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A quantum internet that connects remote quantum processors1,2 should enable a number of revolutionary applications such as distributed quantum computing. Its realization will rely on entanglement of remote quantum memories over long distances. Despite enormous progress3-12, at present the maximal physical separation achieved between two nodes is 1.3 kilometres10, and challenges for longer distances remain. Here we demonstrate entanglement of two atomic ensembles in one laboratory via photon transmission through city-scale optical fibres. The atomic ensembles function as quantum memories that store quantum states. We use cavity enhancement to efficiently create atom-photon entanglement13-15 and we use quantum frequency conversion16 to shift the atomic wavelength to telecommunications wavelengths. We realize entanglement over 22 kilometres of field-deployed fibres via two-photon interference17,18 and entanglement over 50 kilometres of coiled fibres via single-photon interference19. Our experiment could be extended to nodes physically separated by similar distances, which would thus form a functional segment of the atomic quantum network, paving the way towards establishing atomic entanglement over many nodes and over much longer distances.
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MicroRNAs (miRNAs) play crucial regulatory roles in controlling immune responses, but their dynamic expression mechanisms are poorly understood. Here, we firstly confirm that the conserved miRNA miR-210 negatively regulates innate immune responses of Drosophila and human via targeting Toll and TLR6, respectively. Secondly, our findings demonstrate that the expression of miR-210 is dynamically regulated by NF-κB factor Dorsal in immune response of Drosophila Toll pathway. Thirdly, we find that Dorsal-mediated transcriptional inhibition of miR-210 is dependent on the transcriptional repressor Su(Hw). Mechanistically, Dorsal interacts with Su(Hw) to modulate cooperatively the dynamic expression of miR-210 in a time- and dose-dependent manner, thereby controlling the strength of Drosophila Toll immune response and maintaining immune homeostasis. Fourthly, we reveal a similar mechanism in human cells, where NF-κB/RelA cooperates with E4F1 to regulate the dynamic expression of hsa-miR-210 in the TLR immune response. Overall, our study reveals a conservative regulatory mechanism that maintains animal innate immune homeostasis and provides new insights into the dynamic regulation of miRNA expression in immune response.
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Proteínas de Drosophila , Inmunidad Innata , MicroARNs , Factores de Transcripción , MicroARNs/genética , MicroARNs/metabolismo , Animales , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Humanos , Inmunidad Innata/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Regulación de la Expresión Génica , Drosophila melanogaster/genética , Drosophila melanogaster/inmunología , FN-kappa B/metabolismo , Receptor Toll-Like 6/genética , Receptor Toll-Like 6/metabolismo , Factor de Transcripción ReIA/metabolismo , Factor de Transcripción ReIA/genética , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Transducción de Señal , Línea Celular , Drosophila/genética , Drosophila/inmunología , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Proteínas Nucleares , FosfoproteínasRESUMEN
Stem cells are essential to plant growth and development. Through data mining, we identified five DEVIL-like (DVL) small peptide genes that are preferentially expressed in the quiescent center of Arabidopsis (Arabidopsis thaliana) root but whose functions are unknown. When overexpressed, these genes caused a dramatic decrease in root length and pleiotropic phenotypes in the shoot. No root-growth defect was observed in the single-gene mutants, but the quintuple mutant exhibited slightly longer roots than the wild type (WT). Through transcriptome analysis with DVL20-overexpressing plants, we found that many genes involved in abscisic acid (ABA) signaling were regulated by these peptides. Consistent with this finding, we demonstrated that, relative to the WT, DVL20-overexpressing plants were more tolerant whereas the quintuple mutant was more sensitive to ABA. Using RT-qPCR, we showed that ABA signaling-associated genes were affected in an opposite manner when the plants were grown in normal or ABA-containing medium. Strikingly, ectopic expression of ABA signaling genes such as PYRABACTIN RESISTANCE 1-LIKE (PYL) 4, 5, or 6 or suppression of HIGHLY ABA-INDUCED 2 (HAI2) and MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 18 (MAPKKK18) not only largely rescued the root growth defects in DVL20-overexpressing plants in normal growth condition but also conferred tolerance to ABA. Based on these results, we propose that DVL1, 2, 5, 8 and 20 function redundantly in root stem-cell maintenance under abiotic stress, and this role is achieved via ABA signaling.
