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Copyright of Food & Fermentation Industries is the property of Food & Fermentation Industries and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The development of an environmentally benign method for the synthesis of nanoparticles has been facilitated by green chemistry. "Green synthesis" uses a range of biological elements like microbes, plants, and other biodegradable materials to produce NPs. Active biomolecules that are secreted by natural strains and present in the plant extracts serve as both reducing and capping/stabilizing agents. Microorganisms' intracellular enzymes can reduce metal ions, which explains how NPs might potentially nucleate. Plant-based synthesis of nanomaterials is particularly promising owing to abundant resources, simplicity of synthesis, and low cost. Silver nanoparticles (AgNPs) are attracting great attention in the research community due to their wide variety of applications in chemistry, food technology, microbiology, and biomedicine. Recent years have seen a large amount of research on the bio-genic synthesis of AgNPs employing biomaterials like plant extract and bacteria as reducing agents. Herein we discuss a thorough overview of the plant-based synthesis of silver nanoparticles (AgNPs), characterization approaches, applications, and toxicity. The review covers the green chemistry and nanotechnology elements of producing AgNPs, including a thorough discussion of the plant extract mediated synthesis, detailed formation mechanism, and a well-balanced emphasis on hazards and advantages. Based on current developments, the optimisation strategies, applications, and interdisciplinary characteristics are also covered in detail. • Plant-based synthesis of nanomaterials is particularly promising. • A comprehensive review on plant-based AgNPs synthesis. • Synthesis, characterization approaches, applications and toxicity are discussed. [ABSTRACT FROM AUTHOR]

Background: Limited research has been conducted on energy fluctuation during the transition state, despite the critical role of energy supply in microbial physiological metabolism. Results: This study aimed to investigate the regulatory function of transition state transcription factor AbrB on energy metabolism in Bacillus licheniformis WX-02. Firstly, the deletion of abrB was found to prolong the cell generation time, significantly reducing the intercellular ATP concentration and NADH/NAD+ ratio at the early stage. Subsequently, various target genes and transcription factors regulated by AbrB were identified through in vitro verification assays. Specifically, AbrB was shown to modulate energy metabolism by directly regulating the expression of genes pyk and pgk in substrate-level phosphorylation, as well as genes narK and narGHIJ associated with nitrate respiration. In terms of oxidative phosphorylation, AbrB not only directly regulated ATP generation genes, including cyd, atpB, hmp, ndh, qoxA and sdhC, but also influenced the expression of NAD-dependent enzymes and intracellular NADH/NAD+ ratio. Additionally, AbrB positively affected the expression of transcription factors CcpN, Fnr, Rex, and ResD involved in energy supply, while negatively affected the regulator CcpA. Overall, this study found that AbrB positively regulates both substrate-level phosphorylation and oxidative phosphorylation, while negatively regulating nitrate respiration. Conclusions: This study proposes a comprehensive regulatory network of AbrB on energy metabolism in Bacillus, expanding the understanding of regulatory mechanisms of AbrB and elucidating energy fluctuations during the transition state. [ABSTRACT FROM AUTHOR]

Systemic glucocorticoid excess causes several adverse metabolic conditions, most notably Cushing's syndrome. These effects are amplified by the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Here, we determined the less well-characterised effects of glucocorticoid excess, and the contribution of 11β-HSD1 amplification on metabolic rate in mice. Male and female C57BL/6J (wild type, WT) and 11β-HSD1 knockout (11β- HSD1 KO) mice were treated with high-dose corticosterone or a vehicle control for 3 weeks. Indirect calorimetry was conducted during the final week of treatment, with or without fasting, to determine the impact on metabolic rate. We found that corticosterone treatment elevated metabolic rate and promoted carbohydrate utilisation primarily in female WT mice, with effects more pronounced during the light phase. Corticosterone treatment also resulted in greater fat accumulation in female WT mice. Corticosterone induced hyperphagia was identified as a likely causal factor altering the respiratory exchange ratio (RER) but not energy expenditure (EE). Male and female 11β-HSD1 KO mice were protected against these effects. We identify novel metabolic consequences of sustained glucocorticoid excess, identify a key mechanism of hyperphagia, and demonstrate that 11β-HSD1 is required to manifest the full metabolic derangement. [ABSTRACT FROM AUTHOR]

Background: Bruton's tyrosine kinase (BTK) is an intracellular signaling enzyme that regulates B-lymphocyte and myeloid cell functions. Due to its involvement in both innate and adaptive immune compartments, BTK inhibitors have emerged as a therapeutic option in autoimmune disorders such as multiple sclerosis (MS). Brain-penetrant, small-molecule BTK inhibitors may also address compartmentalized neuroinflammation, which is proposed to underlie MS disease progression. BTK is expressed by microglia, which are the resident innate immune cells of the brain; however, the precise roles of microglial BTK and impact of BTK inhibitors on microglial functions are still being elucidated. Research on the effects of BTK inhibitors has been limited to rodent disease models. This is the first study reporting effects in human microglia. Methods: Here we characterize the pharmacological and functional properties of fenebrutinib, a potent, highly selective, noncovalent, reversible, brain-penetrant BTK inhibitor, in human microglia and complex human brain cell systems, including brain organoids. Results: We find that fenebrutinib blocks the deleterious effects of microglial Fc gamma receptor (FcγR) activation, including cytokine and chemokine release, microglial clustering and neurite damage in diverse human brain cell systems. Gene expression analyses identified pathways linked to inflammation, matrix metalloproteinase production and cholesterol metabolism that were modulated by fenebrutinib treatment. In contrast, fenebrutinib had no significant impact on human microglial pathways linked to Toll-like receptor 4 (TLR4) and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) signaling or myelin phagocytosis. Conclusions: Our study enhances the understanding of BTK functions in human microglial signaling that are relevant to MS pathogenesis and suggests that fenebrutinib could attenuate detrimental microglial activity associated with FcγR activation in people with MS. [ABSTRACT FROM AUTHOR]

The study focused on the nitrilo‐tris‐(methylene phosphonate) [K2ntpH4]2 and [(K1−yTly)2ntpH4]2 complexes, which are a series of isovalent substitutions. The crystals of [K2ntpH4]2 are monoclinic and belong to the space group of symmetry P21/c with Z=4. When thallium substitutes potassium, the molecular structure remains the same, but the symmetry of the crystal packing changes to a triclinic system, space group of symmetry P1‾ ${\bar{1}}$ , with Z=2. One coordination polyhedra maintains an isometric configuration, while the other undergoes significant distortions. Polarization‐selective coordination is observed, where the thallium(I) ion, which is easily polarizable, populates the highly distorted polyhedron. The low polarizable potassium ion populates the weakly distorted one. The crystal is formed with an average thallium fraction higher than the initial aqueous solution. This suggests that replacing potassium ions in the complex with thallium ions is energetically favourable. It could explain why thallium is toxic to intracellular enzymes and carriers of genetic information. The isovalent substitution of potassium made it possible to observe the step‐by‐step formation of a super‐strong hydrogen bond, a phenomenon that is rarely detected under normal conditions. The O...O interatomic distance in the hydrogen bond decreases gradually from 2.55 Å for [K2ntpH4]2 to 2.474 Å for [Tl2ntpH4]2. [ABSTRACT FROM AUTHOR]

Cytokines function as communication tools of the immune system, serving critical functions in many biological responses and shaping the immune response. When cytokine production or their biological activity goes awry, the homeostatic balance of the immune response is altered, leading to the development of several pathologies such as autoimmune and inflammatory disorders. Cytokines bind to specific receptors on cells, triggering the activation of intracellular enzymes known as Janus kinases (JAKs). The JAK family comprises four members, JAK1, JAK2, JAK3 and tyrosine kinase 2, which are critical for intracellular cytokine signalling. Since the mid-2010s multiple JAK inhibitors have been approved for inflammatory and haematological indications. Currently, approved JAK inhibitors have demonstrated clinical efficacy; however, improved selectivity for specific JAKs is likely to enhance safety profiles, and different strategies have been used to accomplish enhanced JAK selectivity. In this update, we discuss the background of JAK inhibitors, current approved indications and adverse effects, along with new developments in this field. We address the issue of JAK selectivity and its relevance in terms of efficacy, and describe new modalities of JAK targeting, as well as new aspects of JAK inhibitor action. This Review provides an update on developments in Janus kinase inhibitors, including new disease indications and adverse effects. The authors discuss issues surrounding selectivity and efficacy, as well as new routes for administration of Janus kinase inhibitors. Key points: Januse kinase (JAK) inhibitors show equivalent or superior efficacy compared with biologic DMARDs in several autoimmune and inflammatory diseases. The use of JAK inhibitors has been hampered by adverse events, which could be linked to the JAKs that are blocked. Assessment of individual JAK inhibitor selectivity is still a matter of debate, as different assays can yield different results. Selective JAK inhibitors are generally equally effective, but improved, long-term safety has not been fully established. Tissue-targeted JAK inhibitors could circumvent the problem of adverse effects resulting from systemic administration. Alternative strategies for JAK inhibition with small interfering RNAs or metabolite derivatives constitute an exciting area of development. [ABSTRACT FROM AUTHOR]

