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Covalent inhibitors have been a rapidly growing field in drug discovery due to their therapeutic potential and unique advantages in cancer therapy. As opposed to noncovalent inhibitory drugs, covalent inhibitors reversibly or irreversibly modify proximal nucleophilic amino acid residues on proteins, aiming to selectively recognize and bind to protein targets and addressing some of the challenges faced by noncovalent drugs. Most successful targeted covalent inhibitors depend primarily on binding‐site cysteine residues, but this has limitations for certain protein targets that lack targetable cysteine residues. Recently, the rational design of covalent inhibitors or covalent probes targeting other nucleophilic residues, such as lysine, tyrosine, serine, has turned out to be another promising strategy for cancer therapy. Thus, the development of novel strategies to extend the scope of covalent binding and improve the binding properties is required. This review gives a summary of the development of covalent inhibitors targeting noncysteine from different aspects, including target identification, structure–activity relationships, drug discovery strategies, and binding properties, in the hope of providing a scientific reference for future covalent drug discovery as a means of expanding research in cancer therapy. The noncysteine covalent inhibitors are a class of small molecule inhibitors that can bind irreversibly to their target enzymes through covalent bonding with noncysteine residues. They have shown promise as potential therapeutics for a variety of diseases, including cancer, infectious diseases, and autoimmune disorders. Examples of noncysteine covalent inhibitors. The illustration emphasizes the representative noncysteine covalent inhibitors in drug discovery and development.

Under ultra-high-pressure full-ocean-depth conditions, the rolling bearings of seawater pumps are often subjected to coupled stress conditions, including high external pressure, oil–water emulsification, and sustained high loads. Early failure tends to occur, which severely compromises system stability and reliability. This study focuses on identifying the typical failure mechanisms of bearings and proposing key optimization measures. A high-pressure experimental system rated at 120 MPa was constructed. Long-term water injection and drainage cycling tests were performed, followed by teardown inspections of failed prototypes. The bearing degradation was found to involve multiple failure modes, including rolling element fracture, cage breakage, lubricant emulsification, and three-dimensional embedded abrasive wear. The combined effects of lubricant degradation and particulate contamination primarily caused these failures. Comparative tests were conducted on ceramic bearings, PEEK bearings, and tapered roller bearings. The results confirmed that the tapered roller bearing exhibited superior environmental adaptability under lubrication with No. 10 aviation hydraulic oil. To enhance system performance, two engineering measures were proposed: (1) the use of heavy-duty tapered roller bearings to increase load capacity and fatigue life; (2) the addition of molybdenum disulfide (MoS₂) anti-wear additives to the lubricant to improve lubrication stability and wear resistance. Validation results showed that, after optimization, the prototype achieved significantly higher mechanical efficiency under 120 MPa conditions, and bearing wear was substantially reduced. These findings provide theoretical support and engineering guidance for selecting bearings and developing lubrication strategies in high-pressure, deep-sea hydraulic systems.

With the rapid development of material science and manufacturing capabilities, hydraulic technology is increasingly high-pressure, lightweight and miniaturizing. Micro plunger pump is widely used in the field of deep-sea hydraulic equipment and advanced intelligent hydraulic equipment, owing to its high-power density, high output pressure and many other advantages. Its broad application aims to examine the inlet and outlet distribution valve spring parameters change on the micro high-pressure plunger pump volumetric efficiency, by changing the inlet and outlet distribution valve. This paper is based on the simulation of AMESim engineering software to derive multiple sets of data. It compared and analysed the specific effect of different spring stiffness and opening pressure on the volumetric efficiency of the micro high-pressure plunger pump which was then verified through experiment. Results of this study have certain reference significance for the design of the spring of the inlet and outlet distribution valve of the micro high-pressure plunger pump, which facilitates the optimization and improvement of the dynamic performance of the micro high-pressure plunger pump.

Hydraulic water plunger pumps have come to be widely used in coal mining, seawater desalination, and oil exploitation due to their high output pressure and large flow characteristics. In a high-pressure large-flow plunger pump, the leakage of the annular channel of the plunger pair is an essential factor affecting volume efficiency. The axial pressure gradient exists in the fluid inside the annular channel, resulting in the plunger and plunger sleeve forming similar funnel-like shapes. Moreover, the characteristics of large diameter, high working pressure, and low fluid viscosity of the plunger pump will lead to the complicated flow of the annular channel. The influence of eccentricity and structural deformation on leakage is difficult to evaluate. Therefore, considering the deformation gradient and eccentricity of the plunger pair and the compressibility of the water, the deformation equations and leakage equations of the annular channel under the laminar and turbulent flow state are derived in this study. The eccentricity and leakage of the annular channel under different pressure conditions are measured using a built sealing test bench. It is proved that the discrepancy between the calculated model and the experimental results is less than 6% under different pressures, which effectively predicts the sealing performance of plunger pumps. The results show that under the laminar flow condition, the effects of eccentricity, structural deformation, and medium compressibility on leakage are 148%, 4.92%, and 0.92%, respectively. In turbulent conditions, they were 31%, 2.84%, and 1.19%, respectively. Besides, the reasonable material pairing of the plunger friction pair can reduce the variation of leakage due to structural deformation.

