A New Residual Subsidence Prediction Method of Short Working Face Goaf for Safety Construction of Urban Viaduct.

The planned viaduct in Jining, Shandong is a priority project in the city. However, the 63 working faces of a mine in Jining is only 3 m away from the planned viaduct, posing a serious threat to the safety of the viaduct's construction. Consequently, it is essential to evaluate the stability of the planned viaduct's goaf area under the influence of the 63 working faces. However, the 63 working faces are short faces, and there is a lack of corresponding prediction of surface residual subsidence. To address this issue, this paper employs theoretical analysis and numerical simulation to uncover the foundation deformation mechanism and characteristics of fractured rock and soil mass in the short goaf. Subsequently, a residual subsidence prediction method for the short goaf was proposed for the viaduct mined-out area. This new approach was implemented for the planned viaduct in Jining, and its effectiveness was validated through InSAR and leveling monitoring results. The research findings offer technical support for viaduct construction in areas affected by underground mining.

Promotion of Adrenal Pheochromocytoma (PC-12) Cell Proliferation and Outgrowth Using Schwann Cell-Laden Gelatin Methacrylate Substrate.

Peripheral nerve injuries cause different degrees of nerve palsy and function loss. Due to the limitations of autografts, nerve tissue engineering (TE) scaffolds incorporated with various neurotrophic factors and cells have been investigated to promote nerve regeneration. However, the molecular mechanism is still poorly understood. In this study, we co-cultured Schwann cells (SCs) and rat adrenal pheochromocytoma (PC-12) cells on 50% degrees of methacryloyl substitution gelatin methacrylate (GelMA) scaffold. The SCs were encapsulated within the GelMA, and PC-12 cells were on the surface. A 5% GelMA was used as the co-culture scaffold since it better supports SCs proliferation, viability, and myelination and promotes higher neurotrophic factors secretion than 10% GelMA. In the co-culture, PC-12 cells demonstrated a higher cell proliferation rate and axonal extension than culturing without SCs, indicating that the secretion of neurotrophic factors from SCs can stimulate PC-12 growth and axonal outgrowth. The mRNA level for neurotrophic factors of SCs in 5% GelMA was further evaluated. We found significant upregulation when compared with a 2D culture, which suggested that this co-culture system could be a potential scaffold to investigate the mechanism of how SCs affect neuronal behaviors.

PIK3CA mutation affects the proliferation of colorectal cancer cells through the PI3K-MEK/PDK1-GPT2 pathway.

The phosphatidylinositol­3­kinase catalytic subunit α (PIK3CA) gene is mutated in numerous human cancers. This mutation promotes the proliferation of tumor cells; however, the underlying mechanism is still not clear. In the present study, it was revealed that the PIK3CA mutation in colorectal cancer (CRC) HCT116 (MUT) rendered the cells more dependent on glutamine by regulating the glutamic­pyruvate transaminase 2 (GPT2). The dependence of glutamine increased the proliferation of cells in a normal environment and resistance to a suboptimal environment. Further study revealed that the mutated PIK3CA could regulate GPT2 expression not only through signal transduction molecule 3­phosphoinositide­dependent kinase (PDK1) but also through mitogen­activated protein kinase (MEK) molecules. In HCT116 cells, MEK inhibitor treatment could reduce the expression of GPT2 signaling molecules, thereby inhibiting the proliferation of CRC cells. A new signal transduction pathway, the PI3K/MEK/GPT2 pathway was identified. Based on these findings, MEK and PDK1 inhibitors were combined to inhibit the aforementioned pathway. It was revealed that the combined application of MEK and PDK1 inhibitors could promisingly inhibit the proliferation of MUT compared with the application of PI3K inhibitors, PDK1 inhibitors, or MEK inhibitors alone. In vivo, MEK inhibitors alone and combined inhibitors had stronger tumor­suppressing effects. There was no significant difference between the PDK1­inhibitor group and normal group in vivo. Thus, these results indicated that mutated PI3K affected GPT2 mediated by the MEK/PDK1 dual pathway, and that the PI3K/MEK/GPT2 pathway was more important in vivo. Inhibiting MEK and PDK1 concurrently could effectively inhibit the proliferation of CRC cells. Targeting the MEK and PDK1 signaling pathway may provide a novel strategy for the treatment of PIK3CA­mutated CRC.

Efficacy of Large Groove Texture on Rat Sciatic Nerve Regeneration In Vivo Using Polyacrylonitrile Nerve Conduits.

