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Abstract Background The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. Methods Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. Results A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2–78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3–46.7, P

Abstract Background Extensive hepatocyte mortality and the absence of specific medical therapy significantly contribute to the unfavorable prognosis of acute liver failure (ALF). Ferroptosis is a crucial form of cell death involved in ALF. In this study, we aimed to determine the impact of Mediator complex subunit 1 (Med1) on ferroptosis and its potential hepatoprotective effects in ALF. Results Med1 expression is diminished in the liver of lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced ALF mice, as well as in hepatocytes damaged by H2O2 or TNF-α/D-GalN in vitro. Med1 overexpression mitigates liver injury and decreases the mortality rate of ALF mice by ferroptosis inhibition. The mechanism by which Med1 inhibits erastin-induced ferroptosis in hepatocytes involves the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes heme oxygenase-1 (HO-1), glutamate cysteine ligase catalytic (GCLC), and NAD(P)H quinone oxidoreductase 1 (NQO1). Furthermore, Med1 overexpression suppresses the transcription of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the liver of mice with LPS/D-GalN-induced ALF. Conclusion Overall, our research findings indicate that Med1 suppresses ferroptosis and alleviates liver injury in LPS/D-GalN-induced ALF through the activation of Nrf2. These findings substantiate the therapeutic viability of targeting the Med1-Nrf2 axis as a means of treating individuals afflicted with ALF. Graphical Abstract

The effects of cold rolling deformation on microstructure, texture, and formability of Al–Mg–Si–Zn alloy were systematically investigated using OM, SEM, TEM, XRD, and tensile tests. The results indicated that the effect of cold rolling deformation on the recrystallized microstructure and texture of the sheets mainly depended on the differences in dislocation structure and texture distribution. With the increase of cold rolling deformation, the dislocation structure gradually changed from a mixture of density dislocation walls and microbands to a lamellar bands structure, the large-angle boundary gradually increased, and the size of dislocation cells gradually decreased, which indicated a gradual increase of the stored deformation energy. In addition, the deformation texture increased gradually with the raise of cold rolling deformation. After T4P treatment, the recrystallized grain size gradually reduced with the increase of cold rolling deformation. The main recrystallization textures in the sheets with 41 % and 55 % deformation were Cube {001} and CubeRD {310} textures, respectively. The CubeND {001} texture was predominantly present in the sheets with 69 % and 82 % deformation, meanwhile some P {011} texture was also observed in the sheets with 82 % deformation. It was found that the dislocation structure and deformation texture distribution formed in the sheet with 82 % cold rolling deformation contributed to smaller recrystallized grains and weaker P texture after solution heat treatment, which enhanced the average plastic strain ratio r value and improved the formability.

As wireless communication devices gain popularity, concerns about the potential risks of environmental exposure to complex frequency electromagnetic radiation (EMR) on mental health have become a public health issue. Historically, EMR research has predominantly focused on single- frequency electromagnetic waves, neglecting the study of multi-frequency electromagnetic waves, which more accurately represent everyday life. To address these concerns, our study compared the emotional effects of single-frequency and dual-frequency EMR while exploring potential molecular mechanisms and intervention targets. Our results revealed that single-frequency EMR at 2.65 or 0.8 GHz did not induce anxiety-like behavior in mice. However, exposure to dual-frequency EMR at 2.65/0.8 GHz significantly led to anxiety-like behavior in mice. Further analysis of mouse sera revealed substantial increases in corticosterone and corticotrophin releasing hormone levels following exposure to 2.65/0.8 GHz EMR. Transcriptome sequencing indicated a significant decrease in the expression of Cnr1, encoding cannabinoid receptor 1 Type (CB1R), in the cerebral. This finding was consistently verified through western blot analysis, revealing a substantial reduction in CB1R content. Additionally, a significant decrease in the endocannabinoid 2-arachidonoylglycerol was observed in the cerebral cortex. Remarkably, administering the cannabinoid receptor agonist Win55-212-2 significantly alleviated the anxiety-like behavior, and the cannabinoid receptor antagonist AM251 effectively counteracted the anti-anxiety effects of Win55-212-2. In summary, our research confirmed that dual-frequency EMR is more likely to induce anxiety-like behavior in mice than single-frequency EMR, with implications for the hypothalamic–pituitary–adrenal axis and the endocannabinoid system. Furthermore, our findings suggest that Win55-212-2 may represent a novel avenue for researching and developing anti-EMR drugs.

