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1.
Plant Physiol Biochem ; 216: 109161, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39378645

RESUMO

Strigolactones (SLs) play crucial roles in both plant growth and stress responses. However, their impact on the secondary metabolites of woody plants remains elusive. Here, we found that exogenous strigolactone analogue GR24 positively regulates tea plant flavor secondary metabolites, concurrently inhibiting caffeine biosynthesis and promoting the accumulation of caffeine catabolic pathway products. In this process, SL directly or indirectly inhibits the expression of CsSAMSs by inducing CsbHLH80, thereby reducing caffeine biosynthesis. Furthermore, CsbHLH80 enhances caffeine degradation, leading to increased allantoin. Under normal conditions, heightened allantoin reduces abscisic acid (ABA) accumulation. This inhibition reverses under drought stress. Increased ABA significantly enhances tea plant tolerance to both drought and Phyllosticta theicola Petch. In summary, this study offers novel insights for improving tea plant adaptation and quality in arid regions, particularly emphasizing the selection of stress-tolerant varieties and the refinement of production measures with a focus on high-quality production and environmentally friendly biological control methods.

2.
Sci Rep ; 14(1): 22092, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333276

RESUMO

This research work focuses on addressing the challenges of electric load forecasting through the combination of Support Vector Regression and Long Short-Term Memory (SVR/LSTM) methodology. The model has been modified by a flexible version of the Gorilla Troops optimization algorithm. The objective of this study is to enhance the precision and effectiveness of load forecasting models by integrating the adaptive functionalities of the Gorilla Troops algorithm within the SVR/LSTM framework. To assess the efficacy of the proposed methodology, a comprehensive series of experiments and evaluations have been undertaken, utilizing authentic data obtained from 200 residential properties located in Texas, United States of America. The dataset comprises historical records of electricity consumption, meteorological data, and other pertinent variables that exert an impact on energy demand. The presence of this general dataset enhances the dependability and inclusiveness of the empirical findings. The proposed methodology was evaluated against various contemporary load forecasting techniques that are widely employed in the industry. The results of a comprehensive evaluation and performance analysis indicate that the modified SVR/LSTM model exhibits superior performance compared to the existing methods in terms of accuracy and robustness. The comparison results unequivocally demonstrate the superiority of the proposed method in accurately forecasting electric load demand.

3.
Adv Mater ; 36(39): e2408341, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39097953

RESUMO

The electrosynthesis of hydrogen peroxide (H2O2) from O2 or H2O via the two-electron (2e-) oxygen reduction (2e- ORR) or water oxidation (2e- WOR) reaction provides a green and sustainable alternative to the traditional anthraquinone process. Herein, a paired-electrosynthesis tactic is reported for concerted H2O2 production at a high rate by coupling the 2e- ORR and 2e- WOR, in which the bifunctional oxygen-vacancy-enriched Bi2O3 nanorods (Ov-Bi2O3-EO), obtained through electrochemically oxidative reconstruction of Bi-based metal-organic framework (Bi-MOF) nanorod precursor, are used as both efficient anodic and cathodic electrocatalysts, achieving concurrent H2O2 production at both electrodes with high Faradaic efficiencies. Specifically, the coupled 2e- ORR//2e- WOR electrolysis system based on such distinctive oxygen-defect Bi catalyst displays excellent performance for the paired-electrosynthesis of H2O2, delivering a remarkable cell Faradaic efficiency of 154.8% and an ultrahigh H2O2 production rate of 4.3 mmol h-1 cm-2. Experiments combined with theoretical analysis reveal the crucial role of oxygen vacancies in optimizing the adsorption of intermediates associated with the selective two-electron reaction pathways, thereby improving the activity and selectivity of the 2e- reaction processes at both electrodes. This work establishes a new paradigm for developing advanced electrocatalysts and designing novel paired-electrolysis systems for scalable and sustainable H2O2 electrosynthesis.

