The epidermal growth factor receptor (EGFR) is one of most potent oncogenes that are commonly altered in cancers. As a receptor tyrosine kinase, EGFR's kinase activity has been serving as the primary ...target for developing cancer therapeutics, namely the EGFR inhibitors including small molecules targeting its ATP binding pocket and monoclonal antibodies targeting its ligand binding domains. EGFR inhibitors have produced impressive therapeutic benefits to responsive types of cancers. However, acquired and innate resistances have precluded current anti-EGFR agents from offering sustainable benefits to initially responsive cancers and benefits to EGFR-positive cancers that are innately resistant. Recent years have witnessed a realization that EGFR possesses kinase-independent (KID) pro-survival functions in cancer cells. This new knowledge has offered a different angle of understanding of EGFR in cancer and opened a new avenue of targeting EGFR for cancer therapy. There are already many excellent reviews on the role of EGFR with a focus on its kinase-dependent functions and mechanisms of resistance to EGFR targeted therapies. The present opinion aims to initiate a fresh discussion about the function of EGFR in cancer cells by laying out some unanswered questions pertaining to EGFR in cancer cells, by rethinking the unmet therapeutic challenges from a view of EGFR's KID function, and by proposing novel approaches to target the KID functions of EGFR for cancer treatment.
To respond to the slogan of the national fitness movement, improve the quality of the national fitness movement, and provide scientific reference to public fitness, this paper studies the fitness ...method of Unity3D technology and somatosensory human-computer interaction virtual reality technology. Firstly, we build a somatosensory HCI virtual fitness system with Unity3D and Kinect technology, verify the data with an edge detection operator, get the simulation results of the somatosensory HCI virtual reality fitness system, and then get the fitness method based on the somatosensory HCI virtual reality technology according to the results. The data show that the fitness industry is seeing new highs as the national fitness membership reaches 75.13 million people as of December 2021, while the growth of women among them increases from 13.5 million in 2017 to 55.6 million in 2021. Among the 800 fitness methods, the physical therapy and rehabilitation category accounts for 1/3, and fitness, bodybuilding and health care each account for about 1/5. The comfort zone of fitness differs between men and women, ranging from 0.6-1.2 for men and 0.5-0.9 for women. The research in this paper can provide reasonable fitness advice to the fitness population and promote the healthy development of the fitness industry.
The existing geological disaster monitoring and early warning system has the problems of large monitoring errors and low accuracy. This paper designs a geological disaster monitoring and early ...warning system based on big data analysis. The geological disaster monitoring network module monitors the geological deformation and disaster inducing factors in real time through sensors and transmits them to the large-capacity data remote wireless transmission network module in the multi-dimensional heterogeneous monitoring data integration module through the Beidou satellite communication technology. This module uses a multi-sensor data fusion algorithm based on the D-S evidence theory and fuzzy mathematics to realize the integration of geological multi-dimensional heterogeneous monitoring data. Then, it uses cloud computing-based geological abnormal data mining method to mine abnormal geological information and transmit it to the early warning information release module. Geological disaster warning information will be released in the form of text messages and emails. Through verification, the system has high accuracy in monitoring and early warning of different types of geological disasters and provides a basis for timely and scientific deployment of geological disasters.
•We study the relationship between product quality improvement and remanufacturing.•We find that quality-induced manufacturing cost is the key driver of the results.•Remanufacturing may stifle or ...stimulate quality improvement of new products.•Environmentally neither result is exclusively beneficial or detrimental.
Remanufacturing as well as quality improving innovations are important activities to improve sustainability. However, when coexisting in one company, their interaction is not clear. On the one hand, past research found a positive impact of remanufacturing on product quality. On the other hand, remanufacturing was shown to be negatively affected by an industry’s technology trajectory of quality improvements.
