Matrix metalloproteinases (MMPs) consist of a multigene family of zinc‐dependent extracellular matrix (ECM) remodeling endopeptidases implicated in pathological processes, such as carcinogenesis. In ...this regard, their activity plays a pivotal role in tumor growth and the multistep processes of invasion and metastasis, including proteolytic degradation of ECM, alteration of the cell-cell and cell-ECM interactions, migration and angiogenesis. The underlying premise of the current minireview is that MMPs are able to proteolytically process substrates in the extracellular milieu and, in so doing, promote tumor progression. However, certain members of the MMP family exert contradicting roles at different stages during cancer progression, depending among other factors on the tumor stage, tumor site, enzyme localization and substrate profile. MMPs are therefore amenable to therapeutic intervention by synthetic and natural inhibitors, providing perspectives for future studies. Multiple therapeutic agents, called matrix metalloproteinase inhibitors (MMPIs) have been developed to target MMPs, attempting to control their enzymatic activity. Even though clinical trials with these compounds do not show the expected results in most cases, the field of MMPIs is ongoing. This minireview critically evaluates the role of MMPs in relation to cancer progression, and highlights the challenges, as well as future prospects, for the design, development and efficacy of MMPIs.
The dynamic variation of the expression profile and spatial landscape of multiple enzymes are crucial factors influencing tumor progression and drug treatment. However, the comprehensive analysis of ...these events has been hampered by the limitations of existing imaging technologies. Here we report a cooperatively activatable, DNA‐based fluorescent reporter programmed to detect the correlated activity of dual enzymes, telomerase (TE) and apurinic/apyrimidinic endonuclease 1 (APE1), both in vitro and in vivo. The conformational change of the DNA probe can be orthogonally triggered through TE‐induced DNA elongation and APE1‐mediated specific cleavage, producing a fluorescent signal for imaging the activity of the two enzymes in an AND‐gated manner. Furthermore, we demonstrate the capability of the system for specific tumor imaging through “dual lock‐and‐key” strategy, and visualizing the correlated enzymatic activities during drug treatment of cancer.
A DNA‐based fluorescent reporter operated orthogonally by the two enzymes, telomerase and apurinic/apyrimidinic endonuclease 1, enables the imaging of their correlated activity both in vitro and in vivo. The system was further applied to specific tumor imaging through “dual lock‐and‐key” strategy and analysis of the dual enzymatic activities during drug treatment.
Graphene oxide (GO), an oxidized derivative of graphene, has received much attention for developing novel fluorescent bioanalytic platforms due to its remarkable optical properties and ...biocompatibility. The reliable performance and robustness of GO-based biosensors have enabled various applications in the biomedical field including diagnosis and drug discovery. Here, recent advances in the development of GO-based fluorescent biosensors are overviewed, particularly nucleic acid detection and enzyme activity assay. In addition, practical applications in biomarker detection and high-throughput screening are also examined. Lastly, basic design principles and remaining challenges of these types of biosensors are discussed for further progress.
This feature article highlights graphene oxide-based fluorescent biosensors as one of the most useful tools for biomedical applications such as diagnosis and drug discovery.
A novel two-dimensional nanolayered Ti3C2Cl2 MXene material derived from MAX phase was synthesized through a HF-free method based on elemental replacement reaction in the A atom of traditional ...Ti3AlC2 MAX phase and ZnCl2 molten salts, which possess large specific surface areas, excellent electric conductivity and reducing property. Then the Au/Pt bimetallic nanoparticles decorated Ti3C2Cl2 nanoflakes were synthesized by a self-reduction method with Ti3C2Cl2 as a natural reducing agent and supporter, which possess peroxidase mimic activity and oxidase mimic activity, simultaneously. Based on the prominent catalytic activity of Au/Pt/Ti3C2Cl2 nanocomposite, a novel colorimetric platform was developed for in situ sensing of hydrogen peroxide (H2O2) released from live HeLa cells and colorimetric detection of glutathione (GSH), with the detection ranges of 50–10000 μM and 0.1–20 μM, the detection limits were 10.24 μM and 0.07 μM, respectively. These results allow utilization of the easily accessible 2D surface for the design and application of 2D layered material-supported MXene nanocomposites catalysts in intracellular biosensing.
