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]

We investigate scaled group consensus problems of high-order multi-agent systems with directed information exchanges. As one of multiple consensus, the scaled group consensus focuses on both cooperations and competitions among multi-agent sub-networks and cooperations among agents belonging to a sub-network. Two distributed protocols are designed to solve the scaled group consensus problems. The (generalised) Routh–Hurwitz stability criterion and matrix theory are utilised to establish necessary and sufficient conditions guaranteeing the agents reaching the scaled group consensus. Finally, several simulations are presented to demonstrate the effectiveness of the theoretical results. [ABSTRACT FROM AUTHOR]

Background. Platinum-based chemotherapy plays an antitumor role by damaging DNA. X-ray repair crosscomplementing protein 1 (XRCC1) participates in DNA repair and thus affects the sensitivity to platinum drugs. Two polymorphisms of XRCC1, rs25487 (Arg399Gln) and rs1799782 (Arg194Trp), have been widely studied for the association with clinical outcomes of platinum-based chemotherapy in Asian patients with non-small-cell lung cancer (NSCLC), but the results remain inconclusive. Thus, we performed the present meta-analysis. Methods. Literature search was performed in PubMed, Web of Science, and EMBASE up to June 2019. Odds ratios (ORs) for objective response ratio (ORR), Cox proportional hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS), and the corresponding 95% confidence intervals (95% CIs) were calculated to assess the association strengths between XRCC1 polymorphisms and clinical outcomes. Comparisons were performed in homozygous, heterozygous, dominant, and recessive models. Results. Finally, a total of 23 studies involving 5567 patients were included in the meta-analysis. Compared to ArgArg of rs25487, GlnGln (OR = 1.71 , 95% CI: 1.16-2.52, p =.007 , I 2 = 56.8 %) and GlnArg (OR = 1.23 , 95% CI: 1.07-1.40, p =.003 , I 2 = 29.0 %) were associated with higher ORR. Meanwhile, GlnGln indicated a favorable OS (HR = 0.60 , 95% CI: 0.40-0.88) and PFS (HR = 0.64 , 95% CI: 0.46-0.90). We also found positive associations between rs1799782 and ORR in all comparison models with low between-study heterogeneity. The association strength increased with the number of variant alleles (TrpTrp vs. ArgArg: OR = 1.73 , 95% CI:1.31-2.27; TrpArg vs. ArgArg: OR = 1.28 , 95% CI: 1.06-1.55), suggesting a gene dosage effect. In addition, TrpTrp predicted a longer OS. Conclusion. Our results showed that rs25487 and rs1799782 of XRCC1 are potential markers to predict clinical outcomes of platinum-based chemotherapy in Asian patients with NSCLC. [ABSTRACT FROM AUTHOR]

Background: Apatinib has been proved to be effective and well tolerated among patients in phase II and III studies. Here, we evaluated the safety and effectiveness of apatinib in advanced gastric cancer patients in a real-world setting. Methods: This study enrolled advanced gastric cancer patients who had progressed or relapsed despite systemic chemotherapy. The primary outcome was safety and the secondary outcomes included overall survival (OS) and progression-free survival (PFS). Results: A total of 337 patients were included. In total, 62 (18.4%), 102 (30.3%), and 173 (51.3%) patients received first, second, and third or higher line apatinib therapy, respectively. Grade 3/4 treatment-emergent adverse events (AEs) were infrequent (<5%), with hypertension (6.8%) being the only grade 3/4 AE occurring in more than 5% of the patients and across the low-dose (250 mg, 7.3%), mid-dose (425–500 mg, 6.1%), and high-dose group (675–850 mg, 2/15, 13.3%). The median OS and PFS were 7.13 months (95% CI, 6.17–7.93) and 4.20 months (95% CI, 4.60–4.77), respectively, and were comparable among the low-, mid-, and high-dose groups. Conclusion: Lower daily doses of apatinib achieved comparable OS and PFS versus higher daily doses of apatinib while maintaining a more benign safety profile in advanced gastric cancer patients. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02668380. [ABSTRACT FROM AUTHOR]

