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1.
Int J Biol Macromol ; : 134275, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39084445

RESUMO

Flame-retardant epoxy resins with tough, transparent, ultraviolet shielding, and low dielectric properties have fascinating prospects in electronic and electrical applications, but it is still challenging at present. In this work, a bio-based macromolecule was synthesized from vanillin (a lignin derivative), phenyl dichlorophosphate, 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO), and poly(propylene glycol) bis(2-aminopropyl ether). The bio-based macromolecule, namely, MFR, was designed and added to the epoxy resin (EP). The cured EP containing 15 wt% MFR (i.e., EP/MFR15) exhibits excellent flame retardancy with an Underwriter Laboratory 94 (UL-94) V-0 rating and a limiting oxygen index (LOI) of 29.2 %. Furthermore, the peak heat release rate (PHRR) and total heat release rate (THR) are drastically reduced by 59.5 % and 40.7 %, respectively. Meanwhile, EP/MFR15 shows 20.3 % and 43.8 % improvements in tensile strength and toughness, respectively. Moreover, MFR simultaneously endows EP with accessional ultraviolet shielding performance and low dielectric constant without sacrificing transparency. This work provides a promising strategy for fabricating a bio-based macromolecular flame retardant and preparing a high-performance EP composite with versatile properties.

2.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38984881

RESUMO

A rod pinch diode (RPD) is a feasible load configuration to generate a high-brightness, small-size hard x-ray radiation source. In this paper, the radiography performance of a wire-shorted low-impedance RPD on a compactly designed table-top driver (WRPD-1) is demonstrated for the first time. The driver consists of four high-power discharge branches connected in parallel, with each branch consisting of two metal-film capacitors and one multigap field-distortion switch in series. The four branches are triggered synchronously to generate a fast-rising current pulse: the inductance of the load section at the short circuit is ∼10 nH, and the short-circuit current amplitude is ∼325 kA at ±90 kV charging voltage, with a 10%-90% rise time of 110 ns. With a low-impedance RPD shorted by an 18-µm-diameter aluminum wire, a quasi-spherical x-ray focal spot with diameter <0.6 mm (width of the half-maximum grayscale) and a pulse duration of ∼25 ns (half-width of the radiation pulse) is obtained at ±70 kV charging voltage, and the imaging resolution excels 10 lp/mm under 1.56× magnification. According to the transmission-absorption x-ray spectrum estimation, the average emitted photon energy is ∼30 keV with a distinct peak in the 10-15 keV range that corresponds to the L-lines of tungsten, and the total energy of photons >10 keV reaches ∼1.16 J. The present results show that the device can serve well for the flash radiography diagnosis and potentially as an efficient light source for dynamic x-ray diffraction.

3.
Anim Nutr ; 17: 447-462, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38846720

RESUMO

This study aimed to investigate the application of cottonseed protein concentrate (CPC) in Chinese mitten crabs (Eriocheir sinensis). First, the apparent digestibility coefficient (ADC) of CPC, fish meal and soybean meal were compared in crabs (21.72 ± 0.33 g). The protein ADC of CPC was 90.42%, which was significantly higher than that of soybean meal (83.16%) (P < 0.05). The ADC of Phe, Cys and Glu of CPC were significantly higher than those of fish meal, while the ADC of Ile, Leu, Lys, Met, Thr and Ala of CPC were significantly lower (P < 0.05). Second, we investigated the effects of fish meal substitution by CPC on growth performance, free amino acid profile, and expression of genes related to nutrient metabolism in crabs. Six diets were formulated by replacing 0%, 15%, 30%, 45%, 60% and 75% fish meal with CPC, namely FM, CPC15, CPC30, CPC45, CPC60, and CPC75. A total of 630 crabs (1.68 ± 0.00 g) were randomly divided into 18 tanks (3 tanks per group) and fed 3 times daily for 9 weeks. Results showed that CPC75 group significantly reduced growth performance, feed conversion efficiency, and free Ile, Leu, Lys, Met, and Thr contents in muscle (P < 0.05). The contents of free amino acids (Arg, His, Ile, Leu, Lys, Met, Phe, Thr, Val, Ala, Cys, Glu, Gly, Ser and Tyr) in hepatopancreas decreased linearly with the increase of dietary CPC level (P < 0.05). The substitution of more than 45% fish meal with CPC significantly decreased the concentration of delicious amino acids (Ala, Glu and Gly) in hepatopancreas (P < 0.05), which might adversely affect crab flavor. The expression of genes related to antioxidant capacity, protein transport, TOR pathway and lipid metabolism was significantly downregulated by increasing dietary CPC level (P < 0.05). In conclusion, based on the quadratic regression analysis of FCR and PER, the optimal replacement levels of fish meal with CPC in crab diet containing 35% fish meal were 32.36% and 35.38%, respectively. It is recommended that Ile, Leu and Thr be supplemented in addition to Met and Lys in the application of CPC.

