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1.
Proc Natl Acad Sci U S A ; 120(23): e2215195120, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37253004

RESUMO

The gaseous hormone ethylene is perceived in plants by membrane-bound receptors, the best studied of these being ETR1 from Arabidopsis. Ethylene receptors can mediate a response to ethylene concentrations at less than one part per billion; however, the mechanistic basis for such high-affinity ligand binding has remained elusive. Here we identify an Asp residue within the ETR1 transmembrane domain that plays a critical role in ethylene binding. Site-directed mutation of the Asp to Asn results in a functional receptor that has a reduced affinity for ethylene, but still mediates ethylene responses in planta. The Asp residue is highly conserved among ethylene receptor-like proteins in plants and bacteria, but Asn variants exist, pointing to the physiological relevance of modulating ethylene-binding kinetics. Our results also support a bifunctional role for the Asp residue in forming a polar bridge to a conserved Lys residue in the receptor to mediate changes in signaling output. We propose a new structural model for the mechanism of ethylene binding and signal transduction, one with similarities to that found in a mammalian olfactory receptor.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Receptores de Superfície Celular/metabolismo , Etilenos/metabolismo , Transdução de Sinais/fisiologia
2.
Nano Lett ; 24(5): 1635-1641, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38277778

RESUMO

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.

3.
J Hepatol ; 80(6): 928-940, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38336346

RESUMO

BACKGROUND & AIMS: Men are more prone to develop and die from liver fibrosis than women. In this study, we aim to investigate how sex-determining region Y gene (SRY) in hepatocytes promotes liver fibrosis. METHODS: Hepatocyte-specific Sry knock-in (KI), Sry knockout (KO), and Sry KI with platelet-derived growth factor receptor α (Pdgfrα) KO mice were generated. Liver fibrosis was induced in mice by bile duct ligation for 2 weeks or carbon tetrachloride treatment for 6 weeks. In addition, primary hepatocytes, hepatic stellate cells (HSCs), and immortalized cell lines were used for in vitro studies and mechanistic investigation. RESULTS: Compared to females, the severity of toxin- or cholestasis-induced liver fibrosis is similarly increased in castrated and uncastrated male mice. Among all Y chromosome-encoded genes, SRY was the most significantly upregulated and consistently increased gene in fibrotic/cirrhotic livers in male patients and in mouse models. Sry KI mice developed exacerbated liver fibrosis, whereas Sry KO mice had alleviated liver fibrosis, compared to age- and sex-matched control mice after bile duct ligation or administration of carbon tetrachloride. Mechanistically, both our in vivo and in vitro studies illustrated that SRY in hepatocytes can transcriptionally regulate Pdgfrα expression, and promote HMGB1 (high mobility group box 1) release and subsequent HSC activation. Pdgfrα KO or treatment with the SRY inhibitor DAX1 in Sry KI mice abolished SRY-induced HMGB1 secretion and liver fibrosis. CONCLUSIONS: SRY is a strong pro-fibrotic factor and accounts for the sex disparity observed in liver fibrosis, suggesting its critical role as a potentially sex-specific therapeutic target for prevention and treatment of the disease. IMPACT AND IMPLICATION: We identified that a male-specific gene, sex-determining region Y gene (SRY), is a strong pro-fibrotic gene that accounts for the sex disparity observed in liver fibrosis. As such, SRY might be an appropriate target for surveillance and treatment of liver fibrosis in a sex-specific manner. Additionally, SRY might be a key player in the sexual dimorphism observed in hepatic pathophysiology more generally.


Assuntos
Células Estreladas do Fígado , Hepatócitos , Cirrose Hepática , Camundongos Knockout , Proteína da Região Y Determinante do Sexo , Animais , Masculino , Feminino , Camundongos , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/fisiopatologia , Humanos , Hepatócitos/metabolismo , Proteína da Região Y Determinante do Sexo/genética , Proteína da Região Y Determinante do Sexo/metabolismo , Células Estreladas do Fígado/metabolismo , Caracteres Sexuais , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Tetracloreto de Carbono/toxicidade , Tetracloreto de Carbono/efeitos adversos , Colestase/genética , Colestase/metabolismo , Colestase/fisiopatologia , Modelos Animais de Doenças
4.
Biochem Biophys Res Commun ; 720: 150102, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-38759302

