Bacterial biofilms are complex surface attached communities of bacteria held together by self-produced polymer matrixs mainly composed of polysaccharides, secreted proteins, and extracellular DNAs. ...Bacterial biofilm formation is a complex process and can be described in five main phases: (i) reversible attachment phase, where bacteria non-specifically attach to surfaces; (ii) irreversible attachment phase, which involves interaction between bacterial cells and a surface using bacterial adhesins such as fimbriae and lipopolysaccharide (LPS); (iii) production of extracellular polymeric substances (EPS) by the resident bacterial cells; (iv) biofilm maturation phase, in which bacterial cells synthesize and release signaling molecules to sense the presence of each other, conducing to the formation of microcolony and maturation of biofilms; and (v) dispersal/detachment phase, where the bacterial cells depart biofilms and comeback to independent planktonic lifestyle. Biofilm formation is detrimental in healthcare, drinking water distribution systems, food, and marine industries, etc. As a result, current studies have been focused toward control and prevention of biofilms. In an effort to get rid of harmful biofilms, various techniques and approaches have been employed that interfere with bacterial attachment, bacterial communication systems (quorum sensing, QS), and biofilm matrixs. Biofilms, however, also offer beneficial roles in a variety of fields including applications in plant protection, bioremediation, wastewater treatment, and corrosion inhibition amongst others. Development of beneficial biofilms can be promoted through manipulation of adhesion surfaces, QS and environmental conditions. This review describes the events involved in bacterial biofilm formation, lists the negative and positive aspects associated with bacterial biofilms, elaborates the main strategies currently used to regulate establishment of harmful bacterial biofilms as well as certain strategies employed to encourage formation of beneficial bacterial biofilms, and highlights the future perspectives of bacterial biofilms.
Extensive studies have shown that cells can sense and modulate the biomechanical properties of the ECM within their resident microenvironment. Thus, targeting the mechanotransduction signaling ...pathways provides a promising way for disease intervention. However, how cells perceive these mechanical cues of the microenvironment and transduce them into biochemical signals remains to be answered. Förster or fluorescence resonance energy transfer (FRET) based biosensors are a powerful tool that can be used in live-cell mechanotransduction imaging and mechanopharmacological drug screening. In this review, we will first introduce FRET principle and FRET biosensors, and then, recent advances on the integration of FRET biosensors and mechanobiology in normal and pathophysiological conditions will be discussed. Furthermore, we will summarize the current applications and limitations of FRET biosensors in high-throughput drug screening and the future improvement of FRET biosensors. In summary, FRET biosensors have provided a powerful tool for mechanobiology studies to advance our understanding of how cells and matrices interact, and the mechanopharmacological screening for disease intervention.
The limited sensitivity of Förster Resonance Energy Transfer (FRET) biosensors hinders their broader applications. Here, we develop an approach integrating high-throughput FRET sorting and ...next-generation sequencing (FRET-Seq) to identify sensitive biosensors with varying substrate sequences from large-scale libraries directly in mammalian cells, utilizing the design of self-activating FRET (saFRET) biosensor. The resulting biosensors of Fyn and ZAP70 kinases exhibit enhanced performance and enable the dynamic imaging of T-cell activation mediated by T cell receptor (TCR) or chimeric antigen receptor (CAR), revealing a highly organized ZAP70 subcellular activity pattern upon TCR but not CAR engagement. The ZAP70 biosensor elucidates the role of immunoreceptor tyrosine-based activation motif (ITAM) in affecting ZAP70 activation to regulate CAR functions. A saFRET biosensor-based high-throughput drug screening (saFRET-HTDS) assay further enables the identification of an FDA-approved cancer drug, Sunitinib, that can be repurposed to inhibit ZAP70 activity and autoimmune-disease-related T-cell activation.
In recent years, although resin composite has played an important role in the restoration of tooth defects, it still has several disadvantages, including being biodegraded by saliva, bacteria and ...other enzymes in the oral cavity, which may result in repair failure. This factor is not conducive to the long-term survival of the prosthesis in the mouth. In this article, we review the causes, influencing factors and prevention methods of resin biodegradation. Biodegradation is mainly caused by esterase in saliva and bacteria, which breaks the ester bond in resin and causes the release of monomers. The mechanical properties of the prosthesis can then be affected. Meanwhile, cathepsin and MMPs are activated on the bonding surface, which may decompose the dentin collagen. In addition, neutrophils and residual water on the bonding surface can also aggravate biodegradation. Currently, the primary methods to prevent biodegradation involve adding antibacterial agents to resin, inhibiting the activity of MMPs and enhancing the crosslinking of collagen fibers. All of the above indicates that in the preparation and adhesion of resin materials, attention should be paid to the influence of biodegradation to improve the prosthesis’s service life in the complex environment of the oral cavity.