With the enhancement of environmental protection awareness of the international community and the continuous promotion of green and sustainable development of manufacturing industry, water lubrication instead of mineral oil has become the future development trend due to its green, pollution-free, clean, safe, and sustainable advantages especially in ships, marine, coal mining, and other fields. In recent years, with the rapid development of water lubrication research, significant progress has been made in related research knowledge domain and discipline. A systematic and extensive assessment of water lubrication research has become increasingly important. The objective of this research is to reveal the research status, research hotspots, and development trends in the field of water lubrication. Therefore, CiteSpace was used to conduct a systematic bibliometric and scientometrical analysis of 1,792 publications from Web of Science core collection database (1997–2021). The results show that China and USA are the most productive countries in the field of water lubrication and have made outstanding contributions. Through the analysis of hot key words and co-citation references, this paper reviews the research status of water lubrication in three aspects: (1) lubricating medium modification; (2) material preparation; (3) surface optimization. It has become a research hotspot to promote the superlubricity contact interface and the application of nanotechnology. The results of this study can make a significant contribution to the development of water lubrication by providing a comprehensive understanding of the research status and research hotspots in this field. Personal understanding and discussion of research hotspots and research status are expected to provide insights into future research trends. In addition, this study will provide valuable references and guidelines for researchers who are interested in this field.

With the advancement of deep-sea exploration, the demand for underwater manipulators capable of long-duration heavy-duty operations has intensified. Water-hydraulic systems exhibit less viscosity variation with increasing depth than oil-based systems, offering better adaptability to deep-sea conditions. Using seawater as the driving medium inherently eliminates issues such as oil contamination by water, frequent maintenance limiting underwater operation time, and environmental pollution caused by oil leaks. This paper introduces a deep-sea manipulator directly driven by seawater from the deep-sea environment. To address the challenges of weak lubrication and high corrosion associated with water hydraulics, a reciprocating plunger seal was adopted, and a water-hydraulic actuator was developed. The installation positions of actuator hinges and maximum output force requirements were optimized using particle swarm optimization (PSO), effectively reducing the manipulator’s self-weight. Through kinematic and inverse kinematic analyses and joint performance tests, a six-degree-of-freedom water-hydraulic manipulator was designed with a maximum reach of 2.5 m, a lifting capacity of 5000 N, and end-effector positioning accuracy within 18 mm.

Water hydraulic technology is a potential application to deep-sea manipulators and their proportional valves. In the ocean, water is a better choice as the working medium than mineral oil because of its environmentally friendly advantages. However, no water hydraulic proportional valve for deep sea exists yet. In this study, a novel water hydraulic rotary proportional valve with a four-way, three-position principle and a plane sealing method for the environment-friendly manipulator is invented. The static and dynamic performance of the proportional valve is studied using a mathematical model and experiments. A valve-control swing cylinder system, which simulates the working state of the manipulator, is also facilitated in a deep-sea simulation device for simulating a depth of 6500 m in the ocean. Results show that the numerical and experimental data match well. The proportional valve can achieve zero leakage, and the dead zone is approximately 10%. The bandwidths are 30 and 6 Hz when the input signal amplitude is 5% and 100% of the valve's full stroke, respectively. The proportional valve can accurately control the swing cylinder on the manipulator's elbow joint with a rotation angle error of ±0.1°. The rotary proportional valve has excellent application to deep-sea manipulators.

In ocean exploration, underwater hydraulic manipulators (UHMs) driven by water hydraulics may become favored over oil-based systems because of their eco-friendliness and ability for continuous operation. A water hydraulic high-speed on/off valve (WHSV), with good sealing and fast response, may be used as a core control component of UHM. The comprehensive performance of the WHSV needs to be improved to enhance the accuracy, continuity, and reliability of UHM. In this study, the relationship between the negative voltage and the WHSV characteristics, including dynamic performance, power losses, and impact performance, is studied by finite element simulation. Furthermore, a multi-objective optimization method is proposed to improve the comprehensive performance of the WHSV. This method integrates the optimal Latin hypercube sampling method, universal Kriging surrogate model, non-dominated sorting genetic algorithm II, and Technique for Order Preference by Similarity to Ideal Solution methods to optimize the equivalent amplitude and duration of the negative voltage. Our findings reveal that the closing time decreases with the increase in the equivalent amplitude and duration of the negative voltage, while the opposite is observed in the power losses and maximum impact equivalent stress of the valve seat. Optimization results show a slight 3.3% increase in closing time of the WHSV but significant reductions in total power loss (9.8%), maximum impact equivalent stress (14.5%), and maximum total deformation (19.8%). This study provides a practical optimization approach for enhancing the comprehensive performance of the WHSV for improved UHM operation.

Balance valve is a core component of the 11000-meter manned submersible “struggle,” and its sealing performance is crucial and challenging when the maximum pressure difference is 118 MPa. The increasing sealing force improves the sealing performance and increases the system’s energy consumption at the same time. A hybrid analytical–numerical–experimental (ANE) model is proposed to obtain the minimum sealing force, ensuring no leakage at the valve port and reducing energy consumption as much as possible. The effects of roundness error, environmental pressure, and materials on the minimum sealing force are considered in the ANE model. The basic form of minimum sealing force equations is established, and the remaining unknown coefficients of the equations are obtained by the finite element method (FEM). The accuracy of the equation is evaluated by comparing the independent FEM data to the equation data. Results of the comparison show good agreement, and the difference between the independent FEM data and equation data is within 3% when the environmental pressure is 0–118 MPa. Finally, the minimum sealing force equation is applied in a balance valve to be experimented using a deep-sea simulation device. The balance valve designed through the minimum sealing force equation is leak-free in the experiment. Thus, the minimum sealing force equation is suitable for the ultrahigh pressure balance valve and has guiding significance for evaluating the sealing performance of ultrahigh pressure balance valves.