Search Results (1,282)

Heme metabolism is central to the biology of malaria parasites and to the mechanism of action of artemisinin-based therapies. Within malaria-infected red blood cells (RBCs), heme-related chemistry arises from multiple nested metabolic sources that function as “Russian dolls”: the truncated heme biosynthetic capacity of the host erythrocyte, the parasite’s own heme synthesis pathway, and host heme released through hemoglobin digestion in the parasite food vacuole. These overlapping metabolic layers create distinct pools of heme that can influence redox balance and drug activation. Recent studies highlight that exogenous 5-aminolevulinic acid (5-ALA) can perturb host heme biosynthesis in infected erythrocytes, potentially increasing intracellular levels of the heme intermediate protoporphyrin IX and sensitizing parasites to oxidative stress. However, the extent to which such metabolic perturbations affect artemisinin susceptibility depends strongly on parasite stage and exposure duration. Here we review the compartmentalized architecture of heme metabolism in malaria-infected RBCs and discuss how these nested vulnerabilities may be exploited for therapeutic intervention. Full article

The objective of this study was to investigate the effects of supplemental starter feeding on the development of the ruminal epithelium in suckling yak calves using transcriptomic analysis. Twenty healthy one-month-old male yak calves with similar body weights were selected and randomly assigned to two groups. The pre-feeding adaptation period lasted 14 days, followed by a 120-day experimental feeding period. At the end of the trial, five calves from each group were slaughtered, and samples of abomasum tissue and ruminal contents were collected for subsequent analyses. The results demonstrated that early concentrate supplementation markedly increased the final body weight and ruminal NH₃-N concentration of calves in the RAS group compared with the control (RA) group (p < 0.05). Similarly, dry matter intake and ruminal microbial protein (MCP) content were significantly higher in the RAS group (p < 0.05). In contrast, the concentration of acetic acid in ruminal fluid was significantly higher in the RA group, whereas valeric acid concentration was higher in the RAS group. Furthermore, ruminal TNF-α, TNF-γ, and IL-2 concentrations were significantly elevated in the RAS group (p < 0.05), suggesting enhanced ruminal immune function. Transcriptomic analysis revealed that both up- and down-regulated gene expression contributed to the morphological development and overall health of the ruminal epithelium. Up-regulated genes were enriched in pathways related to chemical carcinogenesis, cytochrome P450 metabolism, steroid hormone biosynthesis, retinol metabolism, ascorbate and aldarate metabolism, drug metabolism-cytochrome P450, pentose and glucuronate interconversions, ovarian steroidogenesis, and porphyrin and chlorophyll metabolism. Conversely, down-regulated genes were mainly associated with cytokine–cytokine receptor interactions, mineral absorption, arachidonic acid metabolism, and viral protein interactions with cytokine receptors. Overall, early supplementation with concentrate feed enhanced the expression of genes associated with ruminal epithelial development, improved immune responses, and promoted better growth performance in suckling yak calves. Full article

Soil salinization impacts over one billion hectares, threatening global food security. Here, a salt-tolerant bacterial strain, Pseudomonas fluorescens G3, was isolated from the rhizosphere of maize (Jinongyu-719) growing in saline–alkali soils in Gansu Province, China. This strain demonstrated the ability to secrete indole-3-acetic acid (IAA), 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, and extracellular polysaccharides. It also exhibited notable phosphate-solubilizing activity and robust siderophore production capabilities. Under salt stress conditions (200 mM NaCl), the P. fluorescens G3 strain significantly improved maize’s growth parameters, namely its plant height, root length, and dry weight. Further, it enhanced antioxidant enzyme activity while reducing the accumulation of malondialdehyde (MDA), mitigating stress-induced oxidative damage. In P. fluorescens G3-inoculated plants, leaf and root Na⁺ contents decreased by 34.90% and 33.91%, while their K⁺ contents increased by 40.20% and 33.47%, respectively. Inoculation with P. fluorescens G3 enhanced taxonomic richness (ACE, Chao1) and evenness (Shannon, Simpson) in the rhizosphere bacterial community, leading to a significantly greater relative abundance of several bacterial genera: Pseudomonas, Methylophaga, Enhygromyxa, Desulfuromonas, and Devosia. These shifts in the microbial community composition suggest a potential restructuring of functional profiles, possibly enhancing processes beneficial to plant salt tolerance, such as ion homeostasis and stress mitigation: the biosynthesis of cofactors and secondary metabolites; bacterial secretion and two-component systems; porphyrin metabolism; flagellar assembly; biofilm formation; and bacterial chemotaxis. Redundancy analysis revealed positive correlations between microbial composition at both the phylum and genus levels and the activity of stress resistance enzymes after treatment with Pseudomonas fluorescens. This study provides important theoretical foundations and microbial resources for utilizing microbial community regulation in saline–alkali soil bioremediation. Full article