Abstract Background To build and validate a radiomics nomogram based on preoperative CT scans and clinical data for detecting synchronous ovarian metastasis (SOM) in female gastric cancer (GC) cases. Methods Pathologically confirmed GC cases in 2 cohorts were retrospectively enrolled. All cases had presurgical abdominal contrast-enhanced CT and pelvis contrast-enhanced MRI and pathological examinations for any suspicious ovarian lesions detected by MRI. Cohort 1 cases (n = 101) were included as the training set. Radiomics features were obtained to develop a radscore. A nomogram combining the radscore and clinical factors was built to detect SOM. The bootstrap method was carried out in cohort 1 as internal validation. External validation was carried out in cohort 2 (n = 46). Receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA) and the confusion matrix were utilized to assess the performances of the radscore, nomogram and subjective evaluation model. Results The nomogram, which combined age and the radscore, displayed a higher AUC than the radscore and subjective evaluation (0.910 vs 0.827 vs 0.773) in the training cohort. In the external validation cohort, the nomogram also had a higher AUC than the radscore and subjective evaluation (0.850 vs 0.790 vs 0.675). DCA and the confusion matrix confirmed the nomogram was superior to the radscore in both cohorts. Conclusions This pilot study showed that a nomogram model combining the radscore and clinical characteristics is useful in detecting SOM in female GC cases. It may be applied to improve clinical treatment and is superior to subjective evaluation or the radscore alone.

IntroductionHypothyroidism has been found to be influenced by gut microbiota. However, it remains unclear which a taxon of gut microbiota plays a key role in this function. Identifying the key bacteria affects hypothyroidism and through what mechanism will be helpful for the prevention of hypothyroidism through specific clinical pathways.Materials and methodsIn Study A, 35 families and 130 genera of gut microbiota are used as exposures, with hypothyroidism as the outcome. The causal effect of the gut microbiota on hypothyroidism is estimated through two-sample Mendelian randomization. Combining the results of the two taxonomical levels, key taxa are selected, which in Study B are investigated for their causal association with multiple generally admitted causes of hypothyroidism and their more upstream factors. For validating and revealing the potential mechanism, enrichment analyses of the related genes and interacting transcription factors were performed.ResultsIn Study A, Defluviitaleaceae (OR: 0.043, 95% CI: 0.005–0.363, P = 0.018)/Defluviitaleaceae_UCG_011 (OR: 0.385, 95% CI: 0.172–0.865, P = 0.021) are significantly causally associated with hypothyroidism at both taxonomical levels. In Study B, Defluviitaleaceae family and Defluviitaleaceae_UCG_011 genus show the causal association with decreased thyroiditis (Family: OR: 0.174, 95% CI: 0.046–0.653, P = 0.029; Genus: OR: 0.139, 95% CI: 0.029–0.664, P = 0.043), decreased subacute thyroiditis (Family: OR: 0.028, 95% CI: 0.004–0.213, P = 0.007; Genus: OR: 0.018, 95% CI: 0.002–0.194, P = 0.013), decreased influenza (Family: OR: 0.818, 95% CI: 0.676–0.989, P = 0.038; Genus: OR: 0.792, 95% CI: 0.644–0.974, P = 0.027), and increased anti-influenza H3N2 IgG levels (Family: OR: 1.934, 95% CI: 1.123–3.332, P = 0.017; Genus: OR: 1.675, 95% CI: 0.953–2.943, P = 0.073). The results of the enrichment analysis are consistent with the findings and the suggested possible mechanisms.ConclusionDefluviitaleaceae of the gut microbiota displays the probability of causally inhibiting the clinical pathway of “Influenza–Subacute Thyroiditis–Hypothyroidism” and acts as the potential probiotics to prevent influenza, subacute thyroiditis, and hypothyroidism.

Quercus kerrii Craib 1911 (section Cyclobalanopsis) is a widespread tree species in the tropical seasonal forests of southwest China and Northern Indo-China areas. In this study, we sequenced, assembled and annotated the complete chloroplast genome of Q. kerrii. The circular genome was 160,743 bp in length and had a GC content of 36.89%. The Q. kerrii chloroplast genome has a typical quadripartite structure, including two inverted repeat regions (length, 25,825 bp; GC content, 42.76%), a large single-copy region (length, 90,196 bp; GC content, 34.74%), and a small single-copy region (length, 18,897 bp; GC content, 30.60%). Genome annotation has indicated that the Q. kerrii chloroplast genome contained 131 genes, including 86 protein-coding genes, 37 tRNA, and eight rRNA. The phylogenetic tree showed that Q. kerrii had a close relationship with Q. schottkyana Rehder & E.H.Wilson 1916.

The problem of large stockpiles of red mud needs to be solved, and the use of red mud to prepare inorganic fibers is a new way of applying red mud on a large scale. The role of CaO/Al2O3 in the melting point and melt structure of red mud was investigated by molecular dynamics simulations and thermodynamic calculations. Liquid phase line temperatures for different CaO/Al2O3 systems were calculated using the Factsage program. The radial distribution function and the type of oxygen bonding were used to characterize the effect of different CaO/Al2O3 on the structure of the red mud melt. The melting point of MgAl2O4 is lower than that of CaTiO3 due to the fact that the type of oxygen bonding in MgAl2O4 is predominantly bridging oxygen bonds. When the red mud system has a low SiO2 content and CaO/Al2O3 is between 0.3 and 3.9, the melting point temperature increases significantly, which is not conducive to the fibrillation of the red mud melt.

