Regulation Of Enzyme Activity Research Articles

Dual-enzyme decorated semiconducting polymer nanoagents for second near-infrared photoactivatable ferroptosis-immunotherapy.

Enzymes provide a class of potential options to treat cancer, while the precise regulation of enzyme activities for effective and safe therapeutic actions has been poorly reported. Dual-enzyme decorated semiconducting polymer nanoagents for second near-infrared (NIR-II) photoactivatable ferroptosis-immunotherapy are reported in this study. Such nanoagents (termed SPHGA) consist of hemoglobin (Hb)-based semiconducting polymer (SP@Hb), adenosine deaminase (ADA) and glucose oxidase (GOx) with loadings in a thermal-responsive nanoparticle shell. NIR-II photoactivation of SPHGA results in the generation of heat to trigger on-demand releases of two enzymes (ADA and GOx) via destroying the thermal-responsive nanoparticle shells. In the tumor microenvironment, GOx oxidizes glucose to form hydrogen peroxide (H2O2), which promotes the Fenton reaction of iron in SP@Hb, resulting in an enhanced ferroptosis effect and immunogenic cell death (ICD). In addition, ADA degrades high-level adenosine to reverse the immunosuppressive microenvironment, thus amplifying antitumor immune responses. Via NIR-II photoactivatable ferroptosis-immunotherapy, SPHGA shows an improved effect to absolutely remove bilateral tumors and effectively suppress tumor metastases in subcutaneous 4T1 breast cancer models. This study presents a dual-enzyme-based nanoagent with controllable therapeutic actions for effective and precise cancer therapy.

Genome-wide identification of poplar GSTU gene family and its PtrGSTU23 and PtrGSTU40 to improve salt tolerance in poplar

Glutathione S-transferases (GSTs) are abundant proteins encoded by a highly differentiated family of ancient genes. GSTs play an important role in plant cell detoxification and growth and development. However, their precise function in growth and response to abiotic stresses in poplar remains unclear. We have identified 81 GST genes from Populus trichocarpa, which have been categorized into 8 subfamilies. Among these subfamilies, the Tau subfamily stands out as the largest, consisting of 58 members. We isolated two Tau-like Glutathione S-transferases encoding genes, PtrGSTU23 and PtrGSTU40, and investigated the biological functions of these two genes in transgenic poplar to regulate salt tolerance in poplar. Under salt stress, reactive oxygen species (ROS) accumulate in plants, and overexpression of PtrGSTU23/40 in 84 K poplar (Populus alba × Populus glandulosa) could play a crucial role in regulating ROS scavenging by controlling the activity of plant GST enzyme. This regulation of GST enzyme activity enhanced the tolerance of poplar to salt stress. Ultimately, our findings contribute to the availability of genetic resources that can be utilized in the breeding of salt tolerance traits within fast-growing tree species.

Comprehensive analysis of Pigeon egg proteins: Composition, function, and health significance

Pigeon eggs have been used as a valuable source of high-quality proteins, which play a crucial role to regulate metabolism, immunity, and other physiological functions in humans. However, the specific composition and function of pigeon egg proteins remain underexplored. In this study, a comprehensive into the common proteome and modified proteins (phosphorylated proteins and N-glycosylated proteins) of whole pigeon eggs was carried out using proteomics. The results showed that a total of 189 proteins were identified, including 27 phosphorylated proteins (containing 90 phosphorylation modification sites) and 73 N-glycosylated proteins (containing 203 N-glycosylation modification sites). Motif analysis indicated that serine (Ser) accounted for 72.6% of the phosphorylation events, while the sequence "N-X-T" emerged as the predominant motif for N-glycosylation, representing 58.7% of such modifications. Functional enrichment analysis further demonstrated that the majority of pigeon egg proteins, modified proteins were involved in binding and catalytic activities and contributed to enzyme activity regulation and inhibition. Pigeon egg proteins were predominantly associated with the lysosomal pathway, as outlined in the KEGG database. This study could pave the way for the development of innovative food products and nutritional interventions based on pigeon egg proteins.

