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1.
Nat Mater ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937585

RESUMO

Organic semiconductors (OSCs) are one of the most promising candidates for flexible, wearable and large-area electronics. However, the development of n-type OSCs has been severely held back due to the poor stability of their most candidates, that is, the intrinsically high reactivity of negatively charged polarons to oxygen and water. Here we demonstrate a general strategy based on vitamin C to stabilize n-type OSCs, remarkably improving the performance and stability of their device, for example, organic field-effect transistors. Vitamin C scavenges reactive oxygen species and inhibits their generation by sacrificial oxidation and non-sacrificial triplet quenching in a cascade process, which not only lastingly prevents molecular structure from oxidation damage but also passivates the latent electron traps to stabilize electron transport. This study presents a way to overcome the long-standing stability problem of n-type OSCs and devices.

2.
Proc Natl Acad Sci U S A ; 119(39): e2117988119, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36126099

RESUMO

Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype for its high rates of relapse, great metastatic potential, and short overall survival. How cancer cells acquire metastatic potency through the conversion of noncancer stem-like cells into cancer cells with stem-cell properties is poorly understood. Here, we identified the long noncoding RNA (lncRNA) TGFB2-AS1 as an important regulator of the reversibility and plasticity of noncancer stem cell populations in TNBC. We revealed that TGFB2-AS1 impairs the breast cancer stem-like cell (BCSC) traits of TNBC cells in vitro and dramatically decreases tumorigenic frequency and lung metastasis in vivo. Mechanistically, TGFB2-AS1 interacts with SMARCA4, a core subunit of the SWI/SNF chromatin remodeling complex, and results in transcriptional repression of its target genes including TGFB2 and SOX2 in an in cis or in trans way, leading to inhibition of transforming growth factor ß (TGFß) signaling and BCSC characteristics. In line with this, TGFB2-AS1 overexpression in an orthotopic TNBC mouse model remarkably abrogates the enhancement of tumor growth and lung metastasis endowed by TGFß2. Furthermore, combined prognosis analysis of TGFB2-AS1 and TGFß2 in TNBC patients shows that high TGFB2-AS1 and low TGFß2 levels are correlated with better outcome. These findings demonstrate a key role of TGFB2-AS1 in inhibiting disease progression of TNBC based on switching the cancer cell fate of TNBC and also shed light on the treatment of TNBC patients.


Assuntos
Neoplasias Pulmonares , RNA Longo não Codificante , Neoplasias de Mama Triplo Negativas , Animais , DNA Helicases/genética , Humanos , Neoplasias Pulmonares/secundário , Camundongos , Recidiva Local de Neoplasia , Proteínas Nucleares/genética , RNA Longo não Codificante/genética , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta2/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
3.
Rheumatology (Oxford) ; 63(1): 251-258, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-37184873

RESUMO

OBJECTIVES: Galectin-9, as immune checkpoint protein, plays a role in regulating autoimmunity and tumour immunity. Therefore, we explored the pathophysiological link between galectin-9 and malignancy in cancer-related DM (CRDM). METHODS: Serum galectin-9 were quantified via enzyme-linked immunosorbent assay, and its association with serological indices was evaluated using Spearman analysis. Receiver operating characteristic (ROC) analysis was utilized to determine the cut-off value of galectin-9. RESULTS: Serum levels of galectin-9 were significantly higher in DM patients [23.38 (13.85-32.57) ng/ml] than those in healthy controls (HCs) [6.81 (5.42-7.89) ng/ml, P < 0.0001], and were positively correlated with the cutaneous dermatomyositis disease area severity index activity (CDASI-A) scores (rs=0.3065, P = 0.0172). DM patients with new-onset and untreated cancer (new-CRDM) [31.58 (23.85-38.84) ng/ml] had higher levels of galectin-9 than those with stable and treated cancer (stable-CRDM) [17.49 (10.23-27.91) ng/ml, P = 0.0288], non-cancer-related DM (non-CRDM) [21.05 (11.97-28.02) ng/ml, P = 0.0258], and tumour patients without DM [7.46 (4.90-8.51) ng/ml, P < 0.0001]. Serum galectin-9 levels significantly decreased [27.79 (17.04-41.43) ng/ml vs 13.88 (5.15-20.37) ng/ml, P = 0.002] after anti-cancer treatment in CRDM patients. The combination of serum galectin-9 and anti-transcriptional intermediary factor 1-γ (anti-TIF1-γ) antibody (AUC = 0.889, 95% CI 0.803-0.977) showed the highest predictive value for the presence of cancer in DM. CONCLUSION: Increased galectin-9 levels were related to tumor progression in CRDM, and galectin-9 was downregulated upon cancer treatment. Monitoring serum galectin-9 levels and anti-TIF1-γ antibodies might be an attractive strategy to achieve tumour diagnosis and predict CRDM outcome.


