Search Results (14,420)

Zinc-based alloys are promising candidates for biodegradable implant applications; however, their rapid initial corrosion and limited cytocompatibility remain major challenges. In this study, a Zn-Ca-P layer in a form of parascholzite (CaZn₂(PO₄)₂·2H₂O) was prepared on a Zn-0.8Mg-0.2Sr alloy via anodic oxidation followed by short-time biomimetic calcium–phosphate deposition. The formation mechanism, corrosion behaviour, and preliminary biological response of the modified surface were systematically investigated. The Zn-Ca-P layer formed a compact and crystalline phosphate layer that significantly altered the corrosion response of the zinc substrate in Leibovitz L-15 medium containing foetal bovine serum. Electrochemical measurements revealed a pronounced improvement in corrosion resistance and a transition from rapid active dissolution to a controlled, ion-exchange-driven degradation mechanism. The moderate solubility of parascholzite enabled the gradual release of Zn²⁺ and Ca²⁺ ions while maintaining surface stability during immersion. Preliminary cell adhesion experiments demonstrated a clear enhancement of cytocompatibility for the Zn-Ca-P-layer-coated samples, where cells readily adhered and spread, in contrast to the bare alloy surface, which showed lower cell attachment. The improved biological response is attributed to the phosphate-rich surface chemistry, favourable surface morphology, and moderated corrosion behaviour. Overall, the parascholzite-like layer provides an effective strategy with which to regulate both corrosion and early cell–material interactions of zinc-based biodegradable alloys, highlighting its potential for temporary biomedical implant applications. Full article

Additive manufacturing has been adopted in several industries including the medical field to develop new personalised medical implants including tissue engineering scaffolds. Custom patient-specific scaffolds can be additively manufactured to speed up the wound healing process. The aim of this study was to design, fabricate, and evaluate a range of materials and scaffold architectures for 3D-printed wound dressings intended for soft tissue applications, such as skin repair. Multiple biocompatible polymers, including polylactic acid (PLA), polyvinyl alcohol (PVA), butenediol vinyl alcohol copolymer (BVOH), and polycaprolactone (PCL), were fabricated using a material extrusion additive manufacturing technique. Eight scaffolds, five with circular designs (knee meniscus angled (KMA), knee meniscus stacked (KMS), circle dense centre (CDC), circle dense edge (CDE), and circle no gradient (CNG)), and three square scaffolds (square dense centre (SDC), square dense edge (SDE), and square no gradient (SNG), with varying pore widths and gradient distributions) were designed using an open-source custom toolpath generator to enable precise control over scaffold architecture. An in vitro degradation study in phosphate-buffered saline demonstrated that PLA exhibited the greatest material stability, indicating minimal degradation under the tested conditions. In comparison, PVA showed improved performance relative to BVOH, as it was capable of absorbing a greater volume of exudate fluid and remained structurally intact for a longer duration, requiring up to 60 min to fully dissolve. Tensile testing of PLA scaffolds further revealed that designs with increased porosity towards the centre exhibited superior mechanical performance. The strongest scaffold design exhibited a Young’s modulus of 1060.67 ± 16.22 MPa and withstood a maximum tensile stress of 21.89 ± 0.81 MPa before fracture, while maintaining a porosity of approximately 52.37%. This demonstrates a favourable balance between mechanical strength and porosity that mimics key properties of engineered tissues such as the meniscus. Overall, these findings highlight the potential of 3D-printed, patient-specific scaffolds to enhance the effectiveness and customisation of tissue engineering treatments, such as meniscus repair, offering a promising approach for next-generation regenerative applications. Full article

Integrated multi-trophic aquaculture (IMTA) has emerged as an ecological intensification strategy capable of enhancing nutrient utilization and improving environmental stability in mariculture systems, yet the microbial mechanisms driving nutrient transformations remain insufficiently understood. This study investigated how culture mode (IMTA vs. monoculture) shape water quality, sediment microbial communities, and nutrient cycling processes in a shrimp–sea urchin system by combining water-quality monitoring, nutrient analysis, 16S rRNA high-throughput sequencing, and redundancy analysis. IMTA significantly increased turbidity, chlorophyll-a, phosphate, ammonium, and nitrite compared with monoculture, while physico-chemical parameters remained stable. Sediment microbiota in IMTA exhibited substantially higher alpha diversity and showed a clear compositional separation from monoculture communities. At the genus level, IMTA sediments were enriched in Vibrio, Motilimonas, and Ruegeria, distinguishing them from monoculture systems. At the phylum level, IMTA was characterized by increased abundances of Proteobacteria and Bacteroidota, accompanied by a marked decline in Spirochaetota. Functional predictions indicated that microbial communities were predominantly characterized by pathways related to amino acid and carbohydrate metabolism, as well as nutrient remineralization. RDA and correlation analyses further identified turbidity, chlorophyll-a, phosphate, ammonium, and nitrite as the principal drivers of microbial divergence. Overall, the findings demonstrate that IMTA reshapes sediment microbial communities toward more efficient nutrient-processing assemblages, thereby promoting active nitrogen and phosphorus transformations and improving biogeochemical functioning relative to monoculture. These results provide mechanistic insight into how IMTA supports nutrient recycling and environmental sustainability in modern mariculture systems. Full article

