Journal of Zhejiang University SCIENCE B最新文献

Adenosine triphosphate (ATP)-binding cassette (ABC) transporter systems are divided into importers and exporters that facilitate the movement of diverse substrate molecules across the lipid bilayer, against the concentration gradient. These transporters comprise two highly conserved nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). Unlike ABC exporters, prokaryotic ABC importers require an additional substrate-binding protein (SBP) as a recognition site for specific substrate translocation. The discovery of a large number of ABC systems in bacterial pathogens revealed that these transporters are crucial for the establishment of bacterial infections. The existing literature has highlighted the roles of ABC transporters in bacterial growth, pathogenesis, and virulence. These roles include importing essential nutrients required for a variety of cellular processes and exporting outer membrane-associated virulence factors and antimicrobial substances. This review outlines the general structures and classification of ABC systems to provide a comprehensive view of the activities and roles of ABC transporters associated with bacterial virulence and pathogenesis during infection.

Hexavalent chromium Cr(VI), as a well-established carcinogen, contributes to tumorigenesis for many human cancers, especially respiratory and digestive tumors. However, the potential function and relevant mechanism of Cr(VI) on the initiation of esophageal carcinogenesis are largely unknown. Here, immortalized human esophageal epithelial cells (HEECs) were induced to be malignantly transformed cells, termed HEEC-Cr(VI) cells, via chronic exposure to Cr(VI), which simulates the progress of esophageal tumorigenesis. In vitro and in vivo experiments demonstrated that HEEC-Cr(VI) cells obtain the ability of anchorage-independent growth, greater proliferative capacity, cancer stem cell properties, and the capacity to form subcutaneous xenografts in BALB/c nude mice when compared to their parental cells, HEECs. Additionally, HEEC-Cr(VI) cells exhibited weakened cell motility and enhanced cell adhesion. Interestingly, HEECs with acute exposure to Cr(VI) failed to display those malignant phenotypes of HEEC-Cr(VI) cells, suggesting that Cr(VI)‍-induced malignant transformation, but not Cr(VI) itself, is the cause for the tumor characteristics of HEEC-Cr(VI) cells. Mechanistically, chronic exposure to Cr(VI) induced abnormal activation of Notch signaling, which is crucial to maintaining the capacity for malignant proliferation and stemness of HEEC-Cr(VI) cells. As expected, N-‍[N-‍(3,5-difluorophenacetyl)‍-L-alanyl]‍-S-phenylglycine t-butyl ester (DAPT), an inhibitor for the Notch pathway, drastically attenuated cancerous phenotypes of HEEC-Cr(VI) cells. In conclusion, our study clarified the molecular mechanism underlying Cr(VI)‍-induced esophageal tumorigenesis, which provides novel insights for further basic research and clinical therapeutic strategies about Cr(VI)‍-associated esophageal cancer.

Brain signals refer to electrical signals or metabolic changes that occur as a consequence of brain cell activity. Among the various non-invasive measurement methods, electroencephalogram (EEG) stands out as a widely employed technique, providing valuable insights into brain patterns. The deviations observed in EEG reading serve as indicators of abnormal brain activity, which is associated with neurological diseases. Brain‒computer interface (BCI) systems enable the direct extraction and transmission of information from the human brain, facilitating interaction with external devices. Notably, the emergence of artificial intelligence (AI) has had a profound impact on the enhancement of precision and accuracy in BCI technology, thereby broadening the scope of research in this field. AI techniques, encompassing machine learning (ML) and deep learning (DL) models, have demonstrated remarkable success in classifying and predicting various brain diseases. This comprehensive review investigates the application of AI in EEG-based brain disease diagnosis, highlighting advancements in AI algorithms.

Polyphenolic compounds have received tremendous attention in biomedicine because of their good biocompatibility and unique physicochemical properties. In recent years, phenolic-enabled nanotechnology (PEN) has become a hotspot of research in the medical field, and many promising studies have been reported, especially in the application of central nervous system (CNS) diseases. Polyphenolic compounds have superior anti-inflammatory and antioxidant properties, and can easily cross the blood‒brain barrier, as well as protect the nervous system from metabolic damage and promote learning and cognitive functions. However, although great advances have been made in this field, a comprehensive review regarding PEN-based nanomaterials for CNS therapy is lacking. A systematic summary of the basic mechanisms and synthetic strategies of PEN-based nanomaterials is beneficial for meeting the demand for the further development of novel treatments for CNS diseases. This review systematically introduces the fundamental physicochemical properties of PEN-based nanomaterials and their applications in the treatment of CNS diseases. We first describe the different ways in which polyphenols interact with other substances to form high-quality products with controlled sizes, shapes, compositions, and surface chemistry and functions. The application of PEN-based nanomaterials in the treatment of CNS diseases is then described, which provides a reference for subsequent research on the treatment of CNS diseases.

