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Background Previous studies have demonstrated that by injecting uPA into the lumbar facet joints (LFJ) of normal rats, a rat LFJOA animal model can be successfully established. However, there is no evidence that intraarticular injection of uPA can induce or much serious osteoarthritis in bipedal rats, which biomechanics is much more similar to human than normal rats. To investigate whether intraarticular injection of urinary plasminogen activator (uPA) can induce LFJOA and low back pain symptoms in bipedal rats. Methods An experimental study on the construction of a modified animal model of lumbar facet joints osteoarthritis (LFJOA) which biomechanics is similar to human. Sprague–Dawley rats were treated with intraarticular injection of uPA in the L5–L6 facet joints (uPA group, n = 15) or saline (saline group, n = 15). The forelimbs of both two group rats were amputated. Mechanical and thermal hyperalgesia in the ipsilateral hind paws were evaluated using von Frey hairs and a thermoalgesia instrument, respectively. Toluidine blue staining, hematoxylin–eosin staining, and immunohistochemical examination of the LFJ was performed. Results The saline group rats have not demonstrated significant osteoarthritis in rats LFJ after surgery. The uPA group has not been induced significantly higher mechanical and thermal hyperalgesia in comparison with the saline group. But intraarticular injection of uPA in biped rats induced significantly stronger articular cartilage damage, synovitis, and proliferation of synovial cells in the LFJ. Inflammatory factors such as iNOS, IL-1β, and TNF-a were more significantly expressed in bipedal rat injected with uPA (p Conclusions Intraarticular injection of uPA can induce LFJOA in bipedal rats, while upright posture does not induce osteoarthritis in rats LFJ in the short term.

Under the background that the Earth’s aerosphere contains Kolmogorov and non-Kolmogorov turbulence, it is significant to research the combined influence of these two kinds of atmospherical turbulence on laser-satellite communication. In this paper, based on the power spectra of refractive-index fluctuations for non-Kolmogorov turbulence in the free troposphere and stratosphere, using the extended Rytov theory, the scintillation indices of the spherical wave in the free troposphere and the stratosphere are derived, respectively, which are valid in all regimes of turbulent fluctuations. On this basis, using a three-layer altitude-dependent turbulent spectrum model for vertical/slant path describing the variations of turbulent statistical characteristics with altitude in the aerosphere, which is more accurate than the two-layer model, we present the scintillation index of a spherical wave propagating through Kolmogorov and non-Kolmogorov turbulence along laser-satellite communication uplink at large zenith angles and estimate the combined influence of Kolmogorov and non-Kolmogorov turbulence on the scintillation index. It is noteworthy that this expression is also valid in all regimes of turbulent fluctuations.

The complex interactions among different immune cells have important functions in the development of malignant pleural effusion (MPE). Here we perform single-cell RNA sequencing on 62,382 cells from MPE patients induced by non-small cell lung cancer to describe the composition, lineage, and functional states of infiltrating immune cells in MPE. Immune cells in MPE display a number of transcriptional signatures enriched for regulatory T cells, B cells, macrophages, and dendritic cells compared to corresponding counterparts in blood. Helper T, cytotoxic T, regulatory T, and T follicular helper cells express multiple immune checkpoints or costimulatory molecules. Cell-cell interaction analysis identifies regulatory B cells with more interactions with CD4+ T cells compared to CD8+ T cells. Macrophages are transcriptionally heterogeneous and conform to M2 polarization characteristics. In addition, immune cells in MPE show the general up-regulation of glycolytic pathways associated with the hypoxic microenvironment. These findings show a detailed atlas of immune cells in human MPE and enhance the understanding of potential diagnostic and therapeutic targets in advanced non-small cell lung cancer., Detailed immune cell subset identification in human lung (malignant pleural effusion) MPE is important for diagnosis and prognosis. Here the authors use single cell RNA sequencing to identify immune cell types within MPE and show differential gene expression compared to circulating immune cells in blood.