4.
Proc Natl Acad Sci U S A ; 121(34): e2404199121, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39136985

RESUMO

Low phosphate (Pi) availability decreases photosynthesis, with phosphate limitation of photosynthesis occurring particularly during grain filling of cereal crops; however, effective genetic solutions remain to be established. We previously discovered that rice phosphate transporter OsPHO1;2 controls seed (sink) development through Pi reallocation during grain filling. Here, we find that OsPHO1;2 regulates Pi homeostasis and thus photosynthesis in leaves (source). Loss-of-function of OsPHO1;2 decreased Pi levels in leaves, leading to decreased photosynthetic electron transport activity, CO2 assimilation rate, and early occurrence of phosphate-limited photosynthesis. Interestingly, ectopic expression of OsPHO1;2 greatly increased Pi availability, and thereby, increased photosynthetic rate in leaves during grain filling, contributing to increased yield. This was supported by the effect of foliar Pi application. Moreover, analysis of core rice germplasm resources revealed that higher OsPHO1;2 expression was associated with enhanced photosynthesis and yield potential compared to those with lower expression. These findings reveal that phosphate-limitation of photosynthesis can be relieved via a genetic approach, and the OsPHO1;2 gene can be employed to reinforce crop breeding strategies for achieving higher photosynthetic efficiency.


Assuntos
Oryza , Fosfatos , Fotossíntese , Oryza/genética , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Fosfatos/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Transporte de Fosfato/genética , Proteínas de Transporte de Fosfato/metabolismo , Plantas Geneticamente Modificadas
6.
Front Endocrinol (Lausanne) ; 15: 1428147, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957445

RESUMO

Background: Amphiregulin (AR) is a growth factor that resembles the epidermal growth factor (EGF) and serves various functions in different cells. However, no systematic studies or reports on the role of AR in human oocytes have currently been performed or reported. This study aimed to explore the role of AR in human immature oocytes during in vitro maturation (IVM) and in vitro fertilization (IVF) in achieving better embryonic development and to provide a basis for the development of a pre-insemination culture medium specific for cumulus oocyte complexes (COCs). Methods: First, we examined the concentration of AR in the follicular fluid (FF) of patients who underwent routine IVF and explored the correlation between AR levels and oocyte maturation and subsequent embryonic development. Second, AR was added to the IVM medium to culture immature oocytes and investigate whether AR could improve the effects of IVM. Finally, we pioneered the use of a fertilization medium supplemented with AR for the pre-insemination culture of COCs to explore whether the involvement of AR can promote the maturation and fertilization of IVF oocytes, as well as subsequent embryonic development. Results: A total of 609 FF samples were examined, and a positive correlation between AR levels and blastocyst formation was observed. In our IVM study, the development potential and IVM rate of immature oocytes, as well as the fertilization rate of IVM oocytes in the AR-added groups, were ameliorated significantly compared to the control group (All P < 0.05). Only the IVM-50 group had a significantly higher blastocyst formation rate than the control group (P < 0.05). In the final IVF study, the maturation, fertilization, high-quality embryo, blastocyst formation, and high-quality blastocyst rates of the AR-added group were significantly higher than those of the control group (All P < 0.05). Conclusion: AR levels in the FF positively correlated with blastocyst formation, and AR involvement in pre-insemination cultures of COCs can effectively improve laboratory outcomes in IVF. Furthermore, AR can directly promote the in vitro maturation and developmental potential of human immature oocytes at an optimal concentration of 50 ng/ml.


Assuntos
Anfirregulina , Células do Cúmulo , Fertilização in vitro , Técnicas de Maturação in Vitro de Oócitos , Oócitos , Humanos , Anfirregulina/metabolismo , Fertilização in vitro/métodos , Feminino , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Técnicas de Maturação in Vitro de Oócitos/métodos , Adulto , Células do Cúmulo/metabolismo , Células do Cúmulo/efeitos dos fármacos , Células do Cúmulo/citologia , Líquido Folicular/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/fisiologia , Gravidez , Meios de Cultura/química , Técnicas de Cultura Embrionária/métodos , Blastocisto/metabolismo , Blastocisto/efeitos dos fármacos
7.
Chemosphere ; 363: 142789, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38972461

