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1.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38581419

RESUMO

Piwi-interacting RNAs (piRNAs) play a crucial role in various biological processes and are implicated in disease. Consequently, there is an escalating demand for computational tools to predict piRNA-disease interactions. Although there have been computational methods proposed for the detection of piRNA-disease associations, the problem of imbalanced and sparse dataset has brought great challenges to capture the complex relationships between piRNAs and diseases. In response to this necessity, we have developed a novel computational architecture, denoted as PUTransGCN, which uses heterogeneous graph convolutional networks to uncover potential piRNA-disease associations. Additionally, the attention mechanism was used to adjust the weight parameters of aggregation heterogeneous node features automatically. For tackling the imbalanced dataset problem, the combined positive unlabelled learning (PUL) method comprising PU bagging, two-step and spy technique was applied to select reliable negative associations. The features of piRNAs and diseases were derived from three distinct biological sources by PUTransGCN, including information on piRNA sequences, semantic terms related to diseases and the existing network of piRNA-disease associations. In the experiment, PUTransGCN performs in 5-fold cross-validation with an AUC of 0.93 and 0.95 on two datasets, respectively, which outperforms the other six state-of-the-art models. We compared three different PUL methods, and the results of the ablation experiment indicate that the combined PUL method yields the best results. The PUTransGCN could serve as a valuable piRNA-disease prediction tool for upcoming studies in the biomedical field. The code for PUTransGCN is available at https://github.com/chenqiuhao/PUTransGCN.


Assuntos
RNA de Interação com Piwi
2.
Proc Natl Acad Sci U S A ; 120(34): e2307646120, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37579150

RESUMO

Solid-solid reactions stand out in rechargeable sulfur-based batteries due to the robust redox couples and high sulfur utilization in theory. However, conventional solid-solid reactions in sulfur cathode always present slow reaction kinetics and huge redox polarization due to the low electronic conductivity of sulfur and the generation of various electrochemical inert intermediates. In view of this, it is crucial to improve the electrochemical activity of sulfur cathode and tailor the redox direction. Guided by thermodynamics analysis, short-chain sulfur molecules (S2-4) are successfully synthesized by space-limited domain principle. Unlike conventional cyclic S8 molecules with complex routes in solid-solid reaction, short-chain sulfur molecules not only shorten the length of the redox chain but also inhibit the formation of irreversible intermediates, which brings excellent redox dynamics and reversibility. As a result, the Cu-S battery built by short-chain sulfur molecules can deliver a high reversible capacity of 3,133 mAh g-1. To put this into practice, quasi-solid-state aqueous flexible battery based on short-chain sulfur molecules is also designed and evaluated, showing superior mechanical flexibility and electrochemical property. It indicates that the introduction of short-chain sulfur molecules in rechargeable battery can promote the development and application of high-performance sulfur-based aqueous energy storage systems.

3.
Proc Natl Acad Sci U S A ; 120(13): e2220792120, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36940321

RESUMO

Selenium sulfide (SeS2) features higher electronic conductivity than sulfur and higher theoretical capacity and lower cost than selenium, attracting considerable interest in energy storage field. Although nonaqueous Li/Na/K-SeS2 batteries are attractive for their high energy density, the notorious shuttle effect of polysulfides/polyselenides and the intrinsic limitations of organic electrolyte have hindered the deployment of this technology. To circumvent these issues, here we design an aqueous Cu-SeS2 battery by encapsulating SeS2 in a defect-enriched nitrogen-doped porous carbon monolith. Except the intrinsic synergistic effect between Se and S in SeS2, the porous structure of carbon matrix has sufficient internal voids to buffer the volume change of SeS2 and provides abundant pathways for both electrons and ions. In addition, the synergistic effect of nitrogen doping and topological defect not only enhances the chemical affinity between reactants and carbon matrix but also offers catalytic active sites for electrochemical reactions. Benefiting from these merits, the Cu-SeS2 battery delivers superior initial reversible capacity of 1,905.1 mAh g-1 at 0.2 A g-1 and outstanding long-span cycling performance over 1,000 cycles at 5 A g-1. This work applies variable valence charge carriers to aqueous metal-SeS2 batteries, providing valuable inspiration for the construction of metal-chalcogen batteries.