Background Radiosensitivity is limited in cervical cancer (CC) patients due to acquired radiation resistance. In our previous studies, we found that immediate-early response 5 (IER5) is upregulated in CC cells upon radiation exposure and decreases cell survival by promoting apoptosis. The details on the transcriptional regulation of radiation-induced IER5 expression are unknown. Studies in recent years have suggested that Pol II-associated factor 1 (PAF1) is a pivotal transcription factor for certain genes “induced” during tumor progression. In this study, we investigated the role of PAF1 in regulating IER5 expression during CC radiotherapy. Methods PAF1 expression in CC cells was measured by western blotting, immunohistochemistry, and qRT-PCR, and the localization of PAF1 and IER5 was determined by immunofluorescence. The effect of PAF1 and IER5 knockdown by siRNA in Siha and Hela cells was studied by western blotting, qRT-PCR, CCK-8 assay, and flow cytometry. The physical interaction of PAF1 with the IER5 promoter and enhancers was confirmed using chromatin immunoprecipitation and qPCR with or without enhancers knockout by CRISPR/Cas9. Results We confirmed that PAF1 was highly expressed in CC cells and that relatively low expression of IER5 was observed in cells with highly expressed PAF1 in the nucleus. PAF1 knockdown in Siha and Hela cells was associated with increased expression of IER5, reduced cell viability and higher apoptosis rate in response to radiation exposure, while simultaneous PAF1 and IER5 knockdown had little effect on the proportion of apoptotic cells. We also found that PAF1 hindered the transcription of IER5 by promoting Pol II pausing at the promoter-proximal region, which was primarily due to the binding of PAF1 at the enhancers. Conclusions PAF1 reduces CC radiosensitivity by inhibiting IER5 transcription, at least in part by regulating its enhancers. PAF1 might be a potential therapeutic target for overcoming radiation resistance in CC patients.

Optimal strategies to maximize the two-photon transition amplitude have been well studied. However, for a system with multiple intermediate states linking the same initial and final states, the question that how to achieve an optimal population transfer remains nontrivial. In this work, we propose a systematic block scheme to maximize the transition amplitude by explicitly considering the interferences among different transition pathways. The scheme can probably provide a quasi-optimal solution, even considering the uncertainties and noises in experiments. Cases with infinitesimal and finite spectral resolution are both investigated. A special example with all first transition frequencies being larger than half of the two-photon transition frequencies is employed to demonstrate our scheme. The analysis provides valuable insights on how to manipulate the interferences in control of quantum systems.

Mn-Cu alloys could exhibit high damping ability and excellent mechanical properties after proper heat treatment. In order to reduce the influence of impurity elements on damping capacity of Mn-Cu alloys, rare element cerium (Ce) was added into MnCuNiFe alloys. It is indicated that the contents of C, S and Si which have adverse effects on the damping capacity decrease and the grains are refined with the Ce content increasing. The microstructure of the MnCuNiFeCe alloy was investigated by X-ray diffraction (XRD), scanning electron microscope (SEM) and transmission electron microscopy (TEM). The damping ability (tanδ) of the alloy was characterized by dynamical mechanical analyzer (DMA). It is found that the damping ability (tanδ) retains a very high level which is all above 0.05 from the temperature of −50 to 75 °C with the addition of Ce element. It is expected that the Ce alloying MnCuNiFe alloy with refined grains could find wide applications in the field of industry.

To study the establishment of adjuvant-induced osteoarthritis of the lumbar facet joint in a rat model. Complete Freund's adjuvant (experimental group) and saline (control group) were randomly injected into the right and left side of rat, respectively. The rats were killed, and degeneration of lumbar facet joint was evaluated at macroscopic level and scored based on OARSI scores system. Moreover, Interleukin-1β and tumor necrosis factor-α levels in the synovium were measured. The macroscopic scores and OARSI scores of experimental group were higher than the control group (P < 0.05). The concentration of tumor necrosis factor-α was significantly increased only on 3- and 7-day post-surgery when compared with controls, and interleukin-1β was increased on days 3,7 and 14 post-surgery (P < 0.05). The rat model of adjuvant can induce degeneration of the lumbar facet joint. It can be useful for studies on mechanisms and treatment of lumbar facet joint osteoarthritis.