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Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/farmacología , Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Péptidos/metabolismo , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/metabolismoRESUMEN
The strength and duration of the NF-κB signaling response must be tightly modulated to avoid an inadequate or excessive immune response. Relish, a core NF-κB transcription factor of the Drosophila Imd pathway, can control the expression of antimicrobial peptides, including Dpt and AttA, to defend against Gram-negative bacterial infections, but whether Relish may regulate miRNA expression to participate in the immune response remains unclear. In this study, taking advantage of Drosophila S2 cells and different overexpression/knockout/knockdown flies, we first found that Relish could directly activate the expression of miR-308 to negatively regulate the immune response and promote the survival of Drosophila during Enterobacter cloacae infection. Second, our results demonstrated that Relish-mediated expression of miR-308 could suppress target gene Tab2 to attenuate the Drosophila Imd pathway signal during the middle and late stages of the immune response. Third, we detected the dynamic expression patterns of Dpt, AttA, Relish, miR-308, and Tab2 in wild-type flies after E. coli infection, which further revealed that the feedback regulatory loop of Relish-miR-308-Tab2 plays a crucial role in the immune response and homeostasis maintenance of the Drosophila Imd pathway. Overall, our present study not only illustrates an important mechanism by which this Relish-miR-308-Tab2 regulatory axis can negatively control the Drosophila immune response and participate in homeostasis maintenance but also provides new insights into the dynamic regulation of the NF-κB/miRNA expression network of animal innate immunity.
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Proteínas de Drosophila , MicroARNs , Animales , Drosophila/genética , Drosophila melanogaster , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Escherichia coli/metabolismo , Inmunidad Innata/genética , MicroARNs/genética , FN-kappa B/metabolismoRESUMEN
Piwi-interacting RNAs (piRNAs) are small noncoding RNAs that repress transposable elements to maintain genome integrity. The canonical catalytic hairpin assembly (CHA) circuit relies on random collisions of free-diffused reactant probes, which substantially slow down reaction efficiency and kinetics. Herein, we demonstrate the construction of a spatial-confined self-stacking catalytic circuit for rapid and sensitive imaging of piRNA in living cells based on intramolecular and intermolecular hybridization-accelerated CHA. We rationally design a 3WJ probe that not only accelerates the reaction kinetics by increasing the local concentration of reactant probes but also eliminates background signal leakage caused by cross-entanglement of preassembled probes. This strategy achieves high sensitivity and good specificity with shortened assay time. It can quantify intracellular piRNA expression at a single-cell level, discriminate piRNA expression in tissues of breast cancer patients and healthy persons, and in situ image piRNA in living cells, offering a new approach for early diagnosis and postoperative monitoring.
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ARN Interferente Pequeño , Humanos , ARN Interferente Pequeño/genética , Catálisis , Hibridación de Ácido Nucleico , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Cinética , ARN de Interacción con PiwiRESUMEN
We present an on-chip filter with a broad tailorable working wavelength and a single-mode operation. This is realized through the application of topological photonic crystal nanobeam filters employing synthesis parameter dimensions. By introducing the translation of air holes as a new synthetic parameter dimension, we obtained nanobeams with tunable Zak phases. Leveraging the bulk-edge correspondence, we identify the existence of topological cavity modes and establish a correlation between the cavity's interface morphology and working wavelength. Through experiments, we demonstrate filters with adjustable filtering wavelengths ranging from 1301 to 1570 nm. Our work illustrates the use of the synthetic translation dimension in the design of on-chip filters, and it holds potential for applications in other devices such as microcavities.