Background/Objectives: Nonunion bone healing results from a critical size defect that fails to bridge a bone injury to produce bony union. Novel approaches are critical for refining therapy in clinically challenging bone injuries, but the complex and coordinated nature of fracture callus tissue development requires study outside of the simple closed murine fracture model. Methods: We have utilized a three-dimensional printing approach to develop a scaffold construct with layers designed to sequentially release small molecule therapy within the tissues of a murine endochondral segmental defect to augment different mechanisms of fracture repair during critical stages of nonunion bone healing. Initially, a sonic hedgehog (SHH) agonist is released from a fibrin layer to promote chondrogenesis. A prolyl-hydroxylase domain (PHD)2 inhibitor is subsequently released from a β-tricalcium phosphate (β-TCP) layer to promote hypoxia-inducible factor (HIF)-1α regulation of angiogenesis. This sequential approach to therapy delivery is assisted by the inclusion of bone marrow stromal cells (BMSCs) to increase the cell substrate available for the small molecule therapy. Results: Immunohistochemistry of fracture callus tissue revealed increased expression of PTCH1 and HIF1α, targets of hedgehog and hypoxia signaling pathways, respectively, in the SAG21k/IOX2-treated mice compared to vehicle control. MicroCT and histology analyses showed increased bone in the fracture callus of mice that received therapy compared to control vehicle scaffolds. Conclusions: While our findings establish feasibility for the use of BMSCs and small molecules in the fibrin gel/β-TCP scaffolds to promote new bone formation for segmental defect healing, further optimization of these approaches is required to develop a fracture callus capable of completing bony union in a large defect. Full article

The aim of the study was to investigate the early response of apple fruit infected with Penicillium expansum (P. expansum) to blue light-emitting diode (LED) light (BLL) irradiation. To focus our study on the interaction between apple fruit, the pathogen, and BLL, the effect of BLL was also studied on apples without P. expansum and P. expansum grown on malt extract agar (MEA). Transcriptome analysis revealed that the most pronounced responses among biological processes were observed in inoculated apples under BLL. The upregulated processes included water transport, response to heat, and response to high light intensity. The defence response of apples was enhanced by the upregulation of thaumatin-like proteins and caffeic acid 3-O-methyltransferase, while the cellular response to phosphate deficiency and the regulation of multicellular organism development were downregulated. In P. expansum grown on apples under BLL, transcriptome analysis revealed downregulation of genes related to signalling, response to organic compounds, and regulation of metabolic and biosynthetic processes, while genes involved in the biosynthesis of secondary metabolites were upregulated. In addition, the expression of patulin cluster genes was predominantly downregulated in P. expansum. The significant upregulation of genes related to cryptochrome inhibition, defence response, and caffeic acid metabolism in apples under BLL, together with the reduced virulence of P. expansum, contributes to the inhibition of fungal growth. Full article

This study evaluated the influence of various surface treatments on the bonding performance and mechanical behavior of zirconia, with particular emphasis on the effect of laser surface texturing (LST) compared with conventional 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) and airborne particle abrasion (APA) methods. Two zirconia compositions, 3 mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) and 5 mol% partially stabilized zirconia (5Y-PSZ), were subjected to four surface treatment protocols: as-milled, 10-MDP, APA, and LST (n = 12). Shear bond strength (SBS) to titanium and biaxial flexural strength (BFS) of zirconia were measured. Surface morphology, failure mode, and phase composition were analyzed using scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and X-ray diffraction (XRD). Data were analyzed with two-way ANOVA and Tukey’s post hoc test (α = 0.05), and the reliability of flexural strength was assessed using Weibull analysis. Surface treatment significantly affected SBS (p < 0.05). The LST groups exhibited the highest SBS values and a higher proportion of mixed failures, whereas other groups predominantly showed adhesive failures. However, LST-treated specimens, particularly 5Y-PSZ, showed reduced BFS. XRD confirmed phase stability, although localized microstructural changes were observed after LST. LST enhanced the zirconia–titanium interfacial bond strength and promoted mixed failure modes; however, this improvement was accompanied by a reduction in flexural strength, particularly in 5Y-PSZ. Full article