• The isolated strain Providencia rettgeri was capable of degrading TCPP efficiently. • The degradation of TCPP was mainly via phosphoester bond hydrolysis. • BCPP (C6H13Cl2PO4) and MCPP (C3H8ClPO4) were the main degradation intermediates. • Both intracellular and extracellular enzymes could degrade TCPP. • The presence of Cu2+ had a promoting effect on TCPP degradation by enzyme. Tri (2-chloropropyl) phosphate (TCPP) was an emerging contaminant of global concern because of its frequent occurrence, potential toxic effects, and persistence in the environment. Microbial degradation might be an efficient and safe removal method, but limited information was available. In this study, Providencia rettgeri was isolated from contaminated sediment and showed it could use TCPP as unique phosphorus source to promote growth, and decompose 34.7% of TCPP (1 mg/L) within 5 days. The microbial inoculation and the initial concentration of TCPP could affect the biodegradation efficient. Further study results indicated that TCPP decomposition by Providencia rettgeri was mainly via phosphoester bond hydrolysis, evidenced by the production of bis (2-chloropropyl) phosphate (C 6 H 13 Cl 2 PO 4) and mono-chloropropyl phosphate (C 3 H 8 ClPO 4). Both intracellular and extracellular enzymes could degrade TCPP, but intracellular degradation was dominant in the later reaction stage, and the presence of Cu2+ ions had a promoting effect. These findings developed novel insights into the potential mechanism of TCPP microbial degradation. [Display omitted] [ABSTRACT FROM AUTHOR]

The biophysical characterization and engineering of optogenetic tools and photobiological systems has been hampered by the lack of efficient methods for spectral illumination of microplates for high-throughput analysis of action spectra. Current methods to determine action spectra only allow the sequential spectral illumination of individual wells. Here we present the open-source RainbowCap-system, which combines LEDs and optical filters in a standard 96-well microplate format for simultaneous and spectrally defined illumination. The RainbowCap provides equal photon flux for each wavelength, with the output of the LEDs narrowed by optical bandpass filters. We validated the RainbowCap for photoactivatable G protein-coupled receptors (opto-GPCRs) and enzymes for the control of intracellular downstream signaling. The simultaneous, spectrally defined illumination provides minimal interruption during time-series measurements, while resolving 10 nm differences in the action spectra of optogenetic proteins under identical experimental conditions. The RainbowCap is also suitable for studying the spectral dependence of light-regulated gene expression in bacteria, which requires illumination over several hours. In summary, the RainbowCap provides high-throughput spectral illumination of microplates, while its modular, customizable design allows easy adaptation to a wide range of optogenetic and photobiological applications. [ABSTRACT FROM AUTHOR]

Primordial follicles (PFs) function as the long‐term reserve for female reproduction, remaining dormant in the ovaries and becoming progressively depleted with age. Oxidative stress plays an important role in promoting female reproductive senescence during aging, but the underlying mechanisms remain unclear. Here, we find that low levels of reactive oxygen species (ROS) are essential for sustaining PF dormancy. Compared to growing follicles, oocytes within PFs were shown to be more susceptible to ROS, which accumulates and damages PFs to promote reproductive senescence. Mechanistically, oocytes within PFs were shown to express high levels of the intracellular antioxidant enzyme superoxide dismutase 1 (SOD1), counteracting ROS accumulation. Decreased SOD1 expression, as a result of aging or through the experimental deletion of the Sod1 gene in oocytes, resulted in increased oxidative stress and triggered ferroptosis within PFs. In conclusion, this study identified antioxidant defense mechanisms protecting PFs in mouse ovaries and characterized cell death mechanisms of oxidative stress‐induced PF death. [ABSTRACT FROM AUTHOR]

[Display omitted] The coexistence of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) in the environment poses a potential threat to public health. In our study, we have developed a novel advanced oxidation process for simultaneously removing ARGs and ARB by two types of iron and nitrogen-doped biochar derived from rice straw (FeN-RBC) and sludge (FeN-SBC). All viable ARB (approximately 108 CFU mL−1) was inactivated in the FeN-RBC/ peroxymonosulfate (PMS) system within 40 min and did not regrow after 48 h even in real water samples. Flow cytometry identified 96.7 % of dead cells in the FeN-RBC/PMS system, which verified the complete inactivation of ARB. Thorough disinfection of ARB was associated with the disruption of cell membranes and intracellular enzymes related to the antioxidant system. Whereas live bacteria (approximately 200 CFU mL−1) remained after FeN-SBC/PMS treatment. Intracellular and extracellular ARGs (tetA and tetB) were efficiently degraded in the FeN-RBC/PMS system. The production of active species, primarily •OH, SO 4 •- and Fe (IV), as well as electron transfer, were essential to the effective disinfection of FeN-RBC/PMS. In comparison with FeN-SBC, the better catalytic performance of FeN-RBC was mainly ascribed to its higher amount of pyridine-N and Fe0, and more reactive active sites (such as C O group and Fe-N sites). Density functional theory calculations indicated the greater adsorption energy and Bader charge, more stable Fe-O bond, more easily broken O O bond in FeN-RBC/PMS, which demonstrated the stronger electron transfer capacity between FeN-RBC and PMS. To encapsulate, our study provided an efficient and dependable method for the simultaneous elimination of ARGs and ARB in water. [ABSTRACT FROM AUTHOR]

The Phosphatidylinositol-3-kinase (PI3K) family is well-known to comprise three classes of intracellular enzymes. Class I PI3Ks primarily function in signaling by responding to cell surface receptor stimulation, while class II and III are more involved in membrane transport. Under normal physiological conditions, the PI3K signaling network orchestrates cell growth, division, migration and survival. Aberrant activation of the PI3K signaling pathway disrupts cellular activity and metabolism, often marking the onset of cancer. Currently, the Food and Drug Administration (FDA) has approved the clinical use of five class I PI3K inhibitors. These small-molecule inhibitors, which exhibit varying selectivity for different class I PI3K family members, are primarily used in the treatment of breast cancer and hematologic malignancies. Therefore, the development of novel class I PI3K inhibitors has been a prominent research focus in the field of oncology, aiming to enhance potential therapeutic selectivity and effectiveness. In this review, we summarize the specific structures of PI3Ks and their functional roles in cancer progression. Additionally, we critically evaluate small molecule inhibitors that target class I PI3K, with a particular focus on their clinical applications in cancer treatment. Moreover, we aim to analyze therapeutic approaches for different types of cancers marked by aberrant PI3K activation and to identify potential molecular targets amenable to intervention with small-molecule inhibitors. Ultimately, we propose future directions for the development of therapeutic strategies that optimize cancer treatment outcomes by modulating the PI3K family. [ABSTRACT FROM AUTHOR]

Background: Orlistat (ORS) and metformin (MEF) are robustly used as well-established clinical drugs for the treatment for both obesity and the consequences of diabetes mellitus. Additionally, no study has been conducted to explore the consequence of the combination of both ORS and MEF on the kidneys of rats with obesity-induced renal injury (OBS). Objectives: Therefore, the objective of the current research was designed to explore the possible ameliorative effects of either ORS and/or MEF or their combination against obesity (OBS) induced experimental renal oxidative stress. Methods: Renal oxidative stress was investigated at redox histopathological and immunohistological points in the kidney tissues. Results: The levels of urea, uric acid, and creatinine increased with the obesity effect; in addition, the myeloperoxidase (MPO) and xanthine oxidase (XO) activators were elevated significantly with the induction of OBS. The levels of non-enzymatic antioxidants (glutathione and thiol) declined sharply in OBS rats as compared to the normal group. Conclusion: The data displayed that the combination of both ORS and MEF declined the obesity effects significantly by reducing the level of peroxidation (MDA), and enhancement intracellular antioxidant enzymes. These biochemical findings were supported by histopathology, immunohistochemistry, and Masson-Trichrome evaluation, which showed minor morphological changes in the kidneys of rats. [ABSTRACT FROM AUTHOR]