RESUMO

E-peroxone process is an emerging electrochemical oxidation process, based on ozone and the in-situ cathodic generation of H2O2, but the stability of cathode is one of the key restraining factors. In this study, we designed a multilayer gas diffusion electrode (GDE) decorated with a commercial hydrophobic membrane for the degradation of pyridine. It was found that a proper control of membrane pore sizes and hot-pressing temperature can significantly promote the GDE stability. Subsequently, key operational parameters of the constructed E-peroxone system were investigated, including the ozone concentration, current density, pH value, electrolyte type and initial concentration of pyridine. The degradation pathways were proposed according to six identified transformation products. The toxicity variation along the degradation progress was evaluated with microbial respiration tests and Toxicity Estimation Software Tool (T.E.S.T.) calculation and an efficient detoxification capacity of E-peroxone was observed. This research provides a theoretical basis and technical support for the development of highly efficient and stable E-peroxone system for the elimination of toxic organic contaminants.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Ozônio , Piridinas , Piridinas/química , Piridinas/toxicidade , Ozônio/química , Eletrodos , Oxirredução , Peróxido de Hidrogênio/química , Difusão , Membranas Artificiais
9.
Inorg Chem ; 63(29): 13714-13723, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38965790

RESUMO

The pursuit of a straightforward method to recycle organic dyes from effluents and repurpose them into valuable materials represents a highly sought-after yet huge challenge within the realms of chemistry, environment, and materials science. In this context, we employ a host-guest strategy that leverages the recycling of the rhodamine B molecule within the porous structure of a metal-organic framework to facilitate photothermal conversion. This achievement is realized through the electrostatic interaction, which then gives rise to remarkable selectivity and unparalleled uptake capacity for the cationic rhodamine B molecule. Capitalizing on this approach, the application of a columnar device and membrane technology for efficiently trapping rhodamine B molecules becomes feasible. On account of the aggregation effect resulting from the confined pore structure of the host matrix, the fluorescence emission of the encapsulated RhB molecules is significantly reduced, which consequently enhances the photothermal performance of the hybrid material through nonradiative transition. Moreover, the photothermal conversion achieved showcases a myriad of high-performance applications, including bacterial inhibition against Escherichia coli and seawater desalination.

11.
J Sci Food Agric ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979943

RESUMO

BACKGROUND: Lettuce holds a prominent position in the year-round supply of vegetables, offering a rich array of health-beneficial substances, such as dietary fiber, phenolic compounds, lactucopicrin and lactucin. As such, its flavor has garnered increasing attention. Balancing the enhancement of beneficial compounds with the reduction of undesirable taste is a key focus of scientific research. To investigate short-term management to improve the nutritional quality and flavor of lettuce, combinations of different light intensities (200, 500 and 800 µm ol m-2 s-1) and temperatures (10 and 22 °C) were applied separately to 'Lollo Rosso' and 'Little Butter Lettuce' for 7 days before harvest. RESULTS: The results obtained showed that increasing light intensity at low temperatures decreased nitrate content and increased soluble sugar, soluble protein, anthocyanin and phenolic compound content. In the case of lettuce flavor, the bitterness-related metabolites such as lactucin and lactucopicrin were reduced with high light intensity at a low temperature of 10 °C. With this combination, the fructose and glucose contents increased, significantly improving lettuce flavor. CONCLUSION: Higher light intensity combined with low temperature for 7 days before harvest effectively improved the nutritional quality and flavor of lettuce, suggesting its great potential for use in horticultural practices. © 2024 Society of Chemical Industry.

12.
Genet Test Mol Biomarkers ; 28(8): 322-327, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39084859

RESUMO

Aims: This study aimed to investigate the impact of genetic polymorphisms of thiopurine methyltransferase (TPMT) and NUDT15 on pharmacokinetics profile of mercaptopurine in healthy adults in China. Methods: Blood samples were obtained from 45 healthy adult volunteers who were administered azathioprine. Genomic DNA was extracted and sequenced for TPMT and NUDT15. The plasma concentrations of 6-mercaptopurine (6-MP) were determined by ultra-performance liquid chromatography-tandem mass spectrometry. Finally, pharmacokinetic parameters were calculated based on the time-concentration curve. Results: Among the 45 healthy adult volunteers enrolled in the study, two TPMT allelic variants and three NUDT15 allelic variants were detected. In total, six genotypes were identified, including TPMT*1/*1&NUDT15*1/*1, TPMT*1/*1&NUDT15*1/*2, TPMT*1/*1&NUDT15*1/*9, TPMT*1/*1&NUDT15*2/*5, TPMT*1/*6&NUDT15*1/*2, and TPMT*1/*3&NUDT15*1/*2. The results indicated that Area Under Curve (AUC) of 6-MP in volunteers with TPMT*1/*3&NUDT15*1/*2 and TPMT*1/*6&NUDT15*1/*2 were 1.57-1.62-fold higher than in individuals carrying the wild type (TPMT*1/*1&NUDT15*1/*1). Compared with wild type, the half-life (T1/2) of TPMT*1/*6&NUDT15*1/*2 was extended by 1.98 times, whereas T1/2 of TPMT*1/*3&NUDT15*1/*2 decreased by 67%. The maximum concentration (Cmax) of TPMT*1/*3&NUDT15*1/*2 increased significantly by 2.15-fold, whereas the corresponding clearance (CL/F) decreased significantly by 58.75%. Conclusion: The findings of this study corroborate the notion that various genotypes of TPMT and NUDT15 can impact the pharmacokinetics of mercaptopurine, potentially offering foundational insights for personalized mercaptopurine therapy.