Abstract The advent of single-cell RNA sequencing (scRNA-seq) has provided insight into the tumour immune microenvironment (TIME). This review focuses on the application of scRNA-seq in investigation of the TIME. Over time, scRNA-seq methods have evolved, and components of the TIME have been deciphered with high resolution. In this review, we first introduced the principle of scRNA-seq and compared different sequencing approaches. Novel cell types in the TIME, a continuous transitional state, and mutual intercommunication among TIME components present potential targets for prognosis prediction and treatment in cancer. Thus, we concluded novel cell clusters of cancer-associated fibroblasts (CAFs), T cells, tumour-associated macrophages (TAMs) and dendritic cells (DCs) discovered after the application of scRNA-seq in TIME. We also proposed the development of TAMs and exhausted T cells, as well as the possible targets to interrupt the process. In addition, the therapeutic interventions based on cellular interactions in TIME were also summarized. For decades, quantification of the TIME components has been adopted in clinical practice to predict patient survival and response to therapy and is expected to play an important role in the precise treatment of cancer. Summarizing the current findings, we believe that advances in technology and wide application of single-cell analysis can lead to the discovery of novel perspectives on cancer therapy, which can subsequently be implemented in the clinic. Finally, we propose some future directions in the field of TIME studies that can be aided by scRNA-seq technology.

Abstract In recent years, precision electronic warfare (PREW), an energy‐focussed delivery technology, has been used to solve a series of problems that currently limit traditional electronic warfare. A super‐sparse array of transmitters is used to concentrate the jamming energy as much as possible in the target area and reduce the jamming energy as much as possible in other specific protected areas. However, determining how to design jamming waveforms with jamming characteristics, such as covering the target work bandwidth, while ensuring that the energy transmission meets the requirements, is still an urgent problem. For the first time, this paper considers the task characteristics of PREW applications as constraint conditions. Through a first‐order Taylor expansion, the optimisation problem is approximately transformed into a convex sequential cone programming problem, and jamming waveforms are obtained through an iterative solution method. Experiments showed that the jamming waveforms designed by this algorithm meet the energy distribution requirements of PREW scenarios, and at the same time, the jamming waveforms emitted by each transmitter are superimposed in the jamming area to produce a signal that can cover the target work bandwidth. This method can achieve energy focussing on the space and frequency domains.

Automatic sketch colorization has become an important research topic in computer vision.Previous methods intent to improve the colorization quality with advanced network architecture or innovative pipeline.However, they usually generate results with concentrated hue, unreasonable saturation and gray distribution.To alleviate these problems, this paper proposes a sketch colorization method with drawing priors.Inspired by the actual coloring process, this method learns the widely used drawing priors (such as hue variation, saturation contrast, and gray contrast) to improve the quality of automatic sketch colorization.Speci-fically, it incorporates pixel-level loss in the HSV color space to gain more natural results with less artifacts.Meanwhile, three heuristic loss functions that introduce the drawing priors such as hue variation, saturation and gray contrast are used to train our method to generate results with harmonious color composition.We compare our method with current state-of-the-art methods on test dataset constructed by real sketch images.Fréchet inception distance (FID) and mean opinion score (MOS) are adopted to measure the similarity between the distribution of real and generated images and the visual quality, respectively.Compared to the second-best method, the experimental results show that the FID of our method decreases by 21.00 and the MOS increases by 0.96, respectively.All the experimental results prove that the proposed method effectively improves the visual quality of automa-tic sketch colorization.

Focused energy delivery (FED) is a technique that can precisely bring energy to the specific region, which arouses wide attention in precision electronic warfare (PREW). This paper first proposes a joint optimization model with respect to the locations of the array and the transmitted signals to improve the performance of FED. As the problem is nonconvex and NP-hard, particle swarm optimization (PSO) is adopted to solve the locations of the array, while designing the transmitted signals under a feasible array is considered as a unimodular quadratic program (UQP) subproblem to calculate the fitness criterion of PSO. In the PSO-UQP framework established, two methods are presented for the UQP subproblem, which are more efficient and more accurate respectively than previous works. Furthermore, a threshold value is set in the framework to determine which method to adopt to take full advantages of the methods above. Meanwhile, we obtain the maximum localization error that FED can tolerate, which is significant for implementing FED in practice. Simulation results are provided to demonstrate the effectiveness of the joint optimization algorithm, and the correctness of the maximum localization error derived.