Dye is a substance that imparts colour onto textiles, fabrics, paper, leather, etc. and is not altered by washing, heating, and light. Dyes were extracted from plants, animals, and minerals until synthetic dyes came to the market, as synthetic dyes were more stable, readily available, and inexpensive. Despite being extremely important to the economy, they have been among the most significant global polluters. Textile dye industries have become the chief source of water pollution, with their effluents increasing the turbidity of water and reducing photosynthesis and dissolved oxygen levels. This leads to significant damage to aquatic biodiversity, threatening the survival of many species. Synthetic dyes have carcinogenic, mutagenic, and genotoxic effects on animals and human beings, posing a severe health risk. The degradation of dyes is essential for ensuring the sustainability of the environment for future generations. The traditional physicochemical means of dye treatment are not convenient because of the high solubility in water, cost of method utilisation and other disadvantages related to these techniques. To overcome the disadvantages of physicochemical treatment, biological methods or bioremediation can be used as an alternative. The objective of this review article is to study the mechanisms involved in the degradation of textile dyes by bacteria to obtain sustainable, economically and ecologically sound solutions for dye treatment. This paper will explain the various types of natural and synthetic dyes utilised in the textile industry, their chemistry, and how they affect water and soil ecosystems. The treatment of textile dye by various physicochemical methods and their advantages and disadvantages are also discussed. In bioremediation, the microorganisms utilize organic pollutants as a source of food or energy. Bioremediation uses biosorption and enzymatic activity for dye degradation, which does not disturb natural processes and is thus sustainable. The microorganisms secrete crucial extracellular and intracellular enzymes that carry out decolourisation and degradation through a series of events, which include hydrolysis, acidogenesis, and methanogenesis. We will discuss how aerobic and anaerobic microorganisms degrade these textile dyes through the process of biodegradation and bioaugmentation and how this technology provides a clean and eco-friendly method for removing textile dyes. [ABSTRACT FROM AUTHOR]

Our preliminary study identified dairy cow placenta extract (CPE) as a mixture of peptides with potent antioxidant activity both in vivo and in vitro. However, the specific antioxidant peptides (AOPs) responsible for this activity were not yet identified. In the current study, we employed virtual screening and chromatography techniques to isolate two peptides, ANNGKQWAEVF (CP1) and QPGLPGPAG (CP2), from CPE. These peptides were found to be less stable under extreme conditions such as high temperature, strong acid, strong alkali, and simulated digestive conditions. Nevertheless, under normal physiological conditions, both CP1 and CP2 exhibited significant antioxidant properties, including free-radical scavenging, metal chelating, and the inhibition of lipid peroxidation. They also up-regulated the activities of intracellular antioxidant enzymes in response to hydrogen-peroxide-induced oxidative stress, resulting in reduced MDA levels, a decreased expression of the Keap1 gene and protein, and increased levels of the Nrf2 and HO-1 genes and proteins. Furthermore, CP1 demonstrated superior antioxidant activity compared to CP2. These findings suggest that CP1 and CP2 hold potential for mitigating oxidative stress in vitro and highlight the efficacy of virtual screening as a method for isolating AOPs within CPE. [ABSTRACT FROM AUTHOR]

Essential oils (EOs) represent a pivotal source for developing potent antimicrobial drugs. However, EOs have seldom found their way to the pharmaceutical market due to their instability and low bioavailability. Nanoencapsulation is an auspicious strategy that may circumvent these limitations. In the current study, lemongrass essential oil (LGO) was encapsulated in zein-sodium caseinate nanoparticles (Z-NaCAS NPs). The fabricated nanocomposite was characterized using dynamic light scattering, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy. The antimicrobial activity of LGO loaded NPs was assessed in comparison to free LGO against Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae. Furthermore, their antibacterial mechanism was examined by alkaline phosphatase, lactate dehydrogenase, bacterial DNA and protein assays, and scanning electron microscopy. Results confirmed the successful encapsulation of LGO with particle size of 243 nm, zeta potential of – 32 mV, and encapsulation efficiency of 84.7%. Additionally, the encapsulated LGO showed an enhanced thermal stability and a sustained release pattern. Furthermore, LGO loaded NPs exhibited substantial antibacterial activity, with a significant 2 to 4 fold increase in cell wall permeability and intracellular enzymes leakage versus free LGO. Accordingly, nanoencapsulation in Z-NaCAS NPs improved LGO physicochemical and antimicrobial properties, expanding their scope of pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Parasitic diseases, particularly malaria (caused by Plasmodium falciparum) and theileriosis (caused by Theileria spp.), profoundly impact global health and the socioeconomic well-being of lower-income countries. Despite recent advances, identifying host metabolic proteins essential for these auxotrophic pathogens remains challenging. Here, we generate a novel metabolic model of human hepatocytes infected with P. falciparum and integrate it with a genome-wide CRISPR knockout screen targeting Theileria-infected cells to pinpoint shared vulnerabilities. We identify key host metabolic enzymes critical for the intracellular survival of both of these lethal hemoparasites. Remarkably, among the metabolic proteins identified by our synergistic approach, we find that host purine and heme biosynthetic enzymes are essential for the intracellular survival of P. falciparum and Theileria, while other host enzymes are only essential under certain metabolic conditions, highlighting P. falciparum's adaptability and ability to scavenge nutrients selectively. Unexpectedly, host porphyrins emerge as being essential for both parasites. The shared vulnerabilities open new avenues for developing more effective therapies against these debilitating diseases, with the potential for broader applicability in combating apicomplexan infections. Maurizio and Masid et al. identify common host metabolic pathways essential for Plasmodium falciparum and Theileria parasites, revealing potential for developing shared broad-spectrum antiparasitic therapies to more effectively combat these debilitating infections. [ABSTRACT FROM AUTHOR]

White-rot fungi differentially express laccases when they encounter aromatic compounds. However, the underlying mechanisms are still being explored. Here, proteomics analysis revealed that in addition to increased laccase activity, proteins involved in sphingolipid metabolism and toluene degradation as well as some cytochrome P450s (CYP450s) were differentially expressed and significantly enriched during 48 h of o-toluidine exposure, in Trametes hirsuta AH28-2. Two Zn2Cys6-type transcription factors (TFs), TH8421 and TH4300, were upregulated. Bioinformatics docking and isothermal titration calorimetry assays showed that each of them could bind directly to o-toluidine and another aromatic monomer, guaiacol. Binding to aromatic compounds promoted the formation of TH8421/TH4300 heterodimers. TH8421 and TH4300 silencing in T. hirsuta AH28-2 led to decreased transcriptional levels and activities of LacA and LacB upon o-toluidine and guaiacol exposure. EMSA and ChIP-qPCR analysis further showed that TH8421 and TH4300 bound directly with the promoter regions of lacA and lacB containing CGG or CCG motifs. Furthermore, the two TFs were involved in direct and positive regulation of the transcription of some CYP450s. Together, TH8421 and TH4300, two key regulators found in T. hirsuta AH28-2, function as heterodimers to simultaneously trigger the expression of downstream laccases and intracellular enzymes. Monomeric aromatic compounds act as ligands to promote heterodimer formation and enhance the transcriptional activities of the two TFs. [ABSTRACT FROM AUTHOR]