4.
ACS Appl Mater Interfaces ; 16(26): 33710-33722, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38906849

RESUMO

Li-N2 batteries are a promising platform for electrochemical energy storage, but their performance is limited by the low activity of the cathode catalysts. In this work, density functional theory was used to study the catalytic activity of the pristine M2C and oxygen-functionalized M2CO2 MXenes (M = Sc, Ti, and V) as cathodes for Li-N2 batteries. The calculated results suggest that the pristine M2C MXenes (M = Sc, Ti, and V) show high electrical conductivity due to the Fermi level crossing the metal 3d states. The stable adsorption of N2 occurs on M2C MXenes via a side-on model and strengthens gradually with decreasing metal atomic number. Furthermore, the kinetics of N2 dissociation can be significantly accelerated by the coadsorption of Li on M2C MXenes. However, adsorption and dissociation of N2 on the M2CO2 surfaces are too difficult to occur due to strong electrostatic repulsion. The Li-mediated nitrogen reduction reaction during discharge proceeds favorably via (N + N)* → (LiN + N)* → (LiN + LiN)* → (Li2N + LiN)* → (Li2N + Li2N)* → (Li3N + Li2N)* → (Li3N + Li3N)* to form two isolated Li3N* on M2C MXenes. The calculated charge-discharge overpotentials decrease in the order of Sc2C < Ti2C < V2C. Notably, the Sc2C MXene has great potential as a cathode catalyst for Li-N2 batteries because of its high electrical conductivity, strong N2 adsorption, favorable Li-mediated N2 dissociation, and ultralow discharging, charging, and total overpotentials (0.07, 0.06, and 0.13 V). This study offers a theoretical foundation for future research on Li-N2 batteries.

6.
Cell Death Discov ; 10(1): 243, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773075

RESUMO

Proteins are the keystone for the execution of various life activities, and the maintenance of protein normalization is crucial for organisms. Ubiquitination, as a post-transcriptional modification, is widely present in organisms, and it relies on the sophisticated ubiquitin-proteasome (UPS) system that controls protein quality and modulates protein lifespan. Deubiquitinases (DUBs) counteract ubiquitination and are essential for the maintenance of homeostasis. Ubiquitin specific peptidase 3 (USP3) is a member of the DUBs that has received increasing attention in recent years. USP3 is a novel chromatin modifier that tightly regulates the DNA damage response (DDR) and maintains genome integrity. Meanwhile, USP3 acts as a key regulator of inflammatory vesicles and sustains the normal operation of the innate immune system. In addition, USP3 is aberrantly expressed in a wide range of cancers, such as gastric cancer, glioblastoma and neuroblastoma, implicating that USP3 could be an effective target for targeted therapies. In this review, we retrace all the current researches of USP3, describe the structure of USP3, elucidate its functions in DNA damage, immune and inflammatory responses and the cell cycle, and summarize the important role of USP3 in multiple cancers and diseases.

7.
Behav Brain Res ; 469: 115021, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38692358

RESUMO

This study aims to investigate the brain networks engaged in the comprehension of indirect language, as well as the individual difference in this capacity. Specially, we aim to determine whether the difference is solely influenced by the difference in individuals' default network (DN)/language network or whether it also relies on the networks associated with processing of complex cognitive tasks, particularly the multiple demand network (MDN). Conversational indirectness scale (CIS) scores in the interpretation dimension were used as a behavioral indicator of the indirect comprehension tendency. Reading time difference between indirect replies and direct replies collected through a self-paced reading experiment was deemed as a behavioral indicator of comprehension speed of indirect replies comprehension. The two behavioral indicators were combined with resting-state functional magnetic resonance imaging (rs-fMRI). The behaviour-rfMRI analysis showed that ALFF value of right SPL and the functional connectivity (FC) between the right SPL and right IPL/SMA/ITG/Precuneus/bilateral IFG were positively correlated with the interpretation dimension of CIS scores. In addition, the ALFF value of right fusiform gyrus, the FC between the right fusiform gyrus and right precuneus, and the FCs between right SPL and right IPL/Precuneus/IFG were negatively correlated with indirect replies comprehension speed. Overlapping of these regions with large-scale brain network revealed that the right SPL was mainly located in the MDN, and the right fusiform gyrus was mainly located in the language network. Additionally, the areas showing functional connectivity with these regions were primarily located in the MDN, with a smaller subset located in the DN. Our findings suggest that the ability of individuals to actively and rapidly acquire indirect meaning relies not only on the support of the DN and the language network, but also requires collective support from the MDN.