RESUMO

The emergence of drug-resistant bacteria, facilitated by metallo-beta-lactamases (MBLs), presents a significant obstacle to the effective use of antibiotics in the management of clinical drug-resistant bacterial infections. AFM-1 is a MBL derived from Alcaligenes faecalis and shares 86% homology with the NDM-1 family. Both AFM-1 and NDM-1 demonstrate the ability to hydrolyze ampicillin and other ß-lactam antibiotics, however, their substrate affinities vary, and the specific reason for this variation remains unknown. We present the high-resolution structure of AFM-1. The active center of AFM-1 binds two zinc ions, and the conformation of the key amino acid residues in the active center is in accordance with that of NDM-1. However, the substrate-binding pocket of AFM-1 is considerably smaller than that of NDM-1. Additionally, the mutation of amino acid residues in the Loop3 region, as compared to NDM-1, results in the formation of a dense hydrophobic patch comprised of hydrophobic amino acid residues in this area, which facilitates substrate binding. Our findings lay the foundation for understanding the molecular mechanism of AFM-1 with a high affinity for substrates and provide a novel theoretical foundation for addressing the issue of drug resistance caused by B1 MBLs.


Assuntos
Modelos Moleculares , beta-Lactamases , beta-Lactamases/química , beta-Lactamases/metabolismo , beta-Lactamases/ultraestrutura , beta-Lactamases/genética , Alcaligenes faecalis/enzimologia , Alcaligenes faecalis/química , Conformação Proteica , Zinco/química , Zinco/metabolismo , Cristalografia por Raios X , Domínio Catalítico , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Sequência de Aminoácidos , Sítios de Ligação
5.
Small ; 20(26): e2310248, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38234145

RESUMO

Interfering with intratumoral metabolic processes is proven to effectively sensitize different antitumor treatments. Here, a tumor-targeting catalytic nanoplatform (CQ@MIL-GOX@PB) loading with autophagy inhibitor (chloroquine, CQ) and glucose oxidase (GOX) is fabricated to interfere with the metabolisms of tumor cells and tumor-associated macrophages (TAMs), then realizing effective antitumor chemodynamic therapy (CDT). Once accumulating in the tumor site with the navigation of external biotin, CQ@MIL-GOX@PB will release Fe ions and CQ in the acid lysosomes of tumor cells, the latter can sensitize Fe ions-involved antitumor CDT by blocking the autophagy-dependent cell repair. Meanwhile, the GOX component will consume glucose, which not only generates many H2O2 for CDT but also once again decelerates the tumor repair process by reducing energy metabolism. What is more, the release of CQ can also drive the NO anabolism of TAMs to further sensitize CDT. This strategy of multiple metabolic regulations is evidenced to significantly improve the antitumor effect of traditional CDT nanoagents and might provide a new sight to overcome the bottlenecks of different antitumor treatments.


Assuntos
Glucose Oxidase , Animais , Glucose Oxidase/metabolismo , Humanos , Linhagem Celular Tumoral , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Cloroquina/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Autofagia/efeitos dos fármacos , Nanopartículas/química
6.
J Transl Med ; 22(1): 196, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395901

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a multifaceted metabolic disorder, whose global prevalence is rapidly increasing. Acetyl CoA carboxylases 1 (ACACA) is the key enzyme that controls the rate of fatty acid synthesis. Hence, it is crucial to investigate the function of ACACA in regulating lipid metabolism during the progress of NAFLD. METHODS: Firstly, a fatty liver mouse model was established by high-fat diet at 2nd, 12th, and 20th week, respectively. Then, transcriptome analysis was performed on liver samples to investigate the underlying mechanisms and identify the target gene of the occurrence and development of NAFLD. Afterwards, lipid accumulation cell model was induced by palmitic acid and oleic acid (PA ∶ OA molar ratio = 1∶2). Next, we silenced the target gene ACACA using small interfering RNAs (siRNAs) or the CMS-121 inhibitor. Subsequently, experiments were performed comprehensively the effects of inhibiting ACACA on mitochondrial function and lipid metabolism, as well as on AMPK- PPARα- CPT1A pathway. RESULTS: This data indicated that the pathways significantly affected by high-fat diet include lipid metabolism and mitochondrial function. Then, we focus on the target gene ACACA. In addition, the in vitro results suggested that inhibiting of ACACA in vitro reduces intracellular lipid accumulation, specifically the content of TG and TC. Furthermore, ACACA ameliorated mitochondrial dysfunction and alleviate oxidative stress, including MMP complete, ATP and ROS production, as well as the expression of mitochondria respiratory chain complex (MRC) and AMPK proteins. Meanwhile, ACACA inhibition enhances lipid metabolism through activation of PPARα/CPT1A, leading to a decrease in intracellular lipid accumulation. CONCLUSION: Targeting ACACA can reduce lipid accumulation by mediating the AMPK- PPARα- CPT1A pathway, which regulates lipid metabolism and alleviates mitochondrial dysfunction.