Background/Objectives: Peritoneal micrometastases (micromets) remain a major barrier to durable cytoreduction in ovarian and other intra-abdominal cancers because lesions are difficult to visualize and are often resistant to systemic therapy. Liposomal doxorubicin (Dox) improves pharmacokinetics but can be limited by slow intratumoral release. Porphyrin-phospholipid (PoP) liposomes enable near-infrared light–triggered release of Dox (chemophototherapy (CPT)), creating an opportunity for intraoperative fluorescence-guided treatment planning and monitoring. Here, we evaluate a laparoscopic fluorescence imaging platform for quantifying light-triggered drug delivery. Methods: LC-Dox-PoP was applied to SCC2095sc and SKOV-3 cultures in 2D monolayers and 3D spheroid clusters. Dox fluorescence was quantified using a laparoscopic fluorescence imaging system over 1–9 μg/mL concentrations and compared with standard well-plate reader measurements. Porphyrin fluorescence was monitored to assess spheroid localization and photobleaching after activation light exposure. Results: For both cell lines, Dox fluorescence exhibited an approximate 4-fold increase at the maximum administered LC-Dox-PoP concentration, following a linear trend in both SCC2095sc and SKOV-3 cultures (R² = 0.97, 0.98 for 2D and R² = 0.98, 0.98 for spheroids). Laparoscope-derived fluorescence measurements agreed with well-plate reader measurements (R² = 0.89–0.96). Porphyrin fluorescence provided stronger complementary contrast for localizing spheroid constructs and decreased after activation light exposure, consistent with photobleaching during triggered release. Conclusions: These results support a quantitative imaging framework for fluorescence-guided monitoring of light-triggered liposomal drug release and may enable individualized CPT dosimetry for peritoneal micrometastases. Findings in SCC2095sc additionally suggest potential relevance of fluorescence-guided CPT for head and neck/oral cancer, where localized post-resection adjuvant treatment may improve control of residual disease. Full article

G-quadruplexes (G4s) are noncanonical nucleic acid structures involved in gene regulation and genome stability. Among them, the telomeric repeat-containing RNA (TERRA) forms biologically relevant RNA G4s (rG4s) that participate in telomere maintenance and genome stability. Although many ligands targeting DNA G4s have been reported, the recognition and modulation of RNA G4 topologies remain less explored. In this work, we investigated the interaction between TERRA and the spermine-functionalized Zn(II) porphyrin, ZnTCPPSpm4, using UV–vis absorption, fluorescence, resonance light scattering (RLS), and circular dichroism (CD) spectroscopy. In K⁺, where TERRA adopts a parallel G4 conformation, ZnTCPPSpm4 binds through a stepwise mechanism involving external end-stacking, forming discrete supramolecular complexes without altering the native topology. In contrast, under Na⁺ conditions, ZnTCPPSpm4 induces a gradual conformational rearrangement of TERRA from the antiparallel to a parallel-like G4 topology. A CD melting study showed that ZnTCPPSpm4 stabilizes the parallel RNA G4, while slightly destabilizing the antiparallel topology. Overall, our results demonstrate that ZnTCPPSpm4 is not a simple G4 binder, but a topology-selective ligand capable of remodeling TERRA G4 structures, highlighting the potential of metalloporphyrins as RNA G4-targeting scaffolds. Full article

Leaf-color variation in plants should be associated with chlorophyll metabolism and chloroplast development. Here, we characterized a low-temperature-sensitive pakchoi DH line, 1197, which exhibited green leaves at 25 °C, but showed yellowing at 4 °C. Low temperature significantly reduced chlorophyll accumulation and disrupted chloroplast ultrastructure. After transfer from 4 °C to 25 °C for 7 days, yellow leaves partially regreened, and chlorophyll a content increased by 366.67%. RNA-seq analysis identified 3058 core DEGs associated with the yellowing–regreening transition, which were significantly enriched in photosynthesis–antenna proteins, photosynthesis, and porphyrin metabolism pathways. Leaf yellowing was characterized by repression of chlorophyll biosynthesis genes (e.g., CHLD, CHLM, PORC) and induction of degradation genes (SGR1, SGR2, NYC1, PAO), together with widespread downregulation of chloroplast function-related genes. In addition, GLK2, HBI1, NAC047, and NAC029 were identified as candidate regulators of temperature-dependent leaf-color conversion. This study provides candidate molecular insights into low-temperature-induced yellowing and regreening in pakchoi and offers candidate genes for future functional validation and Brassica breeding. Full article

