Rational Design of a Two-Photon Fluorescent Probe for Human Cytochrome P450 3A and the Visualization of Mechanism-Based Inactivation

Mechanism-based inactivation (MBI) can mediate adverse reactions and hepatotoxicity from drugs, which is a result of their conversion into highly reactive metabolites catalyzed by enzymes such as cytochrome P450 3A (CYP3A). In the present research, we optimized the key interaction domain of the fluorophore with the target protein to develop a two-photon fluorescent probe for CYP3A that is involved in the metabolism of more than half of all clinical drugs. The developed BN-1 probe exhibited appropriate selectivity and sensitivity for the semi-quantitative detection and imaging of endogenous CYP3A activity in various living systems, thereby providing a high-throughput screening system enabling evaluation of MBI-associated hepatotoxicity by CYP3A. Using BN-1 as a fluorescent molecular tool facilitates the efficient discovery and characterization of CYP3A-induced MBI in natural systems.</p

Molecular Design Strategy to Construct the Near-Infrared Fluorescent Probe for Selectively Sensing Human Cytochrome P450 2J2

Cytochrome P450 2J2 (CYP2J2), a key enzyme responsible for oxidative metabolism of various xenobiotics and endogenous compounds, participates in a diverse array of physiological and pathological processes in humans. Its biological role in tumorigenesis and cancer diagnosis remains poorly understood, owing to the lack of molecular tools suitable for real-time monitoring CYP2J2 in complex biological systems. Using molecular design principles, we were able to modify the distance between the catalytic unit and metabolic recognition moiety, allowing us to develop a CYP2J2 selective fluorescent probe using a near-infrared fluorophore (E)-2-(2-(6-hydroxy-2, 3-dihydro-1H-xanthen-4-yl)­vinyl)-3,3-dimethyl-1-propyl-3H-indol-1-ium iodide (HXPI). To improve the reactivity and isoform specificity, a self-immolative linker was introduced to the HXPI derivatives in order to better fit the narrow substrate channel of CYP2J2, the modification effectively shortened the spatial distance between the metabolic moiety (O-alkyl group) and catalytic center of CYP2J2. After screening a panel of O-alkylated HXPI derivatives, BnXPI displayed the best combination of specificity, sensitivity and applicability for detecting CYP2J2 in vitro and in vivo. Upon O-demethylation by CYP2J2, a self-immolative reaction occurred spontaneously via 1,6-elimination of p-hydroxybenzyl resulting in the release of HXPI. Allowing BnXPI to be successfully used to monitor CYP2J2 activity in real-time for various living systems including cells, tumor tissues, and tumor-bearing animals. In summary, our practical strategy could help the development of a highly specific and broadly applicable tool for monitoring CYP2J2, which offers great promise for exploring the biological functions of CYP2J2 in tumorigenesis

Status and development trend of mine positioning technology

Common mine positioning technologies were analyzed from aspects of positioning methods and wireless communication technologies, and application of the mine positioning technologies in personnel positioning system and equipment proximity detection were described. It was pointed out that future mine positioning system or equipment would comprehensively utilize technologies such as wireless ultrahigh frequency ranging, inertial navigation, multi-source hybrid positioning and multi-source information fusion to form a positioning service system oriented service, so as to realize accurate positioning of underground personnel and equipment, proximity detection of large mobile device and personnel, and autonomous navigation and positioning of mining equipment and underground rescue personnel (robot)

Application analysis of LoRa technology in mine wireless communicatio

For status that existing mine wireless communication systems had poor application effect in areas with severe environment and low-speed requirement of data transmission such as top corner, a scheme of applying LoRa technology in mine wireless communication was proposed through analyzing its technical characteristics. Application architecture of LoRa technology in coal mine was analyzed, and application situations were discussed. LoRa technology can wirelessly transmit equipment operation status data and environmental parameters in working face, multi-sensor data in mine pressure monitoring system, gas sensor data in top corner of working face, temperature sensor data in goaf, monitoring data of mine-used electromechanical equipment, etc

Analysis of 5G private network technology and coal mine 5G private network scheme

Most of the existing communication networks except 5G exist in the form of independent private networks. The performance of 5G wireless communication in bandwidth, delay, number of terminal connections, and reliability has been greatly improved. Accordingly, there are new changes in network architecture and networking mode. The private network scheme is no longer a single independent private network scheme. There are also hybrid private networks and virtual private networks. This paper introduces the key technologies of 5G private network, such as network slicing, mobile edge computing, 5G LAN, time-sensitive network and so on. This paper proposes three kinds of 5G private network schemes, namely virtual private network, hybrid private network and independent private network. The virtual private network has the characteristics of wide service scope, high flexibility, low cost, and short construction cycle. It is used for various applications which have wide coverage, have access terminals not fixed in time and space, and have certain service quality requirements and certain degree of data isolation requirements. The hybrid private network has short transmission path, high security, and low end-to-end delay. It can carry out a variety of flexible independent services, but privacy is weak. The independent private network provides a physical exclusive 5G private network to meet the needs of industrial users for high bandwidth, low delay, high security and high-reliability data transmission. This paper puts forward the general principles of 5G private network scheme selection in terms of safety, availability and reliability. This paper also proposes the special requirements of 5G private network in coal mine in terms of dispatching function, integration demand, independent operation and maintenance and intrinsic safety. The selection of 5G special network scheme for coal mine is proposed. In the early stage of intelligent construction of coal mine or there is no strict requirements on data confidentiality, system use convenience, system function expansion in the coal mine, the virtual private network or hybrid private network scheme can be selected. Otherwise, the independent private network scheme can be selected. It is pointed out that relatively more hybrid private network and virtual private network schemes are adopeted in coal mines at present. The hybrid private network and virtual private network will have some advantages in the future. With the gradual establishment of small core network ecology, the independent private network scheme will be recognized by more users. In a certain period in the future, the independent private network, virtual private network and hybrid private network schemes will give full play to their respective advantages. They serve the intelligent construction of coal mines in different periods and with different requirements