Abstract Focussed energy delivery (FED), which transmits energy to a specific area by ultrasparse arrays, is the core technique of precision electronic warfare (PREW). However, array sparsity results in severe grating lobes in practice, which greatly increase the risks of an interference system being attacked and unexpected jamming occurring in other devices. Here, two methods are presented which are aimed at suppressing grating lobes when implementing FED in the application of PREW to avoid the problems mentioned. Regarding the first method, a new metric based on the l∞‐norm is proposed to measure the maximum grating lobe and introduce the metric to the standard FED model. A multiobjective optimisation problem (MOP) is established and solved by the alternating direction penalty method (ADPM) framework. In the second method, the degrees of freedom of the transmitted signals are extended by equipping each platform with a group of linear uniform antennas. The corresponding MOP is established and block coordinate descent is employed to simplify the problem into two subproblems concerning the amplitude and phase components of the transmitted signals. Then, these two subproblems are solved using Taylor expansion and the ADPM framework. Simulation results are provided to demonstrate the advantages of the proposed methods over the state‐of‐the‐art methods.

Abstract Background Medullary thyroid cancer (MTC) represents 13.4 % of all thyroid cancers-related deaths. The treatments for MTC are very limited especially for patients with distal metastasis. Therefore, it is critical to understand the mechanisms of MTC to pursue novel therapeutic avenues. Here, we studied the function of circPVT1/miR-455-5p in MTC. Methods Human MTC tissues and cell lines were used. qRT-PCR and Western blotting were employed to measure expression levels of miR-455-5p, circPVT1, CXCL12, and epithelial mesenchymal transformation (EMT)-related proteins. Colony formation assay, flow cytometry, transwell assay, and scratch wound healing assay were used to assess the abilities of cell proliferation, apoptosis, migration and invasion, respectively. Dual luciferase assay and RNA immunoprecipitation were employed to validate interactions of circPVT1/miR-455-5p and miR-455-5p/CXCL12. Nude mouse xenograft model was used to evaluate the effects of shcircPVT1 and miR-455-5p mimics on tumor growth and metastasis in vivo. Results miR-455-5p was reduced in MTC tissues and cells while circPVT1 was elevated. Their levels were correlated with prognosis of MTC. Overexpression of miR-455-5p or sh-circPVT1 suppressed EMT and MTC cell proliferation, migration and invasion. miR-455-5p targeted CXCL12 while circPVT1 sponged miR-455-5p. Knockdown of CXCL12 or CXCL12/CXCR4 signaling inhibitor reversed the effects of circPVT1 overexpression or miR-455-5p inhibitor on EMT and MTC cell proliferation, migration and invasion. Knockdown of circPVT1 or miR-455-5p overexpression repressed MTC tumor growth and lung metastasis in vivo. Conclusions miR-455-5p suppresses MTC growth and metastasis by targeting CXCL12/CXCR4 signaling pathway while circPVT1 promotes MTC by sponging miR-455-5p. Our study sheds light on the mechanisms of MTC growth and metastasis.

We present a high-resolution non-contact method for the measurement of two-dimensional (2D) phosphor surface temperature distribution (PSTD) of phosphor-coated light-emitting diodes (pc-LEDs) based on advanced hyper-spectral imaging technology. The studied pc-LEDs with a surface-mounted device structure are mainly consisted of blue InGaN/GaN-based LED chips (with a spectral emission at about 456 nm), red (Sr,Ca)AlSiN3: Eu2+ phosphors (with a spectral emission at around 623 nm), and transparent silicone gels. Experimental temperature results are compared with those of micro-thermocouple ( $\mu $ -TC) and infrared thermal imaging (TI), and fairly good agreements can be noticed. However, the spatial resolution of this proposed method is more than one order of magnitude higher than that of TI method, and the proposed method provides more detailed surface temperature information of phosphors than the latter. Therefore, we believe that this proposed method can serve as useful tools for the non-contact measurement of PSTD in pc-LEDs with or without optics lens.

Abstract This letter presents a new method of focused energy delivery (FED) with low grating lobes for precision electronic warfare (PREW). The transmitted signal model is modified by equipping each platform with a linear uniform antenna array, enabling the same performance with lower power and providing a greater degree of freedom in the design of the transmitted signals than traditional methods. Moreover, the L∞‐norm is considered as a regularization term in the model to simultaneously realize FED and alleviate the grating lobes. To solve the nonconvex NP‐hard multiobjective optimization problem (MOP), block coordinate descent (BCD) is employed to separate the problem into two subproblems with respect to the amplitude and phase components of the signals. Then, these two subproblems are solved using Taylor expansion (TE) and the alternating direction penalty method (ADPM), respectively. Simulation results demonstrate that the proposed method exhibits superior performance compared to previous methods.