It has remained unknown how cells reduce cystine taken up from the extracellular space, which is a required step for further utilization of cysteine in key processes such as protein or glutathione synthesis. Here, we show that the thioredoxin-related protein of 14 kDa (TRP14, encoded by TXNDC17) is the rate-limiting enzyme for intracellular cystine reduction. When TRP14 is genetically knocked out, cysteine synthesis through the transsulfuration pathway becomes the major source of cysteine in human cells, and knockout of both pathways becomes lethal in C. elegans subjected to proteotoxic stress. TRP14 can also reduce cysteinyl moieties on proteins, rescuing their activities as here shown with cysteinylated peroxiredoxin 2. Txndc17 knockout mice were, surprisingly, protected in an acute pancreatitis model, concomitant with activation of Nrf2-driven antioxidant pathways and upregulation of transsulfuration. We conclude that TRP14 is the evolutionarily conserved enzyme principally responsible for intracellular cystine reduction in C. elegans, mice, and humans. Synopsis: Metabolic utilization of cysteine requires reduction of cystine taken up from extracellular sources. Here, TXNDC17 -encoded TRP14 is identified as the main enzyme catalyzing this step, regulating protein cysteinylation and cysteine homeostasis in concert with the transsulfuration pathway. Thioredoxin-related protein TRP14 is the rate-limiting enzyme in mammalian cytosolic cystine reduction. Genetic ablation of TRP14 redirects cysteine biosynthesis towards the transsulfuration pathway as alternative, methionine-based source of cysteine. TRP14 also reduces cysteinylated proteins and potentially modulates protein function, such as reactivation of cysteinylated peroxiredoxin 2 through its decysteinylation. Txndc17 -deficient mice are protected from acute pancreatitis pathophysiology through activation of Nrf2-mediated antioxidant pathways and primed upregulation of transsulfuration. Interplay between TRP14 and transsulfuration in cysteine metabolism appears conserved across species, as knockout of both pathways becomes lethal in C. elegans subjected to proteotoxic stress. A thioredoxin-related protein controls cysteine homeostasis in parallel to the transsulfuration pathway, and can also modulate protein function via protein decysteinylation. [ABSTRACT FROM AUTHOR]

Pulsed electric field (PEF) is an up-to-date non-thermal processing technology with a wide range of applications in the food industry. The inactivation effect of PEF on Escherichia coli was different under different conditions. The E. coli inactivated number was 1.13 ± 0.01 lg CFU/mL when PEF was treated for 60 min and treated with 0.24 kV/cm. The treatment times were found to be positively correlated with the inactivation effect of PEF, and the number of E. coli was reduced by 3.09 ± 0.01 lg CFU/mL after 100 min of treatment. The inactivation assays showed that E. coli was inactivated at electrical intensity (0.24 kV/cm) within 100 min, providing an effective inactivating outcome for Gram-negative bacteria. The purpose of this work was to investigate the cellular level (morphological destruction, intracellular macromolecule damage, intracellular enzyme inactivation) as well as the molecular level via transcriptome analysis. Field Emission Scanning Electron Microscopy (TFESEM) and Transmission Electron Microscope (TEM) results demonstrated that cell permeability was disrupted after PEF treatment. Entocytes, including proteins and DNA, were markedly reduced after PEF treatment. In addition, the activities of Pyruvate Kinase (PK), Succinate Dehydrogenase (SDH), and Adenosine Triphosphatase (ATPase) were inhibited remarkably for PEF-treated samples. Transcriptome sequencing results showed that differentially expressed genes (DEGs) related to the biosynthesis of the cell membrane, DNA replication and repair, energy metabolism, and mobility were significantly affected. In conclusion, membrane damage, energy metabolism disruption, and other pathways are important mechanisms of PEF's inhibitory effect on E. coli. [ABSTRACT FROM AUTHOR]

Bacterial degradation mechanism for high chlorinated pentachlorobiphenyl (PentaCB) with worse biodegradability has not been fully elucidated, which could limit the full remediation of environments aicted by the complex pollution of polychlorinated biphenyls (PCBs). In this research, a new PentaCB-degrading bacterium Microbacterium paraoxydans that has not been reported was obtained using enzymatic screening method. The characteristics of its intracellular enzymes, proteome and metabolome variation during PentaCB degradation were investigated systematically compared to non-PentaCB conditions. The findings indicate that the degradation rate of PentaCB (1 mg/L) could reach 23.9% within 4 hours and achieve complete degradation within 12 hours, with the mixture of intracellular enzymes being most eective at a pH of 6.0. During the biodegradation of PentaCB, the 12 up-regulated proteins characterized included ABC transporter PentaCB-binding protein, translocase protein TatA, and signal peptidase I (SPase I), indicating the presence of functional proteins for PentaCB degradation in both the cytoplasm and the outer surface of the cytoplasmic membrane. Furthermore, five dierentially enriched metabolites were strongly associated with the aforementioned proteins, especially the up-regulated 1, 2, 4-benzenetriol which feeds into multiple degradation pathways of benzoate, chlorocyclohexane, chlorobenzene and aminobenzoate. These relevant results help to understand and speculate the complex mechanisms regarding PentaCB degradation by M. paraoxydans, which have both theoretical and practical implications for PCB bioremediation [ABSTRACT FROM AUTHOR]

Intracellular sensors detect changes in levels of essential metals to initiate homeostatic responses. But, a mammalian manganese (Mn) sensor is unknown, representing a major gap in understanding of Mn homeostasis. Using human-relevant models, we recently reported that: 1) the primary homeostatic response to elevated Mn is upregulation of hypoxia-inducible factors (HIFs), which increases expression of the Mn efflux transporter SLC30A10; and 2) elevated Mn blocks the prolyl hydroxylation of HIFs by prolyl hydroxylase domain (PHD) enzymes, which otherwise targets HIFs for degradation. Thus, the mammalian mechanism for sensing elevated Mn likely relates to PHD inhibition. Moreover, 1) Mn substitutes for a catalytic iron (Fe) in PHD structures; and 2) exchangeable cellular levels of Fe and Mn are comparable. Therefore, we hypothesized that elevated Mn directly inhibits PHD by replacing its catalytic Fe. In vitro assays using catalytically active PHD2, the primary PHD isoform, revealed that Mn inhibited, and Fe supplementation rescued, PHD2 activity. However, a mutation in PHD2 (D315E) that selectively reduced Mn binding without substantially impacting Fe binding or enzymatic activity resulted in complete insensitivity of PHD2 to Mn in vitro. Additionally, hepatic cells expressing full-length PHD2D315E were less sensitive to Mn-induced HIF activation and SLC30A10 upregulation than PHD2wild-type. These results: 1) define a fundamental Mn sensing mechanism for controlling Mn homeostasis--elevated Mn inhibits PHD2, which functions as a Mn sensor, by outcompeting its catalytic Fe, and PHD2 inhibition activates HIF signaling to up-regulate SLC30A10; and 2) identify a unique mode of metal sensing that may have wide applicability. [ABSTRACT FROM AUTHOR]

The effect of three rootstocks on the responsiveness of "Superior Seedless" grapes to cold storage was investigated in this study during the growing seasons of 2021 and 2022. The "Superior Seedless" bunches were preserved for 90 days at 4 ± 1°C and 98 ± 2 relative humidity%. The "Superior Seedless" bunch response under cold storage was shown to be influenced by the rootstocks. According to the study, bunches picked from "Superior Seedless" that were grown on the "1103 Paulson" rootstocks performed better in antioxidant enzyme activities (AEAs) than bunches obtained from other rootstocks. Furthermore, during cold storage, the rates of H2O2 and O2−generation decreased more rapidly. However, combined with a low electrolyte leakage percentage (EL%) and malondialdehyde (MDA) accumulation, the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) scavenger concentration increased during the cold storage period. Furthermore, while berry quality traits were harvested from "Superior Seedless" grafted onto "1103 Paulson" rootstock, they were improved compared to other rootstocks. The molecular docking technique is performed to evaluate the binding affinity of antioxidant enzymes with a group of intracellular ligands, including DPPH, MDA, ascorbic acid, and tartaric acid, which show great results with respect to the DPPH compound. Following these findings, it can be concluded that the influence of rootstocks on "Superior Seedless" bunch responses to low cold storage represents a novel potential natural effect of rootstocks on responding bunches of "Superior Seedless" to low cold storage. [ABSTRACT FROM AUTHOR]

Familial epilepsy with auditory features (FEAF), previously known as autosomal‐dominant lateral temporal lobe epilepsy (ADLTE) is a genetically heterogeneous syndrome, clinically characterized by focal seizures with prominent auditory symptoms. It is inherited with autosomal‐dominant pattern with reduced penetrance (about 70%). Sporadic epilepsy with auditory features cases are more frequent and clinically indistinguishable from familial cases. One causal gene, MICAL‐1, encodes MICAL‐1, an intracellular multi‐domain enzyme that is an important regulator of filamentous actin (F‐actin) structures. Pathogenic variants in MICAL‐1 account for approximately 7% of FEAF families. Here, we describe a de novo MICAL‐1 pathogenic variant, p.Arg915Cys, in a sporadic case, an affected 21‐year‐old Italian man with no family history of epilepsy. Genetic testing was performed in the patient and his parents, using a next‐generation sequencing panel. In cell‐based assay, this variant significantly increased MICAL‐1 oxidoreductase activity, which likely resulted in dysregulation of F‐actin organization. This finding provides further support for a gain‐of‐function effect underlying MICAL‐1‐mediated epilepsy pathogenesis, as previously seen with other pathogenic variants. Furthermore, the case study provides evidence that de novo MICAL‐1 pathogenic variants can occur in sporadic cases with epilepsy with auditory feature (EAF). Plain Language Summary: In this study, we report a new MICAL‐1 pathogenic variant in a patient without family history for epilepsy, not inherited from his parents. MICAL‐1 is a protein with enzymatic activity that reorganizes the structure of the cell. We proved the pathological effect of this variant by testing its enzymatic activity and found an increase of this activity. This result suggests that non‐familial cases should be tested to find novel pathogenic variants in this gene. [ABSTRACT FROM AUTHOR]

