Search Results (509)

Sugarcane stores sucrose in a living culm for extended periods, yet the respiratory cost of maintaining this storage tissue remains poorly quantified. We quantified growth and maintenance respiration along the culm (internodes 1 to 12) in three genotypes at mid-season (rapid growth) and end-season (maturation) using a composition-based carbon accounting framework derived from measurements of biomass accumulation and composition. Growth respiration was highest in elongating internodes (3 to 6) and declined with maturation, whereas maintenance respiration increased progressively and dominated in mature storage internodes (10 to 12). Consequently, total sink demand remained substantial even after structural growth slowed, indicating that mature internodes continue to require significant metabolic input despite limited biomass production. To evaluate the potential impact of energetic constraints, we simulated reduced mitochondrial energy contribution to assess the sensitivity of respiratory carbon demand to decreased energetic efficiency. These simulations predicted an increase in glucose requirement for respiration across all internodes, with the largest proportional effect in mature tissue where maintenance costs dominated. Despite this predicted increase in respiratory demand, sucrose accumulation was maintained in mature culms, indicating that respiratory carbon loss remains constrained during storage. This suggests that storage tissue operates with relatively high carbon-use efficiency during maintenance-dominated metabolism. We interpret this pattern as consistent with metabolic configurations that reduce ATP demand, potentially involving partial substitution of ATP-dependent reactions by pyrophosphate (PPi)-dependent pathways, although this mechanism was not directly measured. These findings highlight the importance of maintenance respiration and energetic efficiency in determining sink strength and sucrose yield, and they provide a physiological framework for understanding carbon conservation in long-lived storage organs. Full article

The antimicrobial resistance of Acinetobacter baumannii necessitates the development of novel therapeutic strategies targeting essential enzymes such as Undecaprenyl Pyrophosphate Phosphatase (UppP). This study explored spider venom peptides in silico as potential allosteric inhibitors of A. baumannii UppP. A systematic literature review was conducted to select eight α-helical peptides with reported anti-A. baumannii activity, followed by their computational physicochemical characterization. Three-dimensional models of A. baumannii UppP and the candidate peptides were generated, and a putative allosteric binding site was validated through molecular docking of a known inhibitor of the BacA homolog. The eight peptides were subsequently docked to this validated site using HADDOCK. Results revealed variable binding affinities; peptides LC-AMP-I1, Lycosin-II, and GK37 exhibited the most favorable HADDOCK scores and extensive interaction networks, consistent with their reported high antimicrobial potency. Other candidates, notably Lt-MAP2, showed low binding affinity but high predicted synergistic potential. These findings identify promising spider venom peptide candidates, suggesting dual (membrane disruption/UppP inhibition) or synergistic mechanisms of action, and validate UppP as a viable pharmacological target for peptide-based inhibitors. Full article

Generalized Arterial Calcification of Infancy (GACI) is a rare autosomal recessive disorder characterized by pathological calcium deposition in large and medium-sized arteries, leading to severe cardiovascular complications such as hypertension, heart failure, and stroke. The mortality rate is approximately 50% within the first six months of life if untreated. The disease is primarily caused by mutations in the ENPP1 or ABCC6 genes, resulting in a deficiency of inorganic pyrophosphate (PPi), a key inhibitor of arterial calcification. This review provides a comprehensive overview of the pathophysiology, genetic basis, and clinical features of GACI. In addition, we summarize current and emerging therapeutic strategies, including enzyme replacement therapy with recombinant ENPP1 (INZ-701), critically discussing available preclinical and early clinical evidence, as well as current limitations. Full article

Bone tissue plays a vital role in the human body and possesses intrinsic self-repair mechanisms; however, large defects or pathological fractures may exceed its natural healing capacity. Bone tissue engineering provides promising strategies to restore bone integrity through the use of scaffolds, growth factors, and stem cells. While calcium phosphate (CaP)-based ceramics, such as hydroxyapatite (HAp) and tricalcium phosphate (TCP), represent the current benchmark, their limitations, including slow degradation (HAp) and limited osteoinductivity (TCP), have driven the development of alternative biomaterials. In this context, magnesium phosphate (MgP)-based materials have gained increasing attention due to their tunable resorption rate, improved biodegradability, and ability to stimulate osteogenesis and angiogenesis through the release of magnesium (Mg²⁺) ions. This study reports on composite scaffolds based on electrospun poly(ε-caprolactone) (PCL) fibres coated with MgP layers doped with lithium (Li) and zinc (Zn), designed to mimic the nanofibrous architecture of the extracellular matrix. Lithium and zinc were selected due to their known ability to modulate cellular response, with lithium promoting osteogenic activity and zinc contributing to improved cell proliferation and antibacterial potential. The phosphate phases obtained by coprecipitation were deposited onto the PCL fibres using Matrix-Assisted Pulsed Laser Evaporation (MAPLE), enabling controlled surface functionalization. Following thermal treatment, the formation of the crystalline magnesium pyrophosphate (Mg₂P₂O₇) phase was confirmed by chemical and structural characterization. The combination of a slowly degrading PCL matrix, providing sustained structural support, and a bioactive MgP coating, enabling rapid and controlled ion release, results in improved scaffold performance in terms of biocompatibility, biodegradability, and bioactivity. While the slow degradation rate of PCL ensures mechanical stability over an extended period, the surface-deposited MgP phase allows immediate interaction with the biological environment, facilitating faster ion release and enhancing cell–material interactions. These findings highlight the potential of the developed composites as promising candidates for trabecular bone regeneration and as viable alternatives to conventional CaP-based scaffolds in regenerative medicine. Full article

