Abstract: Ligand-mediated prostate cancer (PCa)-targeting gene delivery is one of the focuses of research in recent years. Our previous study reported the successful preparation of aptamer- modified nanoparticles (APT-NPs) in our laboratory and demonstrated their PCa-targeting ability in vitro. However, the mechanism underlying this PCa-targeting effect and their anticancer ability in vivo have not yet been elucidated. The objective of this study was to assess the feasibility of using APT-NPs to deliver micro RNA (miRNA) systemically to PCa cells, to testify their tumor-targeting efficiency, and to observe their biodistribution after systemic administration to a xenograft mouse model of PCa. In addition, the effect of APT depletion and endocytosis inhibitors on cellular uptake was also evaluated quantitatively in LNCaP cells to explore the internalization mechanism of APT-NPs. Finally, blood chemistry, and renal and liver function parameters were measured in the xenograft mouse model of PCa to see whether APT-NPs had any demonstrable toxicity in mice in vivo. The results showed that APT-NPs prolonged the survival duration of the PCa tumor-bearing mice as compared with the unmodified NPs. In addition, they had a potential PCa-targeting effect in vivo. In conclusion, this research provides a prototype for the safe and efficient delivery of miRNA expression vectors to PCa cells, which may prove useful for preclinical and clinical studies on the treatment of PCa.
Vaccines and drugs have contributed to dramatic improvements in public health worldwide. Over the last decade, there have been efforts in developing biomedical ontologies that represent various areas associated with vaccines and drugs. These ontologies combined with existing health and clinical terminology systems (e.g., SNOMED, RxNorm, NDF-RT, MedDRA, VO, OAE, and AERO) could play significant roles on clinical and translational research. The first “ Vaccine and Drug Ontology in the Study of Mechanism and Effect ” workshop (VDOSME 2012) provided a platform for discussing problems and solutions in the development and application of
Our results show EA at Zusanli to increase ICC num- ber, but to do so in a manner not closely related to myo- electric activity. Therefore it may act through some other mechanism in increasing ICC. Previous studies have implicated local inflammatory activity as a possible cause of decrease in ICC numbers. Resident macro- phages are the most likely source of this inflammatory activity . In a previous study of a rat model of partial bowel obstruction, macrophage number was reported to increase on the oral side of the bowel obstruction although no leukocyte infiltration or other signs of in- flammation were seen . At the same time in this preparation, TNF-α levels increased, spontaneous con- tractions decreased, and there was a reduction in ICC number oral to the occlusion. Macrophage numbers have also been reported to increase in an animal model of Hirschsprung’s disease , a condition that also in- volves partial bowel obstruction. Increased numbers of
Whole of this study focuses on the technology of mobility especially to drive mechanism of AGV: How can a mobile robot make a movement without supervision through real-world environments to fulfill its work? The challenge is about that locomotion itself and related with maneuverability it. What is it about a particular locomotion mechanism that makes it the best to become alternative locomotion mechanisms? The human can implements localization and cognition activities, but depends on the robot’s control scheme itself to provide motion control. Designing a mobile robot such as AGV involves the integration of different disciplines that includes software and hardware design considerations, related technologies, algorithmic techniques, kinematics, signal analysis, information theory, artificial intelligence and probability theory.
tant regulator factors of checkpoints in G2/M phase. Decreased cyclinB1 level can promote the expression of p-Cdk1 and p21, and induce block of cells in G2/M phase . The results of Western blotting experiment in this paper showed that the expression level of cyclinB1 protein in the siRNA interference group was sig- nificantly decreased, while those of the p-Cdk1 protein and p21 protein were significantly increased, leading to block of cells in G2/M phase, which were consistent with the existing studies . The results of an animal experi- ment showed that the tumor volume and mass of nude mice in the XRCC1-siRNA group after radiotherapy were significantly smaller than those of the other two groups, suggesting that XRCC1 silencing could improve the radiothera- peutic response of tumors in vivo. The molecu- lar mechanism of tumor radiation sensitivity is relatively complex. The results of this study indicated that the radiosensitivity of nasopha- ryngeal carcinoma cells was significantly relat- ed to the XRCC1 expression, but whether XRCC1 silencing can improve the clinical radio- sensitivity of patients with nasopharyngeal car- cinomas should be further studied.
along with food and air. Fresh water is also required for agricultural and industrial purposes. The main sources of water are rivers, lakes and underground water reservoirs. However, direct uses of water from such sources are not always advisable, because of the presence of higher amount of salt and harmful organisms. The higher growth rate in world population and industries resulted in a large escalation of demand for fresh water. The natural source can meet a limited demand and this leads to acute shortage of fresh water. Hence, there is an issue to essentially treat the salt and contaminated water into purified water. In this work we can improve the performance of solar still by using PCM and use of Reflector mechanism. Also we study the single and double slope solar still.