Irradiation with ultraviolet A (UVA) plays an important role in the pathogenesis of skin photoaging since it increases oxidative stress and inflammation in the epidermis. There is an urgent need to screen, investigate, and apply the potential anti-photoaging active ingredients. Agaricus blazei Murill (ABM) polysaccharides have a wide range of promising pharmacological applications. Previous studies have confirmed their antioxidant effect, but whether it has an anti-photoaging effect is unclear. In this study, two ABM polysaccharides (AB-J and AB-K) were obtained to discuss the potential photodamage-protective capacity. The free radical scavenging abilities in vitro, the safety assessment, and their protective effects and mechanisms on UVA-induced human fibroblasts (HSFs) were evaluated. The intracellular antioxidant enzyme levels and extracellular matrix proteins, such as COL-I and ELN, were significantly accelerated, and metalloproteinases (MMP-1, and MMP-9) were decreased by AB-J and AB-K. The Keap-1-Nrf2/ARE signaling pathway was activated, thus inducing the upregulated expression of downstream genes (Ho-1 and Nqo-1). The suppression of P38 and Jnk1 by AB-J and AB-K was speculated to be the inducer of the activation of the Keap-1-Nrf2/ARE signaling pathway. Owing to the excellent exhibition of AB-J, its safety assessment and the structural characterization are discussed further. [ABSTRACT FROM AUTHOR]

Sweet taste is the most powerful taste modality shaping feeding behavior and influencing homeostasis. This review summarizes data on the reception and encoding of taste signals at the level of taste buds and cerebral centers during the consumption of sweet substances. The main focus of attention is on the molecular and cellular mechanisms underlying identification of sweet taste and detection of the caloric composition of food, including the role of T1R2/T1R3 membrane protein receptors and the associated intracellular enzyme cascade, along with the metabolic mechanism assessing the concentration of glucose entering the cytoplasm. The genetic aspects of sensitivity to sweetness and the influence of sweet taste receptor gene polymorphism on sensitivity to sugars and low-calorie sweeteners are described. We present results from current studies of the endocrine, paracrine, and autocrine modulation of the reception and perception of sweet taste depending on the metabolic status of the body. A suggestion is made regarding a promising direction of research in this area. [ABSTRACT FROM AUTHOR]

The uricase enzyme yields allantoin, hydrogen peroxide, and carbon dioxide by catalyzing the oxidative opening of the purine ring in the urate pathway. This enzyme is important for biochemical diagnosis and reduces toxic urate accumulation during various diseases (hyperuricemia, gout, and bedwetting). Direct urate oxidase injection is recommended in renal complications-associated gout and to prevent chemotherapy-linked hyperuricemia disorders. Thus, uricase is a promising enzyme with diverse applications in medicine. Microbial production of uricase is featured by high growth rates, cost-effective bioprocessing, and easy optimization of the medium. Microbes produce the enzyme extracellular or intracellular. Extracellular uricase is preferred for biotechnological applications as it minimizes time, effort, and purification processes. This review provides insights into uricase-producing microbes, bacterial uric acid degradation pathways, degrading enzymes, and uricase-encoding genes. Furthermore, aspects influencing the microorganisms' production of the uricase enzyme, its activity, and its purification procedure are also emphasized. Cell disruption is mandatory for intercellular uricase production, which elevates production costs. Therefore, extracellular uricase-producing microbial strains should be investigated, and production factors should be optimized. Future techniques for obtaining extracellular enzymes should feature reduced time and effort, as well as a simple purification methodology. Furthermore, uricase gene-carrying recombinant probiotic microorganisms could become an effective tool for gout treatment. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung that leads rapidly to respiratory failure. Novel approaches to treatment are urgently needed. The bioactive lipid sphingosine‐1‐phosphate (S1P) is increased in IPF lungs and promotes proinflammatory and profibrotic TGF‐β signaling. Hence, decreasing lung S1P represents a potential therapeutic strategy for IPF. S1P is degraded by the intracellular enzyme S1P lyase (SPL). Here we find that a knock‐in mouse with a missense SPL mutation mimicking human disease resulted in reduced SPL activity, increased S1P, increased TGF‐β signaling, increased lung fibrosis, and higher mortality after injury compared to wild type (WT). We then tested adeno‐associated virus 9 (AAV9)‐mediated overexpression of human SGPL1 (AAV‐SPL) in mice as a therapeutic modality. Intravenous treatment with AAV‐SPL augmented lung SPL activity, attenuated S1P levels within the lungs, and decreased injury‐induced fibrosis compared to controls treated with saline or only AAV. We confirmed that AAV‐SPL treatment led to higher expression of SPL in the epithelial and fibroblast compartments during bleomycin‐induced lung injury. Additionally, AAV‐SPL decreased expression of the profibrotic cytokines TNFα and IL1β as well as markers of fibroblast activation, such as fibronectin (Fn1), Tgfb1, Acta2, and collagen genes in the lung. Taken together, our results provide proof of concept for the use of AAV‐SPL as a therapeutic strategy for the treatment of IPF. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the effects of grain (barley and wheat) size on rumen fermentation characteristics in fattening Dalaq breed lambs of the study was (3x2) completely randomized design with 6 treatments including; milled barley grain with sieve number two, milled barley grain with sieve number eight, unmilled barley grain, milled wheat grain with sieve number two, milled wheat grain with sieve number eight and unmilled wheat grain were plotted with 5 repetitions. Animals were housed in individual pens for 84 days. Rumen pH was not affected by experimental treatments. There was not significant (P>0.05) effect of grain paricle size on NH3-N ammonia nitrogen and microbial count although though, processing type it was affected by the type of processing and in the treatment of barley grain it was more than wheat. Also in the type of processing, sieve No. 2 produced more ammonia nitrogen. Counting of protozoa was significant in treatments containing barley and wheat and in barley treatment it was more than wheat (P<0.01). Although the Coliforms and bacteria of lactic acid were not affected by the type of grain (P>0.01). The total concentrations of volatile fatty acids (VFA) was not affected by the type of grain. Microbial nitrogen and microbial protein produced in the rumen were significantly affected by experimental treatments and both of them were more than wheat in the treatment of barley seeds (P<0.01). Allantoin and uric acid were not affected, and absorbed purine and xanthine and hypoxanthine were affected by the grain effect. The activity of carboxy methyl cellulase enzyme was not affected by the treatments although microcrystals cellulase enzyme in intracellular and total was affected by the treatments and it was more in barley. [ABSTRACT FROM AUTHOR]