Steady State Kinetics for Enzymes with Multiple Binding Sites Upstream of the Catalytic Site

The Michaelis–Menten mechanism, which describes the binding of a substrate to an enzyme, is a simplification of the process on a molecular scale. A more detailed model should include the binding of the substrate to precatalytic binding sites (PCBSs) prior to the transition to the catalytic site. Our work shows that the incorporation of PCBSs, in steady-state conditions, generates a Michaelis–Menten-type expression, in which the kinetic parameters KM and Vmax adopt more complex expressions than in the model without PCBSs. The equations governing reaction kinetics can be seen as generalized symmetries, relative to time translation actions over the state space of the underlying chemical system. The study of their structure and defining parameters can be interpreted as looking for invariants associated with these time evolution actions. The expression of KM decreases as the number of PCBSs increases, while Vmax reaches a minimum when the first PCBSs are incorporated into the model. To evaluate the trend of the dynamic behavior of the system, numerical simulations were performed based on schemes with different numbers of PCBSs and six conditions of kinetic constants. From these simulations, with equal kinetic constants for the formation of the Substrate/PCBS complex, it is observed that KM and Vmax are lower than those obtained with the Michaelis–Menten model. For the model with PCBSs, the Vmax reaches a minimum at one PCBS and that value is maintained for all of the systems evaluated. Since KM decreases with the number of PCBSs, the catalytic efficiency increases for enzymes fitting this model. All of these observations are consistent with the general equation obtained. This study allows us to explain, on the basis of the PCBS to KM and Vmax ratios, the effect on enzyme parameters due to mutations far from the catalytic site, at sites involved in the first enzyme/substrate interaction. In addition, it incorporates a new mechanism of enzyme activity regulation that could be fundamental to search for new activity-modulating sites or for the design of mutants with modified enzyme parameters.

Regulation of Rubisco activity in crops.

Efficient plant acclimation to changing environmental conditions relies on fast adjustments of the transcriptome, proteome, and metabolome. Regulation of enzyme activity depends on the activity of specific chaperones, chemical post-translational modifications (PTMs) of amino acid residues, and changes in the cellular and organellar microenvironment. Central to carbon assimilation, and thus plant growth and yield, Rubisco activity is regulated by its chaperone Rubisco activase (Rca) and by adjustments in the chloroplast stroma environment. Focused on crops, this review highlights the main PTMs and stromal ions and metabolites affecting Rubisco and Rca in response to environmental stimuli. Rca isoforms differ in regulatory properties and heat sensitivity, with expression changing according to the surrounding environment. Much of the physiological relevance of Rubisco and Rca PTMs is still poorly understood, though some PTMs have been associated with Rubisco regulation in response to stress. Ion and metabolite concentrations in the chloroplast change in response to variations in light and temperature. Some of these changes promote Rubisco activation while others inhibit activation, deactivate the enzyme, or change the rates of catalysis. Understanding these regulatory mechanisms will aid the development of strategies to improve carbon fixation by Rubisco under rapidly changing environments as experienced by crop plants.

Effects of Natural Products on Enzymes Involved in Ferroptosis: Regulation and Implications

Ferroptosis is a form of regulated cell death that is characterized by the accumulation of iron-dependent lipid peroxides. The regulation of ferroptosis involves both non-enzymatic reactions and enzymatic mechanisms. Natural products have demonstrated potential effects on various enzymes, including GPX4, HO-1, NQO1, NOX4, GCLC, and GCLM, which are mainly involved in glutathione metabolic pathway or oxidative stress regulation, and ACSL3 and ACSL4, which mainly participate in lipid metabolism, thereby influencing the regulation of ferroptosis. In this review, we have provided a comprehensive overview of the existing literature pertaining to the effects of natural products on enzymes involved in ferroptosis and discussed their potential implications for the prevention and treatment of ferroptosis-related diseases. We also highlight the potential challenge that the majority of research has concentrated on investigating the impact of natural products on the expression of enzymes involving ferroptosis while limited attention is given to the regulation of enzyme activity. This observation underscores the considerable potential and scope for exploring the influence of natural products on enzyme activity.

The effects of morin and methotrexate on pentose phosphate pathway enzymes and GR/GST/TrxR enzyme activities: An in vivo and in silico study.