Destrin, also known as actin depolymerizing factor (ADF), is a member of the ADF/Cofilin/destrin superfamily that has the ability to rapidly depolymerize F-actin in a stoichiometric manner. Remodeling of the actin cytoskeleton through actin dynamics (assembly and disassembly of filamentous actin) is known to be essential for numerous basic biological processes including bone formation. The aim of current study was to elucidate whether destrin was involved in the progression of bone loss induced by modeled microgravity. We used the hindlimb suspension (HLS) mice model to simulate microgravity in vivo. Exposure to HLS in mice enhanced femur destrin expression. Destrin deletion in Dstn (-/-) mutant mice enhanced HLS-induced reduction of BMD, ultimate load, stiffness, trabecular thickness, trabecular number, and bone volume fraction in femur, but did not affect them under control static condition. The Rotary wall vessel bioreactor was used to model microgravity in vitro. Exposure to modeled microgravity in cultured 2T3 murine osteoblast precursor cells upregulated destrin expression. RNAi-mediated destrin knockdown enhanced the microgravity-induced reduction of osteoblastic proliferation and differentiation significantly. In conclusion, for the first time we demonstrated that destrin deletion enhances the bone loss in hindlimb suspended mice. Destrin may be a potential target for the prevention or management of microgravity-induced bone loss.

Quantum measurement is a fundamental problem in quantum control theory and experiments. It can obtain unknown information of quantum systems, and can also change state of the systems inevitably. Both the outcome and back action could be used to control quantum systems. This paper presents recent research progress about optimal control of state transformation in finite-dimensional quantum systems by back action of non-selective quantum measurement, and optimal control of signal and background of CARS (coherent anti-Stokes Raman spectroscopy) by phase shaping technique. In measurement sequence control of finite-dimensional quantum systems, the necessary condition for critical points of the underlying state transformation objective is found to be a highly symmetric form as a chain of equalities, and analytical and numerical solutions in several cases are explored. In the CARS control, it is found that the maximal resonant signal and minimal background at a specific frequency can be achieved by shaping the probe pulse only while keeping pump and Stokes pulses in transform limited forms (TLFs). An arctan-type phase function is obtained for the probe pulse to simultaneously enhance the resonant signal and suppress the background. For broadband background elimination, we find that the optimal phase shaping scheme of probe pulse is quasi-time-delay while keeping the pump and Stokes pulses in TLFs. These conclusions could help design control strategies of quantum devices.

Atherosclerosis begins as local inflammation of arterial walls at sites of disturbed flow, such as vessel curvatures and bifurcations with low shear stress. c-Jun NH2-terminal kinase (JNK) is a major regulator of flow-dependent gene expression in endothelial cells in atherosclerosis. However, little is known about the in vivo role of JNK in low shear stress in atherosclerosis. We aimed to observe the effect of JNK on low shear stress-induced atherogenesis in apolipoprotein E-deficient (ApoE−/−) mice and investigate the potential mechanism in human umbilical vein endothelial cells (HUVECs). We divided 84 male ApoE−/− mice into two groups for treatment with normal saline (NS) (n = 42) and JNK inhibitor SP600125 (JNK-I) (n = 42). Perivascular shear stress modifiers were placed around the right carotid arteries, and plaque formation was studied at low shear stress regions. The left carotid arteries without modifiers represented undisturbed shear stress as a control. The NS group showed atherosclerotic lesions in arterial regions with low shear stress, whereas the JNK-I group showed almost no atherosclerotic lesions. Corresponding to the expression of proatherogenic vascular cell adhesion molecule 1 (VCAM-1), phospho-JNK (p-JNK) level was higher in low shear stress regions with NS than with JNK-I inhibitor. In HUVECs under low shear stress, siRNA knockdown and SP600125 inhibition of JNK attenuated nuclear factor (NF)-κB activity and VCAM-1 expression. Furthermore, siRNA knockdown of platelet endothelial cell adhesion molecule 1 (PECAM-1) (CD31) reduced p-JNK and VCAM-1 levels after low shear stress stimulation. JNK may play a critical role in low shear stress-induced atherogenesis by a PECAM-1-dependent mechanosensory pathway and modulating NF-κB activity and VCAM-1 expression.

This paper explores the optimal control of quantum state transformations in finite-dimensional quantum systems by a sequence of non-selective projective measurements. In our schemes, the projectors of each measurement are represented by a unitary matrix. Through variational analysis of the objective function over the unitary group, the necessary condition for a measurement sequence to be a critical point of the underlying state transformation objective is found to be a highly symmetric form as a chain of equalities. Since these equality relations are generally difficult to solve analytically, we focus on the fundamental case employing a single measurement, in which analytical solutions for maximizing the state transformation probability are found between pure states, or between mixed and pure states, or between orthogonal mixed states under two typical type of measurements. These results suggest a new way of designing optimal quantum dynamics control strategies by quantum measurements.