Assuntos
Genótipo , Voluntários Saudáveis , Mercaptopurina , Metiltransferases , Pirofosfatases , Humanos , Metiltransferases/genética , Metiltransferases/metabolismo , Adulto , Pirofosfatases/genética , Pirofosfatases/metabolismo , Masculino , Mercaptopurina/farmacocinética , Mercaptopurina/metabolismo , Feminino , Alelos , Polimorfismo Genético/genética , China , Polimorfismo de Nucleotídeo Único/genética , Povo Asiático/genética , Adulto Jovem , Pessoa de Meia-Idade , Azatioprina/farmacocinética , Azatioprina/metabolismo , Nudix Hidrolases
13.
Int J Biol Macromol ; 273(Pt 2): 133180, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38880453

RESUMO

Surface chemistry of carriers plays a key role in enzyme loading capacity, structure rigidity, and thus catalyze activity of immobilized enzymes. In this work, the two model enzymes of horseradish peroxidase (HRP) and glucose oxidase (GOx) are co-immobilized on the lysozyme functionalized magnetic core-shell nanocomposites (LYZ@MCSNCs) to enhance their stability and activity. Briefly, the HRP and GOx aggregates are firstly formed under the crosslinker of trimesic acid, in which the loading amount and the rigidity of the enzyme can be further increased. Additionally, LYZ easily forms a robust anti-biofouling nanofilm on the surface of SiO2@Fe3O4 magnetic nanoparticles with abundant functional groups, which facilitate chemical crosslinking of HRP and GOx aggregates with minimized inactivation. The immobilized enzyme of HRP-GOx@LYZ@MCSNCs exhibited excellent recovery activity (95.6 %) higher than that of the free enzyme (HRP&GOx). Specifically, 85 % of relative activity was retained after seven cycles, while 73.5 % of initial activity was also remained after storage for 33 days at 4 °C. The thermal stability and pH adaptability of HRP-GOx@LYZ@MCSNCs were better than those of free enzyme of HRP&GOx. This study provides a mild and ecofriendly strategy for multienzyme co-immobilization based on LYZ functionalized magnetic nanoparticles using HRP and GOx as model enzymes.


Assuntos
Estabilidade Enzimática , Enzimas Imobilizadas , Nanopartículas de Magnetita , Reagentes de Ligações Cruzadas/química , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Peroxidase do Rábano Silvestre/química , Peroxidase do Rábano Silvestre/metabolismo , Concentração de Íons de Hidrogênio , Nanopartículas de Magnetita/química , Muramidase/química , Muramidase/metabolismo , Agregados Proteicos , Dióxido de Silício/química , Temperatura
14.
Exp Gerontol ; 194: 112490, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38876449

