Advancements in production, assessment, and food applications of salty and saltiness-enhancing peptides: A review.

Salt is important for food flavor, but excessive sodium intake leads to adverse health consequences. Thus, salty and saltiness-enhancing peptides are developed for sodium-reduction products. This review elucidates saltiness perception process and analyses correlation between the peptide structure and saltiness-enhancing ability. These peptides interact with taste receptors to produce saltiness perception, including ENaC, TRPV1, and TMC4. This review also outlines preparation, isolation, purification, characterization, screening, and assessment techniques of these peptides and discusses their potential applications. These peptides are from various sources and produced through enzymatic hydrolysis, microbial fermentation, or Millard reaction and then separated, purified, identified, and screened. Sensory evaluation, electronic tongue, bioelectronic tongue, and cell and animal models are the primary saltiness assessment approaches. These peptides can be used in sodium-reduction food products to produce "clean label" items, and the peptides with biological activity can also serve as functional ingredients, making them very promising for food industry.

The Nicotinic Acetylcholine Receptor and Its Pentameric Homologs: Toward an Allosteric Mechanism of Signal Transduction at the Atomic Level.

The nicotinic acetylcholine receptor has served, since its biochemical identification in the 1970s, as a model of an allosteric ligand-gated ion channel mediating signal transition at the synapse. In recent years, the application of X-ray crystallography and high-resolution cryo-electron microscopy, together with molecular dynamic simulations of nicotinic receptors and homologs, have opened a new era in the understanding of channel gating by the neurotransmitter. They reveal, at atomic resolution, the diversity and flexibility of the multiple ligand-binding sites, including recently discovered allosteric modulatory sites distinct from the neurotransmitter orthosteric site, and the conformational dynamics of the activation process as a molecular switch linking these multiple sites. The model emerging from these studies paves the way for a new pharmacology based, first, upon the occurrence of an original mode of indirect allosteric modulation, distinct from a steric competition for a single and rigid binding site, and second, the design of drugs that specifically interact with privileged conformations of the receptor such as agonists, antagonists, and desensitizers. Research on nicotinic receptors is still at the forefront of understanding the mode of action of drugs on the nervous system.

Comparison of Thin-Film Capacitor Geometries for the Detection of Volatile Organic Compounds Using a ZIF-8 Affinity Layer.

Their chemical diversity, uniform pore sizes, and large internal surface areas make metal-organic frameworks (MOFs) highly suitable for volatile organic compound (VOC) adsorption. This work compares two geometries of capacitive VOC sensors that use the MOF material ZIF-8 as an affinity layer. When using a permeable top electrode (thickness < 25 nm), the metal-insulator-metal (MIM) sandwich configuration exhibits superior sensitivity, an improved detection limit, and a smaller footprint than the conventional interdigitated electrode layout. Moreover, the transduction of VOC adsorption in ZIF-8 via MIM capacitors is more sensitive to polar VOCs and provides better selectivity at high loadings than gravimetric and optical transductions.

Metal-Organic Framework Coated Devices for Gas Sensing.

The demand for monitoring chemical and physical information surrounding, air quality, and disease diagnosis has propelled the development of devices for gas sensing that are capable of translating external stimuli into detectable signals. Metal-organic frameworks (MOFs), possessing particular physiochemical properties with designability in topology, specific surface area, pore size and/or geometry, potential functionalization, and host-guest interactions, reveal excellent development promises for manufacturing a variety of MOF-coated sensing devices for multitudinous applications including gas sensing. The past years have witnessed tremendous progress on the preparation of MOF-coated gas sensors with superior sensing performance, especially high sensitivity and selectivity. Although limited reviews have summarized different transduction mechanisms and applications of MOF-coated sensors, reviews summarizing the latest progress of MOF-coated devices under different working principles would be a good complement. Herein, we summarize the latest advances of several classes of MOF-based devices for gas sensing, i.e., chemiresistive sensors, capacitors, field-effect transistors (FETs) or Kelvin probes (KPs), electrochemical, and quartz crystal microbalance (QCM)-based sensors. The surface chemistry and structural characteristics were carefully associated with the sensing behaviors of relevant MOF-coated sensors. Finally, challenges and future prospects for long-term development and potentially practical application of MOF-coated sensing devices are pointed out.

A Review on Coupled Bulk Acoustic Wave MEMS Resonators.