In this study, the mechanisms by which the enzymes glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), glutathione reductase (GR), glutathione-S-transferase (GST), and thioredoxin reductase (TrxR) are inhibited by methotrexate (MTX) were investigated, as well as whether the antioxidant morin can mitigate or prevent these adverse effects in vivo and in silico. For 10 days, rats received oral doses of morin (50 and 100 mg/kg body weight). On the fifth day, a single intraperitoneal injection of MTX (20 mg/kg body weight) was administered to generate toxicity. Decreased activities of G6PD, 6PGD, GR, GST, and TrxR were associated with MTX-related toxicity while morin treatment increased the activity of the enzymes. The docking analysis indicated that H-bonds, pi-pi stacking, and pi-cation interactions were the dominant interactions in these enzyme-binding pockets. Furthermore, the docked poses of morin and MTX against GST were subjected to molecular dynamic simulations for 200 ns, to assess the stability of both complexes and also to predict key amino acid residues in the binding pockets throughout the simulation. The results of this study suggest that morin may be a viable means of alleviating the enzyme activities of important regulatory enzymes against MTX-induced toxicity.

Roles of ROS metabolism and phenylpropanoid pathway in quality maintenance of postharvest Pleurotus eryngii under hyperoxia stress

Hyperoxia application has been proven to be effective in mushrooms preservation, however, the possible induction mechanisms of hyperoxia stress on P. eryngii quality maintenance are incompletely understood. In this study, Pleurotus eryngii treated with hyperoxia (80% O2 +20% N2) and the induced resistance responses of fruiting bodies were mainly investigated through ROS metabolism and phenylpropanoid pathway. The application of hyperoxia could significantly alleviate the quality deterioration of P. eryngii during storage, as observed by higher maintenance of firmness, nutrient substance and membrane integrity. Moreover, hyperoxia application induced the production of hydrogen peroxide (H2O2) in the early stage, as well as the enzymatic antioxidant defense system. The NADPH oxidase genes (PeNoxR) and MAPK signaling pathway were also up-regulated during hyperoxia stress. Besides, hyperoxia stress also promoted the accumulation of major secondary metabolites and up-regulated the transcription levels of the key genes involved in phenylpropanoid pathway. Taken together, this study provided substantial evidences that hyperoxia could induce stress resistance in P. eryngii due to its positive regulation of ROS metabolism-modifying enzyme activities and genes, as well as possible activated phenylpropanoid pathway, therefore delaying the quality deterioration of P. eryngii during postharvest period.

Differential effects of Western diet and traumatic muscle injury on skeletal muscle metabolic regulation in male and female mice.

This study was designed to develop an understanding of the pathophysiology of traumatic muscle injury in the context of Western diet (WD; high fat and high sugar) and obesity. The objective was to interrogate the combination of WD and injury on skeletal muscle mass and contractile and metabolic function. Male and female C57BL/6J mice were randomized into four groups based on a two-factor study design: (1) injury (uninjured vs. volumetric muscle loss [VML]) and (2) diet (WD vs. normal chow [NC]). Electrophysiology was used to test muscle strength and metabolic function in cohorts of uninjured+NC, uninjured+WD, VML+NC and VML+WD at 8weeks of intervention. VML-injured male and female mice both exhibited decrements in muscle mass (-17%, P<0.001) and muscle strength (-28%, P<0.001); however, VML+WD females had a 28% greater muscle mass compared to VML+NC females (P=0.034), a compensatory response not detected in males. VML-injured male and female mice both had lower carbohydrate- and fat-supported muscle mitochondrial respiration (JO2 ) and less electron conductance through the electron transport system (ETS); however, male VML-WD had 48% lower carbohydrate-supported JO2 (P=0.014) and 47% less carbohydrate-supported electron conductance (P=0.026) compared to male VML+NC, and this diet-injury phenotype was not present in females. ETS electron conductance starts with complex I and complex II dehydrogenase enzymes at the inner mitochondrial membrane, and male VML+WD had 31% less complex I activity (P=0.004) and 43% less complex II activity (P=0.005) compared to male VML+NC. This was a diet-injury phenotype not present in females. Pyruvate dehydrogenase (PDH), β-hydroxyacyl-CoA dehydrogenase, citrate synthase, α-ketoglutarate dehydrogenase and malate dehydrogenase metabolic enzyme activities were evaluated as potential drivers of impaired JO2 in the context of diet and injury. There were notable male and female differential effects in the enzyme activity and post-translational regulation of PDH. PDH enzyme activity was 24% less in VML-injured males, independent of diet (P<0.001), but PDH enzyme activity was not influenced by injury in females. PDH enzyme activity is inhibited by phosphorylation at serine-293 by PDH kinase 4 (PDK4). In males, there was greater total PDH, phospho-PDHser293 and phospho-PDH-to-total PDH ratio in WD mice compared to NC, independent of injury (P≤0.041). In females, PDK4 was 51% greater in WD compared to NC, independent of injury (P=0.025), and was complemented by greater phospho-PDHser293 (P=0.001). Males are more susceptible to muscle metabolic dysfunction in the context of combined WD and traumatic injury compared to females, and this may be due to impaired metabolic enzyme functions.

