Cryptopleurine Targets NF-κB Pathway, Leading to Inhibition of Gene Products Associated with Cell Survival, Proliferation, Invasion, and Angiogenesis

Cryptopleurine, a phenanthroquinolizidine alkaloid, was known to exhibit anticancer activity; however, the underlying mechanism is poorly understood. Because the nuclear factor-κB (NF-κB) transcription factors control many physiological processes including inflammation, immunity, and development and progression of cancer, we investigated the effects of cryptopleurine on tumor necrosis factor alpha (TNF-α)-induced NF-κB activation pathway and on the expression of NF-κB-regulated gene products associated with many pathophysiological processes.MDA-MB231, MDA-MB435, MCF-7, HEK293, RAW264.7 and Hep3B cells were used to examine cryptopleurine's effect on the NF-κB activation pathway. Major assays were promoter-reporter gene assay, electrophoretic mobility shift assay (EMSA), in vitro immune complex kinase assay, real-time PCR, Western blot analysis, and Matrigel invasion assay. Experiments documenting cell proliferation and apoptosis were analyzed by MTT method and flow cytometry, respectively. The results indicated that cryptopleurine suppressed the NF-κB activation through the inhibition of IκB kinase (IKK) activation, thereby blocking the phosphorylation and degradation of the inhibitor of NF-κB alpha (IκBα) and the nuclear translocation and DNA-binding activity of p65. The suppression of NF-κB by cryptopleurine led to the down-regulation of gene products involved in inflammation, cell survival, proliferation, invasion, and angiogenesis.Our results show that cryptopleurine inhibited NF-κB activation pathway, which leads to inhibition of inflammation, proliferation, and invasion, as well as potentiation of apoptosis. Our findings provide a new insight into the molecular mechanisms and a potential application of cryptopleurine for inflammatory diseases as well as certain cancers associated with abnormal NF-κB activation

Improved Limits on an Exotic Spin- and Velocity-Dependent Interaction at the Micrometer Scale with an Ensemble-NV-Diamond Magnetometer

Searching for exotic interactions provides a path for exploring new particles beyond the standard model. Here, we used an ensemble-NV-diamond magnetometer to search for an exotic spin- and velocity-dependent interaction between polarized electron spins and unpolarized nucleons at the micrometer scale. A thin layer of nitrogen-vacancy electronic spin ensemble in diamond is utilized as both the solid-state spin quantum sensor and the polarized electron source, and a vibrating lead sphere serves as the moving unpolarized nucleon source. The exotic interaction is searched by detecting the possible effective magnetic field induced by the moving unpolarized nucleon source using the ensemble-NV-diamond magnetometer. Our result establishes new bounds for the coupling parameter $f_\perp$ within the force range from 5 to 400 $\rm \mu$m. The upper limit of the coupling parameter at 100 $\rm \mu$m is $\lvert f_\perp \rvert \leq 1.1\times 10^{-11}$, which is 3 orders of magnitude more stringent than the previous constraint. This result shows that NV ensemble can be a promising platform to search for hypothetical particles beyond the standard model

A Nomogram for Predicting Upper Urinary Tract Damage Risk in Children With Neurogenic Bladder

PURPOSE: To establish a predictive model for upper urinary tract damage (UUTD) in children with neurogenic bladder (NB) and verify its efficacy. METHODS: A retrospective study was conducted that consisted of a training cohort with 167 NB patients and a validation cohort with 100 NB children. The clinical data of the two groups were compared first, and then univariate and multivariate logistic regression analyses were performed on the training cohort to identify predictors and develop the nomogram. The accuracy and clinical usefulness of the nomogram were verified by receiver operating characteristic (ROC) curve, calibration curve and decision curve analyses. RESULTS: There were no significant differences in other parameters between the training and validation cohorts except for age (all CONCLUSION: This study presents an effective nomogram incorporating five clinical characteristics that can be conveniently applied to assess NB children\u27 risk of progressing to UUTD