RESUMO

BACKGROUND: Adults with cognitive impairment are prone to living alone in large numbers but receive relatively little attention. This study aimed to evaluate whether living alone with cognitive impairment was associated with a higher burden of functional disability but lack of informal care. METHODS: 982 observations of adults living alone with cognitive impairment and 50,695 observations of adults living with others and with normal cognition were identified from 4 waves (2011/2012, 2013, 2015, and 2018) of the China Health and Retirement Longitudinal Study (CHARLS). A matched comparator was selected using propensity score matching (1:2). Functional disability included disability in Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), and mobility. The time of receiving informal care was measured in monthly hours. RESULTS: Adults living alone with cognitive impairment demonstrated significantly higher odds ratio of ADL disability (OR = 1.59, 95 % CI: 1.30, 1.95), IADL disability (OR = 1.19, 95 % CI: 1.00, 1.44), mobility disability (OR = 1.38, 95 % CI: 1.12, 1.70), but received fewer hours of informal care (ß = -127.7 h per month, standard error = 25.83, P < 0.001), compared to the adults living with others and with normal cognition. CONCLUSIONS: This study highlights the high burden of functional disability but low coverage of informal care among Chinese adults living alone with cognitive impairment and calls for more resources to be allocated to this vulnerable subpopulation to improve the functional health and to increase the provision of long-term care services.


Assuntos
Atividades Cotidianas , Disfunção Cognitiva , Humanos , Masculino , Feminino , China/epidemiologia , Idoso , Estudos Longitudinais , Pessoa de Meia-Idade , Pessoas com Deficiência , Idoso de 80 Anos ou mais , Vida Independente , Cuidadores/psicologia , Pontuação de Propensão , Assistência ao Paciente , População do Leste Asiático
15.
Mult Scler ; 30(9): 1221-1226, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38877717

RESUMO

BACKGROUND: Conflicting data exist around oral contraceptive exposure and subsequent multiple sclerosis (MS). OBJECTIVE: To use routinely collected primary healthcare data to explore the potential association between oral contraceptive exposure and subsequent MS in females at population level. METHODS: We performed a nested case-control study using electronic primary care data, with complete electronic ascertainment from 1990. Logistic regression was used to evaluate associations between contraceptive exposure and MS, without and with adjusting for age, ethnicity and deprivation. RESULTS: A total of 4455 females were included: 891 cases and 3564 controls. No association was seen between oral contraceptive exposure and subsequent MS, or between any contraceptive, combined oral contraceptive pill (COCP) or progesterone-only pill (POP) use 0-2, 2-5 or >5 years prior to MS. Conclusions: In the largest population-based study to date, we find no evidence of an association between oral contraceptive exposure and subsequent MS diagnosis.


Assuntos
Anticoncepcionais Orais , Esclerose Múltipla , Atenção Primária à Saúde , Humanos , Feminino , Estudos de Casos e Controles , Adulto , Esclerose Múltipla/epidemiologia , Atenção Primária à Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Anticoncepcionais Orais/efeitos adversos , Adulto Jovem , Adolescente
17.
Reprod Sci ; 31(10): 3049-3057, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38767769

RESUMO

Endometriosis (EM) is a common gynecologic condition that often leads to infertility in women of reproductive age. Cell adhesion molecule 2 (CADM2) is involved in maintaining cell adhesion and polarity, as well as suppressing tumors. However, the role and mechanism of CADM2 in endometriosis is unclear. Therefore, this study evaluated the expression levels of CADM2 and epithelial-mesenchymal transition (EMT)-related marker proteins (E-cadherin, α-SMA, and N-cadherin). Compared to normal endometrial tissue, CADM2 was expressed at low levels in ectopic endometrial tissue from patients with EM. We performed clone formation assays, wound healing assays, and Transwell cell invasion assays to investigate the effects of CADM2 on the biological behavior of endometriosis epithelial cells (11Z) and ectopic endometrial stromal cells (EESCs). The growth, migration, and invasion abilities of these cells were significantly inhibited by overexpression of CADM2. The results were reversed after the knockdown of CADM2. Finally, western blotting (WB) was utilized to detect the effect of CADM2 on EMT in endometriosis cells. CADM2 inhibited EMT in endometriosis cells. In conclusion, our study suggests that CADM2 is a negative regulator of endometriosis development and may inhibit endometriosis development by suppressing EMT.


