RESUMO
SignificanceThe monotrichous Pseudomonas aeruginosa was usually thought to swim in a pattern of "run and reverse" (possibly with pauses in between), where straight runs alternated with reverses with angular changes of swimming direction near 180°. Here, by simultaneously tracking the cell swimming and the morphology of its flagellum, we discovered a swimming mode in P. aeruginosa-the wrap mode, during which the flagellar filament wrapped around the cell body and induced large fluctuation of the body orientation. The wrap mode randomized swimming direction, resulting in a broad distribution of angular changes over 0 to 180° with a peak near 90°. This allowed the bacterium to explore the environment more efficiently, which we confirmed by stochastic simulations of P. aeruginosa chemotaxis.
Assuntos
Pseudomonas aeruginosa , Natação , Bactérias , Quimiotaxia , Flagelos , MovimentoRESUMO
In a dilute liquid environment in which cell-cell interaction is negligible, flagellated bacteria, such as Escherichia coli, perform chemotaxis by biased random walks alternating between run-and-tumble. In a two-dimensional crowded environment, such as a bacterial swarm, the typical behavior of run-and-tumble is absent, and this raises the question whether and how bacteria can perform chemotaxis in a swarm. Here, by examining the chemotactic behavior as a function of the cell density, we showed that chemotaxis is surprisingly enhanced because of cell crowding in a bacterial swarm, and this enhancement is correlated with increase in the degree of cell body alignment. Cells tend to form clusters that move collectively in a swarm with increased effective run length, and we showed analytically that this resulted in increased drift velocity toward attractants. We also explained the enhancement by stochastically simulating bacterial chemotaxis in a swarm. We found that cell crowding in a swarm enhances chemotaxis if the cell-cell interactions used in the simulation induce cell-cell alignment, but it impedes chemotaxis if the interactions are collisions that randomize cell moving direction. Therefore, collective motion in a bacterial swarm enhances chemotaxis.
Assuntos
Quimiotaxia , Escherichia coli , Bactérias , Simulação por Computador , Modelos Biológicos , Movimento (Física)RESUMO
We developed a robust bead assay for studying flagellar motor behavior of Pseudomonas aeruginosa. Using this assay, we studied the dynamics of the two stator systems in the flagellar motor. We found that the two sets of stators function differently, with MotAB stators providing higher total torque and MotCD stators ensuring more stable motor speed. The motors in wild-type cells adjust the stator compositions according to the environment, resulting in an optimal performance in environmental exploration compared to that of mutants with one set of stators. The bead assay we developed in this investigation can be further used to study P. aeruginosa chemotaxis at the level of a single cell using the motor behavior as the chemotaxis output. IMPORTANCE Cells of Pseudomonas aeruginosa possess a single polar flagellum, driven by a rotatory motor powered by two sets of torque-generating units (stators). We developed a robust bead assay for studying the behavior of the flagellar motor in P. aeruginosa, by attaching a microsphere to shortened flagellar filament and using it as an indicator of motor rotation. Using this assay, we revealed the dynamics of the two stator systems in the flagellar motor and found that the motors in wild-type cells adjust the stator compositions according to the environment, resulting in an optimal performance in environmental exploration compared to that of mutants with one set of stators.
Assuntos
Quimiotaxia , Flagelos/fisiologia , Pseudomonas aeruginosa , Pseudomonas aeruginosa/fisiologiaRESUMO
PURPOSE: To date, it is unclear whether laparoscopic hepatectomy (LH) is a suitable treatment for elderly patients (aged ?65 years) with liver metastases from colorectal cancer. The aim of the present study was to clarify the value of LH in the elderly using the propensity score matching method. METHODS: Data from 385 elderly patients who underwent hepatectomy for liver metastases from colorectal cancer at our institution between January 2008 and January 2016 were prospectively collected. Propensity score matching was applied at a ratio of 1:1 to compare LH and open hepatectomy (OH) groups. The short- and long-term outcomes were compared between the matched groups. RESULTS: The LH group had significantly less blood loss than the OH group. The postoperative length of hospital stay was shorter in the LH group than in the OH group: however, no significant intergroup differences were found in morbidity and mortality. Furthermore, the 5-year overall (OS) and disease-free survival (DFS) rates were similar between the two groups. CONCLUSION: LH for elderly patients with liver metastases from colorectal cancer was feasible and safe with acceptable oncologic outcomes. Therefore, patient age alone should not be considered as a contraindication when deciding between LH and OH as treatment options.
Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/métodos , Laparoscopia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Fatores Etários , Idoso , Perda Sanguínea Cirúrgica , Distribuição de Qui-Quadrado , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Estimativa de Kaplan-Meier , Laparoscopia/efeitos adversos , Laparoscopia/mortalidade , Tempo de Internação , Neoplasias Hepáticas/mortalidade , Masculino , Análise Multivariada , Duração da Cirurgia , Seleção de Pacientes , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Real-time prediction of blood glucose levels (BGLs) in individuals with type 1 diabetes (T1D) presents considerable challenges. Accordingly, we present a personalized multitasking framework aimed to forecast blood glucose levels in patients. The patient data was initially categorized according to gender and age and subsequently utilized as input for a modified GRU network model, creating five prediction sub-models. The model hyperparameters were optimized and tuned after introducing the decay factor and incorporating the TCN network and attention mechanism into the GRU model. This step was undertaken to improve the capability of feature extraction. The Ohio T1DM clinical dataset was used to train and evaluate the performance of the proposed model. The metrics, including Root Mean Square Error (RMSE), Mean Absolute Error (MAE) and Clark Error Grid Analysis (EGA), were used to evaluate the performance. The results showed that the average RMSE and the MAE of the proposed model were 16.896 and 9.978 mg/dL, respectively, over the prediction horizon (PH) of 30 minutes. The average RMSE and the MAE were 28.881 and 19.347 mg/dL, respectively, over the PH of 60 min. The proposed model demonstrated excellent prediction accuracy. In addition, the EGA analysis showed that the proposed model accurately predicted 30-minute and 60-minute PH within zones A and B, demonstrating that the framework is clinically feasible. The proposed personalized multitask prediction model in this study offers robust assistance for clinical decision-making, playing a pivotal role in improving the outcomes of individuals with diabetes.
Assuntos
Diabetes Mellitus Tipo 1 , Humanos , Glicemia/análise , Automonitorização da Glicemia/métodos , PrevisõesRESUMO
This study sought to elucidate the mechanisms underlying the impact of the interferon signaling pathway on Ferroptosis in tumor cells and its correlation with CD8 + T cell exhaustion. Using mouse models and single-cell sequencing, the researchers studied the interaction between CD8 + T cells and the interferon signaling pathway. Differential gene analysis revealed key genes involved in CD8 + T cell exhaustion, and their downstream factors were explored using bioinformatics tools. The expression levels of interferon-related genes associated with Ferroptosis were analyzed using data from the TCGA database, and their relevance to tumor tissue Ferroptosis and patients' prognosis was determined. In vitro experiments were conducted to measure the levels of IFN-γ, MDA, and LPO, as well as tumor cell viability and apoptosis. In vivo validation using a mouse tumor model confirmed the results obtained from the in vitro experiments, highlighting the potential of silencing HSPA6 or DNAJB1 in enhancing the efficacy of PD-1 therapy and inhibiting tumor growth and migration.