Assuntos
Dermatomiosite , Neoplasias , Humanos , Dermatomiosite/complicações , Neoplasias/complicações , Galectinas , Anticorpos , Biomarcadores , Autoanticorpos
4.
PLoS Comput Biol ; 19(11): e1011636, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37976299

RESUMO

Schooling fish heavily rely on visual cues to interact with neighbors and avoid obstacles. The availability of sensory information is influenced by environmental conditions and changes in the physical environment that can alter the sensory environment of the fish, which in turn affects individual and group movements. In this study, we combine experiments and data-driven modeling to investigate the impact of varying levels of light intensity on social interactions and collective behavior in rummy-nose tetra fish. The trajectories of single fish and groups of fish swimming in a tank under different lighting conditions were analyzed to quantify their movements and spatial distribution. Interaction functions between two individuals and the fish interaction with the tank wall were reconstructed and modeled for each light condition. Our results demonstrate that light intensity strongly modulates social interactions between fish and their reactions to obstacles, which then impact collective motion patterns that emerge at the group level.


Assuntos
Comportamento Social , Interação Social , Animais , Comportamento Animal/fisiologia , Modelos Biológicos , Peixes/fisiologia , Natação/fisiologia
5.
Eur Radiol ; 34(8): 5477-5486, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38329503

RESUMO

OBJECTIVES: Anti-HER2 targeted therapy significantly reduces risk of relapse in HER2 + breast cancer. New measures are needed for a precise risk stratification to guide (de-)escalation of anti-HER2 strategy. METHODS: A total of 726 HER2 + cases who received no/single/dual anti-HER2 targeted therapies were split into three respective cohorts. A deep learning model (DeepTEPP) based on preoperative breast magnetic resonance (MR) was developed. Patients were scored and categorized into low-, moderate-, and high-risk groups. Recurrence-free survival (RFS) was compared in patients with different risk groups according to the anti-HER2 treatment they received, to validate the value of DeepTEPP in predicting treatment efficacy and guiding anti-HER2 strategy. RESULTS: DeepTEPP was capable of risk stratification and guiding anti-HER2 treatment strategy: DeepTEPP-Low patients (60.5%) did not derive significant RFS benefit from trastuzumab (p = 0.144), proposing an anti-HER2 de-escalation. DeepTEPP-Moderate patients (19.8%) significantly benefited from trastuzumab (p = 0.048), but did not obtain additional improvements from pertuzumab (p = 0.125). DeepTEPP-High patients (19.7%) significantly benefited from dual HER2 blockade (p = 0.045), suggesting an anti-HER2 escalation. CONCLUSIONS: DeepTEPP represents a pioneering MR-based deep learning model that enables the non-invasive prediction of adjuvant anti-HER2 effectiveness, thereby providing valuable guidance for anti-HER2 (de-)escalation strategies. DeepTEPP provides an important reference for choosing the appropriate individualized treatment in HER2 + breast cancer patients, warranting prospective validation. CLINICAL RELEVANCE STATEMENT: We built an MR-based deep learning model DeepTEPP, which enables the non-invasive prediction of adjuvant anti-HER2 effectiveness, thus guiding anti-HER2 (de-)escalation strategies in early HER2-positive breast cancer patients. KEY POINTS: • DeepTEPP is able to predict anti-HER2 effectiveness and to guide treatment (de-)escalation. • DeepTEPP demonstrated an impressive prognostic efficacy for recurrence-free survival and overall survival. • To our knowledge, this is one of the very few, also the largest study to test the efficacy of a deep learning model extracted from breast MR images on HER2-positive breast cancer survival and anti-HER2 therapy effectiveness prediction.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Imageamento por Ressonância Magnética , Receptor ErbB-2 , Trastuzumab , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Feminino , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Trastuzumab/uso terapêutico , Adulto , Idoso , Resultado do Tratamento , Medição de Risco , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Estudos Retrospectivos , Radiômica , Anticorpos Monoclonais Humanizados
6.
Chaos ; 34(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38341762

