Antibody-drug conjugates in gastric cancer: from molecular landscape to clinical strategies.

Antibody-drug conjugates (ADCs) represent a crucial component of targeted therapies in gastric cancer, potentially altering traditional treatment paradigms. Many ADCs have entered rigorous clinical trials based on biological theories and preclinical experiments. Modality trials have also been conducted in combination with monoclonal antibody therapies, chemotherapies, immunotherapies, and other treatments to enhance the efficacy of drug coordination effects. However, ADCs exhibit limitations in treating gastric cancer, including resistance triggered by their structure or other factors. Ongoing intensive researches and preclinical experiments are yielding improvements, while enhancements in drug development processes and concomitant diagnostics during the therapeutic period actively boost ADC efficacy. The optimal treatment strategy for gastric cancer patients is continually evolving. This review summarizes the clinical progress of ADCs in treating gastric cancer, analyzes the mechanisms of ADC combination therapies, discusses resistance patterns, and offers a promising outlook for future applications in ADC drug development and companion diagnostics.

Methylation synthetic lethality: Exploiting selective drug targets for cancer therapy.

In cancer, synthetic lethality refers to the drug-induced inactivation of one gene and the inhibition of another in cancer cells by a drug, resulting in the death of only cancer cells; however, this effect is not present in normal cells, leading to targeted killing of cancer cells. Recent intensive epigenetic research has revealed that aberrant epigenetic changes are more frequently observed than gene mutations in certain cancers. Recently, numerous studies have reported various methylation synthetic lethal combinations involving DNA damage repair genes, metabolic pathway genes, and paralogs with significant results in cellular models, some of which have already entered clinical trials with promising results. This review systematically introduces the advantages of methylation synthetic lethality and describes the lethal mechanisms of methylation synthetic lethal combinations that have recently demonstrated success in cellular models. Furthermore, we discuss the future opportunities and challenges of methylation synthetic lethality in targeted anticancer therapies.

PCLLA-nanoHA Bone Substitute Promotes M2 Macrophage Polarization and Improves Alveolar Bone Repair in Diabetic Environments.

The utilization of bioresorbable synthetic bone substitutes with immunomodulatory properties has gained significant attention in dental clinical applications for the absorption of alveolar bone induced by orthodontic treatment. In this study, we developed two distinct materials: a conventional hydroxyapatite (HA) bone powder comprised of hydroxyapatite particles and nanoHA embedded within a poly(caprolactone-co-lactide) (PCLLA) elastomeric matrix. We assessed the physicochemical characteristics of the bone substitute, specifically focusing on its composition and the controlled release of ions. Our findings show that PCLLA-nanoHA has deformable properties under 40 N, and a significant release of Ca and P elements was noted after 7 days in aqueous settings. Moreover, at the protein and gene expression levels, PCLLA-nanoHA enhances the capacity of macrophages to polarize towards an M2 phenotype in vitro. In vivo, PCLLA-nanoHA exhibits comparable effects to standard HA bone powder in terms of promoting alveolar bone regeneration. Extensive investigations reveal that PCLLA-nanoHA surpasses the commonly employed HA bone powder in stimulating bone tissue repair in diabetic mice. We have identified that PCLLA-nanoHA regulates macrophage M2 polarization by activating the PI3K/AKT and peroxisome proliferator-activated receptor gamma (PPAR) signaling pathways, thereby facilitating a favorable local immune microenvironment conducive to bone repair and regeneration. Our findings suggest that PCLLA-nanoHA presents itself as a promising bioresorbable bone substitute with properties that promote macrophage M2 polarization, particularly in the context of regulating the local microenvironment of alveolar bone in diabetic mice, potentially facilitating bone tissue regeneration.

Gas-Liquid Mass Transfer Behavior of Upstream Pumping Mechanical Face Seals.

For gas-liquid medium isolation seals in aero-engines, the upstream pumping function of directional grooves provides an effective way to realize the design of longer service life and lower leakage rate. However, this produces a new problem for gas-liquid mass transfer in the sealing clearance. This study establishes an analytical model to investigate the gas-liquid mass transfer behavior and the change rule for the opening force of mechanical face seals with elliptical grooves. Compared with traditional studies, this model considers not only the gas-liquid transfer but also the cavitation effect. The results obtained show that with the increase of rotational speed, the gas medium transferred from the inner low-pressure side to the outer high-pressure side. In addition, the leakage rate of the liquid medium from the outer high-pressure side to the inner low-pressure side increased with the growth of sealing clearance, rotational speed and seal pressure. The upstream pumping effect of the gas medium with elliptical grooves not only led to a state of gas-liquid mixed lubrication in the sealing surfaces, but also significantly increased the opening capacity of the seal face. This research may provide a reasonable basis for the design of upstream pumping mechanical face seals.

The Role of Autophagy in Lamellar Body Formation and Surfactant Production in Type 2 Alveolar Epithelial Cells.