The olfactory bulb (OB) is the first relay station in the olfactory system and functions as a crucial hub. It can represent odor information precisely and accurately in an ever-changing environment. As the only output neurons in the OB, mitral/tufted cells encode information such as odor identity and concentration. Recently, the neural strategies and mechanisms underlying odor representation and encoding in the OB have been investigated extensively. Here we review the main progress on this topic. We first review the neurons and circuits involved in odor representation, including the different cell types in the OB and the neural circuits within and beyond the OB. We will then discuss how two different coding strategies-spatial coding and temporal coding-work in the rodent OB. Finally, we discuss potential future directions for this research topic. Overall, this review provides a comprehensive description of our current understanding of how odor information is represented and encoded by mitral/tufted cells in the OB.

Cockayne syndrome (CS) group B (CSB), which results from mutations in the excision repair cross-complementation group 6 (ERCC6) genes, which produce CSB protein, is an autosomal recessive disease characterized by multiple progressive disorders including growth failure, microcephaly, skin photosensitivity, and premature aging. Clinical data show that brain atrophy, demyelination, and calcification are the main neurological manifestations of CS, which progress with time. Neuronal loss and calcification occur in various brain areas, particularly the cerebellum and basal ganglia, resulting in dyskinesia, ataxia, and limb tremors in CSB patients. However, the understanding of neurodevelopmental defects in CS has been constrained by the lack of significant neurodevelopmental and functional abnormalities observed in CSB-deficient mice. In this review, we focus on elucidating the protein structure and distribution of CSB and delve into the impact of CSB mutations on the development and function of the nervous system. In addition, we provide an overview of research models that have been instrumental in exploring CS disorders, with a forward-looking perspective on the substantial contributions that brain organoids are poised to further advance this field.

Patients with depression are more likely to have chronic gastrointestinal (GI) symptoms than the general population, but such symptoms are considered only somatic symptoms of depression and lack special attention. There is a chronic lack of appropriate diagnosis and effective treatment for patients with depression accompanied by GI symptoms, and studying the association between depression and GI disorders (GIDs) is extremely important for clinical management. There is growing evidence that depression is closely related to the microbiota present in the GI tract, and the microbiota-gut-brain axis (MGBA) is creating a new perspective on the association between depression and GIDs. Identifying and treating GIDs would provide a key opportunity to prevent episodes of depression and may also improve the outcome of refractory depression. Current studies on depression and the microbially related gut-brain axis (GBA) lack a focus on GI function. In this review, we combine preclinical and clinical evidence to summarize the roles of the microbially regulated GBA in emotions and GI function, and summarize potential therapeutic strategies to provide a reference for the study of the pathomechanism and treatment of depression in combination with GI symptoms.

Oligodendrocytes are the myelinating cells of the central nervous system. Brain injury and neurodegenerative disease often lead to oligodendrocyte death and subsequent demyelination-related pathological changes, resulting in neurological defects and cognitive impairment (Spaas et al., 2021; Zhang J et al., 2022). Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system. The pathology of MS is characterized by the loss of myelin, oligodendrocytes, and axons in the brain, brain stem, and spinal cord, as well as by white matter lesions (Lassmann et al., 2007). Unfortunately, no definitive cure for MS has been developed. Immunomodulatory and anti-inflammatory drugs are effective in the relapsing-remitting phase of MS because they reduce the frequency of relapses and the formation of inflammatory lesions; however, they do not alter the course of progressive MS and are insufficient to cure chronic neurological dysfunction (Xiao et al., 2015; Zhang et al., 2021). The treatment outcome is even worse for MS patients with primary and secondary progressions. Mesenchymal stem cells (MSCs) are stromal cells that can self-renew and exhibit multilineage differentiation. MSCs are easy to expand in vitro and exhibit low immunogenicity, no tumorigenic risks, and ethical controversies, making them a promising candidate for regenerative medicine (Zhang L et al., 2022; Xu et al., 2023). Many studies have confirmed the neural differentiation potential of MSCs under certain conditions, making them a prime candidate for treating neurodegenerative diseases (Jang et al., 2010; Yan et al., 2013). The present study investigated the effects of cranial bone-marrow mesenchymal stem cells (cBMMSCs) and oligodendrocyte-specific protein 2-positive (Olig2⁺) single-colony-derived cBMMSC (sc-cBMMSC), isolated in our previous work (Yang et al., 2022), in a central nervous system demyelination mouse model.

Neurodegenerative diseases (NDDs), mainly including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD), are sporadic and rare genetic disorders of the central nervous system. A key feature of these conditions is the slow accumulation of misfolded protein deposits in brain neurons, the excessive aggregation of which leads to neurotoxicity and further disorders of the nervous system.

Type 1 diabetes (T1D) is a T lymphocyte-mediated autoimmune disease caused by pancreatic β‍-cell destruction, which eventually leads to reduced insulin level and increased blood glucose level (Syed, 2022). As a multifactorial disease, T1D is characterized by a genetic predisposition associated with various environmental and cellular elements (Syed, 2022). Pancreatic β cells have long been considered the "innocent victims" in T1D pathogenesis since the pancreas is attacked by the immune cells, resulting in a process known as insulitis, in which the immune cells infiltrate pancreatic islets and secrete pro-inflammatory cytokines. However, growing evidence suggests that various β‍-cell stresses, dysfunction, and death contribute to T1D pathogenesis, as it has been observed that β‍-cell dysfunction in autoantibody-positive (Aab⁺) individuals exists long before T1D diagnosis (Evans-Molina et al., 2018).