RESUMO

Collective ordering behaviors are typical macroscopic manifestations embedded in complex systems and can be ubiquitously observed across various physical backgrounds. Elements in complex systems may self-organize via mutual or external couplings to achieve diverse spatiotemporal coordinations. The order parameter, as a powerful quantity in describing the transition to collective states, may emerge spontaneously from large numbers of degrees of freedom through competitions. In this minireview, we extensively discussed the collective dynamics of complex systems from the viewpoint of order-parameter dynamics. A synergetic theory is adopted as the foundation of order-parameter dynamics, and it focuses on the self-organization and collective behaviors of complex systems. At the onset of macroscopic transitions, slow modes are distinguished from fast modes and act as order parameters, whose evolution can be established in terms of the slaving principle. We explore order-parameter dynamics in both model-based and data-based scenarios. For situations where microscopic dynamics modeling is available, as prototype examples, synchronization of coupled phase oscillators, chimera states, and neuron network dynamics are analytically studied, and the order-parameter dynamics is constructed in terms of reduction procedures such as the Ott-Antonsen ansatz, the Lorentz ansatz, and so on. For complicated systems highly challenging to be well modeled, we proposed the eigen-microstate approach (EMP) to reconstruct the macroscopic order-parameter dynamics, where the spatiotemporal evolution brought by big data can be well decomposed into eigenmodes, and the macroscopic collective behavior can be traced by Bose-Einstein condensation-like transitions and the emergence of dominant eigenmodes. The EMP is successfully applied to some typical examples, such as phase transitions in the Ising model, climate dynamics in earth systems, fluctuation patterns in stock markets, and collective motion in living systems.

7.
Br J Cancer ; 129(8): 1274-1283, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37604930

RESUMO

BACKGROUND: HER2-low breast cancers (BC) show a good response to novel anti-HER2 antibody-drug conjugates (ADCs) in advanced setting. Nevertheless, little is known about the response, category change, and prognosis of HER2-low BC receiving neoadjuvant treatment (NAT). METHODS: Consecutive invasive BC patients who underwent ≥ 4 cycles of NAT and surgery from January 2009 to December 2020 were retrospectively reviewed. HER2-low was defined as IHC 1+ or 2+ and FISH negative. Concordance rates of HER2 and other biomarkers were analyzed by Kappa test. Kaplan-Meier analysis and Cox regression were used to assess the recurrence-free interval (RFI) and overall survival (OS). RESULTS: A total of 2489 patients were included, of whom 1023 (41.1%) had HER2-low tumors. HER2-low patients had a higher ER positivity rate than HER2-0 patients (78.5% vs. 63.6%, P < 0.001), and a similar breast pathological complete response (pCR) rate (20.6% vs. 21.8%, P = 0.617). Among non-pCR cases, 39.5% of HER2-0 tumors changed to HER2-low, and 14.3% of HER2-low tumors changed to HER2-0 after NAT. Low concordance rates of HER2-low status were found in both ER-positive (Kappa = 0.368) and ER-negative (Kappa = 0.444) patients. Primary HER2-low patients had a significantly better RFI than HER2-0 patients (P = 0.014), especially among ER-positive subset (P = 0.016). Moreover, HER2-low category change was associated with RFI in ER-positive subset (adjusted P = 0.043). CONCLUSIONS: Compared with HER2-0 patients, HER2-low patients had a high proportion of ER-positive tumor and a similar pCR rate, which were related with better prognosis, especially in residual cases after NAT. A remarkable instability of HER2-low status was found between the primary and residual tumor, indicating re-testing HER2 status after NAT in the new era of anti-HER2 ADCs therapy.