Abstract Background Systematic evaluation of the successful heartbeat recovery rate (HRR) in patients during the platinum ten minutes after cardiac arrest. Methods The databases of CNKI (January 1979–March 2019), Chongqing VIP (January 1989–March 2019), Wanfang (January 1990–March 2019) and Web of Science (1900-May 2020) were searched. To collect the clinical data of patients with cardiac arrest before hospitalization and analyze the cardiopulmonary resuscitation (CPR) at different times. Literature selection and data extraction were carried out by two researchers independently, and the meta package of R software (version 3. 61) was used for analysis. Results A total of 116 papers met the inclusion criteria, including 37,181 patients. Of these patients, 3367 had their heartbeats successfully restored. The results showed a high degree of heterogeneity (χ 2 = 6999.21, P 15 min group. The HRR were 0.417 (0.341–0.496), 0.143 (0.104–0.193), 0.049 (0.034–0.069), and 0.022 (0.009–0.051), respectively. The HRR was higher in the 0 to ≤5 min group than in the 5 to ≤10 min group, the 10 to ≤15 min group and the > 15 min group. There was no difference between the 10 to ≤15 min group and the > 15 min group. (3) When the groups were stratified with the cutoff of 10 min, the ≤10 min group HRR [0.250 (0.202–0.306)] was higher than the > 10 min group rate [0.041 (0.029–0.057)]. (4) The HRR of the telephone guidance group was [0.273 (0.227–0.325)] lower than that of the 0 to ≤5 min group [0.429 (0.347–0.516)] but higher than that of the 5 to ≤10 min group, the 10 to ≤15 min group, and the > 15 min group. (5) The HRR of the witness group [0.325 (0.216–0.458)] was not different from that of the 0 to ≤5 min group, but it was higher than those of the 5 to ≤10 min group, the 10 to ≤15 min group and the > 15 min group. (6) There was no significant difference HRR between the witnessed group, the telephone guidance group and the ≤10 min group. Conclusions (1) The HRR is time-sensitive, and early rescue can improve it. (2) CPR performed within the platinum ten minutes must be executed by the public, and other forces are auxiliary. (3) The concept of peri-cardiac arrest period (PCAP) should be established and improved to guide CPR.

Addition of Sc is capable of greatly improving the mechanical properties of aluminum alloy welded joints, reducing the hot crack sensitivity coefficient; thus, it could solve the welding problem of ultra-high strength aluminum alloys. Friction stir welding has the advantages of small heat-affected zone, low residual stress, and small deformation of welding work piece, making it a good choice for welding materials with high heat crack sensitivity. In this article, the microstructure and properties of friction stir welding (FSW) joints of Al–Zn–Mg–Cu–Zr–(Sc) alloys were characterized via optical microscopy (OM), transmission electron microscopy (TEM), micro-hardness testing, and universal tensile testing. The mechanism of the effect of adding Sc element on improving the welding properties of the ultra-high strength Al–Zn–Mg–Cu–Zr alloy was explored. The results show that the welding joints of Al–Zn–Mg–Cu–Zr–(Sc) alloy exhibit similar microstructure characteristics. The welding nugget zone (WNZ) displays a dynamic recrystallization feature comprising fine and uniform equiaxed grains with high density dislocations. Most of the aged precipitates dissolve into the matrix in the WNZ. The grains in the thermal-mechanical affected zone (TMAZ) are elongated with higher dislocation density, and residual aged precipitates coarsened remarkably. The heat-affected zone (HAZ) retains the same grain morphology as the base metal. Most of the aged η' precipitates grow, and a few coarsen to be the η phase in this zone. However, 0.17% (mass fraction) Sc addition increases the ultimate tensile strength of FSW joint by 43 MPa, yield strength by 23 MPa, elongation by 2.3%, and the welding coefficient up to 74.1%. Al3(Sc, Zr) dispersoids are found to achieve the following: 1) strongly inhibit the movement of dislocations, sub-grain boundaries, and grain boundaries; 2) significantly refine grains while retaining several sub-structures; and 3) factor in Orowan precipitation strengthening. Therefore, the mechanical properties of FSW joints can be improved using the refined grain, sub-structure, and precipitation strengthening mechanisms.

Objective To investigate the mechanism of propofol on proliferation, migration and invasion of lung adenocarcinoma cells. Methods MTT method was used to detect the inhibition rate or proliferation of A549 and Anip973 human lung adenocarcinoma cell lines treated with propofol (60, 100, 120 μmol/L); The si-NC group (transfected si-NC), the si-PKM2 group (transfected si-PKM2), pcDNA3.1 group (transfected pcDNA3.1), pcDNA3.1-PKM2 group (transfected pcDNA3.1-PKM2), propofol + pcDNA3.1 group (transfected pcDNA3.1 and treated with propofol), propofol + pcDNA3.1-PKM2 group (transfected pcDNA3.1-PKM2 and treated with propofol), all were transfected into Anip973 cells by liposome and treated with propofol; Transwell assay was used to detect cell migration and invasion; RT-qPCR was used to detect the expression of PKM2 mRNA in cells; Western blot was used to detect protein expression of PKM2, E-cadherin, MMP-2, in cells. Results Propofol(0, 60, 100, 120 μmol/L) inhibited the proliferation of human lung adenocarcinoma cells A549 and Anip973 in a concentration-dependent manner. Anip973 cells were more sensitive to propofol, and the optimal concentration was 120 μmol/L; propofol inhibited the proliferation, migration and invasion of Anip973 cells, down-regulated the protein expression of PKM2 and MMP-2, and up-regulated the protein expression of E-cadherin; knockdown of PKM2 has the same inhibition effect as propofol proliferation, migration and invasion, down-regulate the protein expression of MMP-2 and up-regulate the protein expression of E-cadherin of Anip973 cells; over-expression of PKM2 reversed the proliferation, migration and invasion, the effect of protein expression of E-cadherin and MMP-2 of Anip973 cells. Conclusions Propofol inhibits the proliferation, migration and invasion of lung adenocarcinoma cells, and its mechanism is related to down-regulation of PKM2 expression.