Assuntos
Acetil-CoA Carboxilase , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Dieta Hiperlipídica , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Mitocôndrias/metabolismo , Doenças Mitocondriais/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Ácido Palmítico/metabolismo , Ácido Palmítico/farmacologia , PPAR alfa/metabolismo , Acetil-CoA Carboxilase/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo
7.
Clin Endocrinol (Oxf) ; 100(3): 284-293, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172081

RESUMO

OBJECTIVE: Insulin receptor substract 1 (IRS1) protein is an important signal transduction adapter for extracellular signal transduction from insulin-like growth factor-1 receptor and its family members to IRS1 downstream proteins. IRS1 has been reported to be involved in tumourigenesis and metastasis in some of solid tumors. Investigating the role of IRS1 in thyroid cancer can help to screen high risk patients at the initial diagnosis. DESIGN, PATIENTS AND MEASUREMENTS: Immunohistochemical assay was used to detect the expression levels of IRS1 in 131 metastatic thyroid cancer tissues. Wound healing, cell invasion and colony formation assays were used to study the functions of IRS1 in vitro. RNA sequencing (RNA-seq) and Western blot analysis analyses were performed to examine the underlying regulation mechanisms of IRS1 in thyroid cancer cells. RESULTS: IRS1 was highly expressed in thyroid cancers and its expression was positively associated with distant metastasis and advanced clinical stages. In vitro studies demonstrated that IRS1 is an important mediator of migration, invasion and colony formation of thyroid cancer cells. RNA-seq showed that IRS1 promoted the metastasis of thyroid cancer by regulating epithelial-mesenchymal transition and phosphoinositide 3-kinase (PI3K)/AKT pathway. CONCLUSIONS: IRS1 overexpression contributes to the aggressiveness of thyroid cancer and is expected to be a stratified marker and a potential therapeutic target for thyroid cancer.


Assuntos
Fosfatidilinositol 3-Quinase , Neoplasias da Glândula Tireoide , Humanos , Fosfatidilinositol 3-Quinase/genética , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias da Glândula Tireoide/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo
8.
Opt Lett ; 49(4): 1029-1032, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359234

RESUMO

Directional emission of electromagnetic waves plays an essential role in laser radar and free-space communication. For most directional antennas, bandwidth and miniaturization are a pair of contradictions due to their underlying interference mechanism. Connection-type metamaterials exhibit exotic electromagnetic response near zero-frequency, which relies on the global topology of mesh connectivity rather than resonance and thus has a broad working bandwidth. In this Letter, we investigate the broadband orientation-dependent coupling effect of a 3D double mesh metamaterial. Based on this effect, we achieve a broadband directional emission (relative bandwidth of 37.72%) using a compact structure (compared to twice working wavelength). Our work provides a novel, to the best of our knowledge, scheme to manipulate a long-wavelength wave and may pave the way to a miniaturized directional antenna.

9.
Phys Rev Lett ; 132(22): 220402, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38877901

RESUMO

By utilizing biorthogonal bases, we develop a comprehensive framework for studying biorthogonal dynamical quantum phase transitions in non-Hermitian systems. With the help of the previously overlooked associated state, we define the automatically normalized biorthogonal Loschmidt echo. This approach is capable of handling arbitrary non-Hermitian systems with complex eigenvalues and naturally eliminates the negative value of Loschmidt rate obtained without the biorthogonal bases. Taking the non-Hermitian Su-Schrieffer-Heeger model as a concrete example, a 1/2 change of dynamical topological order parameter in biorthogonal bases is observed which is not shown in self-normal bases. Furthermore, we discover that the periodicity of biorthogonal dynamical quantum phase transitions depends on whether the two-level subsystem at the critical momentum oscillates or reaches a steady state.