The endolysosomal system plays a pivotal role in cellular function. Before reaching lysosomes for degradation, the endocytosed cargoes are sorted at various stages of endosomal trafficking for recycling and/or rerouting. The proper execution of these processes depends on tightly regulated ion fluxes across endolysosomal membranes. Recent studies have demonstrated the importance of two-pore channels (TPCs), including TPC1 and TPC2, in endolysosomal trafficking. These channels are expressed in the membranes of distinct populations of endosomes and lysosomes, where they respond to nicotinic acid adenine dinucleotide phosphate (NAADP) and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P₂] to conduct Ca²⁺ and Na⁺ release from these acidic organelles. Here, we discuss the potential implications of Ca²⁺ and Na⁺ fluxes mediated by TPCs across endolysosomal membranes in the physiological and pathophysiological functions of these organellar channels. Full article

Due to improper nutrition, high-density lipoproteins (HDLs) can be subjected to structural changes, acquiring a dysfunctional phenotype. Therefore, research efforts are currently focused on improving HDL functionality despite its blood level. The aim of this study was to evaluate the effect of phycocyanin concentrate (as part of a food matrix) on the functional properties of HDL. Male Wistar rats were fed a high-fat diet containing 2% cholesterol for 113 days. Experimental animals were treated with 30 and 300 mg/kg b.w. of phycocyanin concentrate mixed with soy protein isolate. Serum and hepatic cholesterol and triglyceride levels, and the content of protein, triglycerides, choline-containing phospholipids, malondialdehyde, sphingosine-1-phosphate, and paraoxonase-1 in HDL fractions were assessed. The decrease in protein in HDL particles is characteristic for dysfunctional phenotype of these particles. Phycocyanin concentrate diet prevented the depletion of protein in HDL particles, regardless of the dosage. The functionality of HDL is associated with paraoxonase-1 activity, which inhibits lipid peroxidation in lipoproteins. Our results have shown a significant increase in the level of paraoxonase-1 in HDL particles in groups treated with phycocyanin. HDL particles become more enriched with triglycerides with the development of hyperlipidemia. Triglycerides in HDL particles and in serum decreased by two times in animals receiving 30 mg/kg b.w. of phycocyanin. The MDA content in HDL particles decreased in all animals receiving a high-fat diet with the addition of 2% cholesterol. The introduction of 300 mg/kg of phycocyanin returned this indicator to the values of the Control group. Thus, biomarkers of dysfunctional changes in HDL in rodent hyperlipidemia models may be a useful tool for assessing lipid metabolism disorders. Also, the results confirm the potential ability to use phycocyanin concentrate as part of lipid-lowering products. Full article

Background and Clinical Significance: Malaria remains a significant public health issue in Latin America, where Plasmodium vivax predominates but P. falciparum continues to circulate. Mixed-species infections are uncommon and can pose diagnostic challenges, particularly when parasite densities differ markedly, increasing the risk of underdetecting P. falciparum with conventional methods. Case report: We report a 9-year-old boy from an endemic area with a six-day febrile syndrome. Thick smear and peripheral blood film microscopy, complemented by rapid diagnostic tests for pan-Plasmodium and HRP2 antigens, confirmed a mixed infection with P. vivax (5500 parasites/µL) and P. falciparum (562 parasites/µL). The patient was hemodynamically stable, without severe malaria criteria, and laboratory values were within normal limits. Following confirmation of normal glucose-6-phosphate dehydrogenase activity, treatment with artemether–lumefantrine was initiated, followed by primaquine for hypnozoite eradication. Clinical evolution was favorable, with progressive defervescence, treatment tolerance, and documented parasite clearance. Conclusions: This case illustrates the risk of underestimating P. falciparum in mixed infections with disparate parasitemias and highlights the value of integrated diagnostic approaches in resource-limited endemic settings. It also underscores surveillance limitations that can misclassify mixed infections, potentially affecting epidemiological estimates and treatment strategies. Timely recognition and comprehensive diagnostic evaluation are essential to ensure appropriate antimalarial therapy, prevent complications, and inform public health interventions in regions where both species coexist. Full article