Physical guidance cues play an important role in enhancing the efficiency of nerve conduits for peripheral nerve injury repair. However, very few in vivo investigations have been performed to evaluate the repair efficiency of nerve conduits with micro-grooved inner textures. In this study, polyacrylonitrile nerve conduits were prepared using dry-jet wet spinning, and micro-grooved textures were incorporated on the inner surface. The nerve conduits were applied to treat 10 mm sciatic nerve gaps in Sprague-Dawley (SD) rats. Sixteen weeks following implantation, nerve function was evaluated based on heat sensory tests, electrophysiological assessments and gastrocnemius muscle mass measurements. The thermal latency reaction and gastrocnemii weight of SD rats treated with grooved nerve conduits were almost 25% faster and 60% heavier than those of SD rats treated with smooth nerve conduits. The histological and immunohistochemical stain analyses showed the repair capacity of inner grooved conduits was found to be similar to that of autografts. These results suggest that grooved nerve conduits with groove width larger than 300 µm significantly improve peripheral nerve regeneration by introducing physical guidance cues. The obtained results can support the design of nerve conduits and lead to the improvement of nerve tissue engineering strategies.

Validity of the Use of Wrist and Forehead Temperatures in Screening the General Population for COVID-19: A Prospective Real-World Study.

BACKGROUND: We aimed to compare the accuracy of individuals' wrist and forehead temperatures with their tympanic temperature under different circumstances. METHODS: We performed a prospective observational study in a real-life population in Ningbo First Hospital in China. We consecutively recorded individuals' wrist and forehead temperatures in Celsius (°C) using a non-contact infrared thermometer (NCIT). We also measured individuals' tympanic temperature using a tympanic thermometer (IRTT) and defined fever as a tympanic temperature of ≥37.3 °C. RESULTS: We enrolled 528 participants, including 261 indoor and 267 outdoor participants. We grouped the outdoor participants into four groups according to their means of transportation to the hospital: by foot, by bicycle/electric vehicle, by car, or as a passenger in a car. Under different circumstances, the mean difference in the forehead measurement ranged from -1.72 to -0.56 °C across groups, and that in the wrist measurement ranged from -0.96 to -0.61°C. Both measurements had high fever screening abilities in indoor patients. (Wrist: AUC 0.790; 95% CI: 0.725-0.854, P<0.001; forehead: AUC 0.816; 95% CI: 0.757-0.876, P <0.001). The cut-off value of the wrist measurement for detecting a tympanic temperature of ≥37.3 °C was 36.2 °C, with 86.4% sensitivity and 67.0% specificity, and the best threshold for the forehead measurement was 36.2 °C, with 93.2% sensitivity and 60.0% specificity. CONCLUSION: Wrist measurements are more stable than forehead measurements under different circumstances. Both measurements have favorable fever screening abilities in indoor patients. The cut-off values were both 36.2 °C.

The influence of the stiffness of GelMA substrate on the outgrowth of PC12 cells.

Recent studies have shown the importance of cell-substrate interaction on neurone outgrowth, where the Young's modulus of the matrix plays a crucial role on the neurite length, migration, proliferation, and morphology of neurones. In the present study, PC12 cells were selected as the representative neurone to be cultured on hydrogel substrates with different stiffness to explore the effect of substrate stiffness on the neurone outgrowth. By adjusting the concentration of gelatin methacryloyl (GelMA), the hydrogel substrates with the variation of stiffnesses (indicated by Young's modulus) from approximately 3-180 KPa were prepared. It is found that the stiffness of GelMA substrates influences neuronal outgrowth, including cell viability, adhesion, spreading, and average neurite length. Our results show a critical range of substrate's Young's modulus that support PC12 outgrowth, and modulate the cell characteristics and morphology. The present study provides an insight into the relationship between the stiffness of GelMA hydrogel substrates and PC12 cell outgrowth, and helps the design and optimization of tissue engineering scaffolds for nerve regeneration.

On Maximizing the Throughput of Packet Transmission under Energy Constraints.

More and more Internet of Things (IoT) wireless devices have been providing ubiquitous services over the recent years. Since most of these devices are powered by batteries, a fundamental trade-off to be addressed is the depleted energy and the achieved data throughput in wireless data transmission. By exploiting the rate-adaptive capacities of wireless devices, most existing works on energy-efficient data transmission try to design rate-adaptive transmission policies to maximize the amount of transmitted data bits under the energy constraints of devices. Such solutions, however, cannot apply to scenarios where data packets have respective deadlines and only integrally transmitted data packets contribute. Thus, this paper introduces a notion of weighted throughput, which measures how much total value of data packets are successfully and integrally transmitted before their own deadlines. By designing efficient rate-adaptive transmission policies, this paper aims to make the best use of the energy and maximize the weighted throughput. What is more challenging but with practical significance, we consider the fading effect of wireless channels in both offline and online scenarios. In the offline scenario, we develop an optimal algorithm that computes the optimal solution in pseudo-polynomial time, which is the best possible solution as the problem undertaken is NP-hard. In the online scenario, we propose an efficient heuristic algorithm based on optimal properties derived for the optimal offline solution. Simulation results validate the efficiency of the proposed algorithm.