Assuntos
Compreensão , Individualidade , Imageamento por Ressonância Magnética , Rede Nervosa , Leitura , Humanos , Compreensão/fisiologia , Masculino , Feminino , Adulto Jovem , Adulto , Rede Nervosa/fisiologia , Rede Nervosa/diagnóstico por imagem , Idioma , Mapeamento Encefálico , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Rede de Modo Padrão/fisiologia , Rede de Modo Padrão/diagnóstico por imagem , Conectoma
8.
Int J Surg ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701508

RESUMO

Ubiquitinases are known to catalyze ubiquitin chains on target proteins to regulate various physiological functions like cell proliferation, autophagy, apoptosis, and cell cycle progression. As a member of E3 ligase, ubiquitin protein ligase E3 component n-recognin 5 (UBR5) belongs to the HECT E3 ligase and has been reported to be correlated with various pathophysiological processes. In this review, we give a comprehensive insight into the structure and function of UBR5. We discuss the specific domains of UBR5 and explore their biological functions separately. Furthermore, we describe the involvement of UBR5 in different pathophysiological conditions, including immune response, virus infection, DNA damage response and protein quality control. Moreover, we provide a thorough summary of the important roles and regulatory mechanisms of UBR5 in cancers and other diseases. On the whole, investigating the domains and functions of UBR5, elucidating the underlying mechanisms of UBR5 with various substrates in detail may provide new theoretical basis for the treatment of diseases, including cancers, which could improve future studies to construct novel UBR5-targeted therapy strategies.

10.
Mol Plant Pathol ; 25(4): e13447, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38561315

RESUMO

Genetic engineering using negative regulators of plant immunity has the potential to provide a huge impetus in agricultural biotechnology to achieve a higher degree of disease resistance without reducing yield. Type 2C protein phosphatases (PP2Cs) represent the largest group of protein phosphatases in plants, with a high potential for negative regulatory functions by blocking the transmission of defence signals through dephosphorylation. Here, we established a PP2C functional protoplast screen using pFRK1::luciferase as a reporter and found that 14 of 56 PP2Cs significantly inhibited the immune response induced by flg22. To verify the reliability of the system, a previously reported MAPK3/4/6-interacting protein phosphatase, PP2C5, was used; it was confirmed to be a negative regulator of PAMP-triggered immunity (PTI). We further identified PP2C15 as an interacting partner of BRI1-associated receptor kinase 1 (BAK1), which is the most well-known co-receptor of plasma membrane-localized pattern recognition receptors (PRRs), and a central component of PTI. PP2C15 dephosphorylates BAK1 and negatively regulates BAK1-mediated PTI responses such as MAPK3/4/6 activation, defence gene expression, reactive oxygen species bursts, stomatal immunity, callose deposition, and pathogen resistance. Although plant growth and 1000-seed weight of pp2c15 mutants were reduced compared to those of wild-type plants, pp2c5 mutants did not show any adverse effects. Thus, our findings strengthen the understanding of the mechanism by which PP2C family members negatively regulate plant immunity at multiple levels and indicate a possible approach to enhance plant resistance by eliminating specific PP2Cs without affecting plant growth and yield.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Reprodutibilidade dos Testes , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Fosfoproteínas Fosfatases/farmacologia , Imunidade Vegetal/fisiologia , Regulação da Expressão Gênica de Plantas , Proteínas Quinases/genética , Proteínas Quinases/metabolismo
11.
Plants (Basel) ; 13(7)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38611561

