The process and mechanism of biomineralization and relevant physicochemical properties of mineral crystals are remarkably sophisticated multidisciplinary fields that include biology, chemistry, physics, and materials science. The components of the organic matter, structural construction of minerals, and related mechanical interaction, etc., could help to reveal the unique nature of the special mineralization process. Herein, the paper provides an overview of the biomineralization process from the perspective of molecular vibrational spectroscopy, including the physicochemical properties of biomineralized tissues, from physiological to applied mineralization. These physicochemical characteristics closely to the hierarchical mineralization process include biological crystal defects, chemical bonding, atomic doping, structural changes, and content changes in organic matter, along with the interface between biocrystals and organic matter as well as the specific mechanical effects for hardness and toughness. Based on those observations, the special physiological properties of mineralization for enamel and bone, as well as the possible mechanism of pathological mineralization and calcification such as atherosclerosis, tumor micro mineralization, and urolithiasis are also reviewed and discussed. Indeed, the clearly defined physicochemical properties of mineral crystals could pave the way for studies on the mechanisms and applications.
The role of TLR4 (toll like receptor 4), a key molecule of the classical innate immune pathway, in individual tumors requires further exploration. In this study, numerous databases and tools, such as TCGA, GTEx, cBioportal, GSCALite, and GDSC, were utilized to systematically analyze the prognostic and immunological potential of TLR4 in tumors. The expression levels and mutational dynamics of TLR4 in pan-cancer were investigated. The prognostic potential of TLR4 was analyzed using Kaplan-Meier (KM) analysis. Results showed the levels of TLR4 in tumor tissues were significantly lower as compared to those in normal tissues in most cancers and were strongly correlated with the patient’s outcomes. The mutant genes associated with TLR4 were mainly enriched in the PI3K-AKT pathway. This could be a potential pathway for radiotherapy to activate the tumor immune microenvironment via TLR4/MAP. In tumors, the TLR4 mutations were closely associated with the M1/M2 polarization of macrophages. TLR4 and its ligand CD14 were significantly negatively associated with immunosuppressed MDSCs and TAM M2. The intervention of TLR4-dependent signaling pathways might be a promising strategy to reduce tolerance to ICB treatment in the post-immune era. In conclusion, this study expands the potential of TLR4 as an immune target in tumor therapy.
Owing to the emergence of energy storage and electric vehicles, the desire for safe high-energy-density energy storage devices has increased research interest in anode-free lithium metal batteries (AFLMBs). Unlike general LMBs, in which excess Li exists to compensate for the irreversible loss of Li, only the current collector is employed as an anode and paired with a lithiated cathode in the fabrication of AFLMBs. Owing to their unique cell configuration, AFLMBs have attractive characteristics, including the highest energy density, safety, and cost-effectiveness. However, developing AFLMBs with extended cyclability remains an issue for practical applications because the high reactivity of Li with limited inventory causes severely low Coulombic efficiency, poor cyclability, and dendrite growth. To address these issues, tremendous effort has been devoted to stabilize Li-metal anodes for AFLMBs. In this review, we highlight the importance and challenges of AFLMBs. Then, we thoroughly review diverse strategies, such as modifying current collectors, the formation of robust interfaces by engineering advanced electrolytes, and operation protocols. Finally, a future perspective on the strategy is provided to insight into the basis of future research. We hope that this review provides a comprehensive understanding by reviewing previous research and arousing more interest in this field.
Mechanical forces play a crucial role in biological processes at the molecular and cellular levels. Recent advancements in dynamic force spectroscopies (DFS) have enabled the application and measurement of forces and displacements with high resolutions, providing insights into the mechanical pathways involved in various diseases, including cancer, cardiovascular disease, and COVID-19. Among the various DFS techniques, biomembrane force probe (BFP) advancements have improved our ability to measure bond kinetics and cellular mechanosensing with pico-newton and nano-meter resolutions. In this review, we provide a comprehensive overview of the classical BFP-DFS setup and highlight key advancements, including the development of dual biomembrane force probe (dBFP) and fluorescence biomembrane force probe (fBFP). BFP-DFS not only enables the investigation of dynamic bond behaviors on living cells, but also contributed significantly to our understanding of the specific ligand–receptor axes mediated cell mechanosensing. Besides, we explore the contribution of discoveries made possible by BFP-DFS in cancer biology, thrombosis, and inflammation, as well as predict future BFP upgrades to improve output and feasibility. Although BFP-DFS is still a niche research modality, its contribution to the growing field of cell mechanobiology is unparalleled, and its potential to elucidate novel therapeutic discoveries is significant.
As implantable medical electronics (IMEs) developed for healthcare monitoring and biomedical therapy are extensively explored and deployed clinically, the demand for non-invasive implantable biomedical electronics is rapidly surging. Current rigid and bulky implantable microelectronic power sources are prone to immune rejection and incision, or cannot provide enough energy for long-term use, which greatly limits the development of implantable medical devices. Herein, a comprehensive review of the historical development of IMEs and the applicable miniaturised power sources along with advantages and limitations is given. Despite recent advances in microfabrication techniques, biocompatible materials have facilitated the development of IMEs system toward non-invasive, ultra-flexible, bioresorbable, wireless and multifunctional, progress in the development of minimally invasive power sources in implantable systems has remained limited. Here we summarise three promising minimally invasive power sources, including energy storage devices (biodegradable primary batteries, rechargeable batteries and supercapacitors), human body energy harvesters (nanogenerators and biofuel cells) and wireless power transfer (far-field radiofrequency radiation, near-field wireless power, ultrasonic and photovoltaic power). The energy storage and harvesting mechanism, configurational design, output power and applications in vivo are discussed. It is expected to give a comprehensive understanding of the IMEs for painless health monitoring and biomedical therapy with long-term stable function
Chronic depression is a complex disorder with huge societal repercussions. Although currently used antidepressant drugs are generally effective, most of these drugs display serious adverse effects. Moreover, the incompletely elucidated pathological mechanisms of depression constitutes a bottleneck in development of antidepressants. Among them, the field targeting neuroinflammation, which is associated with depression, remains unexplored. Here, we evaluated neuroprotective and antidepressant properties of a phenolic phytochemical, hydroxytyrosol (HT). We observed that HT treatment alleviated depressive-like behaviors in rodent models of learned helplessness (LH), chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS). HT improved hippocampal neuronal injury with modulation of microglia activation, inflammatory cytokines production, mitochondrial damage and BDNF signaling pathway, as well as the cellular level. In addition, targeted metabolomics results showed that HT compensated for the neurotransmitters deficiency and inhibited the tryptophan-kynurenine metabolism in the brain of CUMS rats. RNA-Seq studies confirmed that the antidepressant effect of HT was modulated by BDNF signaling pathways closely associated with the functions of nerve fibers, myelin formation, microglia differentiation, and nerve regeneration. There is potential for developing neuroprotective agents based on HT to treat depression disorders caused by inflammation-related neuronal injury.