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In wild-type phototrophic organisms, carotenoids (Crts) are primarily packed into specific pigment-protein complexes along with (Bacterio)chlorophylls and play important roles in the photosynthesis. Diphenylamine (DPA) inhibits carotenogenesis but not phototrophic growth of anoxygenic phototrophs and eliminates virtually all Crts from photocomplexes. To investigate the effect of Crts on assembly of the reaction center-light-harvesting (RC-LH) complex from the filamentous anoxygenic phototroph Roseiflexus (Rfl.) castenholzii, we generated carotenoidless (Crt-less) RC-LH complexes by growing cells in the presence of DPA. Here, we present cryo-EM structures of the Rfl. castenholzii native and Crt-less RC-LH complexes with resolutions of 2.86 Å and 2.85 Å, respectively. From the high-quality map obtained, several important but previously unresolved details in the Rfl. castenholzii RC-LH structure were determined unambiguously including the assignment and likely function of three small polypeptides, and the content and spatial arrangement of Crts with bacteriochlorophyll molecules. The overall structures of Crt-containing and Crt-less complexes are similar. However, structural comparisons showed that only five Crts remain in complexes from DPA-treated cells and that the subunit X (TMx) flanked on the N-terminal helix of the Cyt-subunit is missing. Based on these results, the function of Crts in the assembly of the Rfl. castenholzii RC-LH complex and the molecular mechanism of quinone exchange is discussed. These structural details provide a fresh look at the photosynthetic apparatus of an evolutionary ancient phototroph as well as new insights into the importance of Crts for proper assembly and functioning of the RC-LH complex.
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Proteínas Bacterianas , Chloroflexi , Fotosíntesis , Proteínas Bacterianas/metabolismo , Carotenoides/metabolismo , Chloroflexi/metabolismo , Complejos de Proteína Captadores de Luz/químicaRESUMEN
The formation of oil-in-water Pickering emulsions stabilized by lamellar zeolite MWW (International Zeolite Association, three-letters code) emulsifier without surface grafting is investigated. The crucial emulsification factors are the oligolayer morphology and amphiphilicity developed upon acidic treatment (NH4+ exchange/calcination, HNO3 treatment). In contrast with the readily available/abundant hydrophilic ≡Si-OH group in layer MWW, the lipophilicity generated by strong acid sites is another key to the success of emulsification. Hydrocarbon-strong acid site interaction is long known in petrochemistry and superacid research. However, to the best of our knowledge, this interaction was first introduced to gain lipophilicity in emulsion formation. Finally, the Pd-loaded acidic form of the MWW zeolite successfully stabilized the toluene/H2O emulsion system. The biphasic interfacial nitroarene hydrogenation demonstrated excellent catalytic performance. Overall, this work provided not only a new kind of intrinsic solid to emulsify the organic-aqueous biphase system but also a new mechanism to generate lipophilicity. Both are important for the applications and designs of Pickering emulsion materials.
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BACKGROUND: Studies on various thrombopoietic agents for cancer treatment-induced thrombocytopenia (CTIT) in China are lacking. This study aimed to provide detailed clinical profiles to understand the outcomes and safety of different CTIT treatment regimens. METHODS: In this retrospective, cross-sectional study, 1664 questionnaires were collected from 33 hospitals between March 1 and July 1, 2021. Patients aged >18 years were enrolled who were diagnosed with CTIT and treated with recombinant interleukin 11 (rhIL-11), recombinant thrombopoietin (rhTPO), or a thrombopoietin receptor agonist (TPO-RA). The outcomes, compliance, and safety of different treatments were analyzed. RESULTS: Among the 1437 analyzable cases, most patients were treated with either rhTPO alone (49.3%) or rhIL-11 alone (27.0%). The most common combination regimen used was rhTPO and rhIL-11 (10.9%). Platelet transfusions were received by 117 cases (8.1%). In multivariate analysis, rhTPO was associated with a significantly lower proportion of platelet recovery, platelet transfusion, and hospitalization due to chemotherapy-induced thrombocytopenia (CIT) than rhIL-11 alone. No significant difference was observed in the time taken to achieve a platelet count of >100 × 109/L and chemotherapy dose reduction due to CIT among the different thrombopoietic agents. The outcomes of thrombocytopenia in 170 patients who received targeted therapy and/or immunotherapy are also summarized. The results show that the proportion of platelet recovery was similar among the different thrombopoietic agents. No new safety signals related to thrombopoietic agents were observed in this study. A higher proportion of physicians preferred to continue treatment with TPO-RA alone than with rhTPO and rhIL-11. CONCLUSIONS: This survey provides an overview of CTIT and the application of various thrombopoietic agents throughout China. Comparison of monotherapy with rhIL-11, rhTPO, and TPO-RA requires further randomized clinical trials. The appropriate application for thrombopoietic agents should depend on the pretreatment of platelets, treatment variables, and risk of bleeding. PLAIN LANGUAGE SUMMARY: To provide an overview of the outcome of cancer treatment-induced thrombocytopenia in China, our cross-sectional study analyzed 1437 cases treated with different thrombopoietic agents. Most of the patients were treated with recombinant interleukin 11 (rhIL-11) and recombinant thrombopoietin (rhTPO). rhTPO was associated with a significantly lower proportion of platelet recovery and platelet transfusion compared with rhIL-11.
