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The development of triple-negative breast cancer (TNBC) is highly associated with G-quadruplex (G4); thus, targeting G4 is a potential strategy for TNBC therapy. Because concomitant histone deacetylases (HDAC) inhibition could amplify the impact of G4-targeting compounds, we designed and synthesized two novel series of G4/HDAC dual-targeting compounds by connecting the zinc-binding pharmacophore of HDAC inhibitors to the G4-targeting isaindigotone scaffold (

PurposeInvestigating the changes of regional homogeneity (ReHo) values and both static and dynamic functional connectivity (FC) before and after Traditional Chinese Manual Therapy (Tuina) in patients with lumbar disk herniation (LDH) through resting-state functional magnetic resonance imaging (RS-fMRI). Based on this, we observe the effect of Tuina on the above abnormal changes.MethodsPatients with LDH (n = 27) and healthy controls (HCs) (n = 28) were recruited. The functional magnetic resonance imaging (fMRI) scanning was performed two times in LDH patients, before Tuina (time point 1, LDH-pre) and after the sixth Tuina (time point 2, LDH-pos). And for one time in HCs which received no intervention. The ReHo values were compared between LDH-pre and HCs. The significant clusters detected by ReHo analysis were selected as seeds to calculate static functional connectivity (sFC). We also applied the sliding-window to perform dynamic functional connectivity (dFC). To evaluate the Tuina effect, the mean ReHo and FC values (both static and dynamic) were extracted from significant clusters and compared between LDH and HCs.ResultsIn comparison to HCs, LDH patients displayed decreased ReHo in the left orbital part middle frontal gyrus (LO-MFG). For sFC analysis, no significant difference was found. However, we found decreased dFC variance between LO-MFG and the left Fusiform, and increased dFC variance in the left orbital inferior frontal gyrus and left precuneus. Both ReHo and dFC values revealed after Tuina, the brain activities in LDH patients were similar to HCs.ConclusionThe present study characterized the altered patterns of regional homogeneity in spontaneous brain activity and those of functional connectivity in patients with LDH. Tuina can reshape the function of the default mode network (DMN) in LDH patients, which may contribute to the analgesic effect of Tuina in LDH patients.

PurposeLumbar disc herniation (LDH) is one of the leading causes of low-back pain and results in a series of clinical symptoms, including pain, reflex loss, and muscle weakness. Spinal manipulative therapy (SMT) can relieve pain and promote internal and external stabilization of the lumbar spine. In this study, we investigated whether the brain alterations of LDH patients with SMT were frequency-dependent based on the calculation of Amplitude of Low-Frequency Fluctuations (ALFF) and fractional ALFF (fALFF). Further, we established a cohort of LDH patients to evaluate the contribution of SMT treatments to brain functional reorganization.MethodsA total of 55 participants, including 27 LDH patients and 28 health controls (HCs), were collected. All LDH patients underwent two fMRI scans (before SMT and after the sixth SMT session). To represent LDH-related brain oscillatory activities, we calculated the ALFF and fALFF in the conventional band (0.01–0.08 Hz), the slow-4 band (0.027–0.073 Hz), and the slow-5 band (0.01–0.027 Hz). Moreover, we extracted ALFF and fALFF values in clusters with significant differences to evaluate the SMT effect.ResultsCompared with HCs, the LDH patients before SMT (LDH-pre) exhibited increased fALFF in right lingual gyri in the conventional band, and showed increased fALFF in left Cerebelum_Crus1 in the slow-4 band. We further examined the abnormal brain activities changes before and after the SMT intervention. The ALFF and fALFF values of LDH-pre group were higher than those of the HCs and LDH-pos groups. After SMT, the increased ALFF and fALFF values were suppressed for patients in conventional band and slow-4 band.ConclusionThe present study characterized the altered regional patterns in spontaneous neural activity in patients with LDH. Meanwhile, SMT is an effective treatment of LDH, and we supposed that it might have been involved in modulating dysfunctional brain regions which are important for the processing of pain. The findings of the current study may provide new insights to understand pathological mechanism of LDH.