The development of high-performance flame-retardant (FR) polypropylene (PP) with high mechanical integrity remains a challenge. Herein, we demonstrate a synergistic flame retardancy system for PP achieved via partial substitution of piperazine pyrophosphate (PAPP) with 1 wt.% magnesium borate whiskers (MBW) for improved flame retardancy, and thermal and mechanical properties. The optimized PP/24PAPP/1MBW exhibits exceptional FR performance, driven by the formation of a highly ordered, continuous phosphorus–boron hybrid char in the condensed phase. Cone calorimetry test results reveal an 80% reduction in peak heat release rate, a 54% reduction in total heat release, and a 33% reduction in total smoke production compared to neat PP, while the UL-94 test confirms a V-0 rating with complete suppression of flaming drips. Morphological study of the char residue using Raman spectroscopy and SEM attributes this performance to enhanced char graphitization and structural coherence enabled by boron-mediated cross-linking. More importantly, this transformative flame retardancy performance is achieved without severe compromise to mechanical properties, retaining over 89% of the original tensile strength. This work confirms the PAPP/MBW system as a highly efficient, low-additive approach to creating advanced fire-safe polymer composites for engineering applications. Full article

Nicotinamide mononucleotide (NMN), a direct precursor of the essential coenzyme nicotinamide adenine dinucleotide (NAD⁺), confers anti-aging effects and multiple health benefits. Engineered microorganisms represent a promising platform for sustainable industrial production of NMN. Here, the previously reported NMN-producing strain NMN008 was engineered to co-utilize glucose and glycerol for the biosynthesis of NMN from nicotinamide (NAM). First, the glycolytic genes pgi and pykA/pykF were sequentially deleted to disrupt glucose catabolism through the glycolytic pathway, thereby potentially improving precursor availability for NMN biosynthesis. Second, a feedback-resistant glycerol kinase mutant (glpK*) was introduced to enhance glycerol utilization, aiming to compensate for the growth defects associated with impaired glycolysis. These modifications enabled glycerol to primarily support cell growth and energy metabolism, while improving glucose allocation toward NMN biosynthesis by reducing its competitive consumption through glycolysis. As a result, the final strain achieved an NMN titer of 32.92 g/L in a 2 L bioreactor, representing a 26.28% increase in NMN production and a substantial 34.48% improvement in carbon conversion efficiency. Our research provides an effective strategy to achieve industrial-scale production of NMN, laying a foundation for the widespread application of NMN. Full article

By examining a novel nanomaterial that has been modified for use in sustainable construction, this study primarily responds to the growing need for environmentally acceptable materials. The primary goal was to improve the functional and aesthetic qualities of building materials by synthesizing and characterizing environmentally friendly clay-based nanomaterials doped with cobalt pyrophosphate (Co₂P₂O₄). The authors employed contemporary experimental methods, such as scanning electron microscopy (SEM) for morphological characterisation, Fourier transform infrared spectroscopy (FT-IR) for molecular bonding assessment, and X-ray diffraction (XRD) for crystal structure research. The published findings show the doped nanomaterials’ potential durability as well as their structural integrity. An economic assessment is part of the investigation. The study is noteworthy for emphasizing the potential of cobalt-doped pyrophosphate nanoparticles as eco-friendly colour pigments for construction materials made of clay. Full article

