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1.
Addict Biol ; : e13124, 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34894025

RESUMO

Missed chance is a powerful factor in shaping risk-taking behaviour. The abnormal risk-taking behaviour is an obvious feature of individuals with Internet gaming disorder (IGD). However, the relationship between the neural responses to missed chance and risk-taking behaviour in IGD individuals remains unclear. In the current fMRI study, 28 IGD subjects (12 female, 23.04 ± 2.43 years old) and 26 healthy control (HC) subjects (13 female, 23.58 ± 2.67 years old) participated in fMRI scanning during performance of a sequential risk-taking task. The general linear model and the psycho-physiological interaction analyses were conducted to explore the difference in neural responses between the two groups. The results showed that IGD subjects reported more regret for the large missed chance and took more risk than HC subjects. Moreover, compared with HC subjects, IGD subjects exhibited greater activations in brain regions like ventral striatum (VS) and superior frontal gyrus (SFG), and stronger VS-thalamus functional connectivity for the large missed chance. Additionally, among IGD subjects, the SFG activation for the large missed chance was positively correlated with the risk-taking behaviour. Together, the results revealed the altered neural responses to missed chance contributed to the risk-taking behaviour in IGD individuals. The findings could help to clearly understand why IGD individuals continue playing online games despite the risks of widely known and could provide a new perspective for the intervention of IGD.

2.
Brief Bioinform ; 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34962264

RESUMO

Transcription factors (TFs) are proteins specifically involved in gene expression regulation. It is generally accepted in epigenetics that methylated nucleotides could prevent the TFs from binding to DNA fragments. However, recent studies have confirmed that some TFs have capability to interact with methylated DNA fragments to further regulate gene expression. Although biochemical experiments could recognize TFs binding to methylated DNA sequences, these wet experimental methods are time-consuming and expensive. Machine learning methods provide a good choice for quickly identifying these TFs without experimental materials. Thus, this study aims to design a robust predictor to detect methylated DNA-bound TFs. We firstly proposed using tripeptide word vector feature to formulate protein samples. Subsequently, based on recurrent neural network with long short-term memory, a two-step computational model was designed. The first step predictor was utilized to discriminate transcription factors from non-transcription factors. Once proteins were predicted as TFs, the second step predictor was employed to judge whether the TFs can bind to methylated DNA. Through the independent dataset test, the accuracies of the first step and the second step are 86.63% and 73.59%, respectively. In addition, the statistical analysis of the distribution of tripeptides in training samples showed that the position and number of some tripeptides in the sequence could affect the binding of TFs to methylated DNA. Finally, on the basis of our model, a free web server was established based on the proposed model, which can be available at https://bioinfor.nefu.edu.cn/TFPM/.

3.
Nat Commun ; 12(1): 5979, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645801

RESUMO

The lobula giant movement detector (LGMD) is the movement-sensitive, wide-field visual neuron positioned in the third visual neuropile of lobula. LGMD neuron can anticipate collision and trigger avoidance efficiently owing to the earlier occurring firing peak before collision. Vision chips inspired by the LGMD have been successfully implemented in very-large-scale-integration (VLSI) system. However, transistor-based chips and single devices to simulate LGMD neurons make them bulky, energy-inefficient and complicated. The devices with relatively compact structure and simple operation mode to mimic the escape response of LGMD neuron have not been realized yet. Here, the artificial LGMD visual neuron is implemented using light-mediated threshold switching memristor. The non-monotonic response to light flow field originated from the formation and break of Ag conductive filaments is analogue to the escape response of LGMD neuron. Furthermore, robot navigation with obstacle avoidance capability and biomimetic compound eyes with wide field-of-view (FoV) detection capability are demonstrated.