An endophytic symbiont P. aeruginosa-producing anticandidal siderophore was recovered from mangrove leaves for the first time. Production was optimal in a succinate medium supplemented with 0.4% citric acid and 15 µM iron at pH 7 and 35 °C after 60 h of fermentation. UV spectra of the acidic preparation after purification with Amberlite XAD-4 resin gave a peak at 400 nm, while the neutralized form gave a peak at 360 nm. A prominent peak with RP-HPLC was obtained at RT 18.95 min, confirming its homogeneity. It was pH stable at 5.0–9.5 and thermally stable at elevated temperatures, which encourages the possibility of its application in extreme environments. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) against Candida spp. Were in the range of 128 µg/mL and lower. It enhanced the intracellular iron accumulation with 3.2–4.2-fold (as judged by atomic absorption spectrometry) with a subsequent increase in the intracellular antioxidative enzymes SOD and CAT. Furthermore, the malondialdehyde (MDA) concentration due to cellular lipid peroxidation increased to 3.8-fold and 7.3-fold in C. albicans and C. tropicalis, respectively. The scanning electron microscope (SEM) confirmed cellular damage in the form of roughness, malformation, and production of defensive exopolysaccharides and/or proteins after exposure to siderophore. In conclusion, this anticandidal siderophore may be a promising biocontrol, nonpolluting agent against waterborne pathogens and pathogens of the skin. It indirectly kills Candida spp. by ferroptosis and mediation of hyperaccumulation of iron rather than directly attacking the cell targets, which triggers the activation of antioxidative enzymes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ochratoxin A (OTA) is a mycotoxin that contaminates grape‐based products and is extremely harmful to the health of the host. It is effectively removed by yeast during the fermentation of wine, whereas the removal mechanism of OTA remains unclear. Therefore, the present study aimed to investigate the removal mechanism of ochratoxin A by yeast and to evaluate the safety of its degradation products. RESULTS: Cryptococcus albidus (20‐G) with better effect on ochratoxin A (OTA) was screened out in the main fermentation stage of wine. The results showed that 20‐G removed OTA through biosorption and biodegradation. Intracellular enzymes played the main role (18.44%) and yeast cell walls adsorbed a small amount of OTA (8.44%). Furthermore, the identification of proteins in 20‐G revealed that the decrease in OTA content was mainly a result of the action of peroxidase, and validation tests were carried out. By analyzing the degradation products of OTA, OTα and phenylalanine with lower toxicity were obtained. Animal experiments showed that the intervention of yeast 20‐G reduced the damage and adverse effects caused by OTA toxicity to the mice. CONCLUSION: The present study demonstrates the mechanism of OTA removal by 20‐G and the toxicity of OTA was reduced by peroxidase in 20‐G. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Dietary lipids are key ingredients during cooking, processing, and seasoning of carotenoid-rich fruits and vegetables, playing vitals in affecting the absorption and utilization of carotenoids for achieving their health benefits. Besides, dietary lipids have also been extensively studied to construct various delivery systems for carotenoids, such as micro/nanoparticles, micro/nanoemulsions, and liposomes. Currently, the efficacies of these techniques on improving carotenoid bioavailability are often evaluated using the micellization rate or "bioaccessibility" based on in vitro models. However, recent studies have found that dietary lipids may also affect the carotenoid uptake via intestinal epithelial cells and the efflux of intracellular chyle particles via lipid transporters. An increasing number of studies reveal the varied impact of different dietary lipids on the absorption of different carotenoids and some lipids may even have an inhibitory effect. Consequently, it is necessary to clarify the relationship between the addition of dietary lipids and the intestinal absorption of carotenoid to fully understand the role of lipids during this process. This paper first introduces the intestinal absorption mechanism of carotenoids, including the effect of bile salts and lipases on mixed micelles, the types and regulation of lipid transporters, intracellular metabolizing enzymes, and the efflux process of chyle particles. Then, the regulatory mechanism of dietary lipids during intestinal carotenoid absorption is further discussed. Finally, the importance of selecting the dietary lipids for the absorption and utilization of different carotenoids and the design of an efficient delivery carrier are emphasized. This review provides suggestions for precise dietary carotenoid supplementation and offere an important reference for constructing efficient transport carriers for liposoluble nutrients. [ABSTRACT FROM AUTHOR]

Allergic asthma (AA) is a common breathing disorder clinically characterized by the high occurrence of acute and continuous inflammation. However, the current treatment options for AA are lacking in effectiveness and diversity. In this study, we determined that the cell membrane receptor of gamma-glutamyl transferase (GGT) was highly overexpressed on the inflammatory cells that infiltrate the pulmonary tissues in AA cases. Therefore, we developed a GGT-specific dendrimer-dexamethasone conjugate (GSHDDC) that could be administered via aerosol inhalation to treat AA in a rapid and sustained manner. The GSHDDC was fabricated by the covalent attachment of 6-hydroxyhexyl acrylate-modified dexamethasone to polyamidoamine dendrimers via a carbonic ester linkage and the amino Michael addition, followed by the surface modification of the dendrimers with the GGT substrate of glutathione. After aerosol inhalation by the AA mice, the small particle-sized GSHDDC could easily diffuse into pulmonary alveoli and touch with the inflammatory cells via the glutathione ligand/GGT receptor-mediated recognition. The overexpressed GGT on the surface of inflammatory cells then triggers the gamma-glutamyl transfer reactions of glutathione to generate positively charged primary amines, thereby inducing rapid cationization-mediated cellular endocytosis into the inflammatory cells. The dexamethasone was gradually released by the intracellular enzyme hydrolysis, enabling sustained anti-inflammatory effects (e.g., reducing eosinophil infiltration, decreasing the levels of inflammatory factors) in the ovalbumin-induced AA mice. This study demonstrates the effectiveness of an inhalational and active inflammatory cells-targeted dendrimer-dexamethasone conjugate for efficient AA therapy. [ABSTRACT FROM AUTHOR]

Photochemical regulation provides precise control over enzyme activities with high spatiotemporal resolution. A promising approach involves anchoring "photoswitches" at enzyme active sites to modulate substrate recognition. However, current methods often require genetic mutations and irreversible enzyme modifications for the site‐specific anchoring of "photoswitches", potentially compromising the enzyme activities. Herein, we present a pioneering reversible nano‐inhibitor based on molecular imprinting technique for bidirectional regulation of intracellular enzyme activity. The nano‐inhibitor employs a molecularly imprinted polymer nanoparticle as its body and azobenzene‐modified inhibitors ("photoswitches") as the arms. By using a target enzyme as the molecular template, the nano‐inhibitor acquires oriented binding sites on its surface, resulting in a high affinity for the target enzyme and non‐covalently firm anchoring of the azobenzene‐modified inhibitor to the enzyme active site. Harnessing the reversible isomerization of azobenzene units upon exposure to ultraviolet and visible light, the nano‐inhibitor achieves bidirectional enzyme activity regulation by precisely docking and undocking inhibitor at the active site. Notably, this innovative approach enables the facile in situ regulation of intracellular endogenous enzymes, such as carbonic anhydrase. Our results represent a practical and versatile tool for precise enzyme activity regulation in complex intracellular environments. [ABSTRACT FROM AUTHOR]

The occurrence of autophagy in recombinant Chinese hamster ovary (rCHO) cell culture has attracted attention due to its effects on therapeutic protein production. Given the significance of glycosylation in therapeutic proteins, this study examined the effects of autophagy-inhibiting chemicals on sialylation of Fc-fusion glycoproteins in rCHO cells. Three chemical autophagy inhibitors known to inhibit different stages were separately treated with two rCHO cell lines that produce the same Fc-fusion glycoprotein derived from DUKX-B11 and DG44. All autophagy inhibitors significantly decreased the sialylation of Fc-fusion glycoprotein in both cell lines. The decrease in sialylation of Fc-fusion glycoprotein is unlikely to be attributed to the release of intracellular enzymes, given the high cell viability and low activity of extracellular sialidases. Interestingly, the five intracellular nucleotide sugars remained abundant in cells treated with autophagy inhibitors. In the mRNA expression profiles of 27 N-glycosylation-related genes using the NanoString nCounter system, no significant differences in gene expression were noted. With the positive effect of supplementing nucleotide sugar precursors on sialylation, attempts were made to enhance the levels of intracellular nucleotide sugars by supplying these precursors. The addition of nucleotide sugar precursors to cultures treated with inhibitors successfully enhanced the sialylation of Fc-fusion glycoproteins compared to the control culture. This was particularly evident under mild stress conditions and not under relatively severe stress conditions, which were characterized by a high decrease in sialylation. These results suggest that inhibiting autophagy in rCHO cell culture decreases sialylation of Fc-fusion glycoprotein by constraining the availability of intracellular nucleotide sugars. Key points: • The autophagy inhibition in rCHO cell culture leads to a significant reduction in the sialylation of Fc-fusion glycoprotein. • The pool of five intracellular nucleotide sugars remained highly abundant in cells treated with autophagy inhibitors. • Supplementation of nucleotide sugar precursors effectively restores decreased sialylation, particularly under mild stress conditions but not in relatively severe stress conditions. [ABSTRACT FROM AUTHOR]