4.
Proc Natl Acad Sci U S A ; 120(42): e2312091120, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37812706

RESUMO

Metal-sulfur batteries have received great attention for electrochemical energy storage due to high theoretical capacity and low cost, but their further development is impeded by low sulfur utilization, poor electrochemical kinetics, and serious shuttle effect of the sulfur cathode. To avoid these problems, herein, a triple-synergistic small-molecule sulfur cathode is designed by employing N, S co-doped hierarchical porous bamboo charcoal as a sulfur host in an aqueous Cu-S battery. Expect the enhanced conductivity and chemisorption induced by N, S synergistic co-doping, the intrinsic synergy of macro-/meso-/microporous triple structure also ensures space-confined small-molecule sulfur as high utilization reactant and effectively alleviates the volume expansion during conversion reaction. Under a further joint synergy between hierarchical structure and heteroatom doping, the resulting sulfur cathode endows the Cu-S battery with outstanding electrochemical performance. Cycled at 5 A g-1, it can deliver a high reversible capacity of 2,509.8 mAh g-1 with a good capacity retention of 97.9% after 800 cycles. In addition, a flexible hybrid pouch cell built by a small-molecule sulfur cathode, Zn anode, and gel electrolytes can firmly deliver high average operating voltage of about 1.3 V with a reversible capacity of over 2,500 mAh g-1 under various destructive conditions, suggesting that the triple-synergistic small-molecule sulfur cathode promises energetic metal-sulfur batteries.

5.
Nature ; 569(7757): 537-541, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31068693

RESUMO

The discovery of the quantum Hall effect (QHE)1,2 in two-dimensional electronic systems has given topology a central role in condensed matter physics. Although the possibility of generalizing the QHE to three-dimensional (3D) electronic systems3,4 was proposed decades ago, it has not been demonstrated experimentally. Here we report the experimental realization of the 3D QHE in bulk zirconium pentatelluride (ZrTe5) crystals. We perform low-temperature electric-transport measurements on bulk ZrTe5 crystals under a magnetic field and achieve the extreme quantum limit, where only the lowest Landau level is occupied, at relatively low magnetic fields. In this regime, we observe a dissipationless longitudinal resistivity close to zero, accompanied by a well-developed Hall resistivity plateau proportional to half of the Fermi wavelength along the field direction. This response is the signature of the 3D QHE and strongly suggests a Fermi surface instability driven by enhanced interaction effects in the extreme quantum limit. By further increasing the magnetic field, both the longitudinal and Hall resistivity increase considerably and display a metal-insulator transition, which represents another magnetic-field-driven quantum phase transition. Our findings provide experimental evidence of the 3D QHE and a promising platform for further exploration of exotic quantum phases and transitions in 3D systems.

6.
Proc Natl Acad Sci U S A ; 119(12): e2118675119, 2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35286210

RESUMO

SignificanceBased on the analysis of three thermodynamic parameters of various M-S systems (solubility of metal sulfides [MxSy] in aqueous solution, volume change of the metal-sulfur [M-S] battery system, and the potential of S/MxSy cathode redox couple), an aqueous Pb-S battery operated by synergistic dual conversion reactions (cathode: S⇄PbS, anode: Pb2+⇄PbO2) has been officially reported. Benefitting from the inherent insolubility of PbS and a conversion-type counter electrode, the aqueous Pb-S battery exhibited two advantages: it is shuttle effect free and has a dendrite-free nature. Moreover, the practical value of the Pb-S battery was further certified by the prototype S|Pb(NO3)2ǁZn(NO3)2|Zn hybrid cell, which afforded an energy density of 930.9 Wh kg-1sulfur.

7.
Nano Lett ; 24(12): 3631-3637, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38466240

RESUMO

A striking phenomenon of collective cell motion is that they can exhibit a spontaneously emerging wave during epithelia expansions. However, the fundamental mechanism, governing the emergence and its crucial characteristics (e.g., the eigenfrequency and the pattern), remains an enigma. By introducing a mechanochemical feedback loop, we develop a highly efficient discrete vertex model to investigate the spatiotemporal evolution of spreading epithelia. We find both numerically and analytically that expanding cell monolayers display a power-law dependence of wave frequency on the local heterogeneities (i.e., cell density) with a scaling exponent of -1/2. Moreover, our study demonstrates the quantitative capability of the proposed model in capturing distinct X-, W-, and V-mode wave patterns. We unveil that the phase transition between these modes is governed by the distribution of active self-propulsion forces. Our work provides an avenue for rigorous quantitative investigations into the collective motion and pattern formation of cell groups.