After the biological pesticide
Bacillus thuringiensis
(Bt) is applied to the field, it has to remain on the surface of plants to have the insecticidal activities against insect pests. Bt can form ...biofilms on the surface of vegetable leaves, which were rich in polysaccharides. However, the relationship between polysaccharides of the leaves and the biofilm formation as well as the insecticidal activities of Bt is still unknown. Herein, this study focused on the effects of plant polysaccharides pectin and xylan on biofilm formation and the insecticidal activities of Bt strains. By adding pectin, there were 88 Bt strains with strong biofilm formation, 69 strains with weak biofilm formation, and 13 strains without biofilm formation. When xylan was added, 13 Bt strains formed strong biofilms, 98 strains formed weak biofilms, and 59 strains did not form biofilms. This indicated that two plant polysaccharides, especially pectin, modulate the biofilm formation of Bt strains. The ability of pectin to induce biofilm formation was not related to Bt serotypes. Pectin promoted the biofilms formed by Bt cells in the logarithmic growth phase and lysis phase at the air–liquid interface, while it inhibited the biofilms formed by Bt cells in the sporangial phase at the air–liquid interface. The dosage of pectin was positively correlated with the yield of biofilms formed by Bt cells in the logarithmic growth phase or lysis phase at the solid–liquid interfaces. Pectin did not change the free-living growth and the cell motility of Bt strains. Pectin can improve the biocontrol activities of the spore–insecticidal crystal protein mixture of Bt and BtK commercial insecticides, as well as the biofilms formed by the logarithmic growth phase or lysis phase of Bt cells. Our findings confirmed that plant polysaccharides modulate biofilm formation and insecticidal activities of Bt strains and built a foundation for the construction of biofilm-type Bt biopesticides.
Dental caries, particularly secondary caries, which is the main contributor to dental repair failure, has been the subject of extensive research due to its biofilm-mediated, sugar-driven, ...multifactorial, and dynamic characteristics. The clinical utility of restorations is improved by cleaning bacteria nearby and remineralizing marginal crevices. In this study, a novel multifunctional dental resin composite (DRC) composed of Sr-N-co-doped titanium dioxide (Sr-N-TiO2) nanoparticles and nano-hydroxyapatite (n-HA) reinforcing fillers with improved antibacterial and mineralization properties is proposed. The experimental results showed that the anatase-phase Sr-N-TiO2 nanoparticles were synthesized successfully. After this, the curing depth (CD) of the DRC was measured from 4.36 ± 0.18 mm to 5.10 ± 0.19 mm, which met the clinical treatment needs. The maximum antibacterial rate against Streptococcus mutans (S. mutans) was 98.96%, showing significant inhibition effects (p < 0.0001), which was experimentally verified to be derived from reactive oxygen species (ROS). Meanwhile, the resin exhibited excellent self-remineralization behavior in an SBF solution, and the molar ratio of Ca/P was close to that of HA. Moreover, the relative growth rate (RGR) of mouse fibroblast L929 indicated a high biocompatibility, with the cytotoxicity level being 0 or I. Therefore, our research provides a suitable approach for improving the antibacterial and mineralization properties of DRCs.
There is growing interest in developing cell membrane‐coated nanoparticles (CNPs) for unique host cell mimicry and therapeutic applications. The continuous evolution of this technology has motivated ...the coating of nanoparticles with hybrid membranes originating from diverse cell types. The resulting hybrid cell membrane‐coated nanoparticles (hybrid CNPs) exhibit a higher level of synergy among multifunctionalities with better multitasking capabilities than their monotypic membrane‐coated counterparts. This advancement has catalyzed the initiation of numerous research opportunities, marking the advent of a promising frontier in therapeutic applications. This review outlines emerging biomedical applications of hybrid CNPs, focusing on drug targeting, immune modulation, biological neutralization, and disease diagnosis. Within each application, the review underscores how the strategic hybridization of distinct cell membranes augments the resulting nanoparticle therapeutic efficacy. Overall, the insights presented herein consolidate our understanding of current applications and may inspire novel designs with new biomedical applications.