RESUMO

A comprehensive study on maize flowering traits, focusing on the regulation of flowering time and the elucidation of molecular mechanisms underlying the genes controlling flowering, holds the potential to significantly enhance our understanding of the associated regulatory gene network. In this study, three tropical maize inbreds, CML384, CML171, and CML444, were used, along with a temperate maize variety, Shen137, as parental lines to cross with Ye107. The resulting F1s underwent seven consecutive generations of self-pollination through the single-seed descent (SSD) method to develop a multiparent population. To investigate the regulation of maize flowering time-related traits and to identify loci and candidate genes, a genome-wide association study (GWAS) was conducted. GWAS analysis identified 556 SNPs and 12 candidate genes that were significantly associated with flowering time-related traits. Additionally, an analysis of the effect of the estimated breeding values of the subpopulations on flowering time was conducted to further validate the findings of the present study. Collectively, this study offers valuable insights into novel candidate genes, contributing to an improved understanding of maize flowering time-related traits. This information holds practical significance for future maize breeding programs aimed at developing high-yielding hybrids.

12.
Comput Biol Med ; 172: 108260, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492457

RESUMO

BACKGROUND & AIMS: CLSPN, a critical component of the S-phase checkpoint in response to DNA replication stress, has been implicated in the pathogenesis of multiple tumor types. The rising incidence of hepatocellular carcinoma (HCC) poses a significant challenge to global public health. Despite this, the specific functions of CLSPN in the development of HCC remain poorly understood. METHODS: We systematically evaluated the expression of CLSPN, prognosis and immune infiltration in patients with HCC and identified a competing endogenous RNA (ceRNA) network by using public database. The RT-qPCR, western blot, CCK8, transwell, flow cytometry, animal experiments, proteasome inhibition experiment, Co-IP assay and mass spectrometry were applied to explore its biological functions, post-transcriptional modifications and potential molecular mechanisms of CLSPN in HCC. RESULTS: We verified the expression of CLSPN, and its high expression is an independent prognostic factor in HCC. The expression of CLSPN is also associated with the immune microenvironment of HCC. CLSPN silencing inhibited the proliferation, migration, invasion and cell cycle progression of HCC cells. We established a PSMA3-AS1/hsa-miR-101-3p/CLSPN regulator axis in HCC. CLSPN was influenced by ubiquitination and was involved in the Wnt/ß-catenin pathway to regulate HCC progression. CONCLUSIONS: It was the first time to comprehensively discover and identify the expression, prognosis, immunotherapy, RNAs regulator, posttranscriptional modification, and molecular mechanisms of CLSPN in HCC. These novel insights have the potential to expedite the development of personalized treatment strategies and translational medicine approaches for HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Animais , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Prognóstico , Linhagem Celular Tumoral , MicroRNAs/genética , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
13.
Int J Mol Sci ; 25(6)2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38542350

RESUMO

Kernel row number (KRN) is a crucial trait in maize that directly influences yield; hence, understanding the mechanisms underlying KRN is vital for the development of high-yielding inbred lines and hybrids. We crossed four excellent panicle inbred lines (CML312, CML444, YML46, and YML32) with Ye107, and after eight generations of selfing, a multi-parent population was developed comprising four subpopulations, each consisting of 200 lines. KRN was accessed in five environments in Yunnan province over three years (2019, 2021, and 2022). The objectives of this study were to (1) identify quantitative trait loci and single nucleotide polymorphisms associated with KRN through linkage and genome-wide association analyses using high-quality genotypic data, (2) identify candidate genes regulating KRN by identifying co-localized QTLs and SNPs, and (3) explore the pathways involved in KRN formation and identify key candidate genes through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Our study successfully identified 277 significant Quantitative trait locus (QTLs) and 53 significant Single Nucleotide Polymorphism (SNPs) related to KRN. Based on gene expression, GO, and KEGG analyses, SNP-177304649, SNP-150393177, SNP-135283055, SNP-138554600, and SNP-120370778, which were highly likely to be associated with KRN, were identified. Seven novel candidate genes at this locus (Zm00001d022420, Zm00001d022421, Zm00001d016202, Zm00001d050984, Zm00001d050985, Zm00001d016000, and Zm00014a012929) are associated with KRN. Among these, Zm00014a012929 was identified using the reference genome Mo17. The remaining six genes were identified using the reference genome B73. To our knowledge, this is the first report on the association of these genes with KRN in maize. These findings provide a theoretical foundation and valuable insights into the genetic mechanisms underlying maize KRN and the development of high-yielding hybrids through heterosis.


