Metabolic activities in normal cells rely primarily on mitochondrial oxidative phosphorylation (OXPHOS) to generate ATP for energy. Unlike in normal cells, glycolysis is enhanced and OXPHOS capacity ...is reduced in various cancer cells. It has long been believed that the glycolytic phenotype in cancer is due to a permanent impairment of mitochondrial OXPHOS, as proposed by Otto Warburg. This view is challenged by recent investigations which find that the function of mitochondrial OXPHOS in most cancers is intact. Aerobic glycolysis in many cancers is the combined result of various factors such as oncogenes, tumor suppressors, a hypoxic microenvironment, mtDNA mutations, genetic background and others. Understanding the features and complexity of the cancer energy metabolism will help to develop new approaches in early diagnosis and effectively target therapy of cancer.
A basic understanding of how imaging nanoparticles are removed from the normal organs/tissues but retained in the tumors is important for their future clinical applications in early cancer diagnosis ...and therapy. In this review, we discuss current understandings of clearance pathways and tumor targeting of small-molecule- and inorganic-nanoparticle-based imaging probes with an emphasis on molecular nanoprobes, a class of inorganic nanoprobes that can escape reticuloendothelial system (RES) uptake and be rapidly eliminated from the normal tissues/organs via kidneys but can still passively target the tumor with high efficiency through the enhanced permeability permeability and retention (EPR) effect. The impact of nanoparticle design (size, shape, and surface chemistry) on their excretion, pharmacokinetics, and passive tumor targeting were quantitatively discussed. Synergetic integration of effective renal clearance and EPR effect offers a promising pathway to design low-toxicity and high-contrast-enhancement imaging nanoparticles that could meet with the clinical translational requirements of regulatory agencies.
The increase of antibiotic resistance in bacteria has become a major concern for successful diagnosis and treatment of infectious diseases. Over the past few decades, significant progress has been ...achieved on the development of nanotechnology‐based medicines for combating multidrug resistance in microorganisms. Among this, silver nanoparticles (AgNPs) hold great promise in addressing this challenge due to their broad‐spectrum and robust antimicrobial properties. This review illustrates the antibacterial mechanisms of silver nanoparticles and further elucidates how different structural factors including surface chemistry, size, and shape, impact their antibacterial activities, which are expected to promote the future development of more potent silver nanoparticle‐based antibacterial agents.
Silver nanoparticles (AgNPs) hold great promise to address the challenges in multidrug resistance in bacteria. This review briefly summarizes the current understanding of antibacterial mechanisms of AgNPs and how surface chemistry, size, and shape, impact their potencies, which are expected to help further development of AgNP‐based antibacterial agents.
Capsaicin in chili peppers bestows the sensation of spiciness. Since the discovery of its receptor, transient receptor potential vanilloid 1 （TRPV1） ion channel, how capsaicin activates this channel ...has been under extensive investigation using a variety of experimental techniques including mutagenesis, patch-clamp recording, crystallography, cryo-electron microscopy, computational docking and molecular dynamic simu- lation. A framework of how capsaicin binds and acti- vates TRPV1 has started to merge： capsaicin binds to a pocket formed by the channel＇s transmembrane seg- ments, where it takes a ＂tail-up, head-down＂ configu- ration. Binding is mediated by both hydrogen bonds and van der Waals interactions. Upon binding, cap- saicin stabilizes the open state of TRPV1 by ＂pull-and- contact＂ with the $4-$5 linker. Understanding the ligand-host interaction will greatly facilitate pharma- ceutical efforts to develop novel analgesics targeting TRPV1.
One important goal of the current electrocatalysis is to develop integrated electrodes from the atomic level design to multilevel structural engineering in simple ways and low prices. Here, a series ...of oxygen micro‐alloyed high‐entropy alloys (O‐HEAs) is developed via a metallurgy approach. A (CrFeCoNi)97O3 bulk O‐HEA shows exceptional electrocatalytic performance for the oxygen evolution reaction (OER), reaching an overpotential as low as 196 mV and a Tafel slope of 29 mV dec−1, and with stability longer than 120 h in 1 m KOH solution at a current density of 10 mA cm−2. It is shown that the enhanced OER performance can be attributed to the formation of island‐like Cr2O3 microdomains, the leaching of Cr3+ ions, and structural amorphization at the interfaces of the domains. These findings offer a technological‐orientated strategy to integrated electrodes.
A new class of bulk electrodes is designed by incorporating oxide microdomains into the so‐called high‐entropy alloys (HEAs). From these, unprecedented oxygen evolution reaction (OER) activity is achieved, with an ultralow overpotential of 196 mV and a Tafel slope of 29 mV dec−1, and with stability longer than 120 h in 1 m KOH solution at current density of 10 mA cm−2.