4.
Animals (Basel) ; 11(9)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34573493

RESUMO

To better understand the transition of rumen function during the weaning period in dairy calves, sixteen Holstein dairy calves were selected and divided into two groups: pre-weaning (age = 56 ± 7 day, n = 8) and post-weaning (age = 80 ± 6 day, n = 8). The rumen fluid was obtained by an oral gastric tube. The rumen fermentation profile, enzyme activity, bacteria composition, and their inter-relationship were investigated. The results indicated that the post-weaning calves had a higher rumen acetate, propionate, butyrate, and microbial crude protein (MCP) than the pre-weaning calves (p < 0.05). The rumen pH in the post-weaning calves was lower than the pre-weaning calves (p < 0.05). The protease, carboxymethyl cellulase, cellobiohydrolase, and glucosidase in the post-weaning calves had a lower trend than the pre-weaning calves (0.05 < p < 0.1). There was no difference in α and ß diversity between the two groups. Linear discriminant analysis showed that the phylum of Fibrobacteres in the post-weaning group was higher than the pre-weaning group. At the genus level, Shuttleworthia, Rikenellaceae, Fibrobacter, and Syntrophococcus could be worked as the unique bacteria in the post-weaning group. The rumen bacteria network node degree in the post-weaning group was higher than the pre-weaning group (16.54 vs. 9.5). The Shuttleworthia genus was highly positively correlated with MCP, propionate, total volatile fatty acid, glucosidase, acetate, and butyrate (r > 0.65, and p < 0.01). Our study provided new information about the rumen enzyme activity and its relationship with bacteria, which help us to better understand the effects of weaning on the rumen function.

5.
Microorganisms ; 9(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34442867

RESUMO

To understand the effects of diet and age on the rumen bacterial community and function, forty-eight dairy cattle at 1.5 (M1.5), 6 (M6), 9 (M9), 18 (M18), 23 (M23), and 27 (M27) months old were selected. Rumen fermentation profile, enzyme activity, and bacteria community in rumen fluid were measured. The acetate to propionate ratio (A/P) at M9, M18, and M23 was higher than other ages, and M6 was the lowest (p < 0.05). The total volatile fatty acid (TVFA) at M23 and M27 was higher than at other ages (p < 0.05). The urease at M18 was lower than at M1.5, M6, and M9, and the xylanase at M18 was higher than at M1.5, M23, and M27 (p < 0.05). Thirty-three bacteria were identified as biomarkers of the different groups based on the linear discriminant analysis (LDA) when the LDA score >4. The variation partitioning approach analysis showed that the age and diet had a 7.98 and 32.49% contribution to the rumen bacteria community variation, respectively. The richness of Succinivibrionaceae_UCG-002 and Fibrobacter were positive correlated with age (r > 0.60, p < 0.01) and positively correlated with TVFA and acetate (r > 0.50, p < 0.01). The Lachnospiraceae_AC2044_group, Pseudobutyrivibrio, and Saccharofermentans has a positive correlation (r > 0.80, p < 0.05) with diet fiber and a negative correlation (r < -0.80, p < 0.05) with diet protein and starch, which were also positively correlated with the acetate and A/P (r > 0.50, p < 0.01). The genera of Lachnospiraceae_AC2044_group, Pseudobutyrivibrio, and Saccharofermentans could be worked as the target bacteria to modulate the rumen fermentation by diet; meanwhile, the high age correlated bacteria such as Succinivibrionaceae_UCG-002 and Fibrobacter also should be considered when shaping the rumen function.

6.
Front Pharmacol ; 12: 642980, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34140889

RESUMO

Introduction: The population of young women who suffered from female pattern hair loss (FPHL) or female androgenic alopecia (AGA) is gradually increasing. Platelet-rich plasma is a novel and promising therapeutic method as a nonsurgical treatment for FPHL. Objective: To summarize different preparation methods of PRP and treatment regimes in FPHL, qualitatively evaluate the current observations, and quantitively analyze the efficacy of PRP in FPHL treatment. Methods: Six databases, MEDLINE, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, LILACS, and CNKI, were searched with terms "platelet-rich plasma," synonyms for AGA and FPHL. Meta-analysis was conducted with enrolled observational studies and randomized controlled trials separately. Results: We evaluated 636 studies and 12 trials from all searched databases. A total of 42 studies of 1,569 cases, including 776 female participants covering 16 randomized controlled trials and 26 observational trials, were included for qualitative synthesis study and systematic review. PRP showed positive efficacy in treating FPHL in hair density compared to the control groups with odds ratio (OR) 1.61, 95% CI 0.52-2.70, and compared to baseline with OR 1.11, 95% CI 0.86-1.37. Conclusion: PRP showed excellent efficiency as a novel therapy of FPHL through hair density evaluation. Further studies are needed to define standardized protocols, and large-scale randomized trials still need to be conducted to confirm its efficacy.