10.
Phys Rev Lett ; 132(11): 113801, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38563935

RESUMO

Manipulating radiation asymmetry of photonic structures is of particular interest in many photonic applications such as directional optical antenna, high efficiency on-chip lasers, and coherent light control. Here, we proposed a term of pseudopolarization to reveal the topological nature of radiation asymmetry in bilayer metagratings. Robust pseudopolarization vortex with an integer topological charge exists in P-symmetry metagrating, allowing for tunable directionality ranging from -1 to 1 in synthetic parameter space. When P-symmetry breaking, such vortex becomes pairs of C points due to the conservation law of charge, leading to the phase difference of radiation asymmetry from π/2 to 3π/2. Furthermore, topologically enabled coherent perfect absorption is robust with customized phase difference at will between two counterpropagating external light sources. This Letter can not only enrich the understanding of two particular topological photonic behaviors, i.e., bound state in the continuum and unidirectional guided resonance, but also provide a topological view on radiation asymmetry, opening an unexplored avenue for asymmetric light manipulation in on-chip laser, light-light switch, and quantum emitters.

11.
J Magn Reson Imaging ; 59(5): 1820-1831, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37830268

RESUMO

BACKGROUND: The impact of left ventricular mechanical dyssynchrony (LVMD) on the long-term prognosis of ST-segment elevation myocardial infarction (STEMI) is unclear. HYPOTHESIS: MR uniformity ratio estimates (URE) can detect LVMD and assess STEMI prognosis. STUDY TYPE: Retrospective analysis of a prospective multicenter registry (EARLY-MYO trial, NCT03768453). POPULATION: Overall, 450 patients (50 females) with first-time STEMI were analyzed, as well as 40 participants without cardiovascular disease as controls. FIELD STRENGTH/SEQUENCE: 3.0-T, balanced steady-state free precession cine and late gadolinium enhancement imaging. ASSESSMENT: MRI data were acquired within 1 week of symptom onset. Major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal re-infarction, hospitalization for heart failure, and stroke, were the primary clinical outcomes. LVMD was represented by circumferential URE (CURE) and radial URE (RURE) calculated using strain measurements. The patients were grouped according to clinical outcomes or URE values. Patients' clinical characteristics and MR indicators were compared. STATISTICAL TESTS: The Student's t-test, Mann-Whitney U test, chi-square test, Fisher's exact test, receiver operating characteristic curve analysis with area under the curve, Kaplan-Meier analysis, Cox regression, logistic regression, intraclass correlation coefficient, c-index, and integrated discrimination improvement were used. P < 0.05 was considered statistically significant. RESULTS: CURE and RURE were significantly lower in patients with STEMI than in controls. The median follow-up was 60.5 months. Patients with both lower CURE and RURE values experienced a significantly higher incidence of MACEs by 3.525-fold. Both CURE and RURE were independent risk factors for MACEs. The addition of UREs improved diagnostic efficacy and risk stratification based on infarct size and left ventricular ejection fraction (LVEF). The indicators associated with LVMD included male sex, serum biomarkers (peak creatine phosphokinase and cardiac troponin I), infarct size, and LVEF. DATA CONCLUSION: CURE and RURE may be useful to evaluate long-term prognosis after STEMI. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Feminino , Humanos , Masculino , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Volume Sistólico , Função Ventricular Esquerda , Estudos Prospectivos , Meios de Contraste , Estudos Retrospectivos , Gadolínio , Imageamento por Ressonância Magnética/métodos , Prognóstico , Intervenção Coronária Percutânea/efeitos adversos , Imagem Cinética por Ressonância Magnética/métodos
12.
BMC Infect Dis ; 24(1): 707, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026207

