Lnc-PKD2-2-3/miR-328/GPAM ceRNA Network Induces Cholangiocarcinoma Proliferation, Invasion and 5-FU Chemoresistance

PurposeOur previous study observed that long non-coding RNA PKD2-2-3 (lnc-PKD2-2-3) is related to advanced tumor features and worse prognosis in cholangiocarcinoma (CCA). Then, this study aimed to further explore the linkage between lnc-PKD2-2-3, miR-328, and GPAM, as well as their effects on regulating CCA viability, mobility, and chemosensitivity.MethodsLnc-PKD2-2-3, miR-328, and GPAM expression in 30 pairs of CCA tumor and adjacent tissues, as well as in CCA cell lines, were determined. Two CCA cell lines (HuCCT1 and TFK1) were transfected by lnc-PKD2-2-3 overexpression plasmid, lnc-PKD2-2-3 siRNA, miR-328 inhibitor, and GPAM siRNA alone or in combination, followed by cell proliferation, apoptosis, invasion, and 5-FU chemosensitivity detection. Besides, xenograft mice were established for validation.ResultsLnc-PKD2-2-3 and GPAM were higher, whereas miR-328 was lower in CCA tissues versus adjacent tissues and also in CCA cell lines versus control cells; meanwhile, they were correlated with each other (all P <0.05). Lnc-PKD2-2-3 knockdown decreased CCA cell proliferation, invasion, and increased apoptosis (all P <0.05), but lnc-PKD2-2-3 overexpression exhibited the opposite and weaker effect. MiR-328 knockdown induced CCA cell proliferation and invasion and also attenuated the effect of lnc-PKD2-2-3-knockdown in these functions (all P <0.05). Subsequently, GPAM knockdown reduced CCA cell proliferation and invasion and also weakened the effect of miR-328-knockdown in these functions (all P <0.05). Additionally, lnc-PKD2-2-3 positively regulated GPAM while negatively regulating miR-328. MiR-328 negatively modified GPAM in CCA cells. Luciferase gene reporter assays verified that lnc-PKD2-2-3 directly bound miR-328 and miR-328 directly bound GPAM. Finally, the lnc-PKD2-2-3/miR-328/GPAM network also regulated the 5-FU chemosensitivity of CCA cells. In vivo experiments further revealed that lnc-PKD2-2-3 overexpression promoted tumor volume and weight but repressed tumor apoptosis in xenograft mice; meanwhile, it increased GPAM expression but decreased miR-328 expression (all P <0.05). Conversely, lnc-PKD2-2-3 knockdown exhibited the opposite effects (all P <0.05).ConclusionLnc-PKD2-2-3/miR-328/GPAM ceRNA network promotes CCA proliferation, invasion, and 5-FU chemoresistance

Enhanced Anti-diabetic Effect of Berberine Combined With Timosaponin B2 in Goto-Kakizaki Rats, Associated With Increased Variety and Exposure of Effective Substances Through Intestinal Absorption

Objective: Inspired by the traditionally clinical application of herb pair Zhimu-Huangbo to treat diabetes, a combination of plant ingredients, timosaponin B2 (TB-2) and berberine (BBR), was evaluated for their anti-diabetic efficacy and cooperative mechanisms.Methods: The efficacy and pharmacokinetics of orally administered TB-2 (33.3 mg/kg/day), BBR (66.7 mg/kg/day), and TB-2+BBR (100 mg/kg/day) were evaluated in spontaneously non-obese diabetic Goto-Kakizaki (GK) rats, and metformin (200 mg/kg/day) was used as a positive control. The comparative exposure of the parent drugs, timosaponin A3 (TB-2 metabolite), and M1–M5 (BBR metabolites) was quantified in the portal vein plasma (before hepatic disposition), liver, and systemic plasma (after hepatic disposition) of normal rats on single and combination treatments. Cooperative mechanism of TB-2 and BBR on intestinal absorption and hepatic metabolism was investigated in Caco-2 cells and primary hepatocytes, respectively.Results: After a 6-week experiment, non-fasting and fasting blood glucose levels and oral glucose tolerance test results showed that TB-2+BBR treatments (100 mg/kg/day) displayed significantly anti-diabetic efficacy in GK rats, comparable to that on metformin treatments. However, no significant improvement was observed on TB-2 or BBR treatments alone. Compared to single treatments, combination treatments led to the increased circulating levels of BBR by 107% in GK rats. In normal rats, the hepatic exposure of BBR, timosaponin A3, and M1–M5 was several hundred folds higher than their circulating levels. Co-administration also improved the levels in the plasma and liver by 41–114% for BBR, 141–230% for TB-2, and 12–282% for M1–M5. In vitro, the interaction between TB-2 and BBR was mediated by intestinal absorption, rather than hepatic metabolism.Conclusion: Combining TB-2 and BBR enhanced the anti-diabetic efficacy by increasing the in vivo variety of effective substances, including the parent compounds and active metabolites, and improving the levels of those substances through intestinal absorption. This study is a new attempt to assess the effects of combined plant ingredients on diabetes by scientifically utilizing clinical experience of an herb pair