Current situation and development trend of mine wireless communication system

The mine wireless communication system has the advantages of wide communication coverage, convenient connection, good mobility, easy to establish, simple setup and maintenance, etc. It plays an irreplaceable role in in the construction of mine intelligence. The whole mine wireless communication system mainly include WiFi(IEEE 802.11b/g/n/ac), 3G, 4G, 5G and WiFi6(IEEE 802.11ax) system. 3G system is gradually replaced. 4G and WiFi system are gradually reduced. 5G and WiFi6 system are at the initial stage, and will gradually become the mainstream. The 4G, 5G and WiFi/WiFi6 systems are analyzed from the aspects of technical points, main functions and applications. And the advantages and disadvantages of each system are pointed out in this paper. ① The main disadvantage of the mine 4G wireless communication system is that the bandwidth and real-time indicators cannot meet the needs of application scenarios such as high-definition intelligent video and remote control. ② The problems of 5G in practical use are listed as following points. In the case of multiple systems and multiple antennas, there is a security problem of wireless transmission signals. 5G base stations are mainly explosion-proof and intrinsically safe types, which are large in quality and volume. There are problems of inconvenient to use and limited in use. 5G terminal ecology is lacked. The communication modules are expensive and power consumption is high. It does not have the conditions for large-scale industrial applications. There are few practical application cases, and the application scenarios need to be further explored. ③ WiFi6 wireless communication system has high latency, relatively low mobility and reliability. The mobile phone terminal is not mature enough, which affects the quality of voice calls. Based on the above analysis, it is pointed out that the demand of intelligent mine for wireless communication system is the demand of large bandwidth, low latency, high reliability, multi-access, multi-system, multi-interface, and position information. Finally, this study points out the development trend of mine wireless communication system. The trend includes system fusion (wireless communication and wired communication fusion, wireless communication internal fusion, wireless communication system and other system fusion). It also includes communication and positioning integration, equipment intrinsic safety, terminal module low power consumption and protocol interface standardization

Design and application of mine integration dispatching communication system

In view of problem that most mine communication systems scattered, and could not cross the others for scheduling command, a mine integration dispatching communication system was designed, and composition and functions of the system were introduced. The practical application results show that the system can be compatible with existing coal mine communication system, provide efficient business platform and bridge to leapfrog communication among each system, and effectively improve mine emergency scheduling disposal ability and management level of coal mine safety production

Application research of LTE communication technology in coal mine

Status of current coal mine wireless communication systems and application requirements of wireless communication system for mine informatization and intelligentization were analyzed, advantages of LTE communication technology was introduced, network structure design of mine-used LTE wireless communication system was proposed and application prospect of the LTE communication technology in coal mine was prospected

Force Tracking Control of Functional Electrical Stimulation via Hybrid Active Disturbance Rejection Control

Stroke is a worldwide disease with a high incidence rate. After surviving a stroke, most patients are left with impaired upper or lower limb. Muscle force training is vital for stroke patients to recover limb function and improve their quality of life. This paper proposes a force tracking control method for upper limb based on functional electrical stimulation (FES), which is a promising rehabilitation approach. A modified Hammerstein model is proposed to describe the nonlinear dynamics of biceps brachii, which consists of a nonlinear mapping function, linear dynamics and time delay component to represent the biochemical process of muscle contraction. A quick model identification method is presented based on the least square algorithm. To deal with the variation of muscle dynamics, a hybrid active disturbance rejection control (ADRC) is proposed to estimate and compensate for the model uncertainty and unmeasured disturbances. The parameter tuning process is given. In the end, the performance of the proposed methods is verified via simulations and experiments. Compared with the Proportional integral derivative controller (PID) method, the proposed methods could suppress the model uncertainty and improve the tracking precision

Force Tracking Control of Functional Electrical Stimulation via Hybrid Active Disturbance Rejection Control

Stroke is a worldwide disease with a high incidence rate. After surviving a stroke, most patients are left with impaired upper or lower limb. Muscle force training is vital for stroke patients to recover limb function and improve their quality of life. This paper proposes a force tracking control method for upper limb based on functional electrical stimulation (FES), which is a promising rehabilitation approach. A modified Hammerstein model is proposed to describe the nonlinear dynamics of biceps brachii, which consists of a nonlinear mapping function, linear dynamics and time delay component to represent the biochemical process of muscle contraction. A quick model identification method is presented based on the least square algorithm. To deal with the variation of muscle dynamics, a hybrid active disturbance rejection control (ADRC) is proposed to estimate and compensate for the model uncertainty and unmeasured disturbances. The parameter tuning process is given. In the end, the performance of the proposed methods is verified via simulations and experiments. Compared with the Proportional integral derivative controller (PID) method, the proposed methods could suppress the model uncertainty and improve the tracking precision