Line heating is highly susceptible to plastic deformation leading to structural changes, which seriously affects shipbuilding efficiency. It is extremely important to obtain the precise line heating deformation law. There is much research on plate deformation prediction, but there is still no mature, accurate and fast prediction method. Based on this, it is necessary to research the line heating deformation prediction method. ELM has the advantages of fast learning speed, good generalization performance and strong function approximation ability. To address the poor stability of the regression model due to the randomly generated weights and thresholds of ELM, a combined prediction model (SSA-ELM) based on a squirrel search algorithm (SSA) optimized limit learning machine is proposed. The results show that the relative errors of transverse shrinkage and angular deformation of SSA-ELM are improved by 4.7% and 3.9%. The SSA-ELM prediction model has good regression accuracy and generalization ability. It gives more accurate prediction results in terms of line heating deformation prediction.

PurposeIn the process of cold rolled strip, there is tight coupling between flatness control and gauge control. The variation of the roll gap caused by the change of bending force will lead to the change of rolling force. Furthermore, it can cause a deep impact on the control accuracy of strip exit thickness and exit crown. The purpose of this paper is to improve the accuracy of the bending force preset value for cold rolled strip.Design/methodology/approachIn this paper, the bending force preset control strategy with considering of rolling force was proposed for the first time and the preset objective function of bending force was established on the basis of the two-objective optimization of bending force and rolling force. Meanwhile, the multi-objective intelligent algorithm – INSGA-II – was used to solve the objective function.FindingsThe proposed bending force multi-objective preset model has been tested in a 1,450 mm tandem cold rolling line. The analyzed results of field data show that the deviations of strip exit thickness and exit crown are reduced effectively by using the improved model, and at the same time, more reasonable bending force preset values are obtained, which can enhance the accuracy of flatness preset control.Originality/valueA preset model of bending force with considering flatness and gauge is proposed in this paper and the multi-objective function of bending force preset is established on the basis of the two-objective optimization of bending force and rolling force. The value lies in proposing a new decoupling method of rolling force and bending force.

In order to explore the impact of reclamation on the expansion of Spartina alterniflora (a kind of invasive species)population, the annual and seasonal changes of Spartina alterniflora population distributed inside and outside the embankment was observed in the Yancheng coastal wetland, Jiangsu Province from May 2017 to July 2018 with the help of unmanned aerial vehicle (UAV)monitoring technology. Combined with field monitoring data, the effects of soil moisture content, soil salinity, growth elevation, and surface water level on the growth and population area of Spartina alterniflora were analyzed. The results showed that the reclamation significantly reduced the expansion rate of Spartina alterniflora, and the area inside the embankment increased by 21% during the observation period, while the area outside the embankment increased by more than 400%. The population expansion inside and outside the embankment of Spartina alterniflora had obvious seasonality, and the seasons of expansion were autumn and summer respectively. The soil moisture content and salinity in the reclamation area decreased by 25% and 50% respectively compared with the area outside the embankment. There was a significant positive correlation between the height of Spartina alterniflora and the elevation of the growing area (PSpartina alterniflora population was significantly positively correlated with surface water level (PSpartina alterniflora, and seawater changed the soil water and salt conditions in the reclamation area, and thus inhibited the expansion of Spartina alterniflora.

Coating matching design is one of the important parts of ship coating process design. The selection of coating matching is influenced by various factors such as marine corrosive environment, anti-corrosion period and working conditions. There are also differences in the coating performance requirements for different ship types and different coating parts. At present, the design of coating matching in shipyards depends on the experience of technologist, which is not conducive to the scientific management of ship painting process and the macro control of ship construction cost. Therefore, this paper proposes a hybrid algorithm of fuzzy comprehensive evaluation and collaborative filtering based on user label improvement (IFCE-CF). Based on the analytic hierarchy process (AHP), the evaluation index system of coating matching is constructed, and the weight calculation process of fuzzy comprehensive evaluation is optimized by introducing the user label weight. The collaborative filtering algorithm based on matrix decomposition is used to realize the accurate recommendation of coating matching. Historical coating process data of a shipyard between 2010 and 2020 are selected to verify the recommendation ability of the method in the paper. The results show that using the coating matching intelligent recommendation algorithm proposed in this paper, the root mean square error is