Assuntos
Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Prognóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Terapia Neoadjuvante , Estudos Retrospectivos , Receptor ErbB-2/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antineoplásicos/uso terapêutico
8.
Breast Cancer Res Treat ; 197(3): 525-533, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36525180

RESUMO

PURPOSE: Breast cancer patients with metabolic syndrome (MetS) and its components show worse treatment responses to chemotherapy. Metformin is a widely used antidiabetic drug which also shows potential anticancer effect. This study aims to evaluate the efficacy, safety, and metabolic parameters change of metformin combined with docetaxel, epirubicin, and cyclophosphamide (TEC) in neoadjuvant treatment (NAT) for breast cancer patients with metabolic abnormality. METHODS: Eligible breast cancer patients were randomized to receive six cycles of TEC (docetaxel 75 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2, d1, q3w) or TEC with metformin (TECM, TEC with oral metformin 850 mg once daily for the first cycle, then 850 mg twice daily for the following cycles). The primary end point was total pathological complete response (tpCR, ypTis/0N0) rate. RESULTS: Ninety-two patients were enrolled and randomized from October 2013 to December 2019: 88 patients were available for response and safety assessment. The tpCR rates were 12.5% (5/40) and 14.6% (7/48) in the TEC and TECM groups, respectively (P = 0.777). There was no difference in Ki67 decrease after NAT between two groups (P = 0.456). Toxicity profile were similar between two groups. No grade 3 or higher diarrhea were recorded. Total cholesterol (TC) and high-density lipoprotein cholesterol worsened after NAT in the TEC arm but remained stable in the TECM arm. The absolute increase of TC and low-density lipoprotein cholesterol (LDL-C) was significantly lower in the TECM group compared with the TEC group. After a median follow-up of 40.8 (4.7-70.8) months, no survival difference was observed between TEC and TECM groups (all P > 0.05). CONCLUSION: Adding metformin to TEC didn't increase pCR rate and disease outcome in breast cancer patients with metabolic abnormality. However, additional metformin treatment with chemotherapy would prevent TC and LDL-C increase after NAT. Trial Registration ClinicalTrials.gov Identifier: NCT01929811.


Assuntos
Neoplasias da Mama , Metformina , Humanos , Feminino , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Docetaxel , Epirubicina , Terapia Neoadjuvante/métodos , Metformina/efeitos adversos , LDL-Colesterol/uso terapêutico , Fluoruracila , Receptor ErbB-2/metabolismo , Ciclofosfamida , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento
9.
Small ; 19(50): e2304634, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37626464

RESUMO

Suppressing the photoelectric response of organic semiconductors (OSs) is of great significance for improving the operational stability of organic field-effect transistors (OFETs) in light environments, but it is quite challenging because of the great difficulty in precisely modulating exciton dynamics. In this work, photostable OFETs are demonstrated by designing the micro-structure of OSs and introducing an electrical double layer at the OS/polyelectrolyte dielectric interface, in which multiple exciton dynamic processes can be modulated. The generation and dissociation of excitons are depressed due to the small light-absorption area of the microstripe structure and the excellent crystallinity of OSs. At the same time, a highly efficient exciton quenching process is activated by the electrical double layer at the OS/polyelectrolyte dielectric interface. As a result, the OFETs show outstanding tolerance to the light irradiation of up to 306 mW·cm-2 , which far surpasses the solar irradiance value in the atmosphere (≈138 mW·cm-2 ) and achieves the highest photostability ever reported in the literature. The findings promise a general and practicable strategy for the realization of photostable OFETs and organic circuits.

10.
Small ; 19(38): e2301421, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37264765

RESUMO

Organic semiconductor single crystals (OSSCs) are ideal materials for studying the intrinsic properties of organic semiconductors (OSCs) and constructing high-performance organic field-effect transistors (OFETs). However, there is no general method to rapidly prepare thickness-controllable and uniform single crystals for various OSCs. Here, inspired by the recrystallization (a spontaneous morphological instability phenomenon) of polycrystalline films, a spatial confinement recrystallization (SCR) method is developed to rapidly (even at several second timescales) grow thickness-controllable and uniform OSSCs in a well-controlled way by applying longitudinal pressure to tailor the growth direction of grains in OSCs polycrystalline films. The relationship between growth parameters including the growth time, temperature, longitudinal pressure, and thickness is comprehensively investigated. Remarkably, this method is applicable for various OSCs including insoluble and soluble small molecules and polymers, and can realize the high-quality crystal array growth. The corresponding 50 dinaphtho[2,3-b:2″,3″-f]thieno[3,2-b]thiophene (DNTT) single crystals coplanar OFETs prepared by the same batch have the mobility of 4.1 ± 0.4 cm2 V-1 s-1 , showing excellent uniformity. The overall performance of the method is superior to the reported methods in term of growth rate, generality, thickness controllability, and uniformity, indicating its broad application prospects in organic electronic and optoelectronic devices.