Quantitative proteomics analysis reveals the key proteins related to semen quality in Niangya yaks

BackgroundProteins related to sperm motility and sperm morphology have an important impact on sperm function such as metabolism, motility and fertilisation etc. An understanding of the key proteins related to semen quality in Niangya yaks would help to provide support for breeding. However, the key proteins that affect semen quality in Niangya yaks remain unclear.MethodsHerein, we applied tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC‒MS/MS) to analyze the expression levels of sperm proteins in groups of high- and low-quality semen from Niangya yaks. And fifteen differentially expressed proteins (DEPs) were randomly selected for expression level validation by parallel reaction monitoring (PRM).ResultsOf the 2,092 quantified proteins, 280 were identified as DEPs in the high-quality group versus the low-quality group. Gene Ontology (GO) analysis revealed that in terms of biological pathways, the DEPs were mainly involved in metabolic processes, cell transformation processes, and single organism metabolic processes. In terms of cell composition, the DEPs were mainly located in the cell membrane, organelle, molecular complex. In terms of molecular functions, the most abundant functions of the DEPs were catalytic activity, binding activity, transport activity, and enzyme regulation activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the DEPs were mainly involved in the cytokine and cytokine receptor interaction, notch signaling pathway, lysine biosynthesis, renal function-related protein and proteasome pathway. From protein-protein interaction (PPI) analysis of DEPs involved in important pathways, 6 related proteins affecting the semen quality of Niangya yaks were identified. And the results of the PRM and TMT analysis were consistent.ConclusionsThe differential sperm proteomic analysis of high- and low-quality semen from Niangya yaks, revealed 6 proteins (PSMC5, PSMD8, PSMB3, HSP90AA1, UGP2 and HSPB1), were mainly concentrated in energy production and metabolism, might play important roles in semen quality, which could serve as candidates for the selection and breeding of Niangya yaks.

Characteristics of the Accessible Chromatin Landscape and Transcriptome under Different Temperature Stresses in Bemisia tabaci.

Bemisia tabaci is an important invasive pest with worldwide distribution and strong temperature tolerance. Previous studies have shown that temperature tolerance varies significantly between the different invasive populations. Several key factors involved in epigenetic regulation have been identified and verified in B. tabaci; therefore, epigenetic adaptation mechanisms may also exist. This study aimed to detect changes in the chromatin accessibility landscape and genome-wide transcriptome under different temperature stresses in B. tabaci. Assay for transposase-accessible chromatin with high-throughput sequencing and RNA-seq analyses indicated that transcriptional activity of the genes strongly correlates with chromatin accessibility. Chromatin transcription-activated gene expression regulation is dominant during high-temperature stress in B. tabaci, mainly through the transcriptional repression of genes related to low-temperature stress resistance. Furthermore, B. tabaci resists low-temperature stress by regulating enzyme activities and withstands high-temperature stress by regulating metabolism and synthesis of organic substances, both achieved by altering chromatin accessibility. In summary, this study provides a theoretical basis for exploring changes in gene expression and chromatin accessibility under different temperature stresses, offering a new approach to unravelling regulatory mechanisms underlying the onset of molecular regulation in response to various temperature stress conditions.