Light Chain Phosphatase (MLCP) thereby potentiating the response of contraction to raised intracellular calcium ion concentration.(63) In their experiment, they used 2 specific ROCK inhibitors namely, Y-27632 at 10 µM and GSK-269962 at 50nM. It was discovered that both these agents exhibited a similar inhibitory effect on the pro-contractile nature of LPS. (63) Simultaneously, the authors suggested that, there was an increase in the steady state concentration of phosphorylated myosin light chains, with LPS treatment and this confirms the activation of Rho/ROCK pathway mediated by LPS. It was concluded that, localised elevation of bacterial endotoxin may induce a risk of increased myometrial contractility through direct interactions. This could be a possible in vivo mechanism for preterm labour following gram negative sepsis during pregnancy.(63) Another novel finding of the study was to show that, in presence of TLR-4 (Toll-like receptors) agonists like LPS/Bacterial endotoxins, the reversibility of myometrial contraction will be unsuccessful with calcium channel blockers like Nifedipine or with prostaglandin synthesis inhibitors.(63)
Advisor system is a mode currently widely adopted by China’s universities. It refers to the education management mechanism where advisors provide individual guidance and take full responsibility for graduates’ study, ideology, life, and all other aspects. It defines advisors’ obligation to educate, as well as specifics advisors’ responsibilities and rights during the education process. Every coin has two sides, and in fact, most advisors ignore or avoid graduate students’ ideological and political education. The existing cognitive bias towards graduate education concepts and the indifference towards graduate students’ ideological and political education lead to the detachment of “talents education” and “moral education”, as well as the imperfection of education effect.
The inhibition of tumor cell proliferation is often closely related to cell apoptosis. At present, there still are controversies about whether met- formin can induce tumor cell apoptosis. The study of prostate cancer cells showed that met- formin mainly inhibited the proliferation of tumor cells by inducing cell apoptosis. In this study, flow cytometry was used to detect the effect of metformin on the apoptosis of bladder cancer cells, and we found there was no signifi- cant difference in apoptosis ratio between drug group and control group. It is different from the recently approved mechanism of metformin inducing apoptosis of many kinds of tumor cells such as prostate cancer cell, renal cancer cell, breast cancer cell and gastric cancer cell [17, 18]. Some studies have reported that metfor- min can selectively induce the apoptosis of colon cancer cells with absence of P53 [19, 20]. In the subcutaneous bladder cancer xeno- graft experiment of this study, the results showed that metformin significantly inhibited the growth of subcutaneous xenograft. The results of all these studies suggest that, for tumors cells with different genetic background and different tissue sources and growth state, the mechanism of metformin inhibiting tumor cells is not exactly the same. The inhibitory effect of metformin on bladder cancer may be achieved through other mechanisms, which need to be further studied.
Acupuncture, as a widely used complementary and alternative therapy originating from ancient China, has been used to manage constipation for thousands of years. In recent years, many high-quality randomized controlled trials (RCTs) have also demonstrated the efficacy of acu- puncture treating for FC [11 – 15]. For example, Liu et al. found that electro-acupuncture could significantly in- crease the frequency of spontaneous defecation with rare adverse events in chronic severe constipation . Our recent study also identified that manual acupuncture at Tianshu (ST25) and Shangjuxu (ST37) acupoints were as effective as Mosapride intake in improving spontaneous bowel movements (SBMs) in chronic FC . With the clinical effects being successfully acknowledged, the mechanism of acupuncture treating for FC has also become a focus in acupuncture research [17, 18]. Several studies have found that acupuncture may treat FC by pro- moting the gastrointestinal motility , modulating peripheral gastrointestinal hormones , and keeping the balance of excitatory and inhibitory neurons in the enteric nervous system (ENS) . However, the central integration [22, 23], an essential node of acupuncture treatment for FC, has rarely been explored. In previous studies, we found that the therapeutic effects of acupunc- ture for functional dyspepsia (FD)  and functional diarrhea  were closely related to regulating the cerebral activity of disease-related regions. Whether the
More precisely, this work aimed to study in one hand the removal of organic molecules such as Pyridine in wastewater over Montmorillonite clay, and on the other hand, to compare the adsorption capacity of the activated and non-activated Montmorillonite. In this context and in order to achieve these goals, adsorption process was conducted in a batch apparatus where the effect of various parameters, such as adsorbent dose, pH and temperature was studied.