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Neoplasias , Trombocitopenia , Humanos , China , Estudios Transversales , Interleucina-11/uso terapéutico , Neoplasias/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Trombocitopenia/inducido químicamente , Trombocitopenia/tratamiento farmacológico , Trombopoyetina/uso terapéutico , Adulto Joven , AdultoRESUMEN
To adapt to a terrestrial habitat, the ancestors of land plants must make several morphological and physiological modifications, such as a meristem allowing for three-dimensional growth, rhizoids for water and nutrient uptake, air pore complexes or stomata that permit air exchange, and a defense system to cope with oxidative stress that occurs frequently in a terrestrial habitat. To understand how meristem is determined during land plant evolution, we characterized the function of the closest PLETHORA homolog in the liverwort Marchantia polymorpha, which we named MpPLT. Through transgenic approach, we showed that MpPLT is expressed not only in the stem cells at the apical notch but also in the proliferation zone of the meristem, as well as cells that form the air-pore complex and rhizoids. Using the CRISPR method we then created mutants for MpPLT and found that the mutants are not only defective in meristem maintenance but also compromised in air-pore complex and rhizoid development. Strikingly, at later developmental stages, numerous gemma-like structures were formed in Mpplt mutants, suggesting developmental arrest. Further experiments indicate that MpPLT promotes plant growth by regulating MpWOX, which shared a similar expression pattern as MpPLT, and genes involved in auxin and cytokinin signaling pathways. Through transcriptome analyses, we found that MpPLT also has a role in redox homeostasis and that this role is essential to plant growth. Together, these results suggest that MpPLT has a crucial role in liverwort growth and development and hence may have played a crucial role in early land plant evolution.
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UHMK1 is a nuclear serine/threonine kinase recently implicated in carcinogenesis. However, the functions and action mechanisms of UHMK1 in the pathogenesis of human gastric cancer (GC) are unclear. Here, we observed that UHMK1 was markedly upregulated in GC. UHMK1 silencing strongly inhibited GC aggressiveness. Interestingly, UHMK1-induced GC progression was mediated primarily via enhancing de novo purine synthesis because inhibiting purine synthesis reversed the effects of UHMK1 overexpression. Mechanistically, UHMK1 activated ATF4, an important transcription factor in nucleotide synthesis, by phosphorylating NCOA3 at Ser (S) 1062 and Thr (T) 1067. This event significantly enhanced the binding of NCOA3 to ATF4 and the expression of purine metabolism-associated target genes. Conversely, deficient phosphorylation of NCOA3 at S1062/T1067 significantly abrogated the function of UHMK1 in GC development. Clinically, Helicobacter pylori and GC-associated UHMK1 mutation induced NCOA3-S1062/T1067 phosphorylation and enhanced the activity of ATF4 and UHMK1. Importantly, the level of UHMK1 was significantly correlated with the level of phospho-NCOA3 (S1062/T1067) in human GC specimens. Collectively, these results show that the UHMK1-activated de novo purine synthesis pathway significantly promotes GC development.