8.
Nano Lett ; 24(23): 7069-7076, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38808684

RESUMO

Local cells can actively create reverse bending (evagination) in invaginated epithelia, which plays a crucial role in the formation of elaborate organisms. However, the precise physical mechanism driving the evagination remains elusive. Here, we present a three-dimensional vertex model, incorporating the intrinsic cell polarity, to explore the complex morphogenesis induced by local mechanical modulations. We find that invaginated tissues can spontaneously generate local reverse bending due to the shift of the apicobasal polarity. Their exact shapes can be analytically determined by the local apicobasal differential tension and the internal stress. Our continuum theory exhibits three regions in a phase diagram controlled by these two parameters, showing curvature transitions from ordered to disordered states. Additionally, we delve into epithelial curvature transition induced by the nucleus repositioning, revealing its active contribution to the apicobasal force generation. The uncovered mechanical principles could potentially guide more studies on epithelial folding in diverse systems.


Assuntos
Polaridade Celular , Epitélio/fisiologia , Polaridade Celular/fisiologia , Células Epiteliais/citologia , Modelos Biológicos , Morfogênese , Estresse Mecânico , Animais , Humanos
9.
EMBO J ; 39(1): e102190, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31755573

RESUMO

TGF-ß signaling pathway plays a key role in breast cancer metastasis. Recent studies suggest that TGF-ß regulates tumor progression and invasion not only via transcriptional regulation, but also via translational regulation. Using both bioinformatics and experimental tools, we identified a micropeptide CIP2A-BP encoded by LINC00665, whose translation was downregulated by TGF-ß in breast cancer cell lines. Using TNBC cell lines, we showed that TGF-ß-activated Smad signaling pathway induced the expression of translation inhibitory protein 4E-BP1, which inhibited eukaryote translation initiation factor elF4E, leading to reduced translation of CIP2A-BP from LINC00665. CIP2A-BP directly binds tumor oncogene CIP2A to replace PP2A's B56γ subunit, thus releasing PP2A activity, which inhibits PI3K/AKT/NFκB pathway, resulting in decreased expression levels of MMP-2, MMP-9, and Snail. Downregulation of CIP2A-BP in TNBC patients was significantly associated with metastasis and poor overall survival. In the MMTV-PyMT model, either introducing CIP2A-BP gene or direct injection of CIP2A-BP micropeptide significantly reduced lung metastases and improved overall survival. In conclusion, we provide evidence that CIP2A-BP is both a prognostic marker and a novel therapeutic target for TNBC.


Assuntos
Autoantígenos/metabolismo , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Fragmentos de Peptídeos/metabolismo , RNA Longo não Codificante/genética , Neoplasias de Mama Triplo Negativas/prevenção & controle , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Apoptose , Autoantígenos/genética , Biomarcadores Tumorais/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Progressão da Doença , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Nus , Invasividade Neoplásica , Fragmentos de Peptídeos/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteína Smad4/genética , Proteína Smad4/metabolismo , Taxa de Sobrevida , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Small ; 20(3): e2304981, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37672807

RESUMO

Sodium-potassium (NaK) alloy electrodes are ideal for next-generation dendrite-free alkali metal electrodes due to their dendrite-free nature. However, issues such as slow diffusion kinetics due to the large K+ radius and the loss of active potassium during the reaction severely limit its application. Here a novel cobalt/nitrogen-doped carbon material is designed and it is applied to the construction of a NaK alloy electrode. The experimental and theoretical results indicate that the confining effect of the nitrogen-doped graphitic carbon layer can protect the cobalt nanoparticles from corrosion leaching, while the presence of Co─Nx bonds and cobalt nanoparticles provides more active sites for the reaction, realizing the synergistic effect of adsorption-catalytic modulation, lowering the K+ diffusion energy barrier and promoting charge transfer and ion diffusion. The application of this electrode to a symmetrical battery can achieve more than 1800 stable cycles under a current density of 0.4 mA cm-2 and a charge/discharge specific capacity of 122.64 mAh g-1 under a current of 0.5C in a full battery. This finding provides a new idea to realize a fast, stable, and efficient application of NaK alloy electrodes.