Abstract The DSMC modeling is developed to simulate three-dimensional (3D) rarefied ionization flows and numerically forecast the communication blackout around spacecraft during hypervelocity reentry. A new weighting factor scheme for rare species is introduced, whose key point is to modify the corresponding chemical reaction coefficients involving electrons, meanwhile reproduce the rare species in resultants and preserve/delete common species in reactants according to the weighting factors. The resulting DSMC method is highly efficient in simulating weakly inhomogeneous flows including the Couette shear flow and controlling statistical fluctuation with high resolution. The accurate reliability of the present DSMC modeling is also validated by the comparison with a series of experimental measurements of the Shenzhou reentry capsule tested in a low-density wind tunnel from the HAI of CARDC. The obtained electron number density distribution for the RAM-C II vehicle agrees well with the flight experiment data, while the electron density contours for the Stardust hypervelocity reentry match the reference data completely. In addition, the present 3D DSMC algorithm can capture distribution of the electron, N+ and O+ number densities better than the axis-symmetric DSMC model. The introduction of rare species weighting factor scheme can significantly improve the smoothness of the number density contours of rare species, especially for that of electron in weak ionization case, while it has negligible effect on the macroscopic flow parameters. The ionization characteristics of the Chinese lunar capsule reentry process are numerically analyzed and forecasted in the rarefied transitional flow regime at the flying altitudes between 80 and 97 km, and the simulations predict communication blackout altitudes which are in good agreement with the actual reentry flight data. For the spacecraft reentry with hypervelocity larger than the second cosmic speed, it is forecasted and verified by the present DSMC modeling that ionization reactions will cover the windward capsule surface, leading to reentry communication blackout, and the communication interruption must be considered in the communication design during reentry in rarefied flow regimes.

Abstract How to solve the hypersonic aerothermodynamics around large-scale uncontrolled spacecraft during falling disintegrated process from outer space to earth, is the key to resolve the problems of the uncontrolled Tiangong-No.1 spacecraft reentry crash. To study aerodynamics of spacecraft reentry covering various flow regimes, a Gas-Kinetic Unified Algorithm (GKUA) has been presented by computable modeling of the collision integral of the Boltzmann equation over tens of years. On this basis, the rotational and vibrational energy modes are considered as the independent variables of the gas molecular velocity distribution function, a kind of Boltzmann model equation involving in internal energy excitation is presented by decomposing the collision term of the Boltzmann equation into elastic and inelastic collision terms. Then, the gas-kinetic numerical scheme is constructed to capture the time evolution of the discretized velocity distribution functions by developing the discrete velocity ordinate method and numerical quadrature technique. The unified algorithm of the Boltzmann model equation involving thermodynamics non-equilibrium effect is presented for the whole range of flow regimes. The gas-kinetic massive parallel computing strategy is developed to solve the hypersonic aerothermodynamics with the processor cores 500~45,000 at least 80% parallel efficiency. To validate the accuracy of the GKUA, the hypersonic flows are simulated including the reentry Tiangong-1 spacecraft shape with the wide range of Knudsen numbers of 220~0.00005 by the comparison of the related results from the DSMC and N-S coupled methods, and the low-density tunnel experiment etc. For un-controlling spacecraft falling problem, the finite-element algorithm for dynamic thermal-force coupling response is presented, and the unified simulation of the thermal structural response and the hypersonic flow field is tested on the Tiangong-1 shape under reentry aerodynamic environment. Then, the forecasting analysis platform of end-of-life large-scale spacecraft flying track is established on the basis of ballistic computation combined with reentry aerothermodynamics and deformation failure/disintegration.