Assuntos
Estudo de Associação Genômica Ampla , Zea mays , Mapeamento Cromossômico , Zea mays/genética , Ligação Genética , China , Fenótipo , Polimorfismo de Nucleotídeo Único
14.
J Transl Med ; 21(1): 665, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37752518

RESUMO

Ubiquitination is one of the most significant post-translational modifications that regulate almost all physiological processes like cell proliferation, autophagy, apoptosis, and cell cycle progression. Contrary to ubiquitination, deubiquitination removes ubiquitin from targeted protein to maintain its stability and thus regulate cellular homeostasis. Ubiquitin-Specific Protease 12 (USP12) belongs to the biggest family of deubiquitinases named ubiquitin-specific proteases and has been reported to be correlated with various pathophysiological processes. In this review, we initially introduce the structure and biological functions of USP12 briefly and summarize multiple substrates of USP12 as well as the underlying mechanisms. Moreover, we discuss the influence of USP12 on tumorigenesis, tumor immune microenvironment (TME), disease, and related signaling pathways. This study also provides updated information on the roles and functions of USP12 in different types of cancers and other diseases, including prostate cancer, breast cancer, lung cancer, liver cancer, cardiac hypertrophy, multiple myeloma, and Huntington's disease. Generally, this review sums up the research advances of USP12 and discusses its potential clinical application value which deserves more exploration in the future.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Apoptose , Autofagia , Carcinogênese , Proteases Específicas de Ubiquitina , Microambiente Tumoral , Ubiquitina Tiolesterase
15.
Biosens Bioelectron ; 238: 115560, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37542980

RESUMO

Herein, the short peptide N-fluorenemethoxycarbonyl diphenylalanine (Fmoc-FF) was used to immobilize both diallyl viologen (DAV) and the enzyme formate dehydrogenase (FDH) to form Fmoc-FF/DAV/FDH supramolecular hydrogel films on an electrode surface by a simple solvent-controlled self-assembly method. The DAV component in the films exhibited multiple properties, such as electrochromism and electrofluorochromism, and acted as an electrochemical mediator. A high efficiency of bioelectrocatalytic reduction of CO2 to formate (HCOO-) was obtained by the natural FDH enzyme and the artificial coenzyme factor DAV both immobilized in the same films. The supramolecular hydrogel films with CO2, voltage and light as stimulating factors and current, fluorescence and UV-vis extinction as responsive signals, were further applied for the construction of complex biomolecular logic systems and information encryption. A 3-input/7-output biomolecular logic gate and several logic devices, including an encoder/decoder, a parity checker, and a keypad lock, were constructed. Especially, the biomolecular keypad lock with 3 types of signals as outputs significantly enhanced the security level of information encryption. In this work, a supramolecular self-assembly interface was simply fabricated with complex biomolecular computational functions using immobilized molecules as the computational core, greatly broadening the application range of supramolecular hydrogel films and providing an idea for new designs of bioinformation encryption through the use of a simple film system.


Assuntos
Técnicas Biossensoriais , Dióxido de Carbono , Metilgalactosídeos , Eletrodos
16.
Front Endocrinol (Lausanne) ; 14: 1153802, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37469973

