Search

Lung cancer (LC) is regarded as a fatal cancer, and insulin-like growth factor 1 (IGF1) and its receptor (IGF1R) have been found to play a key role in regulating tumor glycolytic metabolism. The aim of this study is to investigate LC proliferation regulated by metabolite-mediated IGF1R lactylation. IGF1R was highly expressed in LC tissues and cells, and the effects of IGF1R on protein stability were inhibited by Lactate dehydrogenase A (LDHA) inhibition. Moreover, the tightness of IGF1R binding to IGF1 was also enhanced by exogenous lactic acid but suppressed by LDHA silencing, while cell viability and proliferation were promoted by over-expression of IGF1R. Exogenous lactic acid further exacerbated the effects of the IGF1R gene, while LDHA knocking down reduced the IGF1R-induced malignant behaviors. The IGF1R and exogenous lactic acid were also found to increase extracellular acidification rate (ECAR) and decrease oxygen consumption rate to regulate glycolysis, which was inhibited by LDHA deficiency in LC cells. The study concluded that IGF1R-mediated aggressive behaviors of LC cells were associated with higher levels of IGF1R lactylation. Moreover, lactic acid can improve the protein stability of the IGF1R oncogene, thus promoting glycolysis and generating lactic acid, forming a closed loop. Therefore, targeting IGF1R is envisaged to provide a novel strategy for developing therapeutic agents against LC.

This paper studies the bipartite consensus tracking problems of fractional-order multi-agent systems on directed signed graphs. Each agent is modelled as a second-order fractional-order dynamics with the order belonging to $ (0,1] $ (0 , 1 ] , and the cooperative and competitive interactions between the agents coexist in the systems. Two distributed bipartite consensus tracking protocols are proposed for the systems based on continuous information and sampled information, respectively. Under the assumption that the directed signed graph is structurally balanced, it is shown that the second-order fractional-order multi-agent systems can achieve the bipartite consensus tracking if the feedback coefficients are chosen appropriately. Finally, several simulations are provided to verify the effectiveness of the theoretical results. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced thrombocytopenia (CIT) increases the risk of bleeding, necessitates chemotherapy dose reductions and delays, and negatively impacts prognosis. Objectives: This study aimed to evaluate the efficacy and safety of hetrombopag for the management of CIT in patients with advanced solid tumors. Design: A multicenter, randomized, double-blind, placebo-controlled, phase II study. Methods: Patients with advanced solid tumors who experienced a chemotherapy delay of ⩾7 days due to thrombocytopenia (platelet count <75 × 109/L) were randomly assigned (1:1) to receive oral hetrombopag at an initial dose of 7.5 mg once daily or a matching placebo. The primary endpoint was the proportion of treatment responders, defined as patients resuming chemotherapy within 14 days (platelet count ⩾100 × 109/L) and not requiring a chemotherapy dose reduction of ⩾15% or a delay of ⩾4 days or rescue therapy for two consecutive cycles. Results: Between 9 October 2021 and 5 May 2022, 60 patients were randomized, with 59 receiving ⩾1 dose of assigned treatment (hetrombopag/placebo arm, n = 28/31). The proportion of treatment responders was significantly higher in the hetrombopag arm than in the placebo arm [60.7% (17/28) versus 12.9% (4/31); difference of proportion: 47.6% (95% confidence interval (CI): 26.0–69.3); odds ratio = 10.44 (95% CI: 2.82–38.65); p value (nominal) based on the Cochran–Mantel–Haenszel: <0.001)]. During the double-blind treatment period, grade 3 or higher adverse events (AEs) occurred in 35.7% (10/28) of patients with hetrombopag and 38.7% (12/31) of patients on placebo. The most common grade 3 or higher AEs were decreased neutrophil count [35.7% (10/28) versus 35.5% (11/31)] and decreased white blood cell count [17.9% (5/28) versus 19.4% (6/31)]. Serious AEs were reported in 3.6% (1/28) of patients with hetrombopag and 9.7% (3/31) of patients with placebo. Conclusion: Hetrombopag is an effective and well-tolerated alternative for managing CIT in patients with solid tumors. Trial registration: ClinicalTrials.gov identifier: NCT03976882. [ABSTRACT FROM AUTHOR]

Summary: This paper investigates group consensus tracking problems with time‐varying reference velocities. The multiple agents are described as second‐order nonlinear dynamics in directed information exchange settings. For the multi‐agent networks formed by finite agent groups, novel distributed protocols with/without time‐varying transmission delays are designed to solve the group consensus tracking problems. The problems are first transformed into the asymptotical stability of consensus error systems and the input‐to‐state stability of tracking error systems, and then sufficient conditions are derived to guarantee the agents realizing the group consensus tracking based on Lyapunov stability theories. Finally, several simulations are given to verify the effectiveness of the theoretical results. [ABSTRACT FROM AUTHOR]

CO2 emissions from fossil energy have caused global climate problems and threatened human survival. However, there are few studies on the spatiotemporal distribution and driving factors of carbon emissions. This paper takes the Yangtze River Delta (YRD) urban agglomeration as the research object and analyzes the spatiotemporal heterogeneity of carbon dioxide emissions and their driving factors from 2000 to 2017. First, a series of preprocessing, such as resample, interpolation, and image clipping, are conducted on the CO2 emission data and nighttime light remote sensing images. Second, the dynamic time wrapping (DTW) and hierarchical clustering algorithms were involved in manipulating the CO2 emission data. Consequently, the cities' and CO2 emissions' time series were classified into four categories and three stages separately. Finally, the geographical detector model (GDM) and geographical and temporal weighted regression (GTWR) are coupled to evaluate the spatiotemporal heterogeneity and quantify the driving factors. The results show the following: (1) The spatiotemporal distribution of CO2 emissions has spatial consistency from 2000 to 2017. High-emission areas are concentrated in economically developed areas such as Shanghai, Suzhou, and Wuxi. The results are consistent with previous research. (2) Regional aggregation is a revealed new trend. CO2 emissions in the target urban areas are gradually converging into economic center cities and diverse class cities, e.g., Shanghai and Ningbo. (3) In cities of different economic development levels, the driving factors of CO2 emissions are different. The secondary sector and urban infrastructure dominate in the early stages of developed cities. On top of that, the influence of the tertiary industry is more significant in the later development stages. According to the results, in the urban development process, humans should not only pursue the increase in speed but also pay attention to the negative impact of the economic development process on the ecological environment. Besides, since the spatiotemporal characteristics and dominant factors of urban carbon emissions are different in each stage of development, the formulation of carbon reduction policies should be associated with urban features. [ABSTRACT FROM AUTHOR]