Breast cancer is one of the most common cancers worldwide, posing a serious threat to human health. Recently, innate immunity has become a widely discussed topic in antitumor research. The STING ...pathway is an important component of innate immunity, and several STING agonists have been developed and applied in antitumor research. Dimeric amidobenzimidazole (diABZI) is one STING agonist and is a nucleotide analog with low serological stability and cell membrane permeability. In this study, we prepared diABZI-encapsulated liposomes (dLNPs) using the ammonium sulfate gradient method. The average particle size of the dLNPs was 99.76 ± 0.230 nm, and the encapsulation efficiency was 58.29 ± 0.53%. Additionally, in vivo and in vitro assays showed that the dLNPs had a sustained-release effect and that the circulation time in vivo was longer than 48 h. The expression of IFN-β and IFN-γ was elevated in mice treated with dLNPs. Moreover, we found that dLNPs can recruit CD8
T cells to tumor tissue and exert antitumor effects. The dLNPs-treated group showed the most significant efficacy: the average tumor volume was 231.46 mm
, which decreased by 78.16% and 54.47% compared to the PBS group and diABZI group. Meanwhile, the hemolysis rate of the dLNPs was 2%, showing high biocompatibility. In conclusion, dLNPs can effectively suppress tumor growth and possess great potential in breast cancer therapy.
The paired combinatorial logit (PCL) model is one of the recent extended logit models adapted to resolve the overlapping problem in the route choice problem, while keeping the analytical tractability ...of the logit choice probability function. However, the development of efficient algorithms for solving the PCL model under congested and realistic networks is quite challenging, since it has large-dimensional solution variables as well as a complex objective function. In this paper, we examine the computation and application of the PCL stochastic user equilibrium (SUE) problem under congested and realistic networks. Specifically, we develop an improved path-based partial linearization algorithm for solving the PCL SUE problem by incorporating recent advances in line search strategies to enhance the computational efficiency required to determine a suitable stepsize that guarantees convergence. A real network in the city of Winnipeg is applied to examine the computational efficiency of the proposed algorithm and the robustness of various line search strategies. In addition, in order to acquire the practical implications of the PCL SUE model, we investigate the effectiveness of how the PCL model handles the effects of congestion, stochasticity, and similarity in comparison with the multinomial logit stochastic traffic equilibrium problem and the deterministic traffic equilibrium problem.
Tumour cells adapt to nutrient deprivation in vivo, yet strategies targeting the nutrient poor microenvironment remain unexplored. In melanoma, tumour cells often experience low glutamine levels, ...which promote cell dedifferentiation. Here, we show that dietary glutamine supplementation significantly inhibits melanoma tumour growth, prolongs survival in a transgenic melanoma mouse model, and increases sensitivity to a BRAF inhibitor. Metabolomic analysis reveals that dietary uptake of glutamine effectively increases the concentration of glutamine in tumours and its downstream metabolite, αKG, without increasing biosynthetic intermediates necessary for cell proliferation. Mechanistically, we find that glutamine supplementation uniformly alters the transcriptome in tumours. Our data further demonstrate that increase in intra-tumoural αKG concentration drives hypomethylation of H3K4me3, thereby suppressing epigenetically-activated oncogenic pathways in melanoma. Therefore, our findings provide evidence that glutamine supplementation can serve as a potential dietary intervention to block melanoma tumour growth and sensitize tumours to targeted therapy via epigenetic reprogramming.
Gradient projection (GP) algorithm has been shown as an efficient algorithm for solving the traditional traffic equilibrium problem with additive route costs. Recently, GP has been extended to solve ...the nonadditive traffic equilibrium problem (NaTEP), in which the cost incurred on each route is not just a simple sum of the link costs on that route. However, choosing an appropriate stepsize, which is not known a priori, is a critical issue in GP for solving the NaTEP. Inappropriate selection of the stepsize can significantly increase the computational burden, or even deteriorate the convergence. In this paper, a self-adaptive gradient projection (SAGP) algorithm is proposed. The self-adaptive scheme has the ability to automatically adjust the stepsize according to the information derived from previous iterations. Furthermore, the SAGP algorithm still retains the efficient flow update strategy that only requires a simple projection onto the nonnegative orthant. Numerical results are also provided to illustrate the efficiency and robustness of the proposed algorithm.
