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The cantilever gearbox and the traditional gearbox have great difference in the structure and the force condition. The resonance mechanical analysis method of traditional gearbox could not get the accurate fatigue position of the gearbox. Taking a type of shearer cutting unit cantilever gearbox as the research object,the statics analysis and local resonance analysis are used to analyze the mechanical characteristics under the internal incentive and cutting load external excitation. The statics analysis takes into account the influence of the axial force,eccentricity and the torque generated by the gear meshing force on the force state of the case. Based on the shearer cutting test,the local resonance analysis is carried out,and the frequency domain characteristics of the vibration signals of several typical cases are obtained,and compared with the natural characteristics of the box. The results show that high stress and large deformation are caused by low frequency impact（ quasi static load） and local resonance. Neglecting one of these factors will lead to inaccurate analysis of box fatigue. The research result is in good agreement with the engineering practice.

The epidermal growth factor receptor (EGFR) is a validated therapeutic target for RAS/RAF wild-type colorectal cancer (CRC). However, monoclonal antibody-based anti-EGFR therapies such as cetuximab have limited effectiveness. Herein, it is identified that EGFR internalization is associated with poor treatment response and prognosis in patients with CRC, based on a retrospective analysis of patients treated with cetuximab. It is further demonstrated that the endocytosis inhibitor prochlorperazine (PCZ) can move EGFR, which is hidden inside the cell, to the cell surface to improve therapeutic antibody binding. Thus, a thermosensitive hydrogel co-loaded with cetuximab and PCZ (Gel@Cmab/PCZ) is constructed for sustained inhibition of endocytosis and effective cetuximab delivery. Peritumoral injection of Gel@Cmab/PCZ shows strong antitumor efficacy in subcutaneous and orthotopic CRC tumor models and completely abrogated liver metastasis when combined with chemotherapy. In a humanized patient-derived xenograft model, a single injection of Gel@Cmab/PCZ with one-third of the conventional cetuximab dose achieved 91% tumor growth inhibition, which promoted NK cell infiltration into tumor tissues and their antibody-dependent cell-mediated cytotoxicity effect. This study represents a novel strategy to boost the monoclonal antibody-mediated anti-tumor response in CRC., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

KRAS-TP53 co-mutation is strongly associated with poor prognosis and high malignancy in gastrointestinal cancers. Therefore, a novel approach to oncotherapy may lie in combination therapy targeting both KRAS and TP53 . Herein, we present a novel self-assembled nanoparticle (HA-TPP/A) that are functionalized nano-carrier hyaluronic acid (HA)-TPP conjugate (HA-TPP) to degrade mutant p53 proteins (mutp53) and co-deliver AMG510 for treating KRAS-TP53 co-alteration of gastrointestinal cancers by inhibiting the mutant KRAS and mutp53 signaling pathways. The HA-TPP/A nanoparticles led to ubiquitination-dependent proteasomal degradation of mutp53 by targeting damage to mitochondria. Furthermore, these nanoparticles abrogated the gain-of-function (GOF) phenotypes of mutp53 and increased sensitivity to AMG510-induced cell killing, thereby reducing cell proliferation and migration in gastrointestinal cancer with KRAS-TP53 co-mutation. The co-loaded HA-TPP/A nanoparticles demonstrated remarkable therapeutic efficacy in a tumor-bearing mouse model, particularly in KRAS-TP53 double mutant expressing cancer cells, compared with single drug and combined free drug groups. Notably, HA-TPP/A is the first reported nanoparticle with an ability to co-target KRAS-TP53 , providing a promising approach for therapy in highly malignant gastrointestinal tumors and potentially expanding clinical indications for AMG510 targeted therapies in gastrointestinal tumors., Competing Interests: All authors declared no competing interests., (© 2023 The Authors.)

Lipids play an important physiological role in living system. They are the major components of cellular membranes, in addition to participating in energy storage as well as signal recognition and transmission. In recent years, an increasing number of studies have shown that disturbances in lipid metabolism are closely related to the development of some diseases. Lipid analysis is of great significance for understanding the mechanism and the process of diseases. Because of the matrix interference and low concentration of analytes, existing techniques require sample preparation steps to ensure good analytical performance. In the present study, sample preparation methods in lipidomics used in various fields are reviewed, including lipid extraction methods, such as liquid-liquid extraction and solid phase extraction, as well as the chemical derivatization techniques for different lipid categories. In addition, the development of the sample preparation in lipidomics is also prospected.