11.
Plant Biotechnol J ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899717

RESUMO

Rapeseed (Brassica napus) silique is the major carbohydrate source for seed development, and the final silique length has attracted great attention from breeders. However, no studies had focused on the dynamic character of silique elongation length (SEL). Here, the dynamic SEL investigation in a natural population including 588 lines over two years indicate that dynamic SEL during 0-20 days after flowering was the most essential stage associated with seed number per silique (SPS) and thousand seed weight (TSW). Then, nine loci were identified to be associated with SEL based on GWAS analysis, among which five SNPs (over 50%) distributed on the A02 chromosome within 6.08 to 6.48 Mb. Subsequently, we screened 5078 differentially expressed genes between two extreme materials. An unknown protein, BnaA02.SE, was identified combining with GWAS and RNA-Seq analysis. Subcellular localization and expression profiles analysis demonstrated that BnaA02.SE is a chloroplast- and nucleus-localized protein mainly expressed in pericarps and leaves. Furthermore, transgenic verification and dynamic cytological observation reveal that overexpressed BnaA02.SE can promote silique elongation by regulating JA and IAA contents, affecting cell proliferation and expansion, respectively, and finally enhance seed yield by influencing SPS and TSW. Haplotype analysis reveal that the homologs of BnaA02.SE may also be involved in silique elongation regulation. Our findings provided comprehensive insights into a newly SEL trait, and cloned the first gene (BnaA02.SE) controlling silique elongation in B. napus. The identified BnaA02.SE and its homologs can offer a valuable target for improving B. napus yield.

12.
Hepatology ; 77(4): 1106-1121, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35344606

RESUMO

BACKGROUND AND AIMS: Hepatocarcinogenesis goes through HCC progenitor cells (HcPCs) to fully established HCC, and the mechanisms driving the development of HcPCs are still largely unknown. APPROACH AND RESULTS: Proteomic analysis in nonaggregated hepatocytes and aggregates containing HcPCs from a diethylnitrosamine-induced HCC mouse model was screened using a quantitative mass spectrometry-based approach to elucidate the dysregulated proteins in HcPCs. The heterotrimeric G stimulating protein α subunit (GαS) protein level was significantly increased in liver cancer progenitor HcPCs, which promotes their response to oncogenic and proinflammatory cytokine IL-6 and drives premalignant HcPCs to fully established HCC. Mechanistically, GαS was located at the membrane inside of hepatocytes and acetylated at K28 by acetyltransferase lysine acetyltransferase 7 (KAT7) under IL-6 in HcPCs, causing the acyl protein thioesterase 1-mediated depalmitoylation of GαS and its cytoplasmic translocation, which were determined by GαS K28A mimicking deacetylation or K28Q mimicking acetylation mutant mice and hepatic Kat7 knockout mouse. Then, cytoplasmic acetylated GαS associated with signal transducer and activator of transcription 3 (STAT3) to impede its interaction with suppressor of cytokine signaling 3, thus promoting in a feedforward manner STAT3 phosphorylation and the response to IL-6 in HcPCs. Clinically, GαS, especially K28-acetylated GαS, was determined to be increased in human hepatic premalignant dysplastic nodules and positively correlated with the enhanced STAT3 phosphorylation, which were in accordance with the data obtained in mouse models. CONCLUSIONS: Malignant progression of HcPCs requires increased K28-acetylated and cytoplasm-translocated GαS, causing enhanced response to IL-6 and driving premalignant HcPCs to fully established HCC, which provides mechanistic insight and a potential target for preventing hepatocarcinogenesis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Lisina Acetiltransferases , Humanos , Camundongos , Animais , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/patologia , Interleucina-6/metabolismo , Proteômica , Citoplasma/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Lisina Acetiltransferases/metabolismo , Fator de Transcrição STAT3/metabolismo , Histona Acetiltransferases/metabolismo
13.
Ann Surg Oncol ; 31(1): 284-302, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37725224