7.
Nanotechnology ; 32(39)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34161928

RESUMO

TiO2is usually employed as a protective layer for Cu2O in photoelectrocatalytic CO2reduction. However, the role of TiO2layer on CO2reduction activity and selectivity is still elusive. In this work, a systematic investigation is carried out to probe the impact of the deposition parameters of TiO2overlayer, including the temperature and thickness, on CO2reduction performance. Compositional and (photo-)electrochemical analysis is performed to explore the property of TiO2overlayers. Carrier behavior, including donor density and electron energy, and stability of TiO2are demonstrated to be influenced by atomic layer deposition conditions and thus play a role in controlling CO2reduction reaction. Specifically, as the thickness of the TiO2layer increases from 2 to 50 nm, the electron energy tends to be lowered accompanying the electron transfer mode from tunneling for TiO2thin layers to type II for thick TiO2, leading to a decrease in CO2reduction selectivity. With an increase of the TiO2deposition temperature, the stability increases with a loss of conductivity. Cu2O coated with 2 nm TiO2at 150 °C is proven to be the optimized candidate in this work for photoelectrochemical reduction of CO2to CO, HCOOH and CH3COOH under an applied bias of -0.4 versus RHE.

8.
Front Cell Infect Microbiol ; 11: 673222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33996641

RESUMO

RtxA1 is a major cytotoxin of Vibrio vulnificus (V. vulnificus) causing fatal septicemia and necrotic wound infections. Our previous work has shown that RpoS regulates the expression and secretion of V. vulnificus RtxA1 toxin. This study was conducted to further investigate the potential mechanisms of RpoS on RtxA1 secretion. First, V. vulnificus TolCV1 and TolCV2 proteins, two Escherichia coli TolC homologs, were measured at various time points by Western blotting. The expression of TolCV1 was increased time-dependently, whereas that of TolCV2 was decreased. Expression of both TolCV1 and TolCV2 was significantly downregulated in an rpoS deletion mutation. Subsequently, we explored the roles of TolCV1 and TolCV2 in V. vulnificus pathogenesis. Western blot analysis showed that RtxA1 toxin was exported by TolCV1, not TolCV2, which was consistent with the cytotoxicity results. Furthermore, the expression of TolCV1 and TolCV2 was increased after treatment of the host signal bile salt and the growth of tolCV1 mutant was totally abolished in the presence of bile salt. A tolCV1 mutation resulted in significant reduction of V. vulnificus induced-virulence in mice. Taken together, TolCV1 plays key roles in RtxA1 secretion, bile salt resistance, and mice lethality of V. vulnificus, suggesting that TolCV1 could be an attractive target for the design of new medicines to treat V. vulnificus infections.


Assuntos
Vibrioses , Vibrio vulnificus , Animais , Proteínas de Bactérias/genética , Escherichia coli , Camundongos , Vibrio vulnificus/genética , Virulência
9.
J Immunol ; 206(11): 2527-2535, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33980582

RESUMO

The T cell response is an important detection index in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine development. The present study was undertaken to determine the T cell epitopes in the spike (S) protein of SARS-CoV-2 that dominate the T cell responses in SARS-CoV-2-infected patients. PBMCs from rhesus macaques vaccinated with a DNA vaccine encoding the full-length S protein were isolated, and an ELISPOT assay was used to identify the recognized T cell epitopes among a total of 158 18-mer and 10-aa-overlapping peptides spanning the full-length S protein. Six multipeptide-based epitopes located in the S1 region, with four of the six located in the receptor-binding domain, were defined as the most frequently recognized epitopes in macaques. The conservation of the epitopes across species was also verified, and peptide mixtures for T cell response detection were established. Six newly defined T cell epitopes were found in the current study, which may provide a novel potential target for T cell response detection and the diagnosis and vaccine design of SARS-CoV-2 based on multipeptide subunit-based epitopes.