The lamellar body (LB), a concentric structure loaded with surfactant proteins and phospholipids, is an organelle specific to type 2 alveolar epithelial cells (AT2). However, the origin of LBs has not been fully elucidated. We have previously reported that autophagy regulates Weibel-Palade bodies (WPBs) formation, and here we demonstrated that autophagy is involved in LB maturation, another lysosome-related organelle. We found that during development, LBs were transformed from autophagic vacuoles containing cytoplasmic contents such as glycogen. Fusion between LBs and autophagosomes was observed in wild-type neonate mice. Moreover, the markers of autophagic activity, microtubule-associated protein 1 light chain 3B (LC3B), largely co-localized on the limiting membrane of the LB. Both autophagy-related gene 7 (Atg7) global knockout and conditional Atg7 knockdown in AT2 cells in mice led to defects in LB maturation and surfactant protein B production. Additionally, changes in autophagic activity altered LB formation and surfactant protein B production. Taken together, these results suggest that autophagy plays a critical role in the regulation of LB formation during development and the maintenance of LB homeostasis during adulthood.

Flexural and fatigue properties of polyester disk material for milled resin clasps.

To evaluate the flexural and fatigue properties of a polyester disk material used in milled resin clasps of removable partial dentures, experimental polyester disk (mPE), injection-molded polyester (iPE), and polymethyl methacrylate disk (mPMMA) were examined by three-point bending tests and cyclic fatigue tests at 0.75 or 1.50 mm deflection. The mPE exhibited significantly higher flexural strength than the iPE (p<0.05). Meanwhile, the mPMMA displayed higher flexural modulus and strength than the polyesters. The mPE exhibited a significantly lower residual strain than the iPE at the cyclic 0.75 mm deflection (p<0.05); however, microcracks were observed in the mPE at the 1.50 mm deflection. The mPMMA showed a high residual strain at the 0.75 mm deflection and fractured within 1,000 cycles at the 1.5 mm deflection. The higher flexural strength and lower residual strain of the mPE compared with the iPE suggest the advantages of milled resin clasps within a limited deflection.

Bronchiolar Adenoma Transforming to Invasive Mucinous Adenocarcinoma: A Case Report.

Bronchiolar adenoma (BA) is recognized as a neoplasm with benign clinical course. Histologically, BA is characterized by nodular proliferation of the bilayered bronchiolar-type epithelium, including multipartite epithelial cells and a continuous layer of basal cells. Recent reports have revealed the frequent presence of driver gene mutations in BA, suggesting its neoplastic nature. However, it is still debatable whether BA has malignant potential. Herein, we report the first case of BA harboring the same KRAS mutation with the adjacent invasive mucinous adenocarcinoma (IMA). Additionally, the loss of continuity of the basal cell layer in the junctional zone between BA and IMA indicated a malignant transformation from BA to IMA in this particular case.

Lateral movement and angular illuminating non-uniformity corrected TSOM image using Fourier transform.

Through-focus scanning optical microscopy (TSOM) is a high-efficient, low-costed, and nondestructive model-based optical nanoscale method with the capability of measuring semiconductor targets from nanometer to micrometer level. However, some instability issues resulted from lateral movement of the target and angular illuminating non-uniformity during the collection of through-focus (TF) images restrict TSOM's potential applications so that considerable efforts are needed to align optical elements before the collection and correct the experimental TSOM image before differentiating the experimental TSOM image from simulated TSOM image. An improved corrected TSOM method using Fourier transform is herein presented in this paper. First, a series of experimental TF images are collected through scanning the objective of the optical microscopy, and the ideally simulated TF images are obtained by a full-vector formulation. Then, each experimental image is aligned to its corresponding simulated counterpart before constructing the TSOM image. Based on the analysis of precision and repeatability, this method demonstrates its capability to improve the performance of TSOM, and the promising possibilities in application of online and in-machine measurements.

Machine-learning models for analyzing TSOM images of nanostructures.

Through-focus scanning optical microscopy (TSOM) is an economical and nondestructive method for measuring three-dimensional nanostructures. After obtaining a TSOM image, a library-matching method is typically used to interpret optical intensity information and determine the dimensions of a measurement target. To further improve dimensional measurement accuracy, this paper proposes a machine learning method that extracts texture information from TSOM images. The method extracts feature vectors of TSOM images in terms of the Gray-level Co-occurrence Matrix (GLCM), Local Binary Pattern (LBP), and Histogram of Oriented Gradient (HOG). We tested models trained with these vectors in isolation, in pairs, and a combination of all three to test seven possible feature vectors. Once normalized, these feature vectors were then used to train and test three machine-learning regression models: random forest, GBDT, and AdaBoost. Compared with the results of the library-matching method, the measurement accuracy of the machine learning method is considerably higher. When detecting dimensional features that fall into a wide range of sizes, the AdaBoost model used with the combined LBP and HOG feature vectors performs better than the others. For detecting dimensional features within a narrower range of sizes, the AdaBoost model combined with HOG feature extraction algorithm performs better.