Metabolite interactions in the bacterial Calvin cycle and implications for flux regulation

Metabolite-level regulation of enzyme activity is important for microbes to cope with environmental shifts. Knowledge of such regulations can also guide strain engineering for biotechnology. Here we apply limited proteolysis-small molecule mapping (LiP-SMap) to identify and compare metabolite-protein interactions in the proteomes of two cyanobacteria and two lithoautotrophic bacteria that fix CO2 using the Calvin cycle. Clustering analysis of the hundreds of detected interactions shows that some metabolites interact in a species-specific manner. We estimate that approximately 35% of interacting metabolites affect enzyme activity in vitro, and the effect is often minor. Using LiP-SMap data as a guide, we find that the Calvin cycle intermediate glyceraldehyde-3-phosphate enhances activity of fructose-1,6/sedoheptulose-1,7-bisphosphatase (F/SBPase) from Synechocystis sp. PCC 6803 and Cupriavidus necator in reducing conditions, suggesting a convergent feed-forward activation of the cycle. In oxidizing conditions, glyceraldehyde-3-phosphate inhibits Synechocystis F/SBPase by promoting enzyme aggregation. In contrast, the glycolytic intermediate glucose-6-phosphate activates F/SBPase from Cupriavidus necator but not F/SBPase from Synechocystis. Thus, metabolite-level regulation of the Calvin cycle is more prevalent than previously appreciated.

A structural biology view on the enzymes involved in eukaryotic mRNA turnover.

The cellular environment contains numerous ribonucleases that are dedicated to process mRNA transcripts that have been targeted for degradation. Here, we review the three dimensional structures of the ribonuclease complexes (Pan2-Pan3, Ccr4-Not, Xrn1, exosome) and the mRNA decapping enzymes (Dcp2, DcpS) that are involved in mRNA turnover. Structures of major parts of these proteins have been experimentally determined. These enzymes and factors do not act in isolation, but are embedded in interaction networks which regulate enzyme activity and ensure that the appropriate substrates are recruited. The structural details of the higher order complexes that form can, in part, be accurately deduced from known structural data of sub-complexes. Interestingly, many of the ribonuclease and decapping enzymes have been observed in structurally different conformations. Together with experimental data, this highlights that structural changes are often important for enzyme function. We conclude that the known structural data of mRNA decay factors provide important functional insights, but that static structural data needs to be complemented with information regarding protein motions to complete the picture of how transcripts are turned over. In addition, we highlight multiple aspects that influence mRNA turnover rates, but that have not been structurally characterized so far.

Cancer-associated somatic mutations in human phosphofructokinase-1 reveal a critical electrostatic interaction for allosteric regulation of enzyme activity.

Metabolic reprogramming, including increased glucose uptake and lactic acid excretion, is a hallmark of cancer. The glycolytic "gatekeeper" enzyme phosphofructokinase-1 (PFK1), which catalyzes the step committing glucose to breakdown, is dysregulated in cancers. While altered PFK1 activity and expression in tumors have been demonstrated, little is known about the effects of cancer-associated somatic mutations. Somatic mutations in PFK1 inform our understanding of allosteric regulation by identifying key amino acid residues involved in the regulation of enzyme activity. Here, we characterized mutations disrupting an evolutionarily conserved salt bridge between aspartic acid and arginine in human platelet (PFKP) and liver (PFKL) isoforms. Using purified recombinant proteins, we showed that disruption of the Asp-Arg pair in two PFK1 isoforms decreased enzyme activity and altered allosteric regulation. We determined the crystal structure of PFK1 to 3.6Å resolution and used molecular dynamic simulations to understand molecular mechanisms of altered allosteric regulation. We showed that PFKP-D564N had a decreased total system energy and changes in the electrostatic surface potential of the effector site. Cells expressing PFKP-D564N demonstrated a decreased rate of glycolysis, while their ability to induce glycolytic flux under conditions of low cellular energy was enhanced compared to cells expressing wild-type PFKP. Taken together, these results suggest that mutations in Arg-Asp pair at the interface of the catalytic-regulatory domains stabilizes the t-state and presents novel mechanistic insight for therapeutic development in cancer.

Non-Covalent Interactions between dUTP C5-Substituents and DNA Polymerase Decrease PCR Efficiency.