Previous studies have shown that GLP-1 can cause changes in visceral disease and taste in rodents after agonism  . In humans, nausea is the most common side effect. Clinical trials have shown that nausea can be caused by taking duraphinide and benaglutide. However, injection of Ex4 into the ventral tegmental area (VTA), nucleus accumbens, and parahippocampus parabrachial nucleus inhibited feeding, but there was no evidence of nausea  . Here, we found that intra-LHA injection of Ex4 inhibited feeding and did not induce kaolin uptake, suggesting that the inhibitory effect of GLP-1 receptor uptake in LHA is not nausea. We have determined that central GLP-1 plays a role in the regulation of feeding behavior, but the specific brain regions that regulate GLP-1 receptor feeding and the mechanisms of action of these receptors are not fully elucidated. Previous experimental studies have shown that GLP-1 receptor subpopulations in different brain regions and even different subregions of the same brain region may have different effects on rat behavior. In some brain regions, GLP-1 receptors can affect glucose homeostasis and produce taste aversion without affecting food intake. Combined with previous studies, we have found that GLP-1 receptors throughout the central nervous system regulate feeding behavior and energy balance through different mechanisms.
Likewise, we investigate the relation between the networks by visualizing the loss surface. To the best of our knowledge, there has been not been a clear verification on whether the assumptions for the heuristic hold. In order to verify such assumptions and shed some light on what happens through pruning, we visualize the trajectory of the pruning mechanism on a low-dimensional loss surface. Pruning and retraining methods. The typical pruning algorithms prune and retrain the network iteratively to achieve high sparsity and avoid loss in accuracy. The iterative pruning cycle consists of two alternating phases: the pruning phase and the retraining phase. At the pruning phase, a portion of weights or channels are removed. The weight pruning methods aim to identify the importance of the individual weight of a neural network, while the channel pruning methods target the channels in a convolutional layer. Therefore, the channel pruning methods operates in a higher constraint, which often results in greater damage to the network. At the retraining phase, the pruned network is commonly fine-tuned using a small and fixed learning rate, which is usually the last learning rate used at the pretraining stage. In addition, Renda et al. (2020) has shown that rewinding the learning rate scheduling to an earlier time step can boost the validation accuracy of the retrained network. Visualization technique. For a straightforward understanding, we plot the accuracy surface instead of the loss surface in this section. To visualize the points of interest, we follow the 2D planar loss visualization used in Garipov et al. (2018). We construct the 2D plane by affine combinations of three points in the weight space – the pretrained weight (W ∗ ), the pruned weight in the last iterative cycle (W p ), and the final retrained weight (W r ).
Figure 7 shows optical microscope pictures (x200) of the worn surfaces of PTFE under dry sliding at two different normal loads. In all the tests we have observed that the worn track of PTFE pin were parallel to the sliding direction and they do not present any plucked or ploughed marks or adhesion which suggests that the wear mechanism is abrasion.
Studies on the photoluminescence (PL) emission intensity from many of the silicon-based nanostructured systems has attracted extensive interest to identify its mechanism, in particular, in nanocrystalline- Silicon (nc-Si). Despite many recent successes in the field of silicon nanostructures, until now, the origin and properties of the PL are not completely understood. Currently, the underlying mechanisms behind the PL are a major source of debate and dispute among scientist communities. The present paper successfully describes the PL mechanism of nanostructured systems from the Quantum Confinement Effect (QCE) model approach. The selected model (QCE model) assigns the PL to quantum size effects in nc-Si core of the nanostructures. It is widely investigated that one of the fundamental parameters describing the PL mechanisms of nc-Si is the radiative recombination rate. The present investigation revealed that the rate of radiative recombination depends on the diameter d of the spherical nano-crystallites; in particular, the finding clearly confirmed that the radiative recombination rate increases with the decrease in the size of the nc-Si. Certainly, these findings from the QCE model are useful to enhance the PL intensity in nc-Si and possibly useful to tune the PL emission intensity into the visible range.
In this work, we take the hydrogen atom as an example to study the wave func- tion contracting and found that the wave function contracting will lead to in- crease of the total energy of system. If we allow the system to freely relax, under certain condition, the system will emit photon. This kind of wave function con- tracting can be realized in a simple way, such as the collision among the mole- cules/atoms or applying the pressure onto the system. The collision-relaxation or the pressure-release induced the photon emission represents an important but different process from the conventional molecular beam technology, which is unreasonably ignored before. This kind of the collision-relaxation or the pres- sure-release induced the photon emission also offer a new way for us to draw some chemical reaction information, such as the closest distance between the molecules/atoms in reaction. Furthermore, our work here points out a possibili- ty to develop new laser technology by the collision-relaxation or the pres- sure-release cycle, which will find a wide application in scientific research and industry. Further work in this direction will be presented later.
The present study examined the effect of prostaglandin E 1 (PGE 1 ) on renal water excretion in the anesthetized dog. Renal perfusion pressure was kept constant by adjustment of a suprarenal aortic clamp. In seven experiments the intravenous administration of PGE 1 (7 µg/min) significantly increased urinary osmolality from 76 to 381 mosmol (P < 0.001) and decreased free water clearance from 2.2 to - 0.02 ml/min (P < 0.001). These effects promptly were reversed with cessation of the infusion. This antidiuretic effect occurred both in