Net Carbon Balance between Priming and Replenishment of Soil Organic Carbon with Biochar Addition Regulated by N Addition Differing in Contrasting Forest Ecosystems

The replenishment and priming effect (PE) are two decisive processes that determine the carbon (C) sequestration potential of biochar. However, how increased nitrogen (N) availability affect these two processes and the consequent net C balance remains poorly understood. By collecting soils from three forest ecosystems (deciduous broad-leaf forest (DBF), evergreen coniferous forest (ECF), and evergreen broad-leaf forest (EBF)), we conducted a 365-day incubation experiment by adding 13C-labelled biochar plus five rates of inorganic N (0 to 15% N of soil total N). The -results showed that N addition significantly stimulated the early period (0–48 days) but did not affect the late period (49–365 days) of biochar decomposition. The effect of N addition on PE varied largely with the forest type and decomposition period; N addition significantly enhanced the negative PE -in both periods in DBF and at the late period in EBF, whereas it stimulated positive PE in the early period in EBF and ECF. At the end of incubation, the addition of biochar caused net C accumulation across all treatments due to the huge proportion of biochar (98.1%–98.9% of added biochar) retained in soils and the negative or neutral cumulative PE (−11.25–0.35 g C kg−1 SOC), and the magnitude of net C balance increased linearly with the N addition rate in DBF and EBF. Collectively, the results of this study indicate that biochar input can contribute to soil C sequestration and that N addition can enhance the C sequestration potential of biochar

Research on the Influence of Modern Information Technology on Ideological and Political Education of College Students

With the application of information technology becoming more and more mature, ideological and political education is gradually upgrading to precision ideological and political education and wisdom ideological and political education. However, in the use of modern information technology, ideological and political education of college students, due to the lack of a correct and complete understanding of the new ideological and political education model, the quality of ideological and political education has been affected. Based on this, in the context of wisdom education, in order to better carry out the ideological and political education activities of university students, it is necessary to correctly analyze the complex impact of modern information technology on the ideological and Political Education of university students, promoting the innovation of ideological and political education for college students. Through the modern information technology on the ideological and political education of college students to a comprehensive interpretation of the impact of relevant recommendations

Implementation of Construction Waste Recycling under Construction Sustainability Incentives: A Multi-Agent Stochastic Evolutionary Game Approach

Because of the rapid development of the economy and the process of urbanization, construction waste recycling is becoming increasingly important and should be considered. Motivated by effectively managing the construction waste recycling under sustainability incentives, the multi-agent stochastic game model is used to evaluate the evolutionary behavior of the government agencies, waste recyclers, and waste producers. To capture the uncertainty existing in the external environment, the replicator dynamic formula is integrated with Gaussian noise, and the Lyapunov exponent diagram is analyzed to illustrate the nonlinear dynamic behavior. The numerical approximations are then solved by utilizing the random Taylor expansion formula. Finally, a numerical simulation is performed to evaluate the evolutionary trajectories of the participants involved. The findings revealed that: (1) the government agency should adopt a positive supervision approach, which can encourage waste producers and recyclers to collaborate around each other; (2) lower sorting and disposal costs can enhance construction waste recycling; and (3) the existence of uncertainty in the environment around different participants will influence one’s strategy selection

Chance Constrained Programs with Gaussian Mixture Models

10.1080/24725854.2021.2001608IISE Transactions54121117-113

Large-scale ranking and selection using cloud computing

Ranking-and-selection (R&S) procedures are often used to select the best configuration from a set of alternatives, and the set typically has fewer than 500 alternatives. However, there are many R&S or simulation optimization problems having thousands to tens of thousands alternatives. In this paper we discuss how to solve these problems using cloud computing. In particular, we discuss how cloud computing changes the paradigm that is currently used to design R&S procedures, and show a specific procedure that works efficiently under cloud computing. We demonstrate the practical usefulness of our procedure on a simulation optimization problem with more than 2000 feasible solutions using a small-scale cloud of CPUs created by us. © 2011 IEEE

Optimization via simulation using Gaussian process-based search

Random search algorithms are often used to solve optimization-via- simulation (OvS) problems. The most critical component of a random search algorithm is the sampling distribution that is used to guide the allocation of the search effort. A good sampling distribution can balance the tradeoff between the effort used in searching around the current best solution (which is called exploitation) and the effort used in searching largely unknown regions (which is called exploration). However, most of the random search algorithms for OvS problems have difficulties in balancing this tradeoff in a seamless way. In this paper we propose a new random search algorithm, called the Gaussian Process-based Search (GPS) algorithm, which derives a sampling distribution from a fast fitted Gaussian process in each iteration of the algorithm. We show that the sampling distribution has the desired properties and it can automatically balance the exploitation and exploration tradeoff. © 2011 IEEE