Assuntos
Epitopos de Linfócito T/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Macaca mulatta
10.
Mol Ther ; 29(7): 2350-2365, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-33677091

RESUMO

An emerging view regarding cancer metabolism is that it is heterogeneous and context-specific, but it remains to be elucidated in breast cancers. In this study, we characterized the energy-related metabolic features of breast cancers through integrative analyses of multiple datasets with genomics, transcriptomics, metabolomics, and single-cell transcriptome profiling. Energy-related metabolic signatures were used to stratify breast tumors into two prognostic clusters: cluster 1 exhibits high glycolytic activity and decreased survival rate, and the signatures of cluster 2 are enriched in fatty acid oxidation and glutaminolysis. The intertumoral metabolic heterogeneity was reflected by the clustering among three independent large cohorts, and the complexity was further verified at the metabolite level. In addition, we found that the metabolic status of malignant cells rather than that of nonmalignant cells is the major contributor at the single-cell resolution, and its interactions with factors derived from the tumor microenvironment are unanticipated. Notably, among various immune cells and their clusters with distinguishable metabolic features, those with immunosuppressive function presented higher metabolic activities. Collectively, we uncovered the heterogeneity in energy metabolism using a classifier with prognostic and therapeutic value. Single-cell transcriptome profiling provided novel metabolic insights that could ultimately tailor therapeutic strategies based on patient- or cell type-specific cancer metabolism.

12.
Dermatology ; 237(4): 542-552, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33735876

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a widely acquired, relapsing inflammatory skin disease. Biologics are now widely used in patients with moderate-to-severe AD. OBJECTIVE: This work aims to summarize both label and off-label biologics on AD treatment in phase II and phase III stages, and compile evidence on the efficacy of the most-studied biologics. METHODS: We conducted a comprehensive literature search through PubMed, EMBASE, and ClinicalTrials.gov to identify all documented biological therapies for AD. The criteria were further refined to focus on those treatments with the highest evidence level for AD with at least one randomized clinical trial supporting their use. Only studies or articles published in English were enrolled in this study. FINDINGS: Primary searches identified 525 relevant articles and 27 trials. Duplicated articles and papers without a full text were excluded. Only completed trials were enrolled. We included 28 randomized controlled trials, 4 unpublished trials, 2 observational studies, and 1 meta-analysis. Eight kinds of biologics, including IL-4/IL-13 inhibitors, JAK inhibitors, anti-IL-13 antibodies, anti-IL-22 antibodies, anti-IL-33 antibodies, thymic stromal lymphopoietin inhibitor (TSLP), OX40 antibodies, and H4R-antagonists were included in this work. Dupliumab, as the most widely used and investigated biologic, was reported in 1 meta-analysis and 4 trials exploring its long-term use and application in both adults and pediatric patients. Besides dupilumab, four other IL-4/IL-13 inhibitors recruited were all randomized, clinical trials at phase 2-3 stage. Six different kinds of JAK inhibitors were summarized with strong evidence revealing their significant therapeutic effects on AD. There were 3 trials for nemolizumab, an anti-IL-13 antibody, all of which were in the phase 2 clinical trial stage. Results showed nemolizumab could be another alternative therapy for moderate-to-severe AD with long-term efficiency and safety. CONCLUSION: The biological therapies with the most robust evidence on efficacy and long-term safety for AD treatment include dupilumab, barcitinib, abrocitinib, and delgocitinib. Most of the biologics mentioned in this review were still at the exploratory stage. This review will help practitioners advise patients seeking suitable biological therapies and offer experimental study directions for treatment.