11.
BMC Cancer ; 23(1): 615, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400804

RESUMO

BACKGROUND: Insulin resistance is an overlapping risk factor for both heart and breast cancer, while its interaction with cardiotoxicity in breast cancer (BC) patients is not clear. This study investigated the impact of insulin resistance on cardiac remodeling in patients with human epidermal growth factor receptor 2 (HER2)-positive BC during and after trastuzumab therapy in real-world clinical practice. METHODS: HER2-positive BC patients who received trastuzumab treatment between December 2012 and December 2017 were reviewed and 441 patients with baseline metabolic indices and serial echocardiographic measurements (baseline, 6, 12, and 18 months) after trastuzumab therapy initiation were included. Repeated measurement analysis of variance was used to evaluate temporal trends in multiparameter echocardiography. Linear mixed model was applied to further evaluate the role of insulin resistance in forementioned changes. Correlation of homeostasis model assessment-estimated insulin resistance (HOMA-IR) and triglyceride-glucose index (TyG) levels to changes in echocardiography parameters was explored. RESULTS: Of 441 patients (mean age 54 ± 10 [SD] years), 61.8% received anthracycline-based chemotherapy, 33.5% received left-sided radiotherapy, 46% received endocrine therapy. No symptomatic cardiac dysfunction was observed over the therapy course. A total of 19 (4.3%) participants experienced asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), and the peak onset time was 12 months after the initiation of trastuzumab. Albeit relatively low CTRCD incidence, cardiac geometry remodeling, especially left atrial (LA) dilation over therapy was notable and was more severe in high HOMA-IR and TyG level groups (P < 0.01). Noteworthy, a partial reversibility of cardiac remodeling was observed with treatment cessation. Additionally, HOMA-IR level positively correlated to changes in LA diameter from baseline to 12 months (r = 0.178, P = 0.003). No significant association (all P > 0.10) was detected between HOMA-IR or TyG level and dynamic left ventricular parameter evaluation. Multivariate linear regression analysis demonstrated that higher HOMA-IR level was an independent determinant for LA enlargement in BC patients during anti-HER2 targeted therapy course after adjusting for confounding risk factors (P = 0.006). CONCLUSION: Insulin resistance was associated with left atrial adverse remodeling (LAAR) in HER2-positive BC patients that received standard trastuzumab therapy, indicating that insulin resistance could be a supplementation to baseline cardiovascular risk stratification proforma for HER2-targeted antitumor therapies.


Assuntos
Fibrilação Atrial , Neoplasias da Mama , Cardiopatias , Resistência à Insulina , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Fibrilação Atrial/complicações , Neoplasias da Mama/patologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/tratamento farmacológico , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêutico , Remodelação Ventricular
12.
Lasers Surg Med ; 55(2): 178-189, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36573453

RESUMO

BACKGROUND AND OBJECTIVES: Melasma is a refractory skin disease due to its complex pathogenesis and difficult treatment. Studies have found that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) could serve as a novel cell-free therapeutic strategy in regenerative and esthetic medicine. It could potentially treat melasma, but the skin barrier is a challenge. In this study, we aim to explore the safety and efficacy of hUCMSC-Exos in the treatment of melasma and the means to promote its percutaneous penetration. MATERIALS AND METHODS: In the animal study about the effect of penetration, percutaneous penetration of PKH67-labeled hUCMSC-Exos was studied under microneedles, 1565 nm nonablative fractional laser (NAFL), and a plasma named Peninsula Blue Aurora Shumin Master (PBASM) treatments, observed by confocal laser scanning microscopy. In the clinical application study, 60 patients with melasma treated in our department were divided into four groups. NAFL combined with normal saline treatment was used for Group A. Microneedles, NAFL, and PBASM combined with hUCMSC-Exos treatments were used for Groups B, C, and D, respectively. Each patient received four treatments at 1-month intervals. Assessments were done using the degree of pain posttreatment, melasma area and severity score, improvement rate, physician global assessment score, satisfaction, and complications. RESULTS: In the animal study about the effect of penetration, hUCMSC-Exos can penetrate the deep dermis under microneedles, NAFL, and PBASM treatments. In the clinical application study, compared with Group A, Groups B, C, and D showed significantly improved therapeutic effect and patient satisfaction (p < 0.05), and there was no significant difference among Groups B, C, and D.(p > 0.05). Patients in Group B reported higher pain levels than those in the other three groups (p < 0.05); the treatment experience of patients in Group D was better. CONCLUSION: hUCMSC-Exos can improve the symptoms of melasma safely and effectively. Compared with microneedles, NAFL and PBASM can also achieve a good effect toward promoting penetration. These findings are worthy of exploration and clinical application.