Using a stylized model of endogenous product quality improvement and remanufacturing we find that the main driver of the contradicting results is the change in manufacturing costs caused by improving product quality. A strong increase in manufacturing costs due to product quality improvement may induce the firm to take up remanufacturing when introducing the new product. Conversely, a small impact of product quality improvement on manufacturing costs reverses this effect and may indeed lead the firm to cease remanufacturing when introducing the new product. We find that the latter outcome is never beneficial from an environmental point of view, while the former always is. With endogenous product quality improving innovation we then characterize conditions where a remanufacturing manufacturer would take a different product quality improvement decision than a non-remanufacturing manufacturer. We observe that remanufacturing stifles (stimulates) product quality improvement when manufacturing cost of quality improved products are low (high). Neither of the two results are exclusively beneficial or detrimental from an environmental perspective and we characterize the conditions under which product quality improvement is preferable.
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•Multifunctional lignin-based hybrid magnetic nanoparticles were synthesized.•The hybrid nanoparticles showed ultrafast adsorption capabilities for Pb2+ and Cu2+.•The abundant active ...sites from modified lignin enabled high efficiency of adsorption.•Adsorption was driven by ion exchange, hydrogen bonding and electrostatic attraction.
Heavy metals have raised an increasing number of pollution incidents and resulted in potent damages to aquatic ecosystems and human health. Thus, effective and efficient approaches to eliminate heavy metal ions are in urgent needs. Herein, novel hybrid nanoparticles have been prepared by a facile method using epichlorohydrin as a cross-linker between amino-functionalized magnetic nanoparticles and carboxymethylated lignin. Multiple characterization methods including XRD, FTIR, XPS, SEM, and TEM confirmed the formed nanostructures and the chemical features of the lignin-based hybrid nanoparticles. The as-synthesized hybrid nanoparticles exhibited high adsorption capacities of 150.33 and 70.69 mg/g for Pb2+ and Cu2+, respectively. More importantly, the adsorption equilibriums of Pb2+ and Cu2+ onto hybrid nanoparticles can be achieved within 30 s, which are among the fastest functional adsorbents for Pb2+ and Cu2+ removal as reported by now. The ultrafast adsorption is ascribed not only to the nanostructures, but also to the abundant active sites provided by the carboxymethylated lignin. The mechanism of removing Pb2+ and Cu2+ by hybrid nanoparticles could be mainly attributed to ion exchange and hydrogen bonding. The tailored nanostructured hybrid nanoparticles with exceptional adsorption effectiveness and efficiency are low-cost and eco-friendly, which potentially meets the cost-effective criteria for producing the water treatment adsorbents on a large scale.
Lead sorption capacity and mechanisms by sludge-derived biochar (SDBC) were investigated to determine if treatment of acid mine drainage (AMD) containing metals with SDBC is feasible. It was found ...that the biochar derived from pyrolysis treatment of sewage sludge could effectively remove Pb²⁺ from acidic solution with the capacities of 16.11, 20.11, 24.80, and 30.88mgg⁻¹ at initial pH 2, 3, 4 and 5, respectively. Lead sorption processes were pseudo-second order kinetic and faster at a higher pH. Furthermore, the relative contribution of both inorganic mineral composition and organic functional groups of SDBC for Pb²⁺ removal mechanisms, was quantitatively studied at pH 2–5. The results showed that Pb sorption primarily involved the coordination with organic hydroxyl and carboxyl functional groups, which was 38.2–42.3% of the total sorbed Pb varying with pH, as well as the coprecipitation or complex on mineral surfaces, which accounted for 57.7–61.8% and led to a bulk of Ca²⁺ and Mg²⁺ release during sorption process. A new precipitate was solely observed on Pb-loaded SDBC as 5PbO·P₂O₅·SiO₂(lead phosphate silicate) at initial pH 5, confirmed by XRD and SEM–EDX. The coordination of Pb²⁺ with carboxyl and hydroxyl functional groups was demonstrated by FT-IR, and the contribution of free carboxyl was significant, ranging from 26.1% to 35.5%. Results from this study may suggest that the application of SDBC is a feasible strategy for removing metal contaminants from acid solutions.