RESUMO

BACKGROUND: Identification of risk factors facilitates the prevention of breast cancer-related lymphedema (BCRL). Several published systematic reviews have already addressed the risk factors for BCRL. This study aimed to systematically identify potential risk factors for BCRL and evaluate the quality of evidence. METHODS: The study followed methodologic guidance from the Joanna Briggs Institute, and the Cochrane Handbook. The following electronic databases were systematically searched from inception to 15 November 2022: PubMed, Embase, CINAHL, Web of Science, Scopus, CNKI, SinoMed, Wanfang, JBI Database, Cochrane Database, ProQuest, and PROSPERO. Two authors independently screened studies, extracted data, and assessed methodologic quality using AMSTAR2, risk of bias using ROBIS, and evidence quality using GRADE. The study evaluated overlap, assessed the small-study effect, and calculated the I2 statistic and Egger's P value as needed. RESULTS: The study included 14 publications comprising 10 meta-analyses and 4 systematic reviews. The authors identified 39 factors and 30 unique meta-analyses. In the study, 13 innate personal trait-related risk factors, such as higher body mass index (BMI) and axillary lymph nodes dissection, showed statistically significant associations with BCRL incidence. Breast reconstruction was found to be a protective factor. The methodologic quality was low or critically low. The majority of the systematic reviews and/or meta-analyses were rated as having a high risk of bias. Evidence quality was low for 22 associations and moderate for 8 associations. CONCLUSIONS: The currently identified risk factors for BCRL all are innate personal trait-related factors. Future well-designed studies and robust meta-analyses are needed to explore potential associations between behavioral-, interpersonal-, and environmental-related factors and BCRL, as well as the role of genetic variations and pathophysiologic factors.


Assuntos
Linfedema Relacionado a Câncer de Mama , Neoplasias da Mama , Linfedema , Feminino , Humanos , Linfedema Relacionado a Câncer de Mama/etiologia , Neoplasias da Mama/complicações , Excisão de Linfonodo/efeitos adversos , Linfedema/etiologia , Linfedema/patologia , Fatores de Risco , Revisões Sistemáticas como Assunto , Metanálise como Assunto
14.
BMC Cancer ; 24(1): 637, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38790011

RESUMO

OBJECTIVE: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. MATERIALS AND METHODS: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. CONCLUSION: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.


Assuntos
Braquiterapia , Craniofaringioma , Neoplasias Hipofisárias , Humanos , Braquiterapia/métodos , Braquiterapia/efeitos adversos , Craniofaringioma/radioterapia , Seguimentos , Neoplasias Hipofisárias/radioterapia , Intervalo Livre de Progressão , Resultado do Tratamento
15.
Pediatr Res ; 95(6): 1543-1552, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38245633

RESUMO

BACKGROUND: Pulmonary fibrosis (PF) is a progressive lung disorder with a high mortality rate; its therapy remains limited due to the inefficiency of drug delivery. In this study, the system of drug delivery of nintedanib (Nin) by exosomes derived from adipose-derived stem cells (ADSCs-Exo, Exo) was developed to effectively deliver Nin to lung lesion tissue to ensure enhanced anti-fibrosis therapy. METHODS: The bleomycin (BLM)-induced PF model was constructed in vivo and in vitro. The effects of Exo-Nin on BLM-induced PF and its regulatory mechanism were examined using RT-qPCR, Western blotting, immunofluorescence, and H&E staining. RESULTS: We found Exo-Nin significantly improved BLM-induced PF in vivo and in vitro compared to Nin and Exo groups alone. Mechanistically, Exo-Nin alleviated fibrogenesis by suppressing endothelial-mesenchymal transition through the down-regulation of the TGF-ß/Smad pathway and the attenuation of oxidative stress in vivo and in vitro. CONCLUSIONS: Utilizing adipose stem cell-derived exosomes as carriers for Nin exhibited a notable enhancement in therapeutic efficacy. This improvement can be attributed to the regenerative properties of exosomes, indicating promising prospects for adipose-derived exosomes in cell-free therapies for PF. IMPACT: The system of drug delivery of nintedanib (Nin) by exosomes derived from adipose-derived stem cells was developed to effectively deliver Nin to lung lesion tissue to ensure enhanced anti-fibrosis therapy. The use of adipose stem cell-derived exosomes as the carrier of Nin may increase the therapeutic effect of Nin, which can be due to the regenerative properties of the exosomes and indicate promising prospects for adipose-derived exosomes in cell-free therapies for PF.