RESUMO

BACKGROUND: The prevalence and severity of pediatric Mycoplasma pneumoniae pneumonia (MPP) poses a significant threat to the health and lives of children. In this study, we aim to systematically evaluate the value of routine blood parameters in predicting MPP and develop a robust and generalizable ensemble artificial intelligence (AI) model to assist in identifying patients with MPP. METHODS: We collected 27 features, including routine blood parameters and hs-CRP levels, from patients admitted to The Affiliated Dazu's Hospital of Chongqing Medical University with or without MPP between January, 2023 and January, 2024. A classification model was built using seven machine learning (ML) algorithms to develop an integrated prediction tool for diagnosing MPP. It was evaluated on both an internal validation set (982 individuals) and an external validation set (195 individuals). The primary outcome measured the accuracy of the model in predicting MPP. RESULTS: The GBDT is state-of-the-art based on 27 features. Following inter-laboratory cohort testing, the GBDT demonstrated an AUC, accuracy, specificity, sensitivity, PPV, NPV, and F1-score of 0.980 (0.938-0.995), 0.928 (0.796-0.970), 0.929 (0.717-1.000), 0.926 (0.889-0.956), 0.922 (0.727-1.000), 0.937 (0.884-0.963), and 0.923 (0.800-0.966) in stratified 10-fold cross-validation. A GBDT-based AI Lab was developed to facilitate the healthcare providers in remote and impoverished areas. CONCLUSIONS: The GBDT-based AI Lab tool, with high sensitivity and specificity, could help discriminate between pediatric MPP infection and non-MPP infection based on routine blood parameters. Moreover, a user-friendly webpage tool for AI Lab could facilitate healthcare providers in remote and impoverished areas where advanced technologies are not accessible.


Assuntos
Aprendizado de Máquina , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Humanos , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/sangue , Pneumonia por Mycoplasma/microbiologia , Criança , Feminino , Masculino , Mycoplasma pneumoniae/isolamento & purificação , Pré-Escolar , Sensibilidade e Especificidade , Algoritmos
13.
Phys Chem Chem Phys ; 26(10): 8228-8236, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38385276

RESUMO

Group theory is a powerful tool to explore fundamental symmetry constraints for the physical properties of crystal structures, e.g. it is well-known that only a few components of the elastic constants are independent due to the symmetry constraint. This work further applies group theory to derive constraint relationships for high-order elastic constants with respect to the orientation angle, where the constraint relationships are more explicit than the traditional tensor transformation law. These analytic symmetry constraints are adopted to explain the molecular dynamics simulation results, which disclose that the high-order elastic constants are highly anisotropic with an anisotropy percentage of up to 25% for the hexagonal boron nitride monolayer. The elastic constant is a basic quantity in the mechanics field, so its high anisotropy shall cause strong anisotropy for other mechanical properties. Based on the anisotropic high-order elastic constants, we demonstrate that Poisson's ratio is highly anisotropic for the hexagonal boron nitride at large strains. These findings provide fundamental insights into the symmetry dependence of high-order elastic constants and other mechanical properties.

14.
Pacing Clin Electrophysiol ; 47(4): 518-524, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38407374

RESUMO

BACKGROUND: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long-term outcomes of patients with AF and LBBB after catheter ablation. METHODS: Forty-two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non-LBBB group. Late recurrence and a composite endpoint of stroke, all-cause mortality, and cardiovascular hospitalization were compared between the two groups. RESULTS: Late recurrence rate was significantly higher in the LBBB group than that in the non-LBBB group (54.8% vs. 31.5%, p = .034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.40, p = .031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64-9.64, p = .002). CONCLUSIONS: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Acidente Vascular Cerebral , Humanos , Bloqueio de Ramo/etiologia , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Ablação por Cateter/efeitos adversos , Resultado do Tratamento , Recidiva
15.
Exp Cell Res ; 426(2): 113573, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37003558

RESUMO

Ovarian cancer (OC) is a common malignant tumor in gynecology. LMNB1 is an important component of the nuclear skeleton. The expression of LMNB1 in ovarian cancer is significantly higher than that in normal tissues, but its role in tumor still needs comprehensive investigation. In this study, we overexpressed and knocked down LMNB1 in ovarian cancer cells and explore the effect of LMNB1 on the cell proliferation, migration and the underlying mechanism. We analyzed the expression levels of LMNB1 in ovarian cancer and their clinical relevance by using bioinformatics methods, qRT-PCR, Western blot and immunohistochemistry. To state the effect and mechanism of LMNB1 on OC in vitro and in vivo, we performed mouse xenograft studies, CCK8, cloning formation, Edu incorporation, wound healing, transwell and flow cytometry assay in stable LMNB1 knockdown OC cells, following by RNA-seq. Overexpression of LMNB1 indicates the progression of OC. LMNB1 knockdown inhibited the proliferation and migration of OC cells by suppressing the FGF1-mediated PI3K-Akt signaling pathway. Our study shows LMNB1 as a novel prognostic factor and therapeutic target in OC.