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Péptidos y Proteínas de Señalización Intracelular/metabolismo , Coactivador 3 de Receptor Nuclear/metabolismo , Nucleótidos/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Neoplasias Gástricas/genética , Animales , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Coactivador 3 de Receptor Nuclear/genética , Fosforilación , Proteínas Serina-Treonina Quinasas/genética , Estómago/patología , Neoplasias Gástricas/patología , Regulación hacia ArribaRESUMEN
O6-Methylguanine-DNA-methyltransferase (MGMT) is a demethylation protein that dynamically regulates the O6-methylguanine modification (O6 MeG), and dysregulated MGMT is implicated in various malignant tumors. Herein, we integrate demethylation-activated DNAzyme with a single quantum dot nanosensor to sensitively detect MGMT in breast tissues. The presence of MGMT induces the demethylation of the O6 MeG-caged DNAzyme and the restoration of catalytic activity. The activated DNAzyme then specifically cleaves the ribonucleic acid site of hairpin DNA to expose toehold sequences. The liberated toehold sequence may act as a primer to trigger a cyclic exponential amplification reaction for the generation of enormous signal strands that bind with the Cy5/biotin-labeled probes to form sandwich hybrids. The assembly of sandwich hybrids onto 605QD obtains 605QD-dsDNA-Cy5 nanostructures, inducing efficient FRET between the 605QD donor and Cy5 acceptor. Notably, the introduction of a mismatched base in hairpin DNA can greatly minimize the background and improve the signal-to-noise ratio. This nanosensor achieves a dynamic range of 1.0 × 10-8 to 0.1 ng/µL and a detection limit of 155.78 aM, and it can screen MGMT inhibitors and monitor cellular MGMT activity with single-cell sensitivity. Moreover, it can distinguish the MGMT level in tissues of breast cancer patients and healthy persons, holding great potential in clinical diagnostics and epigenetic research studies.
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Carbocianinas , ADN Catalítico , Guanina/análogos & derivados , Puntos Cuánticos , Humanos , ADN Catalítico/metabolismo , O(6)-Metilguanina-ADN Metiltransferasa/metabolismo , ADN/química , DesmetilaciónRESUMEN
Telomerase is an important biomarker for early diagnosis of cancers, but current telomerase assays usually rely on measuring the extension products of telomerase substrates, which increases the assay complexity. More evidence indicates that human telomerase RNA (hTR), as a core component of telomerase, is positively correlated with the telomerase activity. Herein, we demonstrate the development of a duplex-specific nuclease (DSN)-propelled 3D quantum dot (QD) nanoassembly with two-step Föster resonance energy transfer (FRET) for the one-step sensing of hTR in breast cancer cells and tissues. This assay involves only one hairpin probe modified with a Cy5 at the sixth base from the 5'-biotin end and a BHQ2 at the 3'-terminus, which integrates three functions of target recognition, target recycling amplification, and signal readout. The anchoring of the hairpin probe on the 605QD surface results in the formation of a 3D 605QD-Cy5-probe-BHQ2 nanoassembly in which two-step FRET occurs among the 605QD, Cy5, and BHQ2 quencher. Notably, the formation of 605QD-Cy5-probe-BHQ2 nanoassembly facilitates the reduction of background signal and the increase of signal-to-background ratio due to its dense, highly oriented nucleic acid shell-induced steric hindrance effect. This assay can achieve one-step and rapid detection of hTR with a detection limit of 2.10 fM, which is the simplest and most rapid hTR assay reported so far. Moreover, this assay can efficiently distinguish single-base mismatched sequences, and it can discriminate the hTR level between breast cancer patients and healthy donors with a high accuracy of 100%, with great prospects for early diagnosis of cancers.