Chronic diabetic wounds are at lifelong risk of developing diabetic foot ulcers owing to severe hypoxia, excessive reactive oxygen species (ROS), a complex inflammatory microenvironment, and the potential for bacterial infection. Here we develop a programmed treatment strategy employing live Haematococcus (HEA). By modulating light intensity, HEA can be programmed to perform a variety of functions, such as antibacterial activity, oxygen supply, ROS scavenging, and immune regulation, suggesting its potential for use in programmed therapy. Under high light intensity (658 nm, 0.5 W/cm2), green HEA (GHEA) with efficient photothermal conversion mediate wound surface disinfection. By decreasing the light intensity (658 nm, 0.1 W/cm2), the photosynthetic system of GHEA can continuously produce oxygen, effectively resolving the problems of hypoxia and promoting vascular regeneration. Continuous light irradiation induces astaxanthin (AST) accumulation in HEA cells, resulting in a gradual transformation from a green to red hue (RHEA). RHEA effectively scavenges excess ROS, enhances the expression of intracellular antioxidant enzymes, and directs polarization to M2 macrophages by secreting AST vesicles via exosomes. The living HEA hydrogel can sterilize and enhance cell proliferation and migration and promote neoangiogenesis, which could improve infected diabetic wound healing in female mice. The treatment of infected diabetic wounds faces obstacles of bacterial infection, hypoxia, hyperexpression of reactive oxygen species, and inflammation. Here, the authors address these issues by developing a programmed treatment strategy that utilizes live Haematococcus to promote healing of diabetic wounds in a comprehensive manner. [ABSTRACT FROM AUTHOR]

Coral mucus secreted by mucocytes provides a protective physicochemical and physiological barrier between coral tissue and external environmental threats. The biomolecules and nutrients of the secreted mucus are derived from endosymbionts, coral polyps and support coral functions, such as feeding, sediment clearing and protection, against numerous biotic and abiotic stressors. The surface mucus layer also houses a diverse community of beneficial microorganisms that defend against pathogens. Enzymes including peptidases, esterases, and glycosidases were observed and described in mucus. Most importantly, the presence of phenoloxidase, an intracellular enzyme in secretory mucus, generally triggers melanin synthesis, providing fast-acting components of invertebrate immunity in disease resistance. However, the purpose and the mechanism of mucus release, effects of mucus components on defense properties, and functional roles in intra- and interspecific interactions are not well described. Thus, the present review aims to understand the mucus components and the complex roles played by mucus in microbial associations, feeding, and resilience that influence coral health. [ABSTRACT FROM AUTHOR]

This study was carried out to examine the interaction of enzyme activities, microbial biomass carbon, and CO2 respiration with heavy metals under different land uses in terms of quality and sustainability of the soil. There is a statistically significant positive correlation between dehydrogenase enzyme activity and Mn, Pb, Cd, and Co, while it was negative between Cr. There was a positive correlation between catalase enzyme activity and Mn and Pb and between urease and Co. The higher interaction of dehydrogenase activity with heavy metals, which is included in the endo enzyme group, has been explained as a much stronger effect of heavy metals on living microorganisms and endoenzymes than extracellular enzymes stabilized on clay minerals and organic matter. The high clay content of the soil is thought to reduce some of the negative effects of heavy metals on enzymes. The results of this study may be good indicators of enzyme activities, especially dehydrogenase, catalase, and urease, for soil health and quality, chemical degradation and restoration processes, and ecosystem functioning in soils contaminated or to be contaminated with heavy metals. It shows that the activities of these enzymes are very sensitive and can decrease rapidly in case of high concentrations of heavy metals. [ABSTRACT FROM AUTHOR]

Advances in immunotherapy have brought significant therapeutic benefits to many cancer patients. Nonetheless, many cancer types are refractory to current immunotherapeutic approaches, meaning that further targets are required to increase the number of patients who benefit from these technologies. Protein tyrosine phosphatases (PTPs) have long been recognised to play a vital role in the regulation of cancer cell biology and the immune response. In this review, we summarize the evidence for both the pro-tumorigenic and tumour-suppressor function of non-receptor PTPs in cancer cells and discuss recent data showing that several of these enzymes act as intracellular immune checkpoints that suppress effective tumour immunity. We highlight new data showing that the deletion of inhibitory PTPs is a rational approach to improve the outcomes of adoptive T cell-based cancer immunotherapies and describe recent progress in the development of PTP inhibitors as anti-cancer drugs. [ABSTRACT FROM AUTHOR]

Recently, hyperosmolar hyponatremia following excessive off-label use of two exchanges of 2 L icodextrin daily during peritoneal dialysis (PD) was reported. We encountered a cluster of 3 cases of PD patients who developed hyperosmolar hyponatremia during on-label use of icodextrin. This appeared to be due to absorption of icodextrin since after stopping icodextrin, the serum sodium level and osmol gap returned to normal, while a rechallenge again resulted in hyperosmolar hyponatremia. We excluded higher than usual concentrations of specific fractions of dextrins in fresh icodextrin dialysis fluid (lot numbers of used batches were checked by manufacturer). We speculate that in our patients, either an exaggerated degradation of polysaccharide chains by α-amylase activity in dialysate, lymph, and interstitium and/or rapid hydrolysis of the absorbed larger degradation products in the circulation may have contributed to the hyperosmolality observed, with the concentration of oligosaccharides exceeding the capacity of intracellular enzymes (in particular maltase) to metabolize these products to glucose. Both hyponatremia and hyperosmolality are risk factors for poor outcomes in PD patients. Less conventional PD prescriptions such as off-label use of two exchanges of 2 L icodextrin might raise the risk of this threatening side effect. This brief report is intended to create awareness of a rare complication of on-label icodextrin use in a subset of PD patients and/or PD prescriptions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nowadays, the prevalence of oxidative stress‐related chronic diseases is increasing. The identification of novel antioxidant collagen peptides to counteract oxidative stress for individuals' health has gained significant attention. RESULTS: In this study, collagen peptides with antioxidant activities were separated and identified by ion chromatography, reversed‐phase high‐performance liquid chromatography and liquid chromatography–tandem mass spectrometry. The identified antioxidant collagen peptides were further screened by molecular docking for Keap1‐targeted peptide inhibitors and their theoretical interaction mechanisms were investigated. Four novel antioxidant collagen peptides, GPAGPIGPVG, GPAGPpGPIG, ISGPpGPpGPA and IDGRPGPIGPA, with high binding affinity to Keap1 were selected. Molecular docking results demonstrated that the putative antioxidant mechanism of the four antioxidant collagen peptides contributed to their blockage of Keap1–Nrf2 interactions. The results of antioxidant activity of the four antioxidant collagen peptides proved that IDGRPGPIGPA exerted a high scavenging capacity for DPPH and ABTS free radicals, while GPAGPpGPIG improved the resistance of cells to hydrogen peroxide‐induced oxidative damage by promoting the activation of intracellular antioxidant enzymes and the production of reduced glutathione in human hepatoma (HepG2) cells. CONCLUSION: The antioxidant collagen peptides (GPAGPIGPVG, GPAGPpGPIG, ISGPpGPpGPA and IDGRPGPIGPA) will be developed as novel functional food for human health in the near future. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Ferroptosis suppressor protein 1 (FSP1) is a glutathione-independent ferroptosis inhibitory factor. FSP1 has been found to play a crucial role in the regulation of mitochondrial function and ferroptosis. However, its function in porcine early embryonic development remains unknown. In the present research, we found that FSP1 was expressed at different stages during porcine early embryo development. Compared with the control condition, inhibition of FSP1 reduced the cleavage rate at 24 h and 48 h and the blastocyst rate at 144 h. In addition, inhibiting FSP1 reduced the blastocyst diameter, total cell number, and proliferation capacity. Further analysis showed that inhibition of FSP1 significantly increased the levels of ferrous ions (Fe2+) and MDA but not GPX4. We also found that inhibition of FSP1 significantly decreased mitochondrial membrane potential and ATP levels, which in turn caused excessive accumulation of ROS and decreased the levels of GSH and the activity of the intracellular antioxidant enzymes SOD and CAT in embryos. In conclusion, FSP1, an important regulator, participates in regulating the development and quality of porcine early embryos. Inhibition of FSP1 impairs blastocyst formation, induces glutathione-independent ferroptosis, and further leads to oxidative stress due to mitochondrial dysfunction, ultimately affecting the developmental competence and impairing the quality of porcine early embryos. • FSP1 is required for porcine early embryo development. • Inhibition of FSP1 leads to ferrous ions and MDA levels increasing in porcine early embryos. • Inhibition of FSP1 leads to oxidative stress and mitochondrial dysfunction in porcine early embryos. [ABSTRACT FROM AUTHOR]