Background/Aims: Renal reperfusion injury occurs after the blood flow to the ischemic kidney is re-established under various clinical conditions, such as organ transplantation, renal artery stenosis, embolic disease, and the repair of descending aortic. The current study aims to explore the effects of src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) on the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells by regulating the TLR4/NF-κB signaling pathway in rats with renal ischemia-reperfusion (I/R) injury. Methods: A total of 60 normal clean Sprague Dawley (SD) (WT) rats were used in this study. The levels of creatinine (Cr) and blood urea nitrogen (BUN) were determined using an automatic biochemical analyzer. The apoptosis in renal tissue was detected by TUNEL assay. The renal tubular epithelial cells of rats were cultured, infected and treated with different lentivirus vectors. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1β and SHP27 were measured. Reverse transcription quantitative polymerases chain reaction and Western blot analysis were performed to measure the expression of relevant genes and proteins. Furthermore, the effect of SHP-2 on the proliferation, cell cycle and apoptosis of renal tubular epithelial cells was also investigated. Results: In the serum of rats with renal I/R injury and prolonged reperfusion time, the contents of Cr and BUN were increased, the positive expression of SHP-2 was higher, the level of apoptosis was promoted, IL-6, TNF-α, IL-1β and SHP27 expression in the serum was increased, the expression of SHP2, TLR4, NF-κB, IL-6, TNF-α and Bax was up-regulated, and the expression of Bcl-2 was down-regulated. Lentivirus-mediated silencing of SHP-2 promoted the proliferation of renal tubular epithelial cells, inhibited their apoptosis, and reduced the expression of inflammatory factors in these cells by functionally suppressing the TLR4/NF-κB signaling pathway. Conclusion: The results indicated that lentivirus-mediated silencing of SHP-2 inhibited the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells, and promoted the proliferation of these cells by inhibiting the TLR4/NF-κB signaling pathway in rats with renal I/R injury.

Background: Interferon-gamma release assay (IGRA) has been used in latent tuberculosis (TB) infection and TB diagnosis, but the results from different high TB-endemic countries are different. The aim of this study was to investigate the value of IGRA in the diagnosis of active pulmonary TB (PTB) in China. Methods: We conducted a large-scale retrospective multicenter investigation to further evaluate the role of IGRA in the diagnosis of active PTB in high TB-epidemic populations and the factors affecting the performance of the assay. All patients who underwent valid T-SPOT.TB assays from December 2012 to November 2015 in six large-scale specialized TB hospitals in China and met the study criteria were retrospectively evaluated. Patients were divided into three groups: Group 1, sputum culture-positive PTB patients, confirmed by positive Mycobacterium tuberculosis sputum culture; Group 2, sputum culture-negative PTB patients; and Group 3, non-TB respiratory diseases. The medical records of all patients were collected. Chi-square tests and Fisher's exact test were used to compare categorical data. Multivariable logistic analyses were performed to evaluate the relationship between the results of T-SPOT in TB patients and other factors. Results: A total of 3082 patients for whom complete information was available were included in the investigation, including 905 sputum culture-positive PTB cases, 914 sputum culture-negative PTB cases, and 1263 non-TB respiratory disease cases. The positive rate of T-SPOT.TB was 93.3% in the culture-positive PTB group and 86.1% in the culture-negative PTB group. In the non-PTB group, the positive rate of T-SPOT.TB was 43.6%. The positive rate of T-SPOT.TB in the culture-positive PTB group was significantly higher than that in the culture-negative PTB group (χ2 = 25.118, P < 0.01), which in turn was significantly higher than that in the non-TB group (χ2 = 566.116, P < 0.01). The overall results were as follows: sensitivity, 89.7%; specificity, 56.37%; positive predictive value, 74.75%; negative predictive value, 79.11%; and accuracy, 76.02%. Conclusions: High false-positive rates of T-SPOT.TB assays in the non-TB group limit the usefulness as a single test to diagnose active TB in China. We highly recommend that IGRAs not be used for the diagnosis of active TB in high-burden TB settings.

AIM: To determine typical corneal changes of congenital aniridic keratopathy (CAK) using corneal topography and confocal systems, and to identify characteristics that might assist in early diagnosis. METHODS: Patients with CAK and healthy control subjects underwent detailed ophthalmic examinations including axial length, corneal thickness, tear film condition, corneal topography, and laser-scanning in vivo confocal microscopy (IVCM). RESULTS: In early stage aniridic keratopathy, Schirmer I test (SIT), break-up time (BUT), mean keratometry (mean K) and simulated keratometry (sim K) were reduced relative to controls (P