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Neoplasias de la Mama , Transferencia Resonante de Energía de Fluorescencia , Puntos Cuánticos , ARN , Telomerasa , Humanos , Telomerasa/metabolismo , Telomerasa/análisis , Puntos Cuánticos/química , ARN/metabolismo , ARN/análisis , Femenino , Carbocianinas/química , Técnicas Biosensibles/métodosRESUMEN
BACKGROUND: Estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER2) negative breast cancer (ER+/HER2-BC) and triple-negative breast cancer (TNBC) are two distinct breast cancer molecular subtypes, especially in tumor immune microenvironment (TIME). The TIME of TNBC is considered to be more inflammatory than that of ER+/HER2-BC. Natural killer (NK) cells are innate lymphocytes that play an important role of tumor eradication in TME. However, studies focusing on the different cell states of NK cells in breast cancer subtypes are still inadequate. METHODS: In this study, single-cell mRNA sequencing (scRNA-seq) and bulk mRNA sequencing data from ER+/HER2-BC and TNBC were analyzed. Key regulator of NK cell suppression in ER+/HER2-BC, S100A9, was quantified by qPCR and ELISA in MCF-7, T47D, MDA-MB-468 and MDA-MB-231 cell lines. The prognosis predictability of S100A9 and NK activation markers was evaluated by Kaplan-Meier analyses using TCGA-BRAC data. The phenotype changes of NK cells in ER+/HER2-BC after overexpressing S100A9 in cancer cells were evaluated by the production levels of IFN-gamma, perforin and granzyme B and cytotoxicity assay. RESULTS: By analyzing scRNA-seq data, we found that multiple genes involved in cellular stress response were upregulated in ER+/HER2-BC compared with TNBC. Moreover, TLR regulation pathway was significantly enriched using differentially expressed genes (DEGs) from comparing the transcriptome data of ER+/HER2-BC and TNBC cancer cells, and NK cell infiltration high/low groups. Among the DEGs, S100A9 was identified as a key regulator. Patients with higher expression levels of S100A9 and NK cell activation markers had better overall survival. Furthermore, we proved that overexpression of S100A9 in ER+/HER2-cells could improve cocultured NK cell function. CONCLUSION: In conclusion, the study we presented demonstrated that NK cells in ER+/HER2-BC were hypofunctional, and S100A9 was an important regulator of NK cell function in ER+BC. Our work contributes to elucidate the regulatory networks between cancer cells and NK cells and may provide theoretical basis for novel drug development.
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Neoplasias de la Mama , Calgranulina B , Células Asesinas Naturales , Receptores de Estrógenos , Humanos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Femenino , Calgranulina B/genética , Calgranulina B/metabolismo , Receptores de Estrógenos/metabolismo , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Microambiente Tumoral/inmunología , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Pronóstico , Línea Celular Tumoral , Regulación Neoplásica de la Expresión GénicaRESUMEN
PURPOSE: To investigate potential differences in pathological complete response (pCR) rates and overall survival (OS) between HER2-low and HER2-zero patients with early-stage hormone receptor (HR)-positive and triple-negative breast cancer (TNBC), in the neoadjuvant chemotherapy setting. METHODS: We identified early-stage invasive HER2-negative BC patients who received neoadjuvant chemotherapy diagnosed between 2010 and 2018 in the National Cancer Database. HER2-low was defined by immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization, and HER2-zero by IHC0. All the methods were applied separately in the HR-positive and TNBC cohorts. Logistic regression was used to estimate the association of HER2 status with pCR (i.e. ypT0/Tis and ypN0). Kaplan-Meier method and Cox proportional hazards model were applied to estimate the association of HER2 status with OS. Inverse probability weighting and/or multivariable regression were applied to all analyses. RESULTS: For HR-positive patients, 