As a bellwether transportation mode, albeit with hot controversy, evacuated tube transport (ETT) can dramatically reduce air friction, and incorporating Maglev technology could also thoroughly ...eliminate wheel-rail friction. It is not difficult to imagine that incorporation of these two technologies could establish an innovative transportation system, with particular advantages in terms of high speed, safety, energy saving, and environmental protection. The integration of these two technologies has been a great challenge, however, due to the composite technology. To realize this revolutionary idea, we have successfully developed the first proof-of-principle prototype of a 45-m-long high-temperature superconducting Maglev evacuated tube transport (HTS Maglev-ETT) test system, called the "Super-Maglev," based on the passive self-stable HTS Maglev conceived in our group in 2000. The system mainly consists of three parts: an HTS Maglev-vehicle-guideway coupling system with 1-t load capability at a levitation gap of 10 mm, a 45-m-long racetrack-type evacuated tube with a 2-m-diameter circular cross section pumped by a hybrid air extraction system, and a 3-m linear induction motor to provide sectional propulsion. The system can achieve a pressure as low as 2.9 kPa in the tube. Experiments show that air drag on the vehicle is greatly reduced at that low air pressure, and a maximum speed of 50 km/h was recorded on the 6-m-diameter test guideway. Theoretically, the reduction of the aerodynamic consumed power could reach as high as to 90% under 10 kPa. This "Super-Maglev" strongly demonstrates the feasibility and potential merits of the HTS Maglev-ETT transportation concept.
•The sludge derived biochar is an excellent sorbent for Pb(II)/Cr(VI) ions.•400°C for 2h seems the optimal conditions for biochar pyrolysis.•A long-time pyrolysis reinforces the Pb(II)/Cr(VI) ...sorption bond on biochar.•Cr(VI) sorption is highly pH-dependent, and the optimal occurs at pH 2.•Reducing Cr(VI) to Cr(III) is the main sorption mechanism on biochar.
To optimize the pyrolysis process of municipal wastewater sludge for metal sorption, this study investigated the characteristics of the produced biochar under different heating conditions with particular interest in Pb(II) or Cr(VI) sorption. Results indicate that the biochar pyrolyzed at 400°C for 2h obtained the largest BET surface area and was rich of organic functional groups, owning the highest Pb(II) (at pH 5.0) and Cr(VI) (at pH 2.0) sorption capacity. The Pb sorption is dominated by the rate-limited chemical processes, and a longer residence during pyrolysis significantly reinforces its sorption bonds. The Cr(VI) sorption is highly pH-dependent, and the optimal occurs at pH 2, where the transformation of Cr(VI) to Cr(III) makes a significant contribution as confirmed by the XPS spectra. Similarly, a longer residence during pyrolysis also facilitates the Cr(VI) sorption in terms of capacity and affinity, likely due to the greater reducing potential of biochar.
Double-unit trains increase passenger capacity but also increase energy consumption. Therefore, research about the aerodynamic resistance of a double-unit train is of great importance to save energy. ...In this study, a commercial long-marshalling high-speed train and 8 kinds of double-unit trains are used to investigate the effect of the gap length on aerodynamic resistance. The results show that the aerodynamic resistance of the double-unit train is 8.5%-12.9% larger than that of the long-marshalling train. It is the tail car (CC1 car) of the first single-unit train and the head car (CC2 car) of the second single-unit train that lead to the difference in resistance. For the double-unit trains with different gap length, the resistance increases incrementally with the gap length, which is also mainly caused by the CC1 and CC2 cars. With increases to the gap length (starting from 0 mm), the resistance of the CC1 car increases with the cremental increases in the gap lengths. The resistance of the CC2 car also gradually increases when the gap lengths become larger. The resistance of the CC1 car with a gap length of 0 mm is slightly greater than that with 25 mm.
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