Cyclic threshold shear strain for pore water pressure generation and stiffness degradation in marine clays at Yangtze estuary

Cyclic threshold shear strain is a fundamental property of saturated soils under cyclic loading. To investigate the cyclic threshold shear strain for pore water pressure generation (γtp) and stiffness degradation (γtd), a series of strain-controlled multistage undrained cyclic triaxial tests were carried out on in-situ saturated marine clay in the Yangtze estuary with different plasticity index Ip. The test results show that both γtp and γtd increase with increasing Ip, and γtp is larger than γtd for the same marine clay tested under the same conditions, with γtp = 0.017 ~ 0.019%, γtd = 0.008 ~ 0.012% for Ip of 17, γtp = 0.033 ~ 0.039%, γtd = 0.020 ~ 0.025% for Ip of 32, and γtp = 0.040 ~ 0.048%, γtd = 0.031 ~ 0.036% for Ip of 40. Moreover, the development of stiffness degradation may not necessarily require the generation of pore water pressure but can be aggravated by it. Furthermore, the γtp and γtd of marine clay are compared with terrestrial soils and marine clays cited from the published literature, the results indicate that the special marine sedimentary environment and the combined action of flow and tidal wave system cause the γtp and γtd of marine clay in the Yangtze estuary to be smaller than that of the terrestrial clays and marine clays in other sea areas

MULTI-AGV SCHEDULING OPTIMIZATION BASED ON NEURO-ENDOCRINE COORDINATION MECHANISM

Ovaj se završni radi bavi mobilnim robotima koji su pokretani nogama. Rad se sastoji od dvije veće cjeline. Prvi dio rada donosi literaturni pregled mobilnih robota pokretanih nogama te daje njihovu podjelu. Mobilne robote pokretane nogama najčešće dijelimo prema broju nogu, ali i po ostalim fizičkim karakteristikama. U radu se govori o osnovnim prednostima i nedostacima pri konstruiranju i upravljanju ovakvih robota. Većina takvih robota izrađena je po uzoru na neku životinju ili čovjeka, odnosno imitirajući prirodu. Takav pristup proučavanja i preslikavanja životinjskih karakteristika u tehničke sustave naziva se biomimikrija. Biomimikrija je očita i u drugom dijelu rada koji se bavi adaptacijom već postojeće robotske platforme. U drugom dijelu rada se razrađuje prilagodba četveronožnog paukolikog robota za novoodabrano elektroničko sklopovlje. Nakon modeliranja konstrukcije u programskom paketu CATIA, izrađen je prototip na uređaju za brzu izradu prototipova. Posebnost ove platforme jest da se svi aktuatori nalaze unutar samog tijela robota, a ne u nogama. Na taj se način eliminira prekomjerna masa nogu. Svaka od ĉetiri noge se pokreće pomoću polužnog mehanizma koji se sastoji od četiri štapa. Zbog te karakteristike javlja se neuobičajena kinematika robota. Ovakvom konstrukcijom robot postaje izazovna platforma za proučavanje algoritama umjetne inteligencije koji se implemetiraju za ostvarivanje gibanja. Takvi algoritmi daju puno bolje rezultate od sekvencijalnog programiranja kod složenijih robotskih struktura.This final project addresses the issue of legged mobile robots. The paper consists of two major parts. First part of the paper brings literature review of legged mobile robots and classifies them. Legged mobile robots most commonly differ by the number of their legs, but they can be distinguished by many other physical characteristics. The paper tackles elementary advantages and disadvantages when designing and controlling this type of a robot. Most legged mobile robots are made by imitating animals and humans. This approach of implementing knowledge obtained form observing nature into technical systems is called biomimetics. Biomimetics is also obvious in the second part of this paper. The second part of the paper elaborates adaptation of already existing quadruped robotic platform for the new electronic circuitry. After 3D designing the model in the CATIA software, prototype is printed on the rapid prototyping printer. This platform is unique because all the actuators are located in the body of the robot, and none of them is in the robot's leggs. Specifically, each of the four legs is controlled by separete four-bar linkage mechanism. Consequently, robot's mass is reduced, however, complexity of control is increased. This design causes unconventional kinematics, thus providing challenging platform for gait-learning algorithms. These algorithms excel in complicated structures like this, where sequential programming tends to underperform