With the introduction of the working principle of coupled resonators, the coupled bulk acoustic wave (BAW) Micro-Electro-Mechanical System (MEMS) resonators have been attracting much attention. In this paper, coupled BAW MEMS resonators are discussed, including the coupling theory, the actuation and sensing theory, the transduction mechanism, and the applications. BAW MEMS resonators normally exhibit two types of vibration modes: lateral (in-plane) modes and flexural (out-of-plane) modes. Compared to flexural modes, lateral modes exhibit a higher stiffness with a higher operating frequency, resulting in a lower internal loss. Also, the lateral mode has a higher Q factor, as the fluid damping imposes less influence on the in-plane motion. The coupled BAW MEMS resonators in these two vibration modes are investigated in this work and their applications for sensing, timing, and frequency reference are also presented.

Computational Methods for Understanding the Selectivity and Signal Transduction Mechanism of Aminomethyl Tetrahydronaphthalene to Opioid Receptors.

Opioid receptors are members of the group of G protein-couple receptors, which have been proven to be effective targets for treating severe pain. The interactions between the opioid receptors and corresponding ligands and the receptor's activation by different agonists have been among the most important fields in opioid research. In this study, with compound M1, an active metabolite of tramadol, as the clue compound, several aminomethyl tetrahydronaphthalenes were designed, synthesized and assayed upon opioid receptors. With the resultant compounds FW-AII-OH-1 (Ki = 141.2 nM for the κ opioid receptor), FW-AII-OH-2 (Ki = 4.64 nM for the δ opioid receptor), FW-DI-OH-2 (Ki = 8.65 nM for the δ opioid receptor) and FW-DIII-OH-2 (Ki = 228.45 nM for the δ opioid receptor) as probe molecules, the structural determinants responsible for the subtype selectivity and activation mechanisms were further investigated by molecular modeling and molecular dynamics simulations. It was shown that Y7.43 was a key residue in determining the selectivity of the three opioid receptors, and W6.58 was essential for the selectivity of the δ opioid receptor. A detailed stepwise discovered agonist-induced signal transduction mechanism of three opioid receptors by aminomethyl tetrahydronaphthalene compounds was proposed: the 3-7 lock between TM3 and TM7, the DRG lock between TM3 and TM6 and rearrangement of I3.40, P5.50 and F6.44, which resulted in the cooperative movement in 7 TMs. Then, the structural relaxation left room for the binding of the G protein at the intracellular site, and finally the opioid receptors were activated.

Metal-Organic Framework Based Gas Sensors.

The ever-increasing concerns over indoor/outdoor air quality, industrial gas leakage, food freshness, and medical diagnosis require miniaturized gas sensors with excellent sensitivity, selectivity, stability, low power consumption, cost-effectiveness, and long lifetime. Metal-organic frameworks (MOFs), featuring structural diversity, large specific surface area, controllable pore size/geometry, and host-guest interactions, hold great promises for fabricating various MOF-based devices for diverse applications including gas sensing. Tremendous progress has been made in the past decade on the fabrication of MOF-based sensors with elevated sensitivity and selectivity toward various analytes due to their preconcentrating and molecule-sieving effects. Although several reviews have recently summarized different aspects of this field, a comprehensive review focusing on MOF-based gas sensors is absent. In this review, the latest advance of MOF-based gas sensors relying on different transduction mechanisms, for example, chemiresistive, capacitive/impedimetric, field-effect transistor or Kelvin probe-based, mass-sensitive, and optical ones are comprehensively summarized. The latest progress for making large-area MOF films essential to the mass-production of relevant gas sensors is also included. The structural and compositional features of MOFs are intentionally correlated with the sensing performance. Challenges and opportunities for the further development and practical applications of MOF-based gas sensors are also given.

A mathematical model for Escherichia coli chemotaxis to competing stimuli.