Preparation of Au/Pt/Ti3C2Cl2 nanoflakes with a HF-free and self-reduction method for in-situ detection of hydrogen peroxide released from live HeLa cells and colorimetric detection of glutathione. Display omitted
In this study, the anti-browning effectiveness of short-term high oxygen pre-stimulation (SHOP), supercooled (SC) storage, or combined (SHOP + SC) treatment for fresh-cut potatoes was explored by ...evaluations on surface color, texture, phenolic anabolism, membrane integrity, antioxidant capacity, and reactive oxygen species (ROS) balancing. Furthermore, enzyme activity ratios (EA ratios) were further proposed to assess the effect of SHOP on enzymatic browning, which were defined as ratios between defense enzymes, including peroxidase (POD), phenylalanine ammonia-lyase (PAL) or catalase (CAT), and attacked enzymes including polyphenol oxidase (PPO) or lipoxygenase (LOX). As a result, SHOP + SC treatment retarded the browning and delayed the softening of fresh-cut potatoes by inhibiting the activities of related enzymes, restraining the accumulation of malondialdehyde (MDA), and promoting the synthesis of phenolic substances against their oxidation in potatoes. Besides, higher POD activities and lower BI were observed in SHOP + SC compared with SC, but PPO activities were non-statistically significant in both. At the early storage stage, the antioxidant capacities of fresh-cut potatoes treated with SHOP and SHOP + SC were enhanced, and the ROS accumulation was inhibited. Moreover, EA ratios and their changing amplitude of the SC group ranked top, followed by the control, SHOP, and SHOP + SC. Results suggested that the antioxidant capacity was reinforced by SHOP in fresh-cut potatoes due to enhanced resistance against membrane lipid damage resulting from mechanical cutting and persistent SC stimulation.
Several types of engineered nanoparticles (ENPs) are being considered for direct application to soils to reduce the application and degradation of pesticides, provide micronutrients, control ...pathogens, and increase crop yields. This study examined the effects of different metal ENPs and their dissolved ions on the microbial community composition and enzyme activity of agricultural soil amended with biosolids. The activity of five extracellular nutrient-cycling enzymes was measured in biosolid-amended soils treated with different concentrations (1, 10, or 100 mg ENP/kg soil) of silver (nAg), zinc oxide (nZnO), copper oxide (nCuO), or titanium dioxide (nTiO2) nanoparticles and their ions over a 30-day period. At 30 days, nZnO and nCuO either had no significant effect on soil enzyme activity or enhanced enzyme activity. In contrast, Ag inhibited selected enzymes when dosed in particulate or dissolved form (at 100 mg/kg). nTiO2 either had no significant effect or slightly decreased enzyme activity. Illumina MiSeq sequencing of microbial communities indicated a shift in soil microbial community composition upon exposure to high doses of metal ions or nAg and negligible shift in the presence of nTiO2. Some taxa responded differently to nAg and Ag+. This work shows how metal ENPs can impact soil enzyme activity and microbial community composition upon introduction into soils amended with biosolids, depending on their type, concentration, and dissolution behavior, hence providing much needed information for the sustainable application of nanotechnology in agriculture.
•Enzymes were more sensitive to litter removal than litter addition.•Roots played more important role in regulating enzyme activities than litter.•Microbes more strongly affected enzymes than ...microclimates in coniferous forest.•Intrinsic relationships among enzymes and their factors varied with forest types.
Litter plays an irreplaceable role in terrestrial ecosystem carbon (C), nitrogen (N) and phosphorus (P) cycling, and its decomposition is largely regulated by litter quality, soil properties and enzyme activities. However, how soil enzyme activities respond to change in litter input under different forest types remains unsolved. Here, we investigated soil enzyme activities involved in C (β-glucosidase, BG), N (N-acetyl-β-glucosaminidase, NAG; leucine aminopeptidase, LAP) and P (acid phosphatase, ACP) under short-term litter manipulations (i.e. Detritus Input and Removal Treatment-DIRT: control, CK; double litter, DL; no roots and double litter, NRDL; no litter, NL; no roots, NR; no roots and no litter, NRNL) and associated influencing drivers in a coniferous forest (Pinus yunnanensis) and a broad-leaved forest (Quercus pannosa) in the subalpine area of Southwest China. Our results showed that litter removal treatment significantly reduced enzyme activities under two forest soils, with the stronger effect of the NR treatment on decreased enzyme activities compared to the NL treatment, possibly because roots could provide more available C sources and nutrient to microorganism and also immediately interact with soil minerals. In contrast, the short-term litter addition did not significantly affect enzyme activities under both two forest soils. Additionally, the BG activities in coniferous forest soil were characterized by a lower effect size compared to those in broad-leaved forest soil under the litter removal (NL and NRNL) treatments, but the higher effect size of LAP and ACP activities were observed under the NRNL treatment in the coniferous forest soil. This finding was attributed to higher organic C sources in the coniferous forest soil which could promote other nutrients utilization by microorganisms, leading to more N and P enzyme productions. We observed that the enzyme activities in the coniferous forest soil were closely related to soil N, P contents and microbial traits (i.e., fungal and bacterial structure), while enzyme activities in the broad-leaved forest soil primarily depended on microclimates (soil temperature and moisture) and soil properties (pH, dissolved organic C and P contents) under short-term litter manipulations. Overall, our results revealed the different pattern and the regulatory mechanism of soil enzyme activities under litter input manipulation of two forests, thereby advancing understanding of soil enzyme dynamics in association with initial litter quality and soil properties under future global change.