The approach based on molecular modeling was developed to study dNTP derivatives characterized by new polymerase-specific properties. For this purpose, the relative efficiency of PCR amplification with modified dUTPs was studied using Taq, Tth, Pfu, Vent, Deep Vent, Vent (exo-), and Deep Vent (exo-) DNA polymerases. The efficiency of PCR amplification with modified dUTPs was compared with the results of molecular modeling using the known 3D structures of KlenTaq polymerase-DNA-dNTP complexes. The dUTPs were C5-modified with bulky functional groups (the Cy5 dye analogs) or lighter aromatic groups. Comparing the experimental data and the results of molecular modeling revealed the decrease in PCR efficiency in the presence of modified dUTPs with an increase in the number of non-covalent bonds between the substituents and the DNA polymerase (about 15% decrease per one extra non-covalent bond). Generalization of the revealed patterns to all the studied polymerases of the A and B families is discussed herein. The number of non-covalent bonds between the substituents and polymerase amino acid residues is proposed to be a potentially variable parameter for regulating enzyme activity.

Assessing food-induced plasticity of digestive enzyme activity during echinoid larval development

Growth and development of planktotrophic larvae are dependent on food availability within a nutritionally heterogeneous ocean. Insufficient food can reduce growth and delay metamorphosis, thereby decreasing survival and recruitment. Phenotypic plasticity allows an organism to adjust its phenotype (morphological, physiological, biochemical) to its environment. Planktotrophic echinoid larvae with low food grow longer arms to increase feeding capacity and with high food grow shorter arms to allocate more resources to faster development of other structures. In this study, we investigated if food-induced plasticity in the Pacific sand dollar, Dendraster excentricus, also involved the regulation of digestive enzyme activities during pre-feeding and early feeding larval stages. We measured protein-specific activities of protein, lipid, and carbohydrate digestive enzymes at 33 h post-fertilization (HPF; pre-feeding stages) and 96 HPF (feeding stages) to examine if algal presence influenced enzyme rates at these stages and if there was an interaction between pre-feeding stage and feeding stage algal presence. While all enzymes studied increased activities during development, there was no significant effect of pre-feeding algae levels on pre-feeding digestive enzyme activities for all three types of enzymes studied. Furthermore, there was no interaction between larval feeding status (pre-feeding vs. feeding stage) and the presence of algal food. Evidence of food-induced plasticity was observed during the 96 HPF feeding stage for esterase (lipid digestion) and amylase (carbohydrate digestion). Both enzymes exhibited an increase in protein-specific rates ~1.6-times greater for larvae reared with algae than for those reared without algae. Protease activities were similar for fed and unfed larvae. The differential responses to food during the larval stage likely reflect the initial biochemical composition of the egg, the composition of algal food, and the unique use of each substrate to sustain larval growth and development. Our results demonstrate a multidimensional food-induced biochemical plasticity response of larvae to their feeding environment which includes discrete temporal windows of sensitivity and different enzyme class-specific responses.

Enhancing rosmarinic acid production and regulating enzyme activity in Melissa officinalis L. using spectrally tunable light-emitting diodes

Melissa officinalis L. (lemon balm) is a renowned medical herb enriched with phenolic compounds, particularly rosmarinic acid (RA) which is known for its antimicrobial and antioxidant activities. This study aimed at improving the medicinal characteristics of M. officinalis by enhancing the production of the total phenolic content (TPC) and RA as well as evaluating the activities of RA-regulatory enzymes, following a series of light treatments, using i) three different spectrally tuned light treatments, ii) white light-emitting diode (LED), and iii) sunlight. Phytochemical analyses revealed that the blue-enriched light treatment (40% red, 35% blue, 15% green and 10% far-red) significantly elevated the TPC, RA, and antioxidant capacity of M. officinalis. Additionally, the application of spectrally tunable LEDs also induced the malondialdehyde level and sugar concentration with minimal effect on the chlorophyll content and antimicrobial activity. Increased activities of RA-regulatory enzymes, namely phenylalanine ammonia-lyase, tyrosine aminotransferase, and hydroxyphenylpyruvate reductase, were associated with RA production. These findings suggest that the elicitation based on spectrally tunable LEDs has promising potential for promoting phenolic compounds production in M. officinalis.

Effect of diminazene on cardiac hypertrophy through mitophagy in rat models with hyperthyroidism induced by levothyroxine.