RESUMO

Background: Increasing evidence elucidated N6-methyladenosine (m6A) dysregulation participated in regulating RNA maturation, stability, and translation. This study aimed to demystify the crosstalk between m6A regulators and the immune microenvironment, providing a potential therapeutic target for patients with hepatocellular carcinoma (HCC). Methods: Totals of 371 HCC and 50 normal patients were included in this study. GSE121248 and GSE40367 datasets were used to validate the expression of HNRNPC. The R package "ConsensusClusterPlus" was performed to screen consensus clustering types based on the expression of m6A regulators in HCC. The R package "pheatmap", "immunedeconv", "survival", "survminer" and "RMS" were applied to investigate the expression, immunity, overall survival, and clinical application in different clusters and expression groups. Comprehensive analysis of HNRNPC in pan-cancer was conducted by TIMER2 database. Besides, HNRNPC mRNA and protein expression were verified by qRT-PCR and immunohistochemistry analysis. Results: Most of m6A regulators were over-expressed excerpt for ZC3H13 in HCC. Three independent clusters were screened based on m6A regulators expression, and the cluster 2 had a favorable prognosis in HCC. Then, the cluster 2 was positively expression in macrophage, hematopoietic stem cell, endothelial cell, and stroma score, while negatively in T cell CD4+ memory and mast cell. We identified HNRNPC was an independent prognostic factor in HCC, and nomogram performed superior application value for clinical decision making. Moreover, PD-L1 was significantly up-regulated in HCC tissues, cluster 1, and cluster 3, and we found PD-L1 expression was positively correlated with HNRNPC. Patients with HCC in high-expression groups was associated with tumor-promoting cells. Besides, HNRNPC was correlated with prognosis, TMB, and immune checkpoints in cancers. Particularly, the experiments confirmed that HNRNPC was positively expression in HCC cells and tissues. Conclusion: The m6A regulators play irreplaceable roles in prognosis and immune infiltration in HCC, and the relationship of HNRNPC and PD-L1 possesses a promising direction for therapeutic targets of immunotherapy response. Exploration of m6A regulators pattern could be build the prognostic stratification of individual patients and move toward to personalized treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Antígeno B7-H1 , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Imunoterapia , Adenosina , Microambiente Tumoral/genética
17.
Apoptosis ; 28(9-10): 1423-1435, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37369808

RESUMO

Pancreatic adenocarcinoma (PAAD) is the eighth leading cause of cancer-related mortality that causes serious physical and mental burden to human. Reactive oxygen species accumulation and iron overload might enable ferroptosis-mediated cancer therapies. This study was to elusive novel ferroptosis regulator and its association with immune microenvironment and PD-L1 in PAAD. RNA-seq data and relevant information were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression. The R packages "ggplot2" and "pheatmap" were used to the expression of 20 ferroptosis regulators between PAAD and normal tissues. The R package "ConsensusClusterPlus", "survival", "survminer", "immunedeconv", and TIDE algorithm performed consensus clustering, overall survival, progression-free survival, disease free survival, immune infiltration level, and immunotherapy responses between cluster 1 and cluster 2. The prognostic value was confirmed by the Kaplan-Meier curves, receiver operating characteristic curve, univariate and multivariate cox regression, and nomogram. Moreover, the relationship of FANCD2 and immunity, drug sensitivity was investigated by R package "ggstatsplot", "immunedeconv", "ggalluvial" and "pRRophetic". Besides, the qRT-PCR, immunohistochemistry and western blotting detected the expression of FANCD2 in PAAD cell lines. Most ferroptosis regulators were up-regulated in PAAD, while the expression of LPCAT3, MT1G, and GLS2 was down-regulated in PAAD (P < 0.05), indicting there was a positively correlation among ferroptosis regulators. Based on clustering parameter, we identified cluster 1 and cluster 2, and cluster 2 had a better prognosis for patients with PAAD. The immune infiltration level of cluster 1 was higher in macrophage M1, myeloid dendritic cell, T cell CD4 + Th2, B cell, T cell CD8 + central memory, immune score, and microenvironment score than cluster 2 in PAAD. Moreover, FANCD2 was up-regulated in PAAD by public databases, immunohistochemistry, qRT-PCR and Western blotting, which had closely related to overall survival, immune microenvironment, and drug sensitivity. A novel crosstalk of ferroptosis exhibits a favourable prognostic performance and builds a robust theoretical foundation for mRNA vaccine and personalized immunotherapy. FANCD2 could be an effective for prognostic recognition, immune efficacy evaluation, and mRNA vaccine for patients with PAAD, providing a vital guidance for further study of regulating tumor immunity and vaccine development.


Assuntos
Adenocarcinoma , Ferroptose , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/genética , Adenocarcinoma/terapia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Ferroptose/genética , Apoptose , Imunoterapia , Vacinas de mRNA , Microambiente Tumoral/genética , Neoplasias Pancreáticas
18.
Sci Total Environ ; 878: 162870, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-36933726