A newly developed polyacrylamide‐co‐methyl acrylate/spiropyran (SP) hydrogel crosslinked by SP mechanophore demonstrates multi‐stimuli‐responsive and mechanically strong properties. The hydrogels not ...only exhibit thermo‐, photo‐, and mechano‐induced color changes, but also achieve super‐strong mechanical properties (tensile stress of 1.45 MPa, tensile strain of ≈600%, and fracture energy of 7300 J m−2). Due to a reversible structural transformation between spiropyran (a ring‐close) and merocyanine (a ring‐open) states, simple exposure of the hydrogels to white light can reverse color changes and restore mechanical properties. The new design approach for a new mechanoresponsive hydrogel is easily transformative to the development of other mechanophore‐based hydrogels for sensing, imaging, and display applications.
A newly developed poly(acrylamide‐co‐methyl acrylate)/spiropyran hydrogel with multi‐stimuli‐responsive and mechanically strong properties is presented. The resulting hydrogel exhibits reversible changes in color response and mechanical properties, making it promising for sensing, imaging, and display applications.
PDZ domains are abundant protein interaction modules that often recognize short amino acid motifs at the C-termini of target proteins. They regulate multiple biological processes such as transport, ...ion channel signaling, and other signal transduction systems. This review discusses the structural characterization of PDZ domains and the use of recently emerging technologies such as proteomic arrays and peptide libraries to study the binding properties of PDZ-mediated interactions. Regulatory mechanisms responsible for PDZ-mediated interactions, such as phosphorylation in the PDZ ligands or PDZ domains, are also discussed. A better understanding of PDZ protein-protein interaction networks and regulatory mechanisms will improve our knowledge of many cellular and biological processes.
An environmentally benign and efficient hydrothermal reduction method was applied for the preparation of three-dimensional (3D) porous graphene hydrogel (GH) adsorbents. The physicochemical ...properties of GH granules were systematically characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectra and Brunauer-Emmett-Teller (BET) method. GH granules showed an excellent adsorption capacity (235.6 mg/g) for ciprofloxacin via combined adsorption interaction mechanisms (e.g. π-π EDA interaction, hydrogen bonding, and hydrophobic interaction). Moreover, reducing the size of the hydrogels can significantly accelerate the adsorption process and enhance the removal efficiency of pollutants from aqueous solution. Water (more than 99 wt%) within hydrogels played a key role in enhancing adsorption performance. The GO hydrogels exhibited an excellent adaptability to environmental factors. These findings demonstrate that GH granules are promising adsorbents for the removal of antibiotic pollutants from aqueous solutions.
Adult hippocampal neurogenesis (AHN) facilitates hippocampal circuits plasticity and regulates hippocampus‐dependent cognition and emotion. However, AHN malfunction has been widely reported in both ...human and animal models of Alzheimer's disease (AD), the most common form of dementia in the elderly. Pro‐neurogenic therapies including rescuing innate AHN, cell engraftment and glia‐neuron reprogramming hold great potential for compensating the neuronal loss and rewiring the degenerated neuronal network in AD, but there are still great challenges to be overcome. This review covers recent advances in unraveling the involvement of AHN in AD and highlights the prospect of emerging pro‐neurogenic remedies.
Innate AHN can be facilitated by pro‐neurogenic drugs, environmental enrichment combined with exercise, neurostimulation and dietary innervation. More extensive neurogenesis can be also induced by transplantation of stem cells or neural progenitors, as well as genetic induction of glia‐neuron conversion.
Wnt signaling is a critical component during embryonic development and also plays an important role in regulating adult tissue homeostasis. Abnormal activation of Wnt signaling has been implicated in ...many cancers, while reduced activity of Wnt signaling leads to poor wound healing and structural formations. Thus, extensive efforts have been focused on developing small molecules that have potential to either inhibit or activate the pathway, hoping these molecules can offer leads for novel approaches in treating different human diseases. Many small‐molecule inhibitors specifically target various elements, such as Frizzled, Disheveled, Porcupine, or Tankyrase, within the Wnt signaling pathways. These small molecules not only have the potential to be further developed as therapeutic reagents, but they may also be used as chemical probes to dissect the underlying mechanism of the Wnt signaling pathways. Therefore, their respective mechanisms and effective dosages are highly pertinent. Aiming to provide an overview of those molecules in a concise, easy‐to‐use manner, we summarize and organize the current research on them so that it may be helpful for utilization in different studies.
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