13.
Sci Adv ; 7(13)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33762332

RESUMO

Metallic nanostructures are commonly densely packed into a few packing variants with slightly different atomic packing factors. The structural aspects and physicochemical properties related with the vacancies in such nanostructures are rarely explored because of lack of an effective way to control the introduction of vacancy sites. Highly voided metallic nanostructures with ordered vacancies are however energetically high lying and very difficult to synthesize. Here, we report a chemical method for synthesis of hierarchical Rh nanostructures (Rh NSs) composed of ultrathin nanosheets, composed of hexagonal close-packed structure embedded with nanodomains that adopt a vacated Barlow packing with ordered vacancies. The obtained Rh NSs exhibit remarkably enhanced electrocatalytic activity and stability toward the hydrogen evolution reaction (HER) in alkaline media. Theoretical calculations reveal that the exceptional electrocatalytic performance of Rh NSs originates from their unique vacancy structures, which facilitate the adsorption and dissociation of H2O in the HER.

14.
Biol Pharm Bull ; 44(2): 245-250, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33518676

RESUMO

Piper crocatum Ruiz & Pav. (P. crocatum), a traditional medicinal plant, has been shown to possess various pharmacological activities, including anticancer activity, antioxidant activity, antibacterial activity, anti-hyperglycemic activity, anti-allergic inflammatory activity and others. To identify the potential anti-allergic inflammatory effective constituents of P. crocatum, 13 single compounds were isolated from the methanol extract of P. crocatum leaves, and their structures were identified by contrasting their NMR spectroscopic data and previously published papers. First, the anti-allergic inflammatory activities of these single compounds were examined by accessing immune function related biomarkers such as nitric oxide (NO) and ß-hexosaminidase. We found that the methanol extract and catechaldehyde (compound 1) potently suppressed NO production. Additionally, Western blot analysis showed that P. crocatum methanol extract and compound 1 suppressed the production of NO by reducing inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Consistent with these observations, P. crocatum methanol extract and compound 1 remarkably decreased ß-hexosaminidase release from RBL-2H3 cells stimulated with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA)-specific immunoglobulin E (IgE) antibodies. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay indicated that P. crocatum methanol extract and compound 1 exhibited no cytotoxicity to RAW264.7 and RBL-2H3 cells. Based on these findings, compound 1 is suggested as an active anti-allergic inflammatory component of P. crocatum.


Assuntos
Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Piper/química , Extratos Vegetais/farmacologia , Animais , Antialérgicos/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Metanol/química , Camundongos , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Células RAW 264.7 , Ratos
17.
Nat Commun ; 12(1): 13, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397895

RESUMO

Energy storage with high energy density and low cost has been the subject of a decades-long pursuit. Sodium-ion batteries are well expected because they utilize abundant resources. However, the lack of competent cathodes with both large capacities and long cycle lives prevents the commercialization of sodium-ion batteries. Conventional cathodes with hexagonal-P2-type structures suffer from structural degradations when the sodium content falls below 33%, or when the integral anions participate in gas evolution reactions. Here, we show a "pillar-beam" structure for sodium-ion battery cathodes where a few inert potassium ions uphold the layer-structured framework, while the working sodium ions could diffuse freely. The thus-created unorthodox orthogonal-P2 K0.4[Ni0.2Mn0.8]O2 cathode delivers a capacity of 194 mAh/g at 0.1 C, a rate capacity of 84% at 1 C, and an 86% capacity retention after 500 cycles at 1 C. The addition of the potassium ions boosts simultaneously the energy density and the cycle life.