The service capacity of each station has a direct impact on the capacity of a subway line and also the whole subway network. Therefore, it is critically important to keep the station capacity above a certain level in its full life cycle. This paper aims at keeping subway station capacity in a certain level range. In consideration of key equipment failure, the expected station capacity model is established. After that the lower bound of equipment reliability is determined by sensitivity analysis based on the equipment reliability-expected station capacity curve. Finally, the maintenance schedule optimization model is also proposed. The validity and practicability of the proposed method are demonstrated by a simulation case study. [ABSTRACT FROM AUTHOR]

Abstract Human Glioblastoma is one deadly disease; the median survival time is reported to be 13.9 months after treatment. In the present study, we discovered that DHX33 is highly expressed in 84% of all Glioblastoma multiforme (GBM). Knockdown of DHX33 led to significant reduced proliferation and migration in glioblastoma cells in vitro and in vivo. Mechanistically, DHX33 regulated a set of critical genes involved in cell cycle and cell migration to promote glioblastoma development. Additionally, DHX33 was found to be induced by inhibitors of PI3K and mTOR whose activation has been detected in 50% of glioblastoma. Overexpression of wild type DHX33 protein, but not the helicase dead mutant, confers resistance to mTOR inhibitors in glioblastoma cells. DHX33 probably functions as a critical regulator to promote GBM development. Our results highlight its therapeutic potential in treating GBM. Highlights • DHX33 is highly expressed in 84% of human Glioblastoma Multiforme (GBM). • DHX33 is pivotal to maintain cell proliferation and migration in glioblastoma cells through regulating a subset of genes. • DHX33 can be induced by PI3K/mTOR inhibitors and confers resistance to mTOR inhibition. [ABSTRACT FROM AUTHOR]

We investigate scaled group consensus problems of multiagent systems with first/second-order linear continuous dynamics. For a complex network consisting of two subnetworks with different physical quantities or task distributions, it is concerned with this case that the agents’ states in one subnetwork converge to a consistent value asymptotically, while the states in the other subnetwork approach another value with a ratio of the former. For the case of the information exchange being directed, novel consensus protocols are designed for both first-order and second-order dynamics to solve the scaled group consensus problems. By utilizing algebra theory, graph theory, and Lyapunov stability theory, several necessary and sufficient conditions are established to guarantee the agents’ states reaching the scaled group consensus asymptotically. Finally, several simulation results are presented to demonstrate the effectiveness of the theoretical results. [ABSTRACT FROM AUTHOR]

This paper investigates a couple-group consensus problem of second-order multi-agent systems with the impact of second-order neighbours’ information. For systems with/without time delays, couple-group consensus criteria are established in the form of linear matrix inequalities by utilizing both model transformation and stability theories. The main results indicate that the group consensus for multi-agent systems under the effect of second-order neighbours’ information can be achieved based on the premise of a generalized balanced couple. Finally, illustrative examples are presented to demonstrate the effectiveness of the theoretical results. [ABSTRACT FROM AUTHOR]

This paper addresses group consensus for multi-agent systems with switching topologies and time-varying delays, where all agents are described by discrete-time second-order dynamics. Based on the relationship between zero/nonzero in-degree graphs and nonnegative matrices group consensus criteria, which is presented in terms of easily checkable graph topology conditions, is obtained for multi-agent systems with time-varying delays under switching topologies. Furthermore, numerical examples are presented to illustrate the obtained results, and the essential of some conditions and assumptions is verified for given switching communication topologies. [ABSTRACT FROM AUTHOR]

In this paper, the extremals of curvature energy actions on non-null regular curves in 2-dimensional de Sitter space are studied. We completely solve the Euler-Lagrange equation by quadratures. By using the Killing field, we construct three special coordinate systems and express the generalized elastica in 2-dimensional de Sitter space by integral explicitly. [ABSTRACT FROM AUTHOR]

