , Citosina , Vírus da Encefalite Japonesa (Espécie)/genética , Edição de Genes , Íntrons/genética , Mamíferos , Mutação , RNA Guia de Sistemas CRISPR-Cas , Suínos
14.
J Vis Exp ; (197)2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37590509

RESUMO

Tui Na or massage therapy alleviates symptoms related to intervertebral disc degeneration (IDD). However, precise, repeatable, standardized instructions for Tuina manipulation are lacking. This study establishes IDD model rabbits induced by fibrous ring puncture, creates targeted Tuina stimulation protocols at the acupuncture points in the lumbar region, and describes in detail the operation methods and requirements of kneading, pointing, and flicking. New Zealand male white rabbits (n = 15) were selected and randomly divided into a blank group, a model group, and a Tuina group. The rabbits in the model group and the Tuina group were molded by fibrous ring puncture; the rabbits in the model group were only immobilized on the operating table without treatment. In contrast, the Tuina group used the "8N/10N, 30 cycles/min" prescription for kneading, pointing, and flicking to perform the intervention, using tactile sensory aids to monitor and regulate the intensity of the Tuina operation. Imaging diagnosis and pathological tests were used to assess the effect of Tuina in rabbits, and the results showed improved imaging features and significantly lowered pathology scores of lumbar disc degeneration in the Tuina group compared to the model group (P < 0.01). Targeted Tuina in the lumbar region may be beneficial in the alleviation of lumbar disc degeneration, but further verification is needed. By regularly performing Tuina and recording the mechanical information involved enables reproducible manipulation prescriptions and helps to observe the basic features of the underlying mechanism of Tuina for IDD.


Assuntos
Terapia por Acupuntura , Degeneração do Disco Intervertebral , Animais , Masculino , Coelhos , Degeneração do Disco Intervertebral/terapia , Região Lombossacral , Massagem , Punção Espinal
15.
Small ; 19(28): e2207196, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37026435

RESUMO

The exploring of economical, high-efficiency, and stable bifunctional catalysts for hydrogen evolution and oxygen evolution reactions (HER/OER) is highly imperative for the development of electrolytic water. Herein, a 3D cross-linked carbon nanotube supported oxygen vacancy (Vo )-rich N-NiMoO4 /Ni heterostructure bifunctional water splitting catalyst (N-NiMoO4 /Ni/CNTs) is synthesized by hydrothermal-H2 calcination method. Physical characterization confirms that Vo -rich N-NiMoO4 /Ni nanoparticles with an average size of ≈19 nm are secondary aggregated on CNTs that form a hierarchical porous structure. The formation of Ni and NiMoO4 heterojunctions modify the electronic structure of N-NiMoO4 /Ni/CNTs. Benefiting from these properties, N-NiMoO4 /Ni/CNTs drives an impressive HER overpotential of only 46 mV and OER overpotential of 330 mV at 10 mA cm-2 , which also shows exceptional cycling stability, respectively. Furthermore, the as-assembled N-NiMoO4 /Ni/CNTs||N-NiMoO4 /Ni/CNTs electrolyzer reaches a cell voltage of 1.64 V at 10 mA cm-2 in alkaline solution. Operando Raman analysis reveals that surface reconstruction is essential for the improved catalytic activity. Density functional theory (DFT) calculations further demonstrate that the enhanced HER/OER performance should be attributed to the synergistic effect of Vo and heteostructure that improve the conductivity of N-NiMoO4 /Ni/CNTs and facilitatethe desorption of reaction intermediates.

16.
Leukemia ; 37(6): 1204-1215, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37095208

RESUMO

Mismatch repair (MMR) deficiency has been linked to thiopurine resistance and hypermutation in relapsed acute lymphoblastic leukemia (ALL). However, the repair mechanism of thiopurine-induced DNA damage in the absence of MMR remains unclear. Here, we provide evidence that DNA polymerase ß (POLB) of base excision repair (BER) pathway plays a critical role in the survival and thiopurine resistance of MMR-deficient ALL cells. In these aggressive resistant ALL cells, POLB depletion and its inhibitor oleanolic acid (OA) treatment result in synthetic lethality with MMR deficiency through increased cellular apurinic/apyrimidinic (AP) sites, DNA strand breaks and apoptosis. POLB depletion increases thiopurine sensitivities of resistant cells, and OA synergizes with thiopurine to kill these cells in ALL cell lines, patient-derived xenograft (PDX) cells and xenograft mouse models. Our findings suggest BER and POLB's roles in the process of repairing thiopurine-induced DNA damage in MMR-deficient ALL cells, and implicate their potentials as therapeutic targets against aggressive ALL progression.