Hyperthyroidism is associated with the alteration in molecular pathways involved in the regulation of mitochondrial mass and apoptosis, which contribute to the development of cardiac hypertrophy. Diminazene (DIZE) is an animal anti-infection drug that has shown promising effects on improving cardiovascular disease. The aim of the present study was to investigate the therapeutic effect of DIZE on cardiac hypertrophy and the signaling pathways involved in this process in the hyperthyroid rat model. Twenty male Wistar rats were equally divided into four groups: control, hyperthyroid, DIZE, and hyperthyroid + DIZE. After 28 days of treatment, serum thyroxine (T4) and thyroid stimulating hormone (TSH) level, cardiac hypertrophy indices, cardiac damage markers, cardiac malondialdehyde (MDA), and superoxide dismutase (SOD) level, the mRNA expression level of mitochondrial and apoptotic genes were evaluated. Hyperthyroidism significantly decreased the cardiac expression level of SIRT1/PGC1α and its downstream involved in the regulation of mitochondrial biogenesis, mitophagy, and antioxidant enzyme activities including TFAM, PINK1/MFN2, Drp1, and Nrf2, respectively, as well as stimulated mitochondrial-dependent apoptosis by reducing Bcl-2 expression and increasing Bax expression. Treatment with DIZE significantly reversed the downregulation of SIRT1, PGC1α, PINK1, MFN2, Drp1, and Nrf2 but did not significantly change the TFAM expression. Moreover, DIZE suppressed apoptosis by normalizing the cardiac expression levels of Bax and Bcl-2. DIZE is effective in attenuating hyperthyroidism-induced cardiac hypertrophy by modulating the mitophagy-related pathway, suppressing apoptosis and oxidative stress.

Pre-cut L-cysteine treatment inhibited the browning of fresh-cut apples by regulating enzyme activities and amino acid levels

This work investigated the effect of pre-cut L-cysteine treatment on the browning of fresh-cut apple slices. The results showed that 1% L-cysteine pre-cut treatment for 15 min could significantly inhibit the browning and extend the shelf life of fresh-cut apple slices. Pre-cut L-cysteine treatment was found to significantly inhibit polyphenol oxidase (PPO) activity and its gene expression, and increased superoxide dismutase (SOD) and catalase (CAT) activity as well as DPPH radical scavenging rate. In addition, pre-cut L-cysteine treatment improved the content of total and individual phenolics, particularly the content of chlorogenic acid and epicatechin in pulp. Pre-cut L-cysteine treatment also increased the cysteine, glutamic acid, serine and leucine level in pulp and peel. Therefore, pre-cut L-cysteine treatment is an effective method to control the browning of fresh-cut apple by inhibiting PPO activity, improving antioxidant ability and regulating the synthesis of phenolics and free amino acids.

Regulation of soil enzyme activity and bacterial communities by food waste compost application during field tobacco cultivation cycle

Food waste (FW) composting is an effective waste resource utilization method; however, only limited approaches of FW compost application in agriculture have been investigated. This study reports changes in soil chemical properties, enzyme activities, and bacterial communities at different tillage stages and its effects on tobacco biomass after FW compost application in tobacco cultivation field experiments. The results showed that FW compost increased tobacco biomass. Also, FW compost functioned as a fertilizer that acted mainly during the maturity (September) and fallow (December) periods of tobacco, and its effect was enhanced with increasing application rates. FW compost significantly increased soil pH, organic carbon, total nitrogen, total phosphorus, alkaliolytic nitrogen, and available phosphorus content. It enhanced soil urease, acid phosphatase, fluorescein diacetate hydrolase, and polyphenol oxidase activities. FW compost application increased soil bacterial diversity, increasing the relative abundance of dominant bacteria such as Proteobacteria and Bacteroidetes while decreasing the relative abundance of Acidobacteria and Chloroflexi. Bacterial chemoheterotrophy, aerobic_chemoheterotrophy, ureolysis, chloroplasts, nitrogen_fixation, and fermentation functions were enhanced, and the complexity of ecological networks among bacterial species increased. A combined ranking analysis showed that the soil's available phosphorus, pH, alkaline nitrogen, and total phosphorus content were the main factors influencing bacterial population dynamics. In conclusion, FW composts can be used as an alternative to fertilizers. They exerts their beneficial properties by regulating bacterial communities mainly through soil chemistry, indirectly enhancing soil enzyme activity, and increasing tobacco yield.