Vaccination with FasL-/TCL plus MHSP65 induces improved anti-lung cancer immunity in mice.

In a previous study, we constructed a MHSP65-TCL anti-lung cancer vaccine with Lewis lung carcinoma TCL plus MHSP65, and illustrated its anti-lung cancer effect through specific and nonspecific anti-tumor immunity. However, TCL contains some immunoinhibit components such as FasL. If this component can be eliminated from TCL, the anti-tumor immunity of MHSP65-TCL constructed with TCL should be improved. In the present study, we knocked down FasL from Lewis lung carcinoma cells and prepared MHSP65-(FasL-/TCL) with this cell line's TCL. After further investigation, MHSP65-(FasL-/TCL) exhibited a better ability to reduce splenocytes apoptosis, promote its activation and secretion of secretingTNF-ß, IL-2 compared with MHSP65-(FasL+/TCL). Accordingly, specific and nonspecific antitumor immunity induced by MHSP65-(FasL-/TCL) is stronger than that of MHSP65-(FasL+/TCL). In vivo, MHSP65-(FasL-/TCL) immunization can prolong survival of Lewis lung carcinoma bearing mice. Thus, we report that the anti-lung cancer effect of MHSP65-TCL can be improved by removal of FasL from the TCL. It provides a new route to construct MHSP65-TCL and other antitumor vaccines based on TCL.

Detection of RACK1 and CTNNBL1­induced activation of mouse splenocytes using an immunoprecipitation­based technique.

Tumor cell lysates (TCLs) have been reported to induce antitumor immunity; however, it remains unclear which elements serve a role in this process. The present study identified 768 proteins that were upregulated in TCL prepared from Lewis lung cancer cells compared with the lysate from type II alveolar epithelial cells. Among the proteins that were upregulated in TCL, receptor for activated C kinase 1 (RACK1) and catenin ß­like 1 (CTNNBL1) are closely associated with cell proliferation and the inhibition of apoptosis. To determine the role of these proteins in TCL, a protein extraction method was designed, which was based on immunoprecipitation. Using this method, RACK1 and CTNNBL1 were extracted, whereas the other proteins within the TCL were not affected. The modified TCL exhibited a stronger ability to induce splenocyte apoptosis, whereas the ability to promote cell activation was reduced. These findings suggested that the TCL depends on RACK1 and CTNNBL1 to activate mouse immunocytes, including monocytes and B lymphocytes, and inhibit apoptosis. Therefore, the present study may provide information regarding the composition of TCLs and their positive regulatory effect on immunocytes.

Tumor cell lysate induces the immunosuppression and apoptosis of mouse immunocytes.

Although tumor cell lysate (TCL) is a type of immunocyte stimulator, its immunosuppressive function must not be ignored. The present study reported that TCL prepared from a Lewis lung cancer cell was able to induce the development of immunosuppressive macrophages (MΦ) and tolerogenic dendritic cells. In addition, TCL upregulated the expression of CD69 in mouse splenocytes, and cell apoptosis and the percentage of regulatory T cells in mouse splenocytes simultaneously increased. Furthermore, the present study found that the immunosuppressive factor, hyaluronan, and the apoptosis inducers, Fas ligand and transforming growth factor-ß, are present in TCL. These components may be associated with the emergence of immunosuppressive cells or splenocyte apoptosis. Thus, the present study has enriched our understanding of the composition of TCL and its negative regulatory effect on immunocytes.

[Effect of MHSP65-TCL anti-melanoma vaccine on the activity of immunocytes].

OBJECTIVE: To evaluate the therapeutic effect of MHSP65-TCL on melanoma and its effect on the activity of the immunocytes. METHODS: MHSP65-TCL was prepared by mixing MHSP65 with TCL derived from B16 melanoma cell lysate by repeated freezing and thawing. The MHSP65-TCL vaccine was administered in mice bearing B16 melanoma, and the changes in melanoma growth was observed. To investigate the influence of TCL in MHSP65-TCL on the activity of the immunocytes, we co-cultured TCL and mouse spleen cells in vitro, and analyzed CD69 expression on the cells, cell apoptosis, and levels of IL-10 and IFN-γ in the cell culture supernatant. RESULTS: The MHSP65-TCL vaccine showed an anti-melanoma effect in the tumor-bearing mice. In the in vitro experiment, TCL in MHSP65-TCL strongly stimulated the activation of mouse spleen cells while causing apoptosis in some of the immunocytes and promoting cellular IL-10 secretion, but not IFN-γ. CONCLUSIONS: MHSP65-TCL derived from B16 melanoma cells has an anti-melanoma effect mediated by the activation of immunocytes. TCL in MHSP65-TCL also has immunosuppressive effect on immunocytes possibly due to the presence of suppressive components in TCL, and identifying and eliminating these components may potentially improve the anti-tumor actovoty of MSHP65-TCL vaccine.