Assuntos
DNA Polimerase beta , Leucemia-Linfoma Linfoblástico de Células Precursoras , Animais , Humanos , Camundongos , Dano ao DNA , DNA Polimerase beta/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Mutações Sintéticas Letais , Reparo de Erro de Pareamento de DNA/genética
17.
Zhen Ci Yan Jiu ; 48(2): 153-7, 2023 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-36858411

RESUMO

Acupuncture therapy has been widely used in clinical treatment of allergic rhinitis (AR), and can induce a positive therapeutic effect through multi-targets and multi-aspects. In recent 10 years, the research on the mechanisms of acupuncture in treating AR mainly focused on humoral immunity, cellular immunity, cell apoptosis, inflammatory mediators and factors, neuropeptides, etc. By regulating the level of immunoglobulin in the blood, acupuncture intervention can restore the relative balance of cellular immune response, reduce the accumulation of eosinophils and promote apoptosis, down-regulate the expression of related inflammatory mediators and factors, regulate the excitability of related nerves, modulate the release of neuropeptides and other ways to diminish the inflammatory reaction of nasal mucosa, and enhance the repair and protection of nasal mucosa, relieve the nasal symptoms at last. On the basis of the existing studies, the follow-up research should make use of the advantages of acupuncture intervention, refine the treatment process, and deeply explore the feasibility of acupuncture treatment of AR, further promote the combination of mechanism study and clinical practice, provide references for clinical application. Moreover, some shortcomings exist, for example, the unknown correlation between the therapeutic effect and duration of treatment, the unknown correlation between the effect of acupuncture and various targets, and disconnection between experimental research achievements and clinical application, etc.


Assuntos
Terapia por Acupuntura , Rinite Alérgica , Humanos , Mucosa Nasal , Inflamação , Apoptose
18.
Sensors (Basel) ; 23(3)2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36772587

RESUMO

The rapid development of the aviation industry has put forward higher and higher requirements for material properties, and the research on smart material structure has also received widespread attention. Smart materials (e.g., piezoelectric materials, shape memory materials, and giant magnetostrictive materials) have unique physical properties and excellent integration properties, and they perform well as sensors or actuators in the aviation industry, providing a solid material foundation for various intelligent applications in the aviation industry. As a popular smart material, piezoelectric materials have a large number of application research in structural health monitoring, energy harvest, vibration and noise control, damage control, and other fields. As a unique material with deformation ability, shape memory materials have their own outstanding performance in the field of shape control, low-shock release, vibration control, and impact absorption. At the same time, as a material to assist other structures, it also has important applications in the fields of sealing connection and structural self-healing. Giant magnetostrictive material is a representative advanced material, which has unique application advantages in guided wave monitoring, vibration control, energy harvest, and other directions. In addition, giant magnetostrictive materials themselves have high-resolution output, and there are many studies in the direction of high-precision actuators. Some smart materials are summarized and discussed in the above application directions, aiming at providing a reference for the initial development of follow-up related research.

20.
Food Sci Nutr ; 11(1): 408-417, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36655103

RESUMO

Tartary buckwheat (Fagopyrum tataricum) is rich in polysaccharides that can be utilized by the gut microbiota (GM) and provide several health benefits. However, the mechanisms underlying the action of these polysaccharides remain unclear to date. In this study, Tartary buckwheat polysaccharides (TBP) were purified, and five fractions were obtained. The composition of these fractions was determined using ion chromatography. Different TBP components were investigated regarding their probiotic effect on three species of Bifidobacteria and Lactobacillus rhamnosus. In addition, the effect of TBP on GM and short-chain fatty acids (SCFAs) was evaluated. Results showed that the probiotic effect of TBP fraction was dependent on their composition. The polysaccharides present in different fractions had specific probiotic effects. TBP-1.0, mainly composed of fucose, glucose, and d-galactose, exhibited the strongest proliferation effect on L. rhamnosus, while TBP-W, rich in glucose, d-galactose, and fructose, had the best promoting effect on Bifidobacterium longum and Bifidobacterium adolescentis growth. Furthermore, TBP-0.2, composed of d-galacturonic acid, d-galactose, xylose, and arabinose, exhibited its highest impact on Bifidobacterium breve growth. The composition of GM was significantly altered by adding TBP during fecal fermentation, with an increased relative abundance of Lactococcus, Phascolarctobacterium, Bacteroidetes, and Shigella. Simultaneously, the level of SCFA was also significantly increased by TBP. Our findings indicate that Tartary buckwheat can provide specific dietary polysaccharide sources to modulate and maintain GM diversity. They provide a basis for Tartary buckwheat commercial utilization for GM modulation.

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