Assuntos
Exossomos , Melanose , Células-Tronco Mesenquimais , Animais , Humanos , Pele , Melanose/terapia , Células-Tronco
13.
Proc Natl Acad Sci U S A ; 117(1): 177-183, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31874928

RESUMO

The El Niño Southern Oscillation (ENSO) is one of the most prominent interannual climate phenomena. Early and reliable ENSO forecasting remains a crucial goal, due to its serious implications for economy, society, and ecosystem. Despite the development of various dynamical and statistical prediction models in the recent decades, the "spring predictability barrier" remains a great challenge for long-lead-time (over 6 mo) forecasting. To overcome this barrier, here we develop an analysis tool, System Sample Entropy (SysSampEn), to measure the complexity (disorder) of the system composed of temperature anomaly time series in the Niño 3.4 region. When applying this tool to several near-surface air temperature and sea surface temperature datasets, we find that in all datasets a strong positive correlation exists between the magnitude of El Niño and the previous calendar year's SysSampEn (complexity). We show that this correlation allows us to forecast the magnitude of an El Niño with a prediction horizon of 1 y and high accuracy (i.e., root-mean-square error = 0.23° C for the average of the individual datasets forecasts). For the 2018 El Niño event, our method forecasted a weak El Niño with a magnitude of 1.11±0.23° C. Our framework presented here not only facilitates long-term forecasting of the El Niño magnitude but can potentially also be used as a measure for the complexity of other natural or engineering complex systems.

14.
Proc Natl Acad Sci U S A ; 117(52): 33295-33304, 2020 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-33318171

RESUMO

Adipocytes have been implicated in breast tumor growth and stemness maintenance through secreted factors. However, the mechanisms by which these cytokines are regulated during diet-induced obesity and contribute to breast tumorigenesis remain largely unknown. Here we show that transcription cofactor TAZ in adipocytes is directly up-regulated by the free fatty acid/PPARγ axis upon dietary fat stimulation. TAZ knockdown alters the expression profile of a series of secreted proteins and attenuates the tumor-supporting function of adipocytes. Moreover, we identify Resistin, an adipose-derived hormone, as a functional downstream target of TAZ, which facilitates tumorigenesis, and its expression correlated with adipocyitc TAZ in triple-negative breast cancer samples. Further, Adiponectin-cre-mediated TAZ knockout in adipocytes mitigates breast tumor growth. Taken together, our findings highlight how diet-induced TAZ expression in adipocytes promotes tumorigenesis, suggesting promising cancer therapeutic targets.


Assuntos
Adipócitos/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinogênese/patologia , Resistina/metabolismo , Transativadores/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Adipócitos/metabolismo , Adiposidade , Animais , Neoplasias da Mama/genética , Carcinogênese/metabolismo , Proliferação de Células , Dieta , Ácidos Graxos/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos C57BL , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Obesidade/patologia , PPAR gama/metabolismo , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
15.
Chaos ; 33(2): 023127, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36859237

RESUMO

The exhaustive random exploration of a complex domain is a fundamental issue in many natural, social, and engineering systems. The key characterizing quantity is the cover time, which is the time to visit every site in the system. One prototypical experimental platform is the confined granular gas, where the random motion of granular particles mimics the wandering of random walkers in a confined region. Here, we investigate the cover-time distribution of the random motion of tracer particles in granular gases confined in four containers to account for different boundary and angle effects and examine whether the cover time of the heterogeneous random motion of the granular gases can be rescaled into the universal Gumbel distribution according to a recent theory [Dong et al., arXiv:2210.05122 (2022)]. It is found that for long cover times, the experimental results are in full accord, while for short cover times, the agreement is reasonable, with noticeable deviations that can be attributed to spatial correlations of the sites in the covering process. Our results, thus, call for further theoretical investigations in order to take into full account these nonideal issues.