It has been reported that long non-coding RNA HOXA distal transcript antisense RNA (lncRNA HOTTIP) functions as a tumor promoter in colorectal cancer (CRC). Hence, we paid attention to exploring whether exosomes could carry lncRNA HOTTIP to affect the mitomycin resistance in CRC and to identify the underlying mechanisms. High expression of HOTTIP was detected in mitomycin-resistant CRC cells. Inhibition of HOTTIP reduced the mitomycin resistance. In the co-culture system of mitomycin-resistant cells or their derived exosomes with CRC cells, the HOTTIP was found to be transferred into the parental cells via extracellular vesicles (EVs) secreted from mitomycin-resistant cells and to contribute to the mitomycin resistance. Based on the bioinformatics databases, possible interaction network of HOTTIP, microRNA-214 (miR-214) and Karyopherin subunit alpha 3 (KPNA3) in CRC was predicted, which was further analyzed by dual-luciferase reporter, RNA binding protein immunoprecipitation and RNA pull-down assays. As HOTTIP down-regulated miR-214 to elevate the KPNA3 expression, HOTTIP enhanced the mitomycin resistance through impairing miR-214-dependent inhibition of KPNA3. Finally, HOTTIP was suggested as an independent factor predicting mitomycin response in patients with CRC. Those data together confirmed the promotive effects of EV-carried HOTTIP on the mitomycin resistance, while targeting HOTTIP might be a promising strategy overcoming drug resistance in CRC.

High temperature of the radiator group is harmful to the power system and hydraulic system. In order to improve the heat dissipation performance of the loader, the flow field characteristics of the cooling chamber are analyzed by simulation and heat balance test. Firstly, the mathematical model of heat flow is established. Secondly, the flow field in the cooling chamber under different speeds is simulated based on CFX. And then the influence of fan position and internal flow field distribution on radiator performance is studied. Through the simulation of four different distances, it is concluded that the optimal distance between cooling fan and radiator is 76mm. Finally, a testing system is built for the temperature acquisition of engine water radiator, torque converter oil radiator, hydraulic oil radiator and air-to-air cooler of the hood structure, and then the simulation results are verified. The test results show that the heat dissipation performance of the whole machine meets the requirements after optimization, and the optimized scheme can make the loader-digger in an efficient and energy-saving operation state.

In ship construction, line heating is a necessary process for forming ship plates with complex curvature. The determination of line heating process parameters has a significant impact on the accuracy of the process and the efficiency of shipbuilding. However, previous studies on this subject only stay at the level of predicting deformation, which has not meet the actual processing production requirements. In this paper, a new idea of forecasting line heating parameters proposed. Firstly, an Radial Basis Function (RBF) proxy model between processing parameters and deformation was constructed based on experimental data, and then the reliability of the proxy model is verified. The optimization objective for proxy model was set as the minimum difference between the final deformation and the target deformation. Meanwhile, an improved Multi-Objective Particle Swarm Optimization (MOPSO) method was employed to search the optimal-set of processing parameters with non-dominated solutions. The performance of the optimized parameter set was ranked by using the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS), and the processing parameters combination ranking first was selected as the parameter forecasting result. The results showed that the predicted processing parameters have some reference for the practical engineering.

To understand the epidemiological features and changing patterns of intestinal parasitic diseases in Jiangxi Province from 1989 to 2014, so as to provide scientific evidence for formulating the preventive and control strategy for intestinal parasitic diseases.The data regarding the status of intestinal parasitic diseases in Jiangxi Province were captured from the 1989 national survey on the distribution of human parasites in China and the 2014 national survey on major human parasitic diseases in China, and the status of human intestinal parasite infections was compared between the two surveys in Jiangxi Province.The prevalence rate of human intestinal parasite infections was 79.59% and 9.64% in Jiangxi Province in 1989 and 2014, with a decline rate of 87.89% during the 25-year period (The prevalence of human intestinal parasite infections shows a remarkable decline tendency in Jiangxi Province, and soil-transmitted nematodes remain the main species of human intestinal parasites in Jiangxi Province.[