70.9% (n = 17,934) were HER2-low, whereas 51.1% (n = 10,238) of TNBC patients were HER2-low. For both HR-positive and TNBC cohorts, HER2-low status was significantly associated with lower pCR rates [HR-positive: 5.0% vs. 6.7%; weighted odds ratio (OR) = 0.81 (95% CI: 0.72-0.91), p < 0.001; TNBC: 21.6% vs. 24.4%; weighted OR = 0.91 (95% CI: 0.85-0.98), p = 0.007] and improved OS [HR-positive: weighted hazard ratio = 0.85 (95% CI: 0.79-0.91), p < 0.001; TNBC: weighted hazard ratio = 0.91 (95% CI: 0.86-0.96), p < 0.001]. HER2-low status was associated with favorable OS among patients not achieving pCR [HR-positive: adjusted hazard ratio = 0.83 (95% CI: 0.77-0.89), p < 0.001; TNBC: adjusted hazard ratio = 0.88 (95% CI 0.83-0.94), p < 0.001], while no significant difference in OS was observed in patients who achieved pCR [HR-positive: adjusted hazard ratio = 1.00 (95% CI: 0.61-1.63), p > 0.99; TNBC: adjusted hazard ratio = 1.11 (95% CI: 0.85-1.45), p = 0.44]. CONCLUSION: In both early-stage HR-positive and TNBC patients, HER2-low status was associated with lower pCR rates. HER2-zero status might be considered an adverse prognostic factor for OS in patients not achieving pCR.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Terapia Neoadyuvante/efectos adversos , Modelos de Riesgos Proporcionales , Receptor ErbB-2/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , PronósticoRESUMEN
Lithium metal-based rechargeable batteries are attracting increasing attention due to their high theoretical specific capacity and energy density. However, the dendrite growth leads to short circuits or even explosions and rapid depletion of active materials and electrolytes. Here, a functionalized and laminated scaffold (PVDF/TiO@C fiber) based on lithiophilic titanium monoxide is rationally designed to inhibit dendrite growth. Specifically, the bottom TiO@C fiber sublayer provides rich Li nucleation sites and facilitates the formation of stable solid electrolyte interphase. Together with the top lithiophobic PVDF sublayer, the prepared freestanding scaffold can effectively suppress the growth of Li dendrite and ensure stable Li plating/stripping. Based on the dendrite-free deposition, the Li/PVDF/TiO@ C fiber anode enables over 1000 h at a current density of 1 mA cm-2 in a symmetrical cell and delivers superior electrochemical performance in both Li || LFP and Li-S batteries. The functional laminated fiber scaffold design provides essential insights for obtaining high-performance lithium metal anodes.
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The low energy efficiency and limited cycling life of rechargeable Zn-air batteries (ZABs) arising from the sluggish oxygen reduction/evolution reactions (ORR/OERs) severely hinder their commercial deployment. Herein, a zeolitic imidazolate framework (ZIF)-derived strategy associated with subsequent thermal fixing treatment is proposed to fabricate dual-atom CoFeâNâC nanorods (Co1 Fe1 âNâC NRs) containing atomically dispersed bimetallic Co/Fe sites, which can promote the energy efficiency and cyclability of ZABs simultaneously by introducing the low-potential oxidation redox reactions. Compared to the mono-metallic nanorods, Co1 Fe1 âNâC NRs exhibit remarkable ORR performance including a positive half-wave potential of 0.933 V versus reversible hydrogen electrode (RHE) in alkaline electrolyte. Surprisingly, after introducing the potassium iodide (KI) additive, the oxidation overpotential of Co1 Fe1 âNâC NRs to reach 10 mA cm-2 can be significantly reduced by 395 mV compared to the conventional destructive OER. Theoretical calculations show that the markedly decreased overpotential of iodide oxidation can be ascribed to the synergistic effects of neighboring CoâFe diatomic sites as the unique adsorption sites. Overall, aqueous ZABs assembled with Co1 Fe1 âNâC NRs and KI as the air-cathode catalyst and electrolyte additive, respectively, can deliver a low charging voltage of 1.76 V and ultralong cycling stability of over 230 h with a high energy efficiency of ≈68%.