RKKY signals characterizing the topological phase transitions in Floquet Dirac semimetals

Recently, the Floquet ${\rm Na_3Bi}$-type material has been proposed as an ideal platform for realizing various phases, i.e., the spin-degenerate Dirac semimetal (DSM) can be turned into the Weyl semimetal (WSM), and even to the Weyl half-metal (WHM). Instead of the conventional electrical methods, we use the RKKY interaction to characterize the topological phase transitions in this paper. It is found that detecting the Ising term $J_I$ is feasible for distinguishing the phase transition of DSM/WSM, since the emergence of $J_I$ is induced by the broken spin degeneracy. For the case with impurities deposited on $z$ axis (the line connecting the Weyl points), the Heisenberg term $J_H$ coexists with $J_I$ in the WSM, while $J_H$ is filtered out and only $J_I$ survives in the WHM. This magnetic filtering effect is a reflection of the fully spin-polarized property (one spin band is in the WSM phase while the other is gapped) of the WHM, and it can act a signal to capture the phase transition of WSM/WHM. This signal can not be disturbed unless the direction of the impurities greatly deviates from $z$ axis. Interestingly, as the impurities are moved into the $x$-$y$ plane, there arises another signal (a dip structure for $J_H$ at the phase boundary), which can also identify the phase transition of WSM/WHM. Furthermore, we have verified that all magnetic signals are robust to the term that breaks the electron-hole symmetry. Besides characterizing the phase transitions, our results also suggest that the Floquet DSMs are power platforms for controlling the magnetic interaction.Comment: 15 pages, 10 figure

Carbon nanoparticles as a multimodal thermoacoustic and photoacoustic contrast agent

We demonstrated the potential of carbon nanoparticles (CNPs) as exogenous contrast agents for both thermoacoustic (TA) tomography (TAT) and photoacoustic (PA) tomography (PAT). In comparison to deionized water, the CNPs provided a four times stronger signal in TAT at 3 GHz. In comparison to blood, The CNPs provided a much stronger signal in PAT over a broad wavelength range of 450-850 nm. Specifically, the maximum signal enhancement in PAT was 9.4 times stronger in the near-infrared window of 635-670 nm. In vivo blood-vessel PA imaging was performed non-invasively on a mouse femoral area. The images, captured after the tail vein injection of CNPs, show a gradual enhancement of the optical absorption in the vessels by up to 230%. The results indicate that CNPs can be potentially used as contrast agents for TAT and PAT to monitor the intravascular or extravascular pathways in clinical applications

Deficient RPE mitochondrial energetics leads to subretinal fibrosis in age-related neovascular macular degeneration

Subretinal fibrosis permanently impairs the vision of patients with neovascular age-related macular degeneration. Despite emerging evidence revealing the association between disturbed metabolism in retinal pigment epithelium (RPE) and subretinal fibrosis, the underlying mechanism remains unclear. In the present study, single-cell RNA sequencing revealed, prior to subretinal fibrosis, genes in mitochondrial fatty acid oxidation are downregulated in the RPE lacking very low-density lipoprotein receptor (VLDLR), especially the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A). We found that overexpression of CPT1A in the RPE of Vldlr−/− mice suppresses epithelial-to-mesenchymal transition and fibrosis. Mechanistically, TGFβ2 induces fibrosis by activating a Warburg-like effect, i.e. increased glycolysis and decreased mitochondrial respiration through ERK-dependent CPT1A degradation. Moreover, VLDLR blocks the formation of the TGFβ receptor I/II complex by interacting with unglycosylated TGFβ receptor II. In conclusion, VLDLR suppresses fibrosis by attenuating TGFβ2-induced metabolic reprogramming, and CPT1A is a potential target for treating subretinal fibrosis