Chemotactic bacteria sense and respond to temporal and spatial gradients of chemical cues in their surroundings. This phenomenon plays a critical role in many microbial processes such as groundwater bioremediation, microbially enhanced oil recovery, nitrogen fixation in legumes, and pathogenesis of the disease. Chemical heterogeneity in these natural systems may produce numerous competing signals from various directions. Predicting the migration behavior of bacterial populations under such conditions is necessary for designing effective treatment schemes. In this study, experimental studies and mathematical models are reported for the chemotactic response of Escherichia coli to a combination of attractant (α-methylaspartate) and repellent (NiCl2 ), which bind to the same transmembrane receptor complex. The model describes the binding of chemoeffectors and phosphorylation of the kinase in the signal transduction mechanism. Chemotactic parameters of E. coli (signaling efficiency σ , stimuli sensitivity coefficient γ , and repellent sensitivity coefficient κ ) were determined by fitting the model with experimental results for individual stimuli. Interestingly, our model naturally identifies NiCl2 as a repellent for κ>1 . The model is capable of describing quantitatively the response to the individual attractant and repellent, and correctly predicts the change in direction of bacterial population migration for competing stimuli with a twofold increase in repellent concentration.

Crossing the blood-brain barrier with AAV vectors.

Central nervous system (CNS) diseases are some of the most difficult to treat because the blood-brain barrier (BBB) almost entirely limits the passage of many therapeutic drugs into the CNS. Gene therapy based on the adeno-associated virus (AAV) vector has the potential to overcome this problem. For example, an AAV serotype AAV9 has been widely studied for its ability to cross the BBB to transduce astrocytes, but its efficiency is limited. The emergence of AAV directed evolution technology provides a solution, and the variants derived from AAV9 directed evolution have been shown to have significantly higher crossing efficiency than AAV9. However, the mechanisms by which AAV crosses the BBB are still unclear. In this review, we focus on recent advances in crossing the blood-brain barrier with AAV vectors. We first review the AAV serotypes that can be applied to treating CNS diseases. Recent progress in possible AAV crossing the BBB and transduction mechanisms are then summarized. Finally, the methods to improve the AAV transduction efficiency are discussed.

Two kanamycin electrochemical aptamer-based sensors using different signal transduction mechanisms: A comparison of electrochemical behavior and sensing performance.

Two typical kanamycin-A (KAN-A) electrochemical aptamer-based sensors employing different signal transduction mechanisms were deliberately designed and constructed with a similar structure. One sensor (sensor-1) was based on the classical probe conformation changing mode (PCCM) with a methylene blue (MB) label used as an electrochemical tag; the other sensor (sensor-2) used the target-induced signal probe shifting (TISPS) method with a free MB label in the assay solution. The difference in signal transduction mechanisms resulted in big differences in basic electrochemical behavior and comprehensive sensing performance. The results show that both sensor types exhibit different electrochemical behavior in square wave voltammetry, cyclic voltammetry, and in sensitivity, with detection limits of 3.0 nM for sensor-1 and 60.0 pM for sensor-2 in buffer. When validated for practical and quantitative detection of tap water and milk samples, both sensing methods performed well with detection limits of <260 nM and measurement times of <40 min. In addition, accuracy was good with mean recoveries of 72.3-92.6% and precision was acceptable with a relative standard deviation (RSD) of ≤14.2%. The basis for the similarities and differences in performance is also presented.

The Role of Transient Receptor Potential (TRP) Channels in the Transduction of Dental Pain.

Dental pain is a common health problem that negatively impacts the activities of daily living. Dentine hypersensitivity and pulpitis-associated pain are among the most common types of dental pain. Patients with these conditions feel pain upon exposure of the affected tooth to various external stimuli. However, the molecular mechanisms underlying dental pain, especially the transduction of external stimuli to electrical signals in the nerve, remain unclear. Numerous ion channels and receptors localized in the dental primary afferent neurons (DPAs) and odontoblasts have been implicated in the transduction of dental pain, and functional expression of various polymodal transient receptor potential (TRP) channels has been detected in DPAs and odontoblasts. External stimuli-induced dentinal tubular fluid movement can activate TRP channels on DPAs and odontoblasts. The odontoblasts can in turn activate the DPAs by paracrine signaling through ATP and glutamate release. In pulpitis, inflammatory mediators may sensitize the DPAs. They could also induce post-translational modifications of TRP channels, increase trafficking of these channels to nerve terminals, and increase the sensitivity of these channels to stimuli. Additionally, in caries-induced pulpitis, bacterial products can directly activate TRP channels on DPAs. In this review, we provide an overview of the TRP channels expressed in the various tooth structures, and we discuss their involvement in the development of dental pain.

Piezothermic Transduction of Functional Composite Materials.