Dysfunction of decidual macrophages (DMs) is considered a critical event in the pathogenesis of pre-eclampsia (PE). T cell immunoglobulin mucin 3 (Tim-3) is an important negative regulatory molecule that induces immune tolerance by interacting with its ligand Galectin-9 (Gal-9) and thus modulating function of various immune cells, including macrophages. However, the regulatory effects of Tim-3/Gal-9 signaling on DMs polarization and its role in PE remain unclear. In this study, we established a PE-like rat model by administering 1.0 μg/kg lipopolysaccharide (LPS) to normal pregnant Sprague-Dawley rats via the tail vein at embryonic day 5 (E5). Apart from the pre-eclamptic manifestations, increased M1 subtype and decreased M2 subtype were observed at the maternal-fetal interface, as well as increased pro-inflammatory cytokines (TNF-α and IL-1β) and reduced anti-inflammatory cytokines (TGF-β and IL-10). Moreover, the expression of Tim-3 in DMs and that of Gal-9 at the maternal-fetal interface were reduced. After administration of recombinant Galectin-9 (rGal-9) protein, we found that liver and renal injuries and maternofetal placental functional deficiency, including inadequate trophoblast cells invasion, impaired spiral artery remodeling and fetal capillary development, were reversed. In addition, the polarization of DMs was inclined to M2 subtype, which was similar to the polarization of DMs in the control rats but contrary to the PE-like rats. Interestingly, at E9, the expression of Tim-3 in DMs and that of Gal-9 at the maternal-fetal interface were significantly increased in the rGal-9 protein intervention group. Taken together, our findings show that administration of rGal-9 protein can alleviate the PE-like rat manifestations induced by LPS. This finding may be related to the activation of the Tim-3/Gal-9 signaling pathway, which promotes DMs polarization dominantly shifting to M2 subtype. Moreover, upregulation of Tim-3 in DMs and Gal-9 at the maternal-fetal interface at E9 suggests that Tim-3/Gal-9 pathway may play some important roles in early pregnancy and even embryo development.

AIM: To investigate therapeutic efficiency of amniotic extraction on dry eye in rabbit model induced by topical benzalkonium chloride(BAC). METHODS: Totally 26 rabbits(26 right eyes)with dry eye model were studied and divided into two groups: group A(control group with PBS eye drops, n=13)and group B(amniotic extraction group, n=13). Another two rabbits were chosen as normal control.The Schirmer Ⅰ tests(SⅠt)and corneal fluorescein staining(FL)were made, and the tear total protein content, amylase activity, lactoferrin, lysozyme contents, goblet cell density were performed in two groups before treatment and 1, 2, 4 and 8 wk after treatment. RESULTS: There were significant differences in SIT, FL scores, lysozyme activity and goblet cell density among different groups at different time points(PP>0.05). After 8wks' treatment with PBS, the mean differences of the group A showed great changes in SⅠt, lysozyme and goblet cell density compared with those before treatment(PP>0.05). As for group B, 8wks after treatment, there were statistical changes in SⅠt, FL, lysozyme(PP>0.05). It was evident that statistical differences were observed in SⅠt, FL scores, lysozyme activity and goblet cell density between two groups at each time point(PP>0.05). Meanwhile there was no significant differences in total protein, lactoferrin, amylase activity between two groups before treatment(P>0.05). But there were significant differences in total protein, lactoferrin, amylase activity between two groups after 4 and 8 wks' treatment(PCONCLUSION: Amniotic extraction has significant therapeutic effect on the dry eye in rabbit model.

Background. EPZ005687 is a selective inhibiter of methyltransferase EZH2. In this article, we investigated the protective role and mechanism of EPZ005687 in transverse aortic constriction-induced pulmonary arterial hypertension in mice. Methods. We assigned 15 (6–8 weeks old) male balb/c mice to 3 groups randomly: Sham control + DMSO group, TAC + DMSO group, and TAC + EPZ005687 group (10 mg kg−1, once a week for 4 weeks). On day 28 following TAC operation, the right ventricular systolic blood pressure (RVSBP) was measured, and lung tissues were collected for laboratory examinations (DHE, Western blot, real-time PCR, and ChIP). Results. Murine PAH model was successfully created by TAC operation as evidenced by increased RVSBP and hypertrophic right ventricle. Compared with the sham control, TAC-induced PAH markedly upregulated the expression of EZH2 and ROS deposition in lungs in PAH mice. The inhibiter of methyltransferase EZH2, EPZ005687 significantly inhibits the development of TAC-induced PAH in an EZH2-SOD1-ROS dependent manner. Conclusion. Our data identified that EZH2 serves a fundamental role in TAC-induced PAH, and administration of EPZ005687 might represent a novel therapeutic target for the treatment of TAC-induced PAH.

Unlike phased array bringing angle-dependent and range-independent beamforming, a new kind of radar system called frequency diverse array (FDA) has been widely used for its ability to generate angle-range-dependent beampattern, which provides a broad prospect of radar application. Nevertheless, FDA beampattern is coupling in the angle and range responses, which results in the difficulty for FDA to differentiate the target in two domains simultaneously. In this paper, a stepped frequency pulse FDA (SFP-FDA) radar is proposed to wipe off the angle-range coupling in FDA and improve the target’s angle and range localization accuracy. Compared to the double-pulse FDA, the proposed system can achieve a better performance in range resolution and multitarget identification. The Cramér-Rao lower bound (CRLB) is derived and used to analyze the performance of the proposed system and double-pulse FDA radar. Numerical results are implemented to verify the validity of the proposed scheme.