Xanthomonas fuscans subsp. fuscans is known as an obligate phytopathogen - the pathogen of small brown spot of beans that gradually expands the range of host plants and spreads worldwide on legumes. The review provides data on the problems of the pathogen's systematics and its change depending on the new research and improvement of methods for studying biological properties. Historical data on the first stages of isolation of X. fuscans subsp. fuscans from bean and new stages of its spread and isolation from soybean in Ukraine, after which the pathogen moved from the mono-phage to polyphage status within the same plant family. The importance of X. fuscans subsp. fuscans as a potentially dangerous phytopathogen, as evidenced by the presence of its samples in many collections of living microorganisms in the world and the quarantine status of the pathogen in a number of European countries are underlined. It has been shown that the phytopathogen X. fuscans subsp. fuscans does not differ significantly from other xanthomonads in terms of its cultural, morphological, physiological, and biochemical properties, especially those that cause diseases of leguminous plants. At the same time, the only but the main feature of this bacterial culture is emphasized -- the increased amount and activity of the intracellular enzyme tyrosinase, which distinguishes X. fuscans from all other bacterial phytopathogens and not only among xanthomonads. The variants of the stage of synthesis of tyrosinase and melanin in bacteria, due to which the black-brown pigment is formed, and the lack of research on the pathway of tyrosinase synthesis in phytopathogenic bacteria, in particular X. fuscans subsp. fuscans, are analized. The data on genotypic properties of X. fuscans subsp. fuscans, its affinity with other pathogens of the genus Xanthomonas that cause diseases of leguminous plants, and the possible role of the phenomenon of «horizontal gene transfer» in their affinity along with differences in biological properties are considered. The analyzed literature indicates the potential danger of the causative agent of small brown spot of legumes and the need for constant monitoring of the spread and study of its biological properties to develop methods for controlling the spread of X. fuscans subsp. fuscans. [ABSTRACT FROM AUTHOR]

Streptococcus pyogenes, or Group A Streptococcus, is an exclusively human pathogen that causes a wide variety of diseases ranging from mild throat and skin infections to severe invasive disease. The pathogenesis of S. pyogenes infection has been extensively studied, but the pathophysiology, especially of the more severe infections, is still somewhat elusive. One key feature of S. pyogenes is the expression of secreted, surface-associated, and intracellular enzymes that directly or indirectly affect both the innate and adaptive host immune systems. Undoubtedly, S. pyogenes is one of the major bacterial sources for immunomodulating enzymes. Major targets for these enzymes are immunoglobulins that are destroyed or modified through proteolysis or glycan hydrolysis. Furthermore, several enzymes degrade components of the complement system and a group of DNAses degrade host DNA in neutrophil extracellular traps. Additional types of enzymes interfere with cellular inflammatory and innate immunity responses. In this review, we attempt to give a broad overview of the functions of these enzymes and their roles in pathogenesis. For those enzymes where experimentally determined structures exist, the structural aspects of the enzymatic activity are further discussed. Lastly, we also discuss the emerging use of some of the enzymes as biotechnological tools as well as biological drugs and vaccines. [ABSTRACT FROM AUTHOR]

Excess cortisol is associated with more severe cognitive decline, Alzheimer's disease, and related dementia phenotypes. The intracellular enzyme 11β-HSD1 regenerates active cortisol from inactive cortisone. In this current issue, high regional brain occupancy of Xanamemtrademark, determined by [11C]TARACT PET imaging of 11β-HSD1, in cognitively normal individuals and mild cognitive impartment/Alzheimer's disease (AD) patients is presented. In the future, comprehensive kinetic modeling using arterial sampling for occupancy studies, and whole-body PET imaging of 11β-HSD1 enzyme levels, in combination with stable isotope studies of cortisol metabolism, can provide broad insight into enzyme levels and activity in AD and other relevant diseases. [ABSTRACT FROM AUTHOR]

Cyanobacteria are promising photosynthetic organisms owing to their ease of genetic manipulation. Among them, Synechococcus elongatus UTEX 2973 exhibits faster growth, higher biomass production efficiency and more robust stress tolerance compared with S. elongatus PCC 7942. This is due to specific genetic differences, including four single-nucleotide polymorphisms (SNPs) in three genes. One of these SNPs alters an amino acid at position 252 of the FoF1 ATP synthase α-subunit from Tyr to Cys (αY252C) in S. elongatus 7942. This change has been shown to significantly affect growth rate and stress tolerance, specifically in S. elongatus. Furthermore, experimental substitutions with several other amino acids have been shown to alter the ATP synthesis rate in the cell. In the present study, we introduced identical amino acid substitutions into Synechocystis sp. PCC 6803 at position 252 to elucidate the amino acid's significance and generality across cyanobacteria. We investigated the resulting impact on growth, intracellular enzyme complex levels, intracellular ATP levels and enzyme activity. The results showed that the αY252C substitution decreased growth rate and high-light tolerance. This indicates that a specific bulkiness of this amino acid's side chain is important for maintaining cell growth. Additionally, a remarkable decrease in the membrane-bound enzyme complex level was observed. However, the αY252C substitution did not affect enzyme activity or intracellular ATP levels. Although the mechanism of growth suppression remains unknown, the amino acid at position 252 is expected to play an important role in enzyme complex formation. [ABSTRACT FROM AUTHOR]

Transglutaminase 2 (TG2), which mediates post‐translational modifications of multiple intracellular enzymes, is involved in the pathogenesis and progression of cancer. We used 1H‐NMR metabolomics to study the effects of AA9, a novel TG2 inhibitor, on two breast cancer cell lines with distinct phenotypes, MCF‐7 and MDA‐MB‐231. AA9 can promote apoptosis in both cell lines, but it is particularly effective in MD‐MB‐231, inhibiting transamidation reactions and decreasing cell migration and invasiveness. This metabolomics study provides evidence of a major effect of AA9 on MDA‐MB‐231 cells, impacting glutamate and aspartate metabolism, rather than on MCF‐7 cells, characterised by choline and O‐phosphocholine decrease. Interestingly, AA9 treatment induces myo‐inositol alteration in both cell lines, indicating action on phosphatidylinositol metabolism, likely modulated by the G protein activity of TG2 on phospholipase C. Considering the metabolic deregulations that characterise various breast cancer subtypes, the existence of a metabolic pathway affected by AA9 further points to TG2 as a promising hot spot. The metabolomics approach provides a powerful tool to monitor the effectiveness of inhibitors and better understand the role of TG2 in cancer. [ABSTRACT FROM AUTHOR]

Oxidative stress and the resulting lipid peroxidation are associated with various pathological states, including neurodegenerative diseases and cancer. The end products of lipid peroxidation, such as 4-oxo-2(E)-nonenal (ONE), 4-hydroxy-2(E)-nonenal (HNE), and methylglyoxal (MG), exert several biological effects through modification of various cellular components, including DNA and proteins. Glutathione peroxidase 1 (GPx1) is an intracellular antioxidant enzyme that uses glutathione (GSH) to reduce a variety of peroxides, thereby modulating cellular oxidative stress and redox-mediated responses. GPx1 contains nucleophilic amino acids at its active (one Sec) and GSH-binding (four Arg and one Lys) sites. We found that lipid peroxidation-derived reactive aldehydes (ONE, HNE, and MG) modified the GSH-binding site, resulting in the inhibition of GPx1 activity. Mass spectrometry-based proteomic analysis identified the sites modified by each aldehyde (ONE, 14 sites; HNE, 7 sites; MG, 9 sites). The GSH-binding sites modified were as follows: ONE, Arg57, 103, 184, and 185; HNE, Lys91; MG, Arg103. Upon incubation of GPx1 with each aldehyde, ONE reduced GPx1 activity more significantly than did HNE or MG in a dose- and time-dependent manner. The addition of GSH to GPx1 3 h after incubation with ONE prevented further inhibition by trapping ONE as a ONE-GSH adduct. However, the activity of GPx1 was not restored to the initial level, indicating that ONE modified GPx1 irreversibly. This study suggests that oxidative damage to lipids, resulting in the formation of reactive aldehydes, can amplify cellular oxidative stress via direct inactivation of GPx1, which increases the production of intracellular peroxides. [Display omitted] • Lipid-derived aldehydes modify GSH-binding site to inhibit the activity of GPx1. • Mass spectrometry-based proteomic analysis identified the modification sites. • ONE reduces GPx1 activity significantly in a dose- and time-dependent manner. • ONE modifies GPx1 irreversibly. • GSH prevents inactivation of GPx1 by trapping ONE as a ONE-GSH adduct. [ABSTRACT FROM AUTHOR]