RESUMO

Recirculating aquaculture system (RAS) has a good prospect in aquaculture, but its nitrogen removal characteristics and microbial community changes in freshwater and marine water remain unclear. In this study, six RAS were designed and divided into freshwater group and marine water group with salinity of 0‰ and 32‰, respectively, and operated for 54 days to test changes in nitrogen (NH4+-N, NO2--N, NO3--N), extracellular polymeric substances and microbial communities. The results showed that ammonia nitrogen was rapidly reduced and almost converted to nitrate nitrogen in the freshwater RAS but to nitrite nitrogen in marine RAS. Compared with freshwater RAS, marine RAS had lower tightly bound extracellular polymeric substances and worse stability and settleability condition. 16S rRNA amplicon sequencing reflected significantly lower bacterial diversity and richness in marine RAS. Microbial community structure at phylum level showed lower relative abundance of Proteobacteria, Actinobacteria, Firmicutes, Nitrospirae, but higher abundance of Bacteroidetes under a salinity of 32‰. High salinity decreased the abundance of funtional genera (Nitrosospira, Nitrospira, Pseudomonas, Rhodococcus, Comamonas, Acidovorax, f_Comamonadaceae), which may account for nitrite accumulation and low nitrogen removal capacity in marine RAS. These findings could provide theoretical and practical basis for improving the start-up speed of high-salinity nitrification biofilm.


Assuntos
Desnitrificação , Microbiota , Nitritos , Nitrogênio , RNA Ribossômico 16S/genética , Reatores Biológicos/microbiologia , Bactérias , Nitrificação , Água Doce , Aquicultura , Água
19.
Asia Pac J Clin Oncol ; 19(5): e183-e194, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36471477

RESUMO

Additional sex combs-like 1 (ASXL1) mutations, a hotspot in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), have been frequently reported for their potential prognostic value, but the results are controversial. Therefore, a meta-analysis was performed. Databases, including PubMed, Embase, and Cochrane Library, were searched for relevant studies published up to January 13, 2022. STATA v16.0 software was used to calculate the combined hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS) and AML transformation. Subgroup analysis was used to explore the effects of the grouping factors on heterogeneity.Ten studies on ASXL1 mutations and the prognosis of MDS were selected. Our results indicate that ASXL1 mutations have an adverse prognostic impact on OS (HR = 1.68,95%CI:1.45-1.94, p < .0001) and AML transformation (HR = 2.20,95% CI:1.68-2.87, p < .0001). The results for different age groups were not significantly different (HR = 1.87,95% CI: 1.31-2.67; HR = 1.62,95% CI:1.35-2.07). Ten studies covering 5816 patients with AML were included. The pooled HR for OS was 1.37 (95% CI:1.20-1.56, p < .0001). ASXL1 mutations were especially associated with a poorer OS in the subgroup aged ≥60 years (HR = 2.86, 95% CI:1.34-6.08, p = .006); when considering cytogenetically normal AML (CN-AML), the HR was 1.78(95% CI:1.27-2.49, p = .001). This meta-analysis indicates an independent, adverse prognostic impact of ASXL1 mutations in patients with MDS and AML, which also applies to patients with CN-AML. Age was a risk factor for patients with AML and ASXL1 mutations but not for patients with MDS.


Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Prognóstico , Mutação , Síndromes Mielodisplásicas/genética , Modelos de Riscos Proporcionais , Leucemia Mieloide Aguda/genética , Proteínas Repressoras/genética
20.
J Sep Sci ; 45(24): 4427-4438, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36226347

RESUMO

Ginseng is the main Chinese herbal medicine for tonifying Qi and invigorating the spleen. It has been used to treat spleen-qi deficiency with good protective effects for thousands of years, however, its biological mechanism has not been fully elucidated. This study aims to explore the mechanism of ginseng in the treatment of spleen-qi deficiency by using a comprehensive method combining metabolomics and network pharmacological analysis. Gas chromatography-mass spectroscopy was applied for investigating the changes in urine metabolites in spleen-qi deficiency rats and after treatment with ginseng. Metabolomics and network pharmacology analysis were applied to screen potential biomarkers and therapeutic targets of ginseng in the treatment of spleen-qi deficiency, respectively. Molecular docking was employed to further evaluate the docking mode of potential biomarkers and therapeutic target proteins. The results of metabolomics showed that the therapeutic effects of ginseng are mainly related to its regulation of three metabolic pathways. The molecular structure of potential biomarkers and common proteins was further analyzed by molecular docking to verify its effectiveness. Ginseng has good pharmacological effects by controlling key targets of related metabolic pathways, signal pathways, and potential biomarkers.


Assuntos
Medicamentos de Ervas Chinesas , Panax , Ratos , Animais , Qi , Baço , Simulação de Acoplamento Molecular , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Metabolômica , Biomarcadores/urina
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