Agricultural production systems are immensely exposed to different environmental stresses in which heavy metal stress receives serious concerns. This study was conducted to explore the deleterious ...effects of different chromium （Cr） stress levels, i.e., O, 30, 60, 90, 120, and 150 μmol L^-1, on two maize genotypes, Wandan 13 and Runnong 35. Both genotypes were evaluated by measuring their growth and yield characteristics, Cr accumulation in different plant tissues, alterations in osmolyte accumulation, generation of reactive oxygen species （ROS）, and anti-oxidative enzyme activity to scavenge ROS. The results showed that Cr stress decreased the leaf area, cob formation, 100-grain weight, shoot fresh biomass, and yield formation, while Cr accumulation in different maize tissues was found in the order of roots 〉 leaves 〉 stem ~ seeds in both genotypes. The increased Cr toxicity resulted in higher free proline, soluble sugars and total phenolic contents, and lower soluble protein contents. However, enhanced lipid peroxidation was noticed in the forms of malondialdehyde, hydrogen peroxide （H2O2） and thiobarbituric acid reactive substance accumulation, and electrolyte leakage. The hyperactivity of superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, especially glutathione peroxidase and glutathione reductase indicated that these anti-oxidative enzymes had a central role in protecting maize from Cr toxicity, especially for Wandan 13. Moreover, higher uptake and less translocation of Cr contents into the grains of Wandan 13 implied its importance as a potential candidate against soil Cr pollution.
Traditional composting is a well-suited biotechnology for on-farm management of livestock manure (LM) but still leads to the release of toxic micropollutants and imbalance of nutrients. One in situ ...exoenzyme-assisted composting has shown promise to ameliorate the agronomical quality of end products by improving humification and polymerization. The naturally occurring extracellular laccase from microorganisms belongs to a multicopper phenoloxidase, which is verified for its versatility to tackle micropollutants and conserve organics through the reactive radical-enabled decomposition and polymerization channels. Laccase possesses an indispensable relationship with humus formation during LM composting, but its potential applications for the harmless disposal and resource utilization of LM have until now been overlooked. Herein, we review the extracellular laccase-aided humification mechanism and its optimizing strategy to maintain enzyme activity and in situ production, highlighting the critical roles of laccase in treating micropollutants and preserving organics during LM composting. Particularly, the functional effects of the formed humification products by laccase-amended composting on plant growth are also discussed. Finally, the future perspectives and outstanding questions are summarized. This critical review provides fundamental insights into laccase-boosted humification that ameliorates the quality of end products in LM composting, which is beneficial to guide and advance the practical applications of exoenzyme in humification remediation, the carbon cycle, and agriculture protection.
•Drought increased enzyme activity C:N and fungi:bacteria ratios.•Microbial C and N use efficiencies increased under drought.•The threshold elemental ratio values were larger than the soil C:N ratio.
...Drought has been observed to decrease the accumulation of carbon (C) and nitrogen (N) in forest ecosystems. The microbial C use efficiency (CUE) and N use efficiency (NUE) are critical to elemental cycling in terrestrial ecosystems, which can be calculated by the C:N stoichiometry of soils, microbial biomass, and extracellular enzyme activities. However, little is known about how drought affects microbial CUE and NUE. We extracted soil samples at different depths (0–15 cm, 15–30 cm, and 30–45 cm) in forest stands that were subjected to 30% and 50% throughfall reduction manipulation experiments, in contrast to those obtained from stands that were left undisturbed from July 2019 to April 2020 in a poplar plantation of Eastern China. Under drought conditions, we found that the soil moisture, soil C:N ratio, and C- and N-acquiring enzyme activities decreased; however, the soil pH, microbial biomass C:N ratio, ecoenzymatic activity C:N ratio, and fungi:bacteria ratio increased. Microbial CUE and NUE, which were calculated based on these C:N stoichiometric ratios, also increased. These responses were similar at different soil depths across sampling dates. Our structural equation models indicated that drought-induced increases in CUE and NUE were driven by changes in the soil moisture, fungi:bacteria ratio, and ecoenzymatic activity C:N ratio. Our results suggested that decreases in soil moisture and increases in the ecoenzymatic activity C:N and fungi:bacteria ratios could stimulate microbial CUE and NUE.
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