18.
ACS Appl Mater Interfaces ; 13(2): 3287-3294, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33400481

RESUMO

Exsolution of catalytic nanoparticles (NPs) from perovskites has arisen as a flexible method to develop high-performance functional materials with enhanced durability for energy conversion and catalytic synthesis applications. Here, we unravel the interface structure of the in situ exsolved alloy nanoparticles from the double perovskite substrate on the atomic scale. The results show that the Co-Fe alloy NPs exsolved topologically from the {100} facets terminations of the Sr2FeMo0.65Co0.35O6-δ (SFMC) double perovskite along ⟨100⟩ directions exhibiting the same orientation and identical crystal structure. The lattice planes of these two phases align and insert into each other at the interface, forming a smooth and continuous coherent connection. The presence of moiré patterns at the interface confirms the topological exsolution mechanism. The coherent interface can significantly reduce the interfacial energy and therefore stabilize the exsolved nanoparticles. Therefore, excellent and stable electrochemical performance of the NP-decorated SFMC perovskite is observed as the anode for solid oxide fuel cells. Our contribution promotes a fundamental understanding of the interface structure of the in situ exsolved alloy nanoparticles from perovskite substrate.

19.
J Diabetes Res ; 2021: 6683937, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33506051

RESUMO

Although percutaneous coronary intervention (PCI) significantly improves the prognosis for myocardial infarction, the no-reflow phenomenon is still the major adverse complication of PCI leading to increased mortality, especially for the patients with ST-segment elevation myocardial infarction (STEMI) combined with diabetes. To reduce the occurrence of no-reflow, prognostic factors must be identified for no-reflow phenomenon before PCI. A total of 262 participants with acute STEMI and diabetes were recruited into our cardiovascular center and underwent primary PCI for the analyses of prognostic factors of no-reflow. The patients were divided into two groups according to thrombolysis in myocardial infarction (TIMI): the normal flow and no-reflow groups, and related factors were analyzed with different statistical methods. In the present investigation, the in-hospital peak glycemia was significantly higher in the no-reflow group than the normal flow group, while more narrowed vessels, higher level of initial TIMI flow, were observed in the patients of the no-reflow group. A multivariate logistic regression analysis further demonstrated that peak glycemia was an independent predictor for no-reflow in the diabetic patients with STEMI. Our data indicated the importance of the proper control of glucose before PCI for the diabetic patients with STEMI before PCI to reduce the occurrence of the no-reflow after operation.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus/sangue , Fenômeno de não Refluxo/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Biomarcadores/sangue , Circulação Coronária , Diabetes Mellitus/diagnóstico , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Fenômeno de não Refluxo/diagnóstico por imagem , Fenômeno de não Refluxo/fisiopatologia , Intervenção Coronária Percutânea/instrumentação , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Stents , Fatores de Tempo , Resultado do Tratamento
20.
Cell Metab ; 33(1): 51-64.e9, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33181091

RESUMO

Triple-negative breast cancer (TNBC) remains an unmet medical challenge. We investigated metabolic dysregulation in TNBCs by using our multi-omics database (n = 465, the largest to date). TNBC samples were classified into three heterogeneous metabolic-pathway-based subtypes (MPSs) with distinct metabolic features: MPS1, the lipogenic subtype with upregulated lipid metabolism; MPS2, the glycolytic subtype with upregulated carbohydrate and nucleotide metabolism; and MPS3, the mixed subtype with partial pathway dysregulation. These subtypes were validated by metabolomic profiling of 72 samples. These three subtypes had distinct prognoses, molecular subtype distributions, and genomic alterations. Moreover, MPS1 TNBCs were more sensitive to metabolic inhibitors targeting fatty acid synthesis, whereas MPS2 TNBCs showed higher sensitivity to inhibitors targeting glycolysis. Importantly, inhibition of lactate dehydrogenase could enhance tumor response to anti-PD-1 immunotherapy in MPS2 TNBCs. Collectively, our analysis demonstrated the metabolic heterogeneity of TNBCs and enabled the development of personalized therapies targeting unique tumor metabolic profiles.


Assuntos
Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Feminino , Humanos , Imunoterapia , Masculino , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/terapia , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Neoplasias de Mama Triplo Negativas/terapia , Células Tumorais Cultivadas
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