Objectives: Doxorubicin, a widely used chemotherapeutic agent, is known to induce hepatotoxicity through oxidative stress and inflammatory pathways. Vitamin D has been reported to exert antioxidant and immunomodulatory effects; however, its potential protective role in doxorubicin-induced liver injury remains insufficiently characterized. Materials and Methods: Adult male Wistar albino rats were randomly assigned to six groups (n = 7): Control, Vitamin D (5000 IU/kg), Vitamin D (60,000 IU/kg), Doxorubicin, DOX + Vitamin D (5000 IU/kg), and DOX + Vitamin D (60,000 IU/kg). Vitamin D₃ (cholecalciferol) was administered orally either as a daily dose (5000 IU/kg for 12 days) or as a single bolus dose (60,000 IU/kg). Doxorubicin (6 mg/kg/day, cumulative dose 18 mg/kg) was administered intraperitoneally on days 10–12. Hepatic injury was evaluated using ⁹⁹mTc-pyrophosphate (⁹⁹mTc-PYP) scintigraphy, serum liver enzymes (AST, ALT, LDH, total bilirubin), renal markers (BUN, creatinine), calcium and 25-hydroxyvitamin D [25(OH)D], oxidative stress parameters (MDA, TOS, TAS, GSH, SOD, Nrf2), and inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-10). Results: Doxorubicin markedly increased hepatic ⁹⁹mTc-PYP uptake and significantly elevated AST, ALT, LDH, bilirubin, MDA, TOS, TNF-α, IL-6, and IL-1β levels while reducing Nrf2, GSH, SOD, TAS, and IL-10 (all p < 0.001). Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D [25(OH)D] levels compared with controls (32.3 ± 2.7 vs. 74.1 ± 3.8 and 69.3 ± 3.2 ng/mL for the 5000 and 60,000 IU/kg groups, respectively; p < 0.001) and attenuated DOX-induced hepatic injury, as indicated by reduced radiotracer uptake and improved oxidative and inflammatory markers. Vitamin D also mitigated DOX-associated increases in renal injury markers (BUN and creatinine) without inducing hypercalcemia. No significant differences were observed between the two vitamin D dosing regimens in most outcome measures. Conclusion: Vitamin D supplementation exerted protective effects against doxorubicin-induced liver injury, likely through modulation of oxidative stress and inflammatory pathways. Additionally, ⁹⁹mTc-PYP scintigraphy may serve as a useful imaging tool for detecting acute hepatocellular injury and evaluating therapeutic responses. Full article

Background: The number of patients with transthyretin amyloid cardiomyopathy (ATTR-CM) has been increasing recently, and the early diagnosis and treatment of it are important. ^99mTc pyrophosphate scintigraphy (^99mTc-PYP) plays a key role in the early diagnosis of ATTR-CM. In patients who underwent ^99mTc-PYP, the early diagnosis of ATTR-CM by echocardiography was evaluated, focusing on left ventricular myocardial form and left ventricular wall thickness. Methods: The present study was conducted on 144 patients who underwent ^99mTc-PYP between February 2020 and March 2024. A comparison was made between the ^99mTc-PYP positive (P) and negative (N) groups, and significant factors were subjected to multivariate analysis. Results: 17 of 144 patients were positive (14.9%), and 15 patients were diagnosed with ATTR-CM by myocardial or skin (fat) biopsy. Other positive patients were also clinically considered to have ATTR-CM based on findings such as poor cardiac function and cerebral hemorrhage. ^99mTc-PYP positive had a significantly larger CTR (60.3% in the P group vs. 53.9% in the N group, p = 0.007) and a larger left atrial diameter (42.8 mm in the P group vs. 40.0 mm in the N group, p = 0.047). On the other hand, the mean LV wall thickness was significantly thicker (15.7 mm in the P group vs. 12.8 mm in the N group, p < 0.001); however the LV end-diastolic diameter was smaller (41.9 mm in the P group vs. 48.4 mm in the P group, p < 0.001). The LV mass was similar in both groups, thus the relative left ventricular wall thickness (RWT), which indicates relative wall thickening, was significantly higher in the P group (0.85 in the P group vs. 0.52 mm in the N group, p < 0.001). The receiver operating characteristic curve of RWT for assessing ^99mTc-PYP positivity had a cut-off value of 0.717 (area under the curve 0.862, 95%CI 0.763–0.961). Conclusions: The evaluation of wall thickness and RWT on echocardiography is important for diagnosing ATTR-CM. Full article