Assuntos
Lamina Tipo B , Neoplasias Ovarianas , Proteínas Proto-Oncogênicas c-akt , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Ovarianas/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Lamina Tipo B/genética , Deleção de Genes
16.
BMC Vet Res ; 20(1): 207, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760783

RESUMO

BACKGROUND: Although ultrasonography (US) has been widely used in the diagnosis of human diseases to monitor the progress of cystic echinococcosis (CE) control, the screening method for hepatic CE in sheep flocks requires adjustment. In this study, we used a US scanner to screen sheep flocks and evaluated the efficacy of dosing dogs once a year with praziquantel for 7 years from 2014 to 2021. METHODS: All sheep in the three flocks were screened using an ultrasound scanner in 2014 and compared with the prevalence of infection in 2021 in Bayinbuluke, Xinjiang, China. Sheep age was determined using incisor teeth. Cyst activity and calcification were determined using US images. The dogs were dewormed with praziquantel once a year to control echinococcosis in the community. RESULTS: Three flocks had 968 sheep in 2014, with 13.22%, 22.62%, 18.7%, 27.27%, 11.88%, and 6.3% of sheep aged 1, 2, 3, 4, 5, and ≥ 6 years old, respectively. US scanning revealed that the overall CE prevalence was 38.43% (372/968), with active cysts and calcified cysts present in 9.40% (91/968) and 29.02% (281/968) of the sheep, respectively. For the young sheep aged 1 and 2 years, the prevalence of active and calcified cysts was: 1.56% and 0.91%, and 10.94% and 18.72%, respectively. Approximately 15.15% and 16.52% of the 4- and 5-year-old sheep, respectively, harbored active cysts. There was no significant difference in the infection rates of sheep between 2014 and 2021 (P > 0.05). CONCLUSIONS: US is a practical tool for the field screening of CE in sheep flocks. One-third of the sheep population in the flocks was 1-2 years old, and these sheep played a very limited role in CE transmission, as most of the cysts were calcified. Old sheep, especially culled aged sheep, play a key role in the transmission of CE. Dosing dogs once a year did not affect echinococcosis control.


Assuntos
Equinococose Hepática , Doenças dos Ovinos , Ultrassonografia , Animais , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/parasitologia , Doenças dos Ovinos/diagnóstico por imagem , Ovinos , China/epidemiologia , Ultrassonografia/veterinária , Equinococose Hepática/veterinária , Equinococose Hepática/epidemiologia , Equinococose Hepática/diagnóstico por imagem , Prevalência , Cães , Praziquantel/uso terapêutico , Anti-Helmínticos/uso terapêutico , Feminino
17.
Cell Mol Life Sci ; 80(2): 49, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690903

RESUMO

Haematopoietic Stem cells (HSCs) have the potential for self-renewal and multilineage differentiation, and their behaviours are finely tuned by the microenvironment. HSC transplantation (HSCT) is widely used in the treatment of haematologic malignancies while limited by the quantity of available HSCs. With the development of tissue engineering, hydrogels have been deployed to mimic the HSC microenvironment in vitro. Engineered hydrogels influence HSC behaviour by regulating mechanical strength, extracellular matrix microstructure, cellular ligands and cytokines, cell-cell interaction, and oxygen concentration, which ultimately facilitate the acquisition of sufficient HSCs. Here, we review recent advances in the application of hydrogel-based microenvironment engineering of HSCs, and provide future perspectives on challenges in basic research and clinical practice.


Assuntos
Neoplasias Hematológicas , Hidrogéis , Humanos , Células-Tronco Hematopoéticas , Diferenciação Celular , Citocinas , Nicho de Células-Tronco , Microambiente Tumoral
18.
Ren Fail ; 46(2): 2374013, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38967153