Background: The management of pediatric inflammatory bowel disease (PIBD) has evolved significantly over the past two decades, transitioning from corticosteroids and immunomodulators to biologic and small-molecule therapies. These advances have aimed not only to control inflammation but also to promote mucosal healing, improve growth, and enhance long-term quality of life. Objectives: This narrative review summarizes current evidence on the efficacy, safety, and clinical applications of biologic and novel small-molecule therapies in PIBD, highlighting emerging trends in personalized and precision-based management. Methods: A literature search was performed across PubMed, Embase, and the Cochrane Library, focusing on studies published within the last five years. Additional data were retrieved from key guidelines and position papers issued by ECCO–ESPGHAN, SIGENP, the FDA, and the EMA. Results: Anti–tumor necrosis factor (TNF) agents such as infliximab and adalimumab remain first-line biologics with proven efficacy in remission induction and maintenance. Newer biologics—vedolizumab, ustekinumab, risankizumab, and mirikizumab—offer alternatives for anti-TNF-refractory cases, showing encouraging short-term results and favorable safety profiles. Although many are approved only for adults with limited pediatric evidence, emerging small molecules—including Janus kinase (JAK) inhibitors (tofacitinib, upadacitinib) and sphingosine-1-phosphate (S1P) modulators (etrasimod)—provide oral, rapidly acting, and non-immunogenic treatment options for refractory disease. Furthermore, the gut microbiome is increasingly recognized as an emerging therapeutic target in PIBD, with growing evidence that host–microbiome interactions can influence both the efficacy and safety of biologics and small-molecule therapies. Conclusions: While biologics and small molecules have transformed PIBD management, challenges remain, including high treatment costs, limited pediatric trial data, and variable access worldwide. Future directions include multicenter pediatric studies, integration of pharmacogenomics, and biomarker-guided precision medicine to optimize early, individualized treatment and improve long-term outcomes. Full article

Background/Objectives: Vascular calcification is a major contributor to cardiovascular mortality and disability. Here, we investigated whether dietary nitrate, an exogenous source of nitric oxide (NO), could inhibit vascular calcification in a rat model induced by excess vitamin D₃. Methods: The rats were injected subcutaneously with phosphate-buffered saline or 200,000 IU/kg cholecalciferol and the abdominal aorta was isolated 7 and 14 d after injection. Results: Von Kossa staining revealed mild vascular calcification 7 d after injection, with the positive area expanding by 14 d. Vasorelaxation induced by the NO donor sodium nitroprusside was normal 7 d after injection but weakened 14 d after injection. In a separate experiment, sodium nitrate (3 or 10 mM in drinking water) was administered for the last 7 and 13 d, prior to sacrifice, 14 d after cholecalciferol injection. Von Kossa staining-positive areas and calcium content in the abdominal aortas did not decrease with short-term administration of sodium nitrate but decreased with long-term administration; no difference in effect based on dosage was observed in either short-term or long-term administration. Low-dose sodium nitrate tended to increase plasma nitrite and nitrate levels, which are indicators of NO bioavailability, similar to both short- and long-term administration, which increased significantly at higher doses. Conclusions: These findings suggest that NO homeostasis in blood vessels deteriorates with the progression of vascular calcification, and that dietary nitrate may be a useful therapeutic approach. Full article

Acetyl phosphate (AcP) is a microbial metabolite acting as a link between cell metabolism and signaling, providing the survival of bacteria in the host. AcP was also identified as an intermediate of pyruvate oxidation in mammalian mitochondria and was found in the human blood in some severe pathologies. The possible contribution of circulating AcP to the maintenance of the physiological or pathological states of the body has not been studied. Since AcP can function as a donor of phosphate groups, we have examined in vitro the influence of AcP on calcium signaling in mitochondria and cells by measuring the membrane potential and the calcium retention capacity of mitochondria by selective electrodes and by assaying the cell calcium signaling by Fura-2AM fluorescent radiometry. AcP was shown to induce a concentration-dependent increase in the mitochondrial resistance to calcium ion loading both in the control and in the presence of ADP. This effect was especially pronounced when mitochondria were incubated in a phosphate-free medium; under these conditions, AcP strongly raised the membrane potential and increased the rate of calcium uptake and the calcium retention capacity several times. Moreover, AcP induced similar changes in human cells when calcium signaling was activated by ATP, to a greater extent in neuroblastoma cells than in astrocytes. In the presence of AcP, a tendency for an increase in the amplitude and a decrease in the continuance of the ATP-induced calcium response was observed. These changes are probably associated with the activation of calcium buffering by mitochondria due to the delivery of phosphate during the hydrolysis of AcP. The results show that AcP is involved in the regulation of the Ca²⁺ balance in cells by activating the accumulation of calcium ions by mitochondria, especially under phosphate deficiency. A shift in calcium signaling mediated by AcP supplementation may be caused by hyperphosphatemia, which is now considered as one of basic contributors to cellular dysfunction and progression of various diseases, including sepsis. Full article