Design and fabrication of high-performance organic semiconductors are still challenging. Here, we designed new D-(A)n type zinc porphyrin end-capped ethynylene-7-(4-hexyl-thiophen-2-yl)-2,1,3-benzothiadiazole (EBTT) oligomers by linking 5,10,15-trisphenyl porphyrin zinc (ZnTPP) with length-variable EBTT oligomers (at the 20-position of porphyrin) [ZnTPP(EBTT)_n (n = 1–6)]. The influence of oligomer length on molecular structures, orbital energies, electronic absorption spectra, ionization energies, electronic affinities, and reorganization energies was systematically studied through density functional theory. The charge-carrier mobility of the simulated crystals and the power conversion efficiencies (PCE) using PCBM as the accepter were also predicted. ZnTPP(EBTT)₆ show excellent hole/electron mobility of 76.161/9.395 cm²V⁻¹s⁻¹ and extremely high PCE of 25.45%. This work would have significance for the design and synthesis of organic semiconductor materials with large charge-carrier mobility and high PCE performance. Full article

Emerging pharmaceutical contaminants, including sulfonamide antibiotics such as sulfamethoxazole (SMX), persist in natural water bodies at ng L⁻¹ to µg L⁻¹ concentrations and are inadequately removed by conventional wastewater treatment technologies, posing significant ecological and public health risks. Porphyrin-based quantum catalysts activated by peroxymonosulfate (PMS) represent a promising advanced oxidation strategy for the remediation of such recalcitrant micro-pollutants. However, the precise molecular mechanisms governing their catalytic activity remain incompletely understood. In this study, we present a comprehensive mechanistic investigation of SMX oxidation catalyzed by Mn (III) meso-tetraphenylporphyrin (Mn-TPP) in the presence of PMS, employing spin-unrestricted density functional theory (DFT) at the Becke, 3-parameter, Lee–Yang–Parr (B3LYP-D3BJ) level of theory with dispersion corrections. Full Gibbs free energy profiles for the catalytic cycle were constructed through geometry optimizations using the LACVP basis set on Mn and 6-31G(d,p) on all non-metal atoms, followed by single-point energy calculation at the 6-311+G(d,p) level, incorporating the SMD implicit solvation model to stimulate aqueous environment conditions. The results demonstrate that the oxidation of Mn TPP by PMS to generate the key high-valent intermediate Mn(V)=O(TPP)⁺ is thermodynamically and kinetically favorable. The activation barrier for Mn(V)=O(TPP)⁺ formation via PMS activation is ΔG† = 17.2 kcal mol⁻¹ (SMD water, 298 K), confirming that this step is kinetically accessible under ambient environmental conditions. Subsequent SMX oxidation processes proceed via concerted radical and non-radical mechanistic pathways, with the most thermodynamically favorable route exhibiting a strongly exergonic reaction-free energy (ΔGr), indicating that significant mineralization of the target pollutant is thermodynamically accessible. The transition state analysis reveals spin density localization characteristic of the Mn-Oxo species, establishing a direct correlation between quantum confinement effects, electronic structure and the observed catalytic selectivity and oxidation stability of the Mn-TPP system. These mechanistic insights provide quantitative molecular-level design parameters, including activation barriers, spin state requirements, and electronic structure descriptors for the rational optimization of next-generation porphyrin-based quantum catalysts capable of efficiently degrading persistent pharmaceutical contaminants in complex aqueous matrices. Full article

[¹¹¹In]In-diethylenetriaminepentaacetic acid-5,10,15,20-tetraphenylporphyrin ([¹¹¹In]In-DTPA-TPP) nanodroplets were developed for cancer theranostics, featuring ultrasound-sensitive properties. The designed nanodroplets that encapsulate the low-boiling-point liquid perfluorocarbon and IR-780 iodide, a near-infrared fluorescent dye, with surface conjugation of ¹¹¹In-labeled porphyrin derivative, were synthesized and evaluated by in vitro and in vivo experiments. The cellular uptake of [¹¹¹In]In-DTPA-TPP nanodroplets was significantly higher than that of control nanodroplets without TPP. Biodistribution experiments revealed greater tumor accumulation in mice injected with [¹¹¹In]In-DTPA-TPP nanodroplets than in those injected with control nanodroplets lacking TPP. Additionally, the accumulation of [¹¹¹In]In-DTPA-TPP nanodroplets in the tumor was visualized by single-photon emission computed tomography. Sonodynamic therapeutic experiments revealed that DTPA-TPP nanodroplets at 10 µmol total lipids/kg weight with a single ultrasound irradiation onto the tumor area significantly inhibited tumor growth. These results indicate that [¹¹¹In]In-DTPA-TPP nanodroplets would be promising cancer theranostic agents. Full article