RESUMO

OBJECTIVE: To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption combined with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute bipyridine herbicide poisoning. METHODS: A retrospective analysis of 18 patients with acute bipyridine herbicide poisoning was conducted, of which 9 patients were poisoned by diquat and 9 patients by paraquat. All patients underwent FPSA-CVVH treatment. The serum cytokine levels in pesticide-poisoned patients were assessed. The efficacy of FPSA-CVVH in eliminating cytokines, the 90-d survival rate of poisoned patients, and adverse reactions to the treatment were observed. RESULTS: Fourteen patients (77.8%) had acute kidney injuries and 10 (55.6%) had acute liver injuries. The serum cytokine levels of high mobility group protein B-1 (HMGB-1), interleukin-6 (IL-6), IL-8, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1ß (MIP-1ß) were significantly elevated. A total of 41 FPSA-CVVH treatment sessions were administered. After a single 8-h FPSA-CVVH treatment, the decreases in HMGB-1, IL-6, IL-8, IP-10, MCP-1, and MIP-1ß were 66.0%, 63.5%, 73.3%, 63.7%, 53.9%, and 54.1%, respectively. During FPSA-CVVH treatment, one patient required a filter change due to coagulation in the plasma component separator, and one experienced a bleeding adverse reaction. The 90-d patient survival rate was 50%, with 4 patients with diquat poisoning and 5 patients with paraquat poisoning, and both liver and kidney functions were restored to normal. CONCLUSION: Cytokine storms may play a significant role in the progression of multiorgan dysfunction in patients with acute bipyridine herbicide poisoning. FPSA-CVVH can effectively reduce cytokine levels, increase the survival rate of patients with acute bipyridine herbicide poisoning, and decrease the incidence of adverse events.


Assuntos
Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Herbicidas , Humanos , Masculino , Feminino , Herbicidas/intoxicação , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Injúria Renal Aguda/terapia , Injúria Renal Aguda/induzido quimicamente , Citocinas/sangue , Paraquat/intoxicação , Diquat/intoxicação , Adulto Jovem , Idoso , Hemofiltração/métodos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/terapia
19.
Sensors (Basel) ; 24(13)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39001068

RESUMO

Synthetic Aperture Radar (SAR) ship detection is applicable to various scenarios, such as maritime monitoring and navigational aids. However, the detection process is often prone to errors due to interferences from complex environmental factors like speckle noise, coastlines, and islands, which may result in false positives or missed detections. This article introduces a ship detection method for SAR images, which employs deep learning and morphological networks. Initially, adaptive preprocessing is carried out by a morphological network to enhance the edge features of ships and suppress background noise, thereby increasing detection accuracy. Subsequently, a coordinate channel attention module is integrated into the feature extraction network to improve the spatial awareness of the network toward ships, thus reducing the incidence of missed detections. Finally, a four-layer bidirectional feature pyramid network is designed, incorporating large-scale feature maps to capture detailed characteristics of ships, to enhance the detection capabilities of the network in complex geographic environments. Experiments were conducted using the publicly available SAR Ship Detection Dataset (SSDD) and High-Resolution SAR Image Dataset (HRSID). Compared with the baseline model YOLOX, the proposed method increased the recall by 3.11% and 0.22% for the SSDD and HRSID, respectively. Additionally, the mean Average Precision (mAP) improved by 0.7% and 0.36%, reaching 98.47% and 91.71% on these datasets. These results demonstrate the outstanding detection performance of our method.

20.
Sensors (Basel) ; 24(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38894236

RESUMO

Frequency agility refers to the rapid variation of the carrier frequency of adjacent pulses, which is an effective radar active antijamming method against frequency spot jamming. Variation patterns of traditional pseudo-random frequency hopping methods are susceptible to analysis and decryption, rendering them ineffective against increasingly sophisticated jamming strategies. Although existing reinforcement learning-based methods can adaptively optimize frequency hopping strategies, they are limited in adapting to the diversity and dynamics of jamming strategies, resulting in poor performance in the face of complex unknown jamming strategies. This paper proposes an AK-MADDPG (Adaptive K-th order history-based Multi-Agent Deep Deterministic Policy Gradient) method for designing frequency hopping strategies in frequency agile radar. Signal pulses within a coherent processing interval are treated as agents, learning to optimize their hopping strategies in the case of unknown jamming strategies. Agents dynamically adjust their carrier frequencies to evade jamming and collaborate with others to enhance antijamming efficacy. This approach exploits cooperative relationships among the pulses, providing additional information for optimized frequency hopping strategies. In addition, an adaptive K-th order history method has been introduced into the algorithm to capture long-term dependencies in sequential data. Simulation results demonstrate the superior performance of the proposed method.

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