The Paleoproterozoic Aravalli Supergroup in northwest India hosts one of the oldest phosphorite deposits on Earth, located in the Jhamarkotra Formation, which was deposited after ca. 1762 Ma. Secondary enrichment is identified in the eastern region, resulting in upgradation of phosphate content, while primary stromatolitic columns are well-preserved in the western area of the Jhamarkotra mines. In this study, drill-core samples were collected from the unaltered western Block B and the upgraded eastern Block E to understand the alteration process. Petrographic studies reveal evidence of structural deformation and alteration. Elemental mapping of petrographic thin sections, employing SEM-EDS, indicates that dolomite has been leached out, resulting in phosphorite upgrading in the E-block. The major element oxide data support the leaching of dolomite. In the upgraded E-block, the weighted average P₂O₅ content nearly doubled (from 21% to 38%), while the MgO content decreased from 21% to 4% compared to the B-block. REE+Y contents in Block E are increased with minor Ce and Eu anomalies developed compared to the B Block. The U and Sr concentrations are also increased in Block E phosphorites. The petrographic and geochemical studies indicate that phosphorite enrichment was driven by structurally controlled, low-temperature hydrothermal alteration in the Jhamarkotra mines. Full article

Steroidal compounds lie at the crossroads of inflammation and cancer, where modulation of common signaling pathways creates opportunities for dual-action therapeutic intervention. Accumulating evidence indicates that their anti-inflammatory and antitumor activities are frequently interconnected, reflecting shared molecular mechanisms that regulate immune signaling, oxidative stress, cell proliferation, and apoptosis. This review provides a critical and comparative analysis of major classes of bioactive steroids—including furanosteroids, neo-steroids, aromatic steroids, α,β-epoxy steroids, peroxy steroids, cyanosteroids, nitro- and epithio steroids, halogenated steroids (fluorinated, chlorinated, brominated, iodinated), and steroid phosphate esters—with emphasis on their dual anti-inflammatory and anticancer potential. More than one thousand steroidal metabolites derived from plants, fungi, marine organisms, bacteria, and synthetic sources are surveyed. While the majority exhibit either anti-inflammatory or antineoplastic activity alone, only a limited subset displays potent activity in both domains. Comparative evaluation highlights the structural features that favor dual functionality, including epoxide, peroxide, nitrile, nitro, halogen, and phosphate ester moieties, as well as rearranged or heteroatom-enriched steroidal frameworks. Where available, biological data from in vitro and in vivo assays (IC₅₀ values, enzyme inhibition, cytokine modulation, and antiproliferative effects) are summarized and critically compared. Special attention is given to rare natural metabolites—such as polyhalogenated marine steroids, phosphorylated sterols, and heteroatom-containing derivatives—as well as synthetic analogues designed to enhance cytotoxic or immunomodulatory efficacy. Mechanistically, steroids exhibiting dual activity commonly modulate convergent signaling pathways, including NF-κB, JAK/STAT, MAPK, PI3K/AKT, redox homeostasis, and apoptosis regulation. Collectively, these findings underscore the potential of structurally optimized steroids as multifunctional therapeutic agents and provide a framework for the rational design of next-generation anti-inflammatory and anticancer drugs. Full article

Copepods are key components of marine food webs, linking primary producers such as microalgae to higher trophic levels, including many fish species. This study investigates long-term changes in the composition, density, and biomass of copepod communities along the Romanian coast of the Black Sea over six decades (1956–2015), based on historical records and recent monitoring from 18 sampling stations. Mean copepod density declined markedly over the study period, particularly during the cold season, decreasing from values exceeding 1000 ind/m³ in the 1960s to <300 ind/m³ after 2000, while biomass showed weaker but comparable long-term fluctuations. Seasonal variability was pronounced, with significantly higher densities and biomass during the warm season. Generalised Additive Models (GAMs) explained up to 40–55% of the variance in copepod density and biomass, depending on the season. During the warm season, phosphate exerted a positive effect on copepod abundance, consistent with bottom-up control via phytoplankton productivity, whereas during the cold season, temperature showed a positive effect and salinity a negative effect, indicating stronger physical control of copepod persistence. Species composition shifted over time, with a reduction in constant species and an increase in rare or accidental taxa in later decades. These results indicate that climate variability and anthropogenic pressures have reshaped copepod communities, with potential consequences for food-web efficiency and ecosystem resilience in the Black Sea. Full article