Pyruvate decarboxylase (PDC) is an intracellular non-oxidizing enzyme that relies on thiamine pyrophosphate (TPP), which is important for plant survival under anaerobic conditions and increasingly recognized for its role in broader stress reaction. However, the PDC gene family of tomato (Solanum lycopersicum), an important waterlogging-sensitive agricultural product, has not yet been discovered. In this study, eight SlPDC genes were discovered within the tomato genome. Gene structure analysis revealed that SlPDC members exhibited varying intron–exon configurations, with SlPDC8 possessing the most complex structure containing seven introns. Promoter analysis revealed a multitude of cis-acting elements responsive to light, hormones, and various stresses. Particularly, the promoter of SlPDC8 contains both ABRE and TGACG/CGTCA-motif. Tissue-specific expression profiles showed that SlPDC8 was mainly highly expressed in the roots. Expression profiling demonstrated that SlPDC genes respond divergently to different abiotic stresses, including salt, hydrogen peroxide (H₂O₂), drought, waterlogging, cold, heat, darkness, and UV radiation stresses. Notably, SlPDC1, SlPDC7, and SlPDC8 were significantly upregulated by waterlogging, with SlPDC8 showing the most robust induction. Functional validation through VIGS proved that SlPDC8-silenced plants exhibited significantly impaired growth, decreased photosynthetic pigment content, severe leaf wilting, and poor root development under waterlogging conditions compared to control plants. Furthermore, silencing SlPDC8 led to increased malondialdehyde (MDA) levels and decreased antioxidant enzyme activities, indicating heightened oxidative damage under waterlogging stress. We conclusively demonstrate that SlPDC8 plays a critical positive regulatory role in waterlogging tolerance by maintaining cellular homeostasis and enhancing antioxidant capacity. Full article

Background: Oral iron supplementation or food fortification is essential for managing or preventing iron deficiency but often causes gastrointestinal side effects. While solubility has traditionally been considered a requirement for iron uptake via the DMT1 transporter, recent evidence shows that insoluble iron can also be absorbed through endocytosis, raising questions about particle size and epithelial responses. Methods: Human intestinal cell lines (Hutu-80 and Caco-2) were exposed to physiologically relevant but elevated iron levels (0.5 mM Fe, 48 h) as ferric pyrophosphate, ferrous fumarate (both prone to precipitation), and soluble ferric EDTA. Cell survival and COX-2 protein were quantified by ELISA, solubility by ICP-OES, and particle size in cell culture medium by dynamic light scattering analyses. Results: Ferric pyrophosphate (0.62–3.8 μm) markedly increased COX-2 expression in Hutu-80 cells (254% ± 37%, n = 3, p = 4.11 × 10⁻⁵) and in Caco-2 cells (78% ± 8%, n = 3, p = 0.01) compared to the control. Ferrous fumarate (237–866 nm) also induced COX-2, but only in Hutu-80 cells (62% ± 11%, n = 3, p = 0.04), whereas ferric EDTA showed no effect in either cell line. COX-2 induction was associated with larger particles in the medium (≥237 nm), whereas smaller particles (<146 nm) were not. Conclusions: Particle size appears to be a critical determinant of cell survival and iron-induced epithelial COX-2 expression. Iron compounds that present as both soluble and particulate forms may optimize bioavailability, but controlling aggregate size (<146 nm) could reduce inflammatory signaling. These findings may have important implications for cell culture systems and warrant in vivo validation in iron supplemental studies. Full article

Background/Objectives: Cutaneous leishmaniasis (CL) is a prevalent vector-borne disease characterized by a broad spectrum of clinical manifestations resulting from protozoan parasites belonging to the genus Leishmania. The challenges associated with the treatment of CL are attributable to various factors, including but not limited to: drug resistance, the adverse effects of conventional therapeutic interventions and the imperative for novel therapeutic alternatives to address the global health burden posed by this neglected tropical disease. Methods: In this study, The therapeutic efficacy of two silver(I)-N-heterocyclic carbene (NHC) complexes, namely chloro[1-methallyl-3-(2,4,6-trimethylbenzyl)-5,6-dimethylbenzimidazole-2-ylidene]silver(I) (2a) and chloro[1-methallyl-3-(4-chlorobenzyl)-5,6-dimethylbenzimidazole-2-ylidene]silver(I) (2b), was evaluated against promastigotes in vitro and in vivo in an experimentally induced CL model in Balb/c mice. Results: The findings of this study indicated that these compounds possess the potential to function as effective therapeutic agents, particularly in the treatment of CL. Subsequently, the silver(I) complexes were analyzed by means of molecular docking against LaGP63, LaARG, N-myristoyltransferase and farnesyl pyrophosphate synthase. Conclusions: According to the docking evaluations, complex 2a emerged as the most notable molecule in terms of its potential antileishmanial activity. Full article