•Chronic back or neck pain and physical-mental comorbidity is very common in China.•Chronic back or neck pain may increase risk of other physical and mental diseases.•Chronic back or neck pain was ...associated with role disability.
To investigate mental and physical health comorbidity with chronic back or neck pain in the Chinese population, and assess the level of disability associated with chronic back or neck pain.
Data were derived from a large-scale and nationally representative community survey of adult respondents on mental health disorders in China (n = 28,140). Chronic back or neck pain, other chronic pain conditions and chronic physical conditions were assessed by self-report. Mental disorders were assessed by the Composite International Diagnostic Interview (CIDI). Role disability during the past 30 days was assessed with the World Health Organization Disability Assessment Schedule (WHO-DAS-II).
The 12-month prevalence of chronic back or neck pain was 10.8%. Most of respondents with chronic back or neck pain (71.2%) reported at least one other comorbid condition, including other chronic pain conditions (53.4%), chronic physical conditions (37.9%), and mental disorders (23.9%). It was found by logistic regression that mood disorders (OR = 3.7, 95%CI:2.8–4.8) showed stronger association with chronic back or neck pain than anxiety disorders and substance disorders. Most common chronic pains and physical conditions were significantly associated with chronic back or neck pain. Chronic back or neck pain was associated with role disability after controlling for demographics and for comorbidities. Physical and mental comorbidities explained 0.7% of the association between chronic back or neck pain and role disability.
Chronic back or neck pain and physical-mental comorbidity is very common in China and chronic back or neck pain may increase the likelihood of other physical and mental diseases. This presents a great challenge for both clinical treatment and public health education. We believe that further study needs to be conducted to improve the diagnostic and management skills for comorbidity conditions.
Accurate forecasting of subway passenger flows is considered essential for the development of efficient train schedules. However, transport capacity constraints as well as station congestion can be ...caused by unexpected concerns with trains or power supply, which endanger passenger safety. Predicting passenger flows at the time of a fault is particularly challenging due to the low probability of failure and the complexity of the factors involved. In addition, deviation from the observed value may be resulted by the point-in-time prediction of passenger flow, thus affecting the efficiency of passenger flow control measures. To address this concern, a three-stage A-LSTM prediction model utilizing an attention mechanism and a double-layer LSTM (Long Short-Term Memory) neural network has been proposed. The model is used to map the impact of fault events on subway transport capacity with respect to delays onto the inbound passenger flow. By analyzing the data from the subway system in a metropolitan city of China, the range of passenger flow fluctuations in 10-minute intervals will be precisely predicted and applied to different subway stations.
Abstract
Background
Percutaneous coronary intervention (PCI) is a safe and effective therapy for patients with obstructive coronary artery disease (CAD). We aimed to assess the correlation between ...the success rate of angiography and the maximum insertion length and resistance of a soft-tipped guidewire.
Methods
Five hundred twenty-one patients were treated by successful radial artery puncture. According to whether the guidewire resistance, the patients were divided to three groups. 17 patients were maximum insertion length of guidewire ≤ 30 cm when resistance was encountered (group 1). 17 patients were maximum insertion length of guidewire between 30 and 45 cm when resistance was encountered (group 2). 487 patients were no resistance encountered (group 3).
Results
The coronary angiography success rates of group 1, 2, and 3 were 52.94%, 47.05%, 98.97%, respectively. Typically, angiography can be completed in patients with Ω-shaped, S-shape or Z-shaped tortuosity.
Conclusions
The maximum insertion length of straight guidewire and resistance can be used to determine radial artery status. The radial artery tortuosity or spasm significantly affects the success rate of coronary angiography.