16.
Breast Cancer Res Treat ; 196(1): 129-141, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36076127

RESUMO

PURPOSE: This study aimed to evaluate whether axillary lymph node dissection (ALND) can be omitted in patients with 1-2 positive sentinel lymph nodes (SLNs) who received total mastectomy (TM). METHODS: Consecutive breast cancer patients with 1-2 positive SLNs were retrospectively reviewed from a multi-institutional database. Patients were divided into sentinel lymph node biopsy (SLNB) group and ALND group. Administration of adjuvant chemotherapy and survival were compared between groups. To further verify the results, a meta-analysis was also conducted. RESULTS: Among the 1161 enrolled patients, 893 (76.9%) received ALND and 268 (23.1%) underwent SLNB alone. Administration of chemotherapy was comparable between the two groups (91.1% vs. 90.6%, P = 0.798), which was consistent in TM (P = 0.638) and BCS cohort (P = 0.576). After a median follow-up of 36 months, no significant difference was observed between the two groups in recurrence-free survival (P = 0.583) regardless of surgery of breast. During further meta-analysis, 13 out of 4733 relative studies reported the association of axillary surgery and disease-free survival (DFS) or overall survival (OS) in 1-2 positive SLNs patients. Pooled analysis showed no difference in adjusted DFS (HR 0.84, 95% CI 0.70-1.02) or OS (HR 1.02, 95% CI 0.93-1.11) between SLNB and ALND groups. Survival benefit of ALND remained non-significant after restricting the analysis in four studies with patients only receiving BCS, or in three studies with patients only receiving TM. CONCLUSION: Further ALND does not impact adjuvant chemotherapy administration or disease outcome in breast cancer patients with 1-2 positive SLNs treated with TM.


Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Axila/patologia , Neoplasias da Mama/patologia , Feminino , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Mastectomia/efeitos adversos , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela/métodos
17.
Acc Chem Res ; 54(4): 1011-1022, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33535000

RESUMO

ConspectusSince the rise of two-dimensional (2D) materials, synthetic methods including mechanical exfoliation, solution synthesis, and chemical vapor deposition (CVD) have been developed. Mechanical exfoliation prepares randomly shaped materials with small size. Solution synthesis introduces impurities that degrade the performances. CVD is the most successful one for low-cost scalable preparation. However, when it comes to practical applications, disadvantages such as high operating temperature (∼1000 °C), probable usage of metal catalysts, contamination, defects, and interstices introduced by postgrowth transfer are not negligible. These are the reasons why plasma-enhanced CVD (PECVD), a method that enables catalyst-free in situ preparation at low temperature, is imperatively desirable.In this Account, we summarize our recent progress on controllable preparation of 2D materials by PECVD and their applications. We found that there was a competition between etching and nucleation and deposition in PECVD, making it highly controllable to obtain desired materials. Under different equilibrium states of the competition, various 2D materials with diverse morphologies and properties were prepared including pristine or nitrogen-doped graphene crystals, graphene quantum dots, graphene nanowalls, hexagonal boron nitride (h-BN), B-C-N ternary materials (BCxN), etc. We also used mild plasma to modify or treat 2D materials (e.g., WSe2) for desired properties.PECVD has advantages such as low temperature, transfer-free process, and industrial compatibility, which enable facile, scalable, and low-cost preparation of 2D materials with clean surfaces and interfaces directly on noncatalytic substrates. These merits significantly benefit the as-prepared materials in the applications. Field-effect transistors with high motilities were directly fabricated on graphene and nitrogen-doped graphene. By use of h-BN as the dielectric interfacial layer, both mobilities and saturated power densities of the devices were improved owing to the clean, closely contacted interface and enhanced interfacial thermal dissipation. High-quality materials and interfaces also enabled promising applications of these materials in photodetectors, pressure sensors, biochemical sensors, electronic skins, Raman enhancement, etc. To demonstrate the commercial applications, several prototypical devices were studied such as distributed pressure sensor arrays, touching module on a robot hand for braille recognition, and smart gloves for recording sign language. Finally, we discuss opportunities and challenges of PECVD as a comprehensive preparation methodology of 2D materials for future applications beyond traditional CVD.