Assuntos
Bleomicina , Exossomos , Indóis , Fibrose Pulmonar , Exossomos/metabolismo , Exossomos/transplante , Animais , Indóis/farmacologia , Fibrose Pulmonar/terapia , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Camundongos , Tecido Adiposo/citologia , Células-Tronco/citologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Pulmão/patologia , Pulmão/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Humanos , Transdução de Sinais , Masculino , Sistemas de Liberação de Medicamentos
16.
BMC Med Imaging ; 24(1): 77, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566000

RESUMO

BACKGROUND: To investigate the value of a nomogram model based on the combination of clinical-CT features and multiphasic enhanced CT radiomics for the preoperative prediction of the microsatellite instability (MSI) status in colorectal cancer (CRC) patients. METHODS: A total of 347 patients with a pathological diagnosis of colorectal adenocarcinoma, including 276 microsatellite stabilized (MSS) patients and 71 MSI patients (243 training and 104 testing), were included. Univariate and multivariate regression analyses were used to identify the clinical-CT features of CRC patients linked with MSI status to build a clinical model. Radiomics features were extracted from arterial phase (AP), venous phase (VP), and delayed phase (DP) CT images. Different radiomics models for the single phase and multiphase (three-phase combination) were developed to determine the optimal phase. A nomogram model that combines clinical-CT features and the optimal phasic radscore was also created. RESULTS: Platelet (PLT), systemic immune inflammation index (SII), tumour location, enhancement pattern, and AP contrast ratio (ACR) were independent predictors of MSI status in CRC patients. Among the AP, VP, DP, and three-phase combination models, the three-phase combination model was selected as the best radiomics model. The best MSI prediction efficacy was demonstrated by the nomogram model built from the combination of clinical-CT features and the three-phase combination model, with AUCs of 0.894 and 0.839 in the training and testing datasets, respectively. CONCLUSION: The nomogram model based on the combination of clinical-CT features and three-phase combination radiomics features can be used as an auxiliary tool for the preoperative prediction of the MSI status in CRC patients.


Assuntos
Neoplasias Colorretais , Nomogramas , Humanos , Instabilidade de Microssatélites , Radiômica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia
17.
Acta Biochim Biophys Sin (Shanghai) ; 56(1): 82-95, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38013468

RESUMO

Osteoarthritis (OA) is a prevalent and chronic joint disease that affects the aging population, causing pain and disability. Macrophages in synovium are important mediators of synovial inflammatory activity and pathological joint pain. Previous studies have demonstrated the significant involvement of κ-opioid receptor (KOR) in the regulation of pain and inflammation. Our study reveals a significant reduction in synovial KOR expression among patients and mice with OA. Here, we find that KOR activation effectively inhibits the expressions of the LPS-induced-inflammatory cytokines TNF-α and IL-6 by inhibiting macrophage M1 phenotype. Mechanistically, KOR activation effectively suppresses the proinflammatory factor secretion of macrophages by inhibiting the translocation of NF-κB into the nucleus. Our animal experiments reveal that activation of KOR effectively alleviates knee pain and prevents synovitis progression in OA mice. Consistently, KOR administration suppresses the expressions of M1 macrophage markers and the NF-κB pathway in the synovium of the knee. Collectively, our study suggests that targeting KOR may be a viable strategy for treating OA by inhibiting synovitis and improving joint pain in affected patients.


Assuntos
Osteoartrite , Receptores Opioides kappa , Sinovite , Idoso , Animais , Humanos , Camundongos , Artralgia/metabolismo , Macrófagos/metabolismo , NF-kappa B/metabolismo , Osteoartrite/metabolismo , Dor/metabolismo , Receptores Opioides kappa/metabolismo , Sinovite/metabolismo
18.
Chaos ; 34(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558041