The investigation aimed to use selected waste plant materials as thiamine matrices for fortification purposes. Thiamine hydrochloride (TCh) and thiamine pyrophosphate (TP) constituted the sources of thiamine. The waste vegetable variables (carrots (crowns, peel), cauliflower, and broccoli (stems, leaves)) were used as a matrix for the thiamine. The peeled carrots, without crowns, as well as the florets of cauliflower and broccoli, were also used as a matrix for thiamine, serving as a reference for the waste used. Fortification effectiveness was analysed based on thiamine content analysis in the product immediately after freeze-drying and after storage (230 days at 4, 21, and 40 °C). The results confirmed that after six months of storage, these products contained thiamine at 55 to 90% of the level found in samples immediately after drying. The results confirm the effectiveness of using analysed waste plant materials as matrices for thiamine. The highest effectiveness was confirmed for broccoli and cauliflower leaves. The analysis of the influence of all predictors on thiamine changes revealed that storage temperature significantly affected thiamine loss in all carriers. It was confirmed that the lower the storage temperature, the lower the dynamics of thiamine loss. It was also confirmed that TP had a lower thiamine retention. Full article

Background/Objectives: Linezolid is an oxazolidinone antibiotic whose prolonged use is associated with peripheral neuropathy, hyperlactatemia, and metabolic acidosis. These adverse effects are primarily linked to the inhibition of mitochondrial protein synthesis, respiratory chain dysfunction, and oxidative stress. Given the central role of impaired energy metabolism and redox imbalance in drug-induced peripheral neuropathy, therapeutic strategies targeting mitochondrial function are of particular interest. Accordingly, this study aimed to comparatively evaluate the effects of adenosine triphosphate (ATP), coenzyme Q10 (CoQ10), pyridoxine, and thiamine pyrophosphate (TPP) on linezolid-induced peripheral neuropathic pain in rats. Methods: Sixty male albino Wistar rats were assigned to ten groups: healthy (HG); ATP-only (ATPG, 5 mg/kg, intraperitoneally); CoQ10-only (CQ10G, 10 mg/kg, orally); pyridoxine-only (PDXG, 50 mg/kg, orally); TPP-only (TPPG, 20 mg/kg, intraperitoneally); linezolid-only (LZDG, 125 mg/kg, orally); linezolid+ATP (ATLG); linezolid+CoQ10 (CQLG); linezolid+pyridoxine (PXLG); and linezolid+TPP (TPLG). Treatments were administered once daily for ATP, CoQ10, and TPP, and twice daily for linezolid and pyridoxine for 14 days. Oxidative stress indices (MDA, tGSH, SOD, CAT) were quantified in the sciatic nerve using ELISA. Serum lactate dehydrogenase (LDH) activity and blood lactate levels were determined to evaluate metabolic disturbances. Mechanical paw withdrawal thresholds were measured using the Randall–Selitto test both before and after treatment. Results: Linezolid significantly reduced paw withdrawal thresholds and induced oxidative stress, antioxidant depletion, increased LDH activity, and hyperlactatemia. Co-treatment with ATP and CoQ10 attenuated oxidative stress but did not significantly improve linezolid-induced reductions in nociceptive thresholds. In contrast, pyridoxine partially alleviated linezolid-induced neuropathic pain and improved biochemical parameters. Notably, TPP exerted the most robust protective effect, preserving nociceptive thresholds and effectively normalizing oxidative stress and metabolic indices. Conclusions: These findings identify TPP as a promising therapeutic strategy for mitigating linezolid-induced peripheral neuropathic pain by targeting mitochondrial energy metabolism and pyruvate–lactate homeostasis. Full article

Magnesium alloys require protective surface coatings for widespread application, with micro-arc oxidation (MAO) being a prominent technique. However, conventional MAO coatings are typically gray or light-colored, necessitating secondary treatments for specific colors like black, which complicates the process. This study aims to develop a one-step method for fabricating black MAO coatings on AZ31 magnesium alloy by introducing cupric pyrophosphate (Cu₂P₂O₇) as a colorant into a silicate-based electrolyte. As the Cu₂P₂O₇ concentration increased from 0 to 5 g/L, the coating color transitioned from grayish-white to pink, then brownish-black, achieving a uniform black appearance at 4–5 g/L. XPS and EDS analyses confirmed the incorporation of copper as CuO, identified as the primary coloring agent. XRD indicated that the phase composition remained MgO, MgSiO₃, and Mg, although the MgO content decreased. Microstructural analysis showed that an optimal concentration of 4 g/L enhanced coating compactness by thickening the dense layer and reducing pore size. However, electrochemical tests revealed that the incorporation of CuO significantly increased the corrosion current density, thereby reducing the coating’s corrosion resistance compared to the unmodified coating. This work successfully demonstrates the one-step fabrication of black MAO coatings, elucidates the coloration mechanism involving CuO formation, and provides insights into the trade-off between aesthetic functionalization and corrosion performance. Full article