We address stabilization problems of networked control systems in the presence of bounded packet losses and time-varying network-induced delays. When the delay is less than the transmission interval, we prove that the stability of the closed-loop system is implied by that of a switched system. Based on theories on switched systems, we present stabilizing conditions by using packet-loss-dependent Lyapunov functions, and design multiple controllers depending on the packet loss and the network-induced delay. Furthermore, based on the stabilizing conditions, we discuss the robustness of the stabilization against the packet loss and the network-induced delay. Several numerical examples and simulations are worked out to demonstrate the effectiveness of the proposed design approach. [ABSTRACT FROM AUTHOR]

This article studies the consensusability of multi‐agent systems with general linear continuous‐time dynamics. It is assumed that each agent can only obtain the information of other agents at sampling instants. Some sufficient and necessary conditions for consensusability in the case of state feedback are established, and it is shown that multi‐agent systems with periodic sampling are consensusable if and only if the system associated with each agent is stabilisable and the topology graph has a spanning tree. Furthermore, some methods are provided to seek controller gain and sampling period which ensure consensus. Simulations are performed to validate the theoretical results. [ABSTRACT FROM AUTHOR]

We discuss a new consensus problem – a group consensus problem – in networks of dynamic agents. For a complex network consisting of several sub-networks owing to physical quantities or task distributions, it is concerned with this case that the agents in a sub-network share a consistent value while there is no agreement between any two sub-networks. When the information exchange is directed, a novel consensus protocol is designed to solve the group consensus problem. The convergence analysis is discussed and several criteria are established based on graph theories and matrix theories. Simulation results are presented to demonstrate the effectiveness of the theoretical results. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common solid tumors worldwide and has an extremely poor prognosis. MicroRNA-429 (miR-429) has been reported to participate in the progression of CRC. However, the pathological mechanisms require further investigation. The aim of the present study was to investigate the association between miR-429 and high mobility group box 3 (HMGB3) in CRC and the associated mechanism. The mRNA expression levels of miR-429 and HMGB3 in 65 paired CRC and adjacent tissues were examined by reverse transcription-quantitative PCR. Furthermore, a dual-luciferase reporter assay was performed to identify the association between miR-429 and HMGB3. Finally, the effects of miR-429 and HMGB3 on the proliferation and apoptosis of CRC cells were detected. As a result, it was identified that miR-429 expression was downregulated and HMGB3 expression was upregulated in CRC tissues compared with in adjacent non-cancer tissues, and the expression levels of miR-429 were negatively associated with those of HMGB3. Notably, HMGB3 was demonstrated to be a direct target of miR-429 by dual-luciferase reporter assay. Furthermore, transfection with a miR-429 mimic significantly inhibited HMGB3 expression and led to decreased proliferation and increased apoptosis of CRC cells. On the other hand, transient overexpression of HMGB3 partially inhibited the antitumor effects of miR-429. To the best of our knowledge, the present study demonstrated for the first time that miR-429 regulated the proliferation and apoptosis of CRC cells via HMGB3, suggesting a specific tumor suppressive function of the miR-429/HMGB3 signaling pathway in CRC. [ABSTRACT FROM AUTHOR]

Herein, a simple route to prepare porous microspheres with tuned pore structure and potential functionality based on epoxy functionalized block copolymers, poly hydroxypropyl methacrylate‐b‐ poly glycidyl methacrylate (PHPMA‐b‐PGMA), through a water‐in‐oil‐in‐water (W/O/W) double emulsion is reported. The effect of surfactant concentration and the composition of block copolymers are investigated. The solvent vapor swelling behavior of porous microspheres before and after cross‐linking is studied. It is interesting that after the swelling, the cross‐linked open pores are self‐healed to form closed pores, whereas the uncross‐linked ones are collapsed. It is believed that this observation will be useful in guest carrying and control release, and find its application in biomedical and pharmaceuticals. [ABSTRACT FROM AUTHOR]