Glioblastoma multiforme (GBM) is the most aggressive and highly vascularized brain tumor with poor prognosis. Endothelial cell-dependent angiogenesis and tumor cell-dependent Vasculogenic mimicry ...(VM) synergistically contribute to glioma vascularization and progression. However, the mechanism underlying GBM vascularization remains unclear. In this study, GBM stem cells (GSCs) were divided into high and low β8 integrin (ITGB8) subpopulations. Co-culture assays followed by Cell Counting Kit-8 (CCK-8), migration, Matrigel tube formation, and sprouting assays were conducted to assess the proliferative, migratory and angiogenic capacity of GBM cells and human brain microvascular endothelial cells (hBMECs). An intracranial glioma model was constructed to assess the effect of ITGB8 on tumor vascularization in vivo. Our results indicated that ITGB8 expression was elevated in GSCs and positively associated with stem cell markers in glioma tissues, and could be induced by hypoxia and p38 activation. ITGB8 in GSCs inhibited the angiogenesis of hBMECs in vitro, while it promoted the ability of network formation and expression of VM-related proteins. The orthotopic GBM model showed that ITGB8 contributed to decreased angiogenesis, meanwhile enhanced invasiveness and VM formation. Mechanistic studies indicated that ITGB8-TGFβ1 axis modulates VM and epithelial-mesenchymal transition (EMT) process via Smad2/3-RhoA signaling. Together, our findings demonstrated a differential role for ITGB8 in the regulation of angiogenesis and VM formation in GBM, and suggest that pharmacological inhibition of ITGB8 may represent a promising therapeutic strategy for treatment of GBM.
As a major and popular groundwater extraction structure, seepage wells are often used to transfer river water into aquifers for harvesting water resources. It can help ameliorate the imbalance ...between supply and demand, in particular, in areas of water scarcity. Large drawdowns due to pumping may cause the river to disconnect from the groundwater and form an unsaturated zone, which seriously affects the efficiency of seepage wells. However, most of the current models of extraction structures of non-tube wells account for only saturated flow and do not consider unsaturated conditions. To address this limitation, a saturated–unsaturated coupling model was developed using the exchange flow rate between the well pipe and the aquifer as the coupling point. Moreover, the model was evaluated with physical simulation test data. The statistical results indicated that the model could estimate the drawdown and pumping rate well with root-mean-square deviations of 0.0114 m and 0.0079 L s
−1
, respectively, for a river with strong leakage capacity; and 0.0129 m and 0.0099 L s
−1
, respectively, for a river with weak leakage capacity. The critical drawdown, where the river disconnects from the aquifer, as well as variations of the unsaturated zone, was also discussed. The present study provides important information for the design of seepage wells with reasonable drawdown, while being able to predict the potential water yield, and at the same time help protect the groundwater environment.
A solid phase membrane adsorbent-a nylon 6 nanofibers membrane coated by polypyrrole (PPy-PA6-NFsM)-was firstly synthesized and used for extraction of two β-lactam antibiotics (oxacillin and ...cloxacillin) in urban river water. Then the analytes were detected by capillary electrophoresis with a diode array detector (CE-DAD). The synthesized nanofibers membrane was characterized by scanning electron microscopy and a Fourier transform infrared spectrometer. The experimental conditions were optimized, including the amount used of PPy-PA6-NFsM, pH of the sample solutions, adsorption volume, and desorption conditions. Under the optimal extraction and separation conditions, the detection limits were found to be 2.0 ng/mL for both oxacillin and cloxacillin. The proposed method was applied to the determination of the two β-lactams in water samples of an urban river. The recoveries of these two β-lactams were found to be in the range 84.2-96.4%, demonstrating that PPy-PA6-NFsM has a high extraction capability for these two antibiotics. The relative standard deviations, ranging from 2.26% to 5.29% for intraday measurements and from 2.38% to 7.02% for inter-day determinations, were derived respectively.
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