18.
Soft Matter ; 18(45): 8687-8699, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36349834

RESUMO

The two-state stochastic phenomenon is observed in various systems and is attracting more interest, and it can be described by the two-state random walk (TSRW) model. The TSRW model is a typical two-state renewal process alternating between the continuous-time random walk state and the Lévy walk state, in both of which the sojourn time distributions follow a power law. In this paper, by discussing the statistical properties and calculating the ensemble averaged and time averaged mean squared displacement, the ergodic property and the ultimate diffusive behavior of the aging TSRW is studied. Results reveal that because of the two-state intermittent feature, ergodicity and nonergodicity can coexist in the aging TSRW, which behave as the time scalings of the time averages and ensemble averages not being identically equal. In addition, we find that the unique state occupation mechanism caused by the diverging mean of the sojourn times of one state, determines the aging TSRW's ultimate diffusive behavior at extremely large timescales, i.e., instead of the term with the larger diffusion exponent, the diffusion is surprisingly characterized by the term with the smaller one, which is distinctly different from previous conclusions and known results. At last, we note that the Lévy walk with rests model which also displays aging and ergodicity breaking, can be generalized by the TSRW model.

19.
Br J Cancer ; 124(5): 975-981, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33335279

RESUMO

BACKGROUND: Invasive ductal carcinoma (IDC) is often accompanied by ductal carcinoma in situ (DCIS). Whether the DCIS component affects the 21-gene recurrence score (RS) is unclear. METHODS: Consecutive ER-positive, HER2-negative, N0-1 patients with RS results were included. Patients were divided into pure IDC and IDC with DCIS (IDC/DCIS) groups. The RS, the expression of its 16 cancer genes and prognosis were compared between IDC and IDC/DCIS patients. RESULTS: A total of 1458 patients were enrolled, 320 of whom had concomitant DCIS. DCIS component was independently associated with lower RS (P = 0.038). IDC/DCIS patients more often had a low-risk RS (P = 0.018) or intermediate-risk RS (P = 0.024). Regarding individual genes in the RS panel, Ki67, CCNB1 and MYBL2 in the proliferation group and MMP11 and CTSL2 in the invasion group were significantly lower among IDC/DCIS patients than pure IDC patients. Among IDC/DCIS patients, lower RS was independently correlated with a higher DCIS proportion and lower DCIS grade. Within a median follow-up of 31 months, the DCIS component in IDC did not significantly influence prognosis. CONCLUSIONS: IDC with DCIS component is associated with a lower 21-gene RS, possibly due to lower expression of proliferation and invasion genes. DCIS proportion and grade independently influenced the 21-gene RS in IDC/DCIS patients. Due to the relatively short follow-up period and low recurrence rate, the impact of the DCIS component in IDC on prognosis needs further evaluation.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Intraductal não Infiltrante/genética , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
20.
Phys Rep ; 896: 1-84, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33041465

RESUMO

Global warming, extreme climate events, earthquakes and their accompanying socioeconomic disasters pose significant risks to humanity. Yet due to the nonlinear feedbacks, multiple interactions and complex structures of the Earth system, the understanding and, in particular, the prediction of such disruptive events represent formidable challenges to both scientific and policy communities. During the past years, the emergence and evolution of Earth system science has attracted much attention and produced new concepts and frameworks. Especially, novel statistical physics and complex networks-based techniques have been developed and implemented to substantially advance our knowledge of the Earth system, including climate extreme events, earthquakes and geological relief features, leading to substantially improved predictive performances. We present here a comprehensive review on the recent scientific progress in the development and application of how combined statistical physics and complex systems science approaches such as critical phenomena, network theory, percolation, tipping points analysis, and entropy can be applied to complex Earth systems. Notably, these integrating tools and approaches provide new insights and perspectives for understanding the dynamics of the Earth systems. The overall aim of this review is to offer readers the knowledge on how statistical physics concepts and theories can be useful in the field of Earth system science.

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