Conveyances of physical energies (such as force, heat, and electricity) from one to another exist in nature and have initiated manifold useful applications. Piezothermic transduction refers to a change in the thermal conduction of a material when a mechanical strain is applied, which can be applied in high-performance pressure sensing and smart energy control. Here, we propose the piezothermic concept and investigate the mechanism of its transduction in three functional composite materials, that is, particle-reinforced composites, porous materials, and series-model materials. Theoretical models for analyzing relatedness effects of material properties (e.g., thermal conductivity, Young's modulus, and volume fraction) are established and validated by both finite element analyses and experimental measurements. The piezothermic transduction provides novel and promising strategies to implement high-performance mechanical sensing as well as energy control through optimizing composite materials. As a demonstration, a pressure sensor with a super high range-to-limit ratio of 50 000 that has a lower detection limit of 3.9 Pa and a large measurement range of 200 kPa is developed.

Recent Developments for Flexible Pressure Sensors: A Review.

Flexible pressure sensors are attracting great interest from researchers and are widely applied in various new electronic equipment because of their distinct characteristics with high flexibility, high sensitivity, and light weight; examples include electronic skin (E-skin) and wearable flexible sensing devices. This review summarizes the research progress of flexible pressure sensors, including three kinds of transduction mechanisms and their respective research developments, and applications in the fields of E-skin and wearable devices. Furthermore, the challenges and development trends of E-skin and wearable flexible sensors are also briefly discussed. Challenges of developing high extensibility, high sensitivity, and flexible multi-function equipment still exist at present. Exploring new sensing mechanisms, seeking new functional materials, and developing novel integration technology of flexible devices will be the key directions in the sensors field in future.

Expression and purification of an FGF9 fusion protein in E. coli, and the effects of the FGF9 subfamily on human hepatocellular carcinoma cell proliferation and migration.

Fibroblast growth factor (FGF) 9 has oncogenic activity and plays an important role in the development of ovarian, lung, prostate, and gastric cancers. In the present study, with the aim of reducing the cost of utilizing growth factors in cancer research, a simple and efficient method for the preparation of recombinant human (rh)FGF9 in Escherichia coli was established. The rhFGF9 fusion protein (6 × His-TEV-rhFGF9) and the native protein released by tobacco etch virus (TEV) protease were obtained using a Ni-NTA system, with > 95% purity. Both purified forms of rhFGF9, with and without fusion tags, significantly stimulated the proliferation of NIH3T3 cells. The FGF9 subfamily, including FGF9, FGF16, and FGF20, in addition to rhFGF16, rhFGF9, and rhFGF20, were shown to stimulate the proliferation and migration of HuH7 human hepatocellular carcinoma (HCC) cells. Mechanistic studies revealed that the stimulation of HuH7 cell proliferation and migration with rhFGF9 and rhFGF20 were associated with the activation of the extracellular signal-regulated kinase (ERK) and nuclear factor κB (NF-κB) pathways and matrix metalloproteinase-26 (MMP26). Inhibition of the ERK and NF-κB pathways blocked cell migration, and NF-κB was demonstrated to be regulated by ERK. Therefore, the present study demonstrates a simple method for the preparation of biologically active rhFGF9 protein. Furthermore, the results indicate that exogenous rhFGF9- and rhFGF20-activated ERK/NF-κB signal transduction pathways play important roles in the regulation of HCC cell proliferation and migration, and this discovery helps to find the potential for new solutions of the treatment of liver cancer.

Nanowire Chemical/Biological Sensors: Status and a Roadmap for the Future.

Chemiresistive sensors are becoming increasingly important as they offer an inexpensive option to conventional analytical instrumentation, they can be readily integrated into electronic devices, and they have low power requirements. Nanowires (NWs) are a major theme in chemosensor development. High surface area, interwire junctions, and restricted conduction pathways give intrinsically high sensitivity and new mechanisms to transduce the binding or action of analytes. This Review details the status of NW chemosensors with selected examples from the literature. We begin by proposing a principle for understanding electrical transport and transduction mechanisms in NW sensors. Next, we offer the reader a review of device performance parameters. Then, we consider the different NW types followed by a summary of NW assembly and different device platform architectures. Subsequently, we discuss NW functionalization strategies. Finally, we propose future developments in NW sensing to address selectivity, sensor drift, sensitivity, response analysis, and emerging applications.