RESUMO

Hypersynchronous (HYP) seizure onset is one of the frequently observed seizure-onset patterns in temporal lobe epileptic animals and patients, often accompanied by hippocampal sclerosis. However, the exact mechanisms and ion dynamics of the transition to HYP seizures remain unclear. Transcranial magneto-acoustic stimulation (TMAS) has recently been proposed as a novel non-invasive brain therapy method to modulate neurological disorders. Therefore, we propose a biophysical computational hippocampal network model to explore the evolution of HYP seizure caused by changes in crucial physiological parameters and design an effective TMAS strategy to modulate HYP seizure onset. We find that the cooperative effects of abnormal glial uptake strength of potassium and excessive bath potassium concentration could produce multiple discharge patterns and result in transitions from the normal state to the HYP seizure state and ultimately to the depolarization block state. Moreover, we find that the pyramidal neuron and the PV+ interneuron in HYP seizure-onset state exhibit saddle-node-on-invariant-circle/saddle homoclinic (SH) and saddle-node/SH at onset/offset bifurcation pairs, respectively. Furthermore, the response of neuronal activities to TMAS of different ultrasonic waveforms revealed that lower sine wave stimulation can increase the latency of HYP seizures and even completely suppress seizures. More importantly, we propose an ultrasonic parameter area that not only effectively regulates epileptic rhythms but also is within the safety limits of ultrasound neuromodulation therapy. Our results may offer a more comprehensive understanding of the mechanisms of HYP seizure and provide a theoretical basis for the application of TMAS in treating specific types of seizures.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Animais , Humanos , Epilepsia do Lobo Temporal/terapia , Eletroencefalografia/métodos , Estimulação Acústica/efeitos adversos , Convulsões/terapia , Hipocampo , Epilepsia/complicações , Potássio
19.
Ren Fail ; 46(1): 2331613, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38561244

RESUMO

OBJECTIVE: To examine the effectiveness of psychoeducational interventions on depression, anxiety, and health-related quality of life (HRQOL) for people undergoing maintenance hemodialysis (MHD). METHODS: This review used systematic review and meta-analysis as the research design. Nine databases, including PubMed, Web of Science, Embase, CINAHL Complete, Cochrane Library, CNKI, WanFang, VIP, and Chinese Biomedical Literature Database, were searched from the inception to the 8th of July 2023. Two reviewers independently identified randomized controlled trials (RCT) examining the effects of psychoeducational interventions on MHD patients. RESULTS: Fourteen studies involving 1134 MHD patients were included in this review. The results of meta-analyses showed that psychoeducational intervention had significant short-term (< 1 m) (SMD: -0.87, 95% CI: -1.54 to -0.20, p = 0.01, I2 = 91%; 481 participants), and medium-term (1-3 m) (SMD: -0.29, 95% CI: -0.50 to -0.08, p = 0.01, I2 = 49%; 358 participants) on anxiety in MHD patients, but the effects could not be sustained at longer follow-ups. Psychoeducational interventions can also have short-term (< 1 m) (SMD: -0.65, 95% CI: -0.91 to -0.38, p < 0.00001, I2 = 65%; 711 participants) and medium-term (1-3 m) (SMD: -0.42, 95% CI: -0.76 to -0.09, p = 0.01, I2 = 69%; 489 participants) effects in reducing depression levels in MHD patients. Psychoeducational interventions that use coping strategies, goal setting, and relaxation techniques could enhance the QOL in MHD patients in the short term (< 1 m) (SMD: 0.86, 95% CI: 0.42 to 1.30, p = 0.02, I2 = 86%; 241 participants). CONCLUSIONS: Psychoeducational interventions have shown great potential to improve anxiety, depression, and quality of life in patients with MHD at the short- and medium-term follow-ups.Trial registration number: CRD42023440561.


Assuntos
Depressão , Angústia Psicológica , Humanos , Depressão/prevenção & controle , Depressão/psicologia , Qualidade de Vida , Ansiedade/etiologia , Ansiedade/prevenção & controle
20.
Nano Lett ; 23(16): 7516-7523, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37540083

RESUMO

Gate tunable two-dimensional (2D) superconductors offer significant advantages in studying superconducting phase transitions. Here, we address superconductivity in exfoliated 1T'-MoTe2 monolayers with an intrinsic band gap of ∼7.3 meV using field effect doping. Despite large differences in the dispersion of the conduction and valence bands, superconductivity can be achieved easily for both electrons and holes. The onset of superconductivity occurs near 7-8 K for both charge carrier types. This temperature is much higher than that in bulk samples. Also the in-plane upper critical field is strongly enhanced and exceeds the BCS Pauli limit in both cases. Gap information is extracted using point-contact spectroscopy. The gap ratio exceeds multiple times the value expected for BCS weak-coupling. All of these observations suggest a strong enhancement of the pairing interaction.

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