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It is challenging yet promising to design highly accessible N-doped carbon skeletons to fully expose the active sites inside single-atom catalysts. Herein, mesoporous N-doped carbon hollow spheres with regulatable through-pore size can be formulated by a simple sequential synthesis procedure, in which the condensed SiO2 is acted as removable dual-templates to produce both hollow interiors and through-pores, meanwhile, the co-condensed polydopamine shell is served as N-doped carbon precursor. After that, FeâNâC hollow spheres (HSs) with highly accessible active sites can be obtained after rationally implanting Fe single-atoms. Microstructural analysis and X-ray absorption fine structure analysis reveal that high-density FeâN4 active sites together with tiny Fe clusters are uniformly distributed on the mesoporous carbon skeleton with abundant through-pores. Benefitted from the highly accessible FeâN4 active sites arising from the unique through-pore architecture, the FeâNâC HSs demonstrate excellent oxygen reduction reaction (ORR) performance in alkaline media with a half-wave potential up to 0.90 V versus RHE and remarkable stability, both exceeding the commercial Pt/C. When employing FeâNâC HSs as the air-cathode catalysts, the assembled Zn-air batteries deliver a high peak power density of 204 mW cm-2 and stable discharging voltage plateau over 140 h.
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In recent years, with advancements in medicine, the survival period of patients with tumours has significantly increased. The adverse effects of tumour treatment on patients, especially cardiac toxicity, have become increasingly prominent. In elderly patients with breast cancer, treatment-related cardiovascular toxicity has surpassed cancer itself as the leading cause of death. Moreover, in recent years, an increasing number of novel antitumour drugs, such as multitargeted agents, antibodyâdrug conjugates (ADCs), and immunotherapies, have been applied in clinical practice. The cardiotoxicity induced by these drugs has become more pronounced, leading to a complex and diverse mechanism of cardiac damage. The risks of unintended cardiovascular toxicity are increased by high-dose anthracyclines, immunotherapies, and concurrent radiation, in addition to traditional cardiovascular risk factors such as smoking, hypertension, diabetes, hyperlipidaemia, and obesity. However, these factors do not fully explain why only a subset of individuals experience treatment-related cardiac toxicity, whereas others with similar clinical features do not. Recent studies indicate that genetics play a significant role in susceptibility to the development of cardiovascular toxicity from cancer therapies. These genes are involved in drug metabolism, oxidative damage, cardiac dysfunction, and other processes. Moreover, emerging evidence suggests that epigenetics also plays a role in drug-induced cardiovascular toxicity. We conducted a review focusing on breast cancer as an example to help oncologists and cardiologists better understand the mechanisms and effects of genetic factors on cardiac toxicity. In this review, we specifically address the relationship between genetic alterations and cardiac toxicity, including chemotherapy-related genetic changes, targeted therapy-related genetic changes, and immune therapy-related genetic changes. We also discuss the role of epigenetic factors in cardiac toxicity. We hope that this review will improve the risk stratification of patients and enable therapeutic interventions that mitigate these unintended adverse consequences of life-saving cancer treatments.
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Antineoplásicos , Humanos , Antineoplásicos/efectos adversos , Cardiotoxicidad/etiología , Neoplasias/genética , Epigénesis Genética , Oncología Médica , Animales , Predisposición Genética a la Enfermedad , CardiooncologíaRESUMEN
Food authentication and origin traceability are popular research topics, especially as concerns about food quality continue to increase. Mass spectrometry (MS) plays an indispensable role in food authentication and origin traceability. In this review, the applications of MS in food authentication and origin traceability by analyzing the main components and chemical fingerprints or profiles are summarized. In addition, the characteristic markers for food authentication are also reviewed, and the advantages and disadvantages of MS-based techniques for food authentication, as well as the current trends and challenges, are discussed. The fingerprinting and profiling methods, in combination with multivariate statistical analysis, are more suitable for the authentication of high-value foods, while characteristic marker-based methods are more suitable for adulteration detection. Several new techniques have been introduced to the field, such as proton transfer reaction mass spectrometry, ambient ionization mass spectrometry (AIMS), and ion mobility mass spectrometry, for the determination of food adulteration due to their fast and convenient analysis. As an important trend, the miniaturization of MS offers advantages, such as small and portable instrumentation and fast and nondestructive analysis. Moreover, many applications in food authentication are using AIMS, which can help food authentication in food inspection/field analysis. This review provides a reference and guide for food authentication and traceability based on MS.