Assuntos
Moléculas de Adesão Celular , Movimento Celular , Endometriose , Transição Epitelial-Mesenquimal , Humanos , Feminino , Transição Epitelial-Mesenquimal/fisiologia , Endometriose/metabolismo , Endometriose/patologia , Moléculas de Adesão Celular/metabolismo , Adulto , Endométrio/metabolismo , Endométrio/patologia , Caderinas/metabolismo , Proliferação de Células/fisiologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Linhagem Celular , Células Estromais/metabolismo , Células Estromais/patologia
18.
Biomark Res ; 12(1): 54, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38816881

RESUMO

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the treatment approach for cancer, autoimmune disease, and heart disease. The integration of CAR into T cells is typically facilitated by retroviral or lentiviral vectors. However, the random insertion of CARs can lead to issues like clonal expansion, oncogenic transformation, variegated transgene expression, and transcriptional silencing. The advent of precise gene editing technology, like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), allows for controlled and precise genome modification, facilitating the translation of CAR-T research to the clinical applications. This review aims to provide a comprehensive analysis of the application of CRISPR gene editing techniques in the context of precise deletion and insertion methodologies, with a specific focus on their potential for enhancing the development and utilization of CAR-T cell therapy.

19.
Theor Appl Genet ; 137(6): 144, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38809285

RESUMO

KEY MESSAGE: A wild melon reference genome elucidates the genomic basis of fruit acidity domestication. Structural variants (SVs) have been reported to impose major effects on agronomic traits, representing a significant contributor to crop domestication. However, the landscape of SVs between wild and cultivated melons is elusive and how SVs have contributed to melon domestication remains largely unexplored. Here, we report a 379-Mb chromosome-scale genome of a wild progenitor melon accession "P84", with a contig N50 of 14.9 Mb. Genome comparison identifies 10,589 SVs between P84 and four cultivated melons with 6937 not characterized in previously analysis of 25 melon genome sequences. Furthermore, the population-scale genotyping of these SVs was determined in 1175 accessions, and 18 GWAS signals including fruit acidity, fruit length, fruit weight, fruit color and sex determination were detected. Based on these genotyped SVs, we identified 3317 highly diverged SVs between wild and cultivated melons, which could be the potential SVs associated with domestication-related traits. Furthermore, we identify novel SVs affecting fruit acidity and proposed the diverged evolutionary trajectories of CmPH, a key regulator of melon fruit acidity, during domestication and selection of different populations. These results will offer valuable resources for genomic studies and genetic improvement in melon.


Assuntos
Cucurbitaceae , Domesticação , Frutas , Genoma de Planta , Cucurbitaceae/genética , Cucurbitaceae/crescimento & desenvolvimento , Frutas/genética , Frutas/crescimento & desenvolvimento , Fenótipo , Genótipo , Locos de Características Quantitativas , Variação Estrutural do Genoma , Genes de Plantas
20.
Aging (Albany NY) ; 16(9): 8000-8018, 2024 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-38709280

RESUMO

Lactate dehydrogenase A (LDHA), a critical enzyme involved in glycolysis, is broadly involved multiple biological functions in human cancers. It is reported that LDHA can impact tumor immune surveillance and induce the transformation of tumor-associated macrophages, highlighting its unnoticed function of LDHA in immune system. However, in human cancers, the role of LDHA in prognosis and immunotherapy hasn't been investigated. In this study, we analyzed the expression pattern and prognostic value of LDHA in pan-cancer and explored its association between tumor microenvironment (TME), immune infiltration subtype, stemness scores, tumor mutation burden (TMB), and immunotherapy resistance. We found that LDHA expression is tumor heterogeneous and that its high expression is associated with poor prognosis in multiple human cancers. In addition, LDHA expression was positively correlated with the presence of mononuclear/macrophage cells, and also promoted the infiltration of a range of immune cells. Genomic alteration of LDHA was common in different types of cancer, while with prognostic value in pan-cancers. Pan-cancer analysis revealed that the significant correlations existed between LDHA expression and tumor microenvironment (including stromal cells and immune cells) as well as stemness scores (DNAss and RNAss) across cancer types. Drug sensitivity analysis also revealed that LDHA was able to predict response to chemotherapy and immunotherapy. Furthermore, it was confirmed that knockdown of LDHA reduced proliferation and migration ability of lung cancer cells. Taken together, LDHA could serve as a prognostic biomarker and a potential immunotherapy marker.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Imunoterapia , Neoplasias , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Prognóstico , Neoplasias/imunologia , Neoplasias/genética , Neoplasias/terapia , Resistencia a Medicamentos Antineoplásicos/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase/genética , Linhagem Celular Tumoral
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