Fascioloidosis is a parasitic disease caused by allochthonous parasite Fascioloides magna. In Europe, three types of final hosts are recognised: definitive, aberrant, and dead end. Several countries have launched disease control programmes using medicated feed, with different drugs, to control F. magna infections. In this study, we used corn treated with Albix^® 10 in a total dose of 60 mg/kg of body weight for five consecutive days (12 mg/kg per day). Following successful treatment, a destroyed pseudocyst with different amounts of degrading material and decaying flukes was detected. A total of 136 livers was examined. The average number of pseudocysts per positive liver was seven (min. 1–max. 45), while the average number of adult flukes was 14.17 (2–70). On average, 1.34 juvenile flukes in the migratory phase were detected per infected liver. The average number of pseudocysts was 7.07 per liver in total. Degrading pseudocysts were either absent or present to a maximum of 120 per liver, with an average of 7.99 per liver. Some livers had multifocal to confluent nodules bulging from the liver parenchyma, which were up to 7 cm in diameter. Histologically, these areas showed disruption, containing bands of fibrous connective tissue, dividing parenchyma into pseudolobules of varying size and shape. These septa contained dark brown to black pigment (iron porphyrin), along with remnants of elliptical, operculated, mainly empty trematode eggs. Nodules were surrounded with fibrous tissue and disorganised hyperplastic hepatocytes arranged in irregular trabeculae supported by fibrous bands occasionally containing blood vessels. This study shows the potential of liver regeneration in the case of acute and chronic liver injury, as well as in cases of fatty liver disease. Full article

Rising atmospheric CO₂ levels have increased the demand for robust, scalable adsorbents for practical CO₂ capture and separation. Porous organic polymers (POPs) are attractive candidates because their pore architecture and binding site properties can be precisely tuned via building blocks and linkage formation. This review summarizes experimental and computational studies of azo-linked POPs and, more broadly, nitrogen–nitrogen (N–N) linked systems, emphasizing how synthetic routes, building blocks, and framework topology govern CO₂ uptake. We highlight key synthetic strategies and representative systems, including porphyrin–azo networks, and discuss the relatively sparse experimental literature on alternative N–N linked POPs incorporating azoxy and azodioxy motifs. Emphasis is placed on reversible nitroso/azodioxide chemistry as a potential pathway to ordered porous organic materials. Computational studies provide a practical route to connect structure with adsorption behavior in largely amorphous or partially ordered networks. We review hierarchical workflows combining periodic DFT and electrostatic potential properties, grand canonical Monte Carlo (GCMC) simulations, and binding energy calculations to rationalize trends and identify favorable binding environments. Computational findings demonstrate that pore accessibility and stacking models can strongly influence predicted CO₂ adsorption. This review provides guidelines for designing POPs with enhanced CO₂ adsorption, offering an outlook and discussing challenges for future studies. Full article

This study presents the synthesis and electrochemical characterization of meso-tetracyanobutadiene (TCBD)-functionalized diphenylporphyrin (DPP) complexes incorporating copper (Cu) and nickel (Ni) metals. These push–pull metallo diphenylporphyrin–TCBD complexes were synthesized via a [2 + 2] cycloaddition–retroelectrocyclization reaction between 5-bromo-15-formyl-10,20-diphenylporphyrin metal(II) complexes (M = Cu, Ni) and tributyl(phenylethynyl)stannate, followed by tetracyanoethylene (TCNE) addition. The resulting TCBD-functionalized porphyrins were obtained in moderate yields (70–75%) and thoroughly characterized by ¹H and ¹³C NMR, UV-Vis spectroscopy, MALDI-TOF-MS, and single-crystal XRD. Although the single-crystal X-ray structure of NiDPP was solved, DFT calculations were used to determine the structures of the donor–acceptor MDPP-TCBD systems and to visualize their electronic structures. HOMO on the porphyrin π system and LUMO on the TCBD entity were observed, and energy level diagrams clearly laid out the electron donor and acceptor parts of the molecular systems. As expected, these novel donor–acceptor porphyrinoid assemblies exhibited enhanced push–pull properties in both the ground and excited states. Femtosecond transient absorption studies revealed that both NiDPP-TCBD and CuDPP-TCBD populate the charge-transfer state upon photoexcitation, with lifetimes of 383.1 ps and 484.7 ps, respectively, in benzonitrile. The charge-transfer states populated the triplet or doublet states (in the case of CuDPP) before returning to the ground state. Full article