This review summarizes recent advancements in developing hybrid cell membrane‐coated nanoparticles (hybrid CNPs), emphasizing their growing applications in drug targeting, immune modulation, biological neutralization, and disease diagnosis. The unique functions resulting from membrane hybridization in each hybrid CNP design are highlighted, and the future perspectives of hybrid CNPs are discussed.
Action potential (AP) induces presynaptic membrane depolarization and subsequent opening of Ca
channels, and then triggers neurotransmitter release at the active zone of presynaptic terminal. ...Presynaptic Ca
channels and SNARE proteins (SNAREs) interactions form a large signal transfer complex, which are core components for exocytosis. Ca
channels serve to regulate the activity of Ca
channels through direct binding and indirect activation of active zone proteins and SNAREs. The activation of Ca
channels promotes synaptic vesicle recruitment, docking, priming, fusion and neurotransmission release. Intracellular calcium increase is a key step for the initiation of vesicle fusion. Various voltage-gated calcium channel (VGCC) subtypes exert different physiological functions. Until now, it has not been clear how different subtypes of calcium channels integrally regulate the release of neurotransmitters within 200 μs of the AP arriving at the active zone of synaptic terminal. In this mini review, we provide a brief overview of the structure and physiological function of Ca
channel subtypes, interactions of Ca
channels and SNAREs in neurotransmitter release, and dynamic fine-tune Ca
channel activities by G proteins (Gβγ), multiple protein kinases and Ca
sensor (CaS) proteins.
Lactose malabsorption occurs in around 68% of the world's population, causing lactose intolerance (LI) symptoms, such as abdominal pain, bloating, and diarrhea. To alleviate LI, previous studies have ...mainly focused on strengthening intestinal β-galactosidase activity while neglecting the inconspicuous drop in the colon pH caused by the fermentation of non-hydrolyzed lactose by the gut microbes. A drop in colon pH will reduce the intestinal β-galactosidase activity and influence intestinal homeostasis.
Here, we synthesized a tri-stable-switch circuit equipped with high β-galactosidase activity and pH rescue ability. This circuit can switch in functionality between the expression of β-galactosidase and expression of L-lactate dehydrogenase in response to an intestinal lactose signal and intestinal pH signal, respectively. We confirmed that the circuit functionality was efficient in bacterial cultures at a range of pH levels, and in preventing a drop in pH and β-galactosidase activity after lactose administration to mice. An impact of the circuit on gut microbiota composition was also indicated.
Due to its ability to flexibly adapt to environmental variation, in particular to stabilize colon pH and maintain β-galactosidase activity after lactose influx, the tri-stable-switch circuit can serve as a promising prototype for the relief of lactose intolerance.
Given their dangerous effects on the nervous system, neurotoxins represent a significant threat to public health. Various therapeutic approaches, including chelating agents, receptor decoys, and ...toxin-neutralizing antibodies, have been explored. While prophylactic vaccines are desirable, it is oftentimes difficult to effectively balance their safety and efficacy given the highly dangerous nature of neurotoxins. To address this, we report here on a nanovaccine against neurotoxins that leverages the detoxifying properties of cell membrane-coated nanoparticles. A genetically modified cell line with constitutive overexpression of the α7 nicotinic acetylcholine receptor is developed as a membrane source to generate biomimetic nanoparticles that can effectively and irreversibly bind to α-bungarotoxin, a model neurotoxin. This abrogates the biological activity of the toxin, enabling the resulting nanotoxoid to be safely delivered into the body and processed by the immune system. When co-administered with an immunological adjuvant, a strong humoral response against α-bungarotoxin is generated that protects vaccinated mice against a lethal dose of the toxin. Overall, this work highlights the potential of using genetic modification strategies to develop nanotoxoid formulations against various biological threats.
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•A nanovaccine against neurotoxins is constructed by using the detoxifying properties of cell membrane-coated nanoparticles.•Genetically engineered nanoparticles overexpressing the α7 nicotinic acetylcholine receptor can irreversibly bind α-bungarotoxin.•When administered with CpG 1826, the nanotoxoid elicited titers that protected mice against lethal toxin challenge.•This work demonstrates that genetic engineering can be used to generate nanotoxoids with enhanced antigen loading.
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