Changzhi Medical College

Human epidermal growth factor receptor 2 (HER2) is a critical biomarker and therapeutic target in gastric/gastroesophageal junction (G/GEJ) cancers, despite the initial success of HER2-targeted therapies, such as trastuzumab, resistance to these drugs has emerged as a major impediment to effective long-term treatment. This review examines the mechanisms of drug resistance in HER2-positive G/GEJ cancer, the primary mechanisms of resistance explored include alterations in the HER2 receptor itself, such as mutations and changes in expression levels, as well as downstream signaling pathways, and interactions with the tumor microenvironment (TME). Furthermore, the review discusses the Novel therapeutic approaches, including the use of antibody-drug conjugates (ADCs) and combination therapies are assessed for their potential to enhance outcomes. By integrating recent research findings and clinical trials, this review aims to provide oncologists and researchers with insights into developing more effective treatments for patients with drug-resistant HER2-positive G/GEJ cancer.

Sensitive and accurate detection and imaging of different microRNAs (miRNAs) in cancer cells hold great promise for early disease diagnosis. Herein, a DNA tetrahedral scaffold (DTS)-corbelled autonomous-motion (AM) molecular machine based fluorescent sensing platform was designed for simultaneous detection of two types of miRNAs (miRNA-21 and miRNA-155) in HeLa cells. Locking-strand-silenced DNAzymes (P:L duplex) were firstly grafted at the loop of target-analogue-embedded double-stem hairpin substrates (TDHS) of DTS, making the sensor in a "signal off" state due to the closely distance between modified fluorophores (FAM and Cy5) with the corresponding quenchers (BHQ1 and BHQ2). The detection of miRNA-21 and miRNA-155 was mainly based on the activation of locking-strand-silenced DNAzymes, cleaving hairpin DNA into single-strand DNA segments, accompanying with the release of modified fluorophores and the signal recovery (signal on). Upon the cyclical stimulation of miRNA targets in such AM molecular machine, sensitive detection of miRNA-21 and miRNA-155 was realized in this self-feedback circuit (SFC) with the detection limit down to 38.8 aM and 27.1 aM, respectively. Moreover, the analytical performance was greatly improved for miRNAs imaging in cancer cells with enhanced tumor cell recognition ability, excellent stability in virtue of DTS, indicating a potential analytical tool in early cancer diseases diagnosis.

Memory is the ability to acquire and store information following an experience, which can be retrieved by related context exposure. Pioneering studies have demonstrated that sparsely distributed neuronal ensembles or engram cells can serve as neural substrates for storing and recalling memory traces. Many studies of neuronal ensembles have focused on the hippocampus, and increasing evidence has indicated that the neuronal oscillation is closely associated with hippocampal memory functions, including both encoding and retrieval processes. In particular, the theta synchronization of hippocampal ensembles with other brain regions mediates the retrieval of multiple types of memory. The recent progress of theta oscillations in the formation of memory engrams is reviewed, as well as the increased theta power and neurotransmitter regulation on memory function. Detailed information based on an analysis of hippocampal local theta rhythms is presented. Moreover, the hippocampus theta synchronization with the sensory cortex, prefrontal cortex and amygdala, which mediate different types of memory retrieval, are also reviewed. Together, these findings contribute to understanding the important role of hippocampal theta oscillation in the storage and recall of memory traces.