Tuberculosis, caused by Mycobacterium tuberculosis, remains a global health challenge, particularly due to multidrug-resistant strains. Photodynamic therapy using porphyrin-based photosensitizers offers a promising alternative by targeting the trehalose-rich cell wall of the bacillus. Motivated by prior experimental observations that shorter linkers improve efficacy, this study probes the molecular basis of linker-length-dependent activity in trehalose–porphyrin glycoconjugates. Here, we show that shorter linker lengths are consistent with improved activity in vitro and, in an Ag85B docking model, constrain conformational flexibility, reduce solvent exposure, and promote tighter packing consistent with stronger predicted interactions. Using computational docking, we analyzed binding scores, RMSD variability, steric clashes, and protein–ligand interactions for conjugates docked into Ag85B, a key enzyme in cell wall synthesis. Shorter linkers (0–2 carbons) were found to exhibit superior binding scores, lower RMSD variability, and stronger interactions with residues such as ARG 43, including unique π–cation interactions. In contrast, longer linkers displayed increased flexibility, reduced binding specificity, and greater solvent exposure. These findings, which support our experimental observations, suggest a molecular basis for linker-dependent efficacy and provide a framework for designing next-generation porphyrin-based therapeutics for tuberculosis treatment. Full article

Background/Objectives: Oxidative stress and iron overload remodel erythrocyte membranes in β-thalassemia, but their systemic metabolic correlates are not well defined. We applied untargeted metabolomics to identify serum biomarkers reflecting these pathophysiological processes. Methods: Thirty-one adults with β-thalassemia [18 transfusion-dependent (TDT), 13 non-transfusion-dependent (NTD)] and 8 age/sex-matched healthy controls were studied. Fasting serum was profiled using untargeted UHPLC–Orbitrap MS. Multivariate modeling (SIMCA-P) and FDR-controlled univariate statistics identified discriminant features, followed by pathway enrichment analysis. Associations with clinical variables (chelation regimen, ferritin, cardiac MRI T2*, and liver iron concentration) were examined. Results: A total of 183 metabolites were detected; versus controls, 124 were decreased, 54 increased, and 5 remained unchanged in patients. Key discriminants included lysophosphatidylcholines (LysoPC 18:1, 18:3), polyunsaturated fatty acid (PUFA)-bearing phosphatidylcholines (PC 20:4/18:0, PC 18:0/20:4), conjugated bile acids (glycocholic acid, glycochenodeoxycholic acid, and glycoursodeoxycholic acid), and bilirubin. Pathway analysis revealed significant enrichment (FDR-corrected) in linoleic acid metabolism (q = 0.024, impact = 1.000) and arachidonic acid metabolism (q = 0.022, impact = 0.433), with supportive nominal signals from glycerophospholipid (impact = 0.401) and porphyrin/heme (impact = 0.242) pathways. No significant metabolic differences were observed between TD and NTD patients. Conclusions: β-thalassemia serum metabolomics reflects oxidative membrane lipid remodeling with a prominent PLA₂/LysoPC–arachidonic axis and evidence of heme turnover and altered bile-acid signaling. These data propose a practical biomarker panel-LysoPCs, arachidonic acid-enriched PCs, and conjugated bile acids-warranting targeted validation alongside conventional clinical parameters for disease monitoring and therapeutic assessment. Full article

Silica nanoparticles (SiNPs) are widely explored as biocompatible platforms for the delivery of photosensitizers in photodynamic therapy (PDT). In this work, porphyrins bearing amine (PNH₂) or carboxyl (PCOOH) groups were covalently conjugated onto functionalized SiNP surfaces via carbodiimide-mediated amide coupling, yielding the silica–porphyrin nanohybrids H-PNH₂ and H-PCOOH. Successful surface functionalization was confirmed by Fourier-transform infrared spectroscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. Photophysical studies demonstrated that both nanohybrids retained efficient singlet oxygen (¹O₂) generation. In vitro biological assays revealed a strong dependence of photodynamic activity on the nature of the conjugated porphyrin, with H-PCOOH exhibiting markedly enhanced photocytotoxicity with respect to the free porphyrins, while H-PNH₂ showed an attenuated light-dose response. Notably, H-PCOOH induced pronounced cell death at low light doses (1 J/cm²), with a half-maximal inhibitory concentration (IC₅₀) below 0.3 µM. These findings highlight the potential of silica–porphyrin nanohybrids as efficient photosensitizers for PDT applications. Full article