Search Results (223)

Bee pollination enhances the yield and fruit quality of loquats (Eriobotrya japonica Lindl.). However, the systemic effects of pollination on fruit metabolomics, particularly the metabolic differences among various cultivars following pollination, remain unclear. This study examined the metabolome of Baihua loquats following pollination by Apis cerana and compared it to that of unpollinated fruits. A total of 1964 metabolites were identified, including 334 differentially expressed metabolites. After analyzing ripe fruits of the white-fleshed loquat (Baihua, BH) and red-fleshed loquat (Dahongpao, DHP) following pollination, a total of 635 differentially expressed compounds were identified, with flavonoids, phenolic acids, and amino acids being the most abundant among the differentially expressed metabolites. This study further elucidated the biosynthetic pathways of phenylpropanoids, which account for the differences in the accumulation of BH and DHP in loquat following pollination. Consequently, these findings enhance our understanding of the overall metabolome of pollinated loquats, deepen our knowledge of polyphenolic metabolism in different loquat varieties, and provide new insights into the flavor differences between white-fleshed and red-fleshed loquats. Full article

Flavor esters are valuable compounds widely used in the food, beverage, and cosmetics industries for their aroma and flavor-enhancing properties. Traditional methods of obtaining these compounds, such as extraction from natural sources or chemical synthesis, present challenges related to cost and toxicity, respectively. Enzymatic synthesis, particularly using immobilized lipases, offers a sustainable and efficient alternative. This study investigates the application of CRL immobilized on Diaion HP-20 for geranyl butyrate synthesis via esterification of geraniol and butanoic acid using Candida rugosa lipase (CRL) immobilized on Diaion HP-20 (CRL-DHP-20). The immobilization process resulted in a protein loading of 29.6 ± 2.2 mg/g support from an initial 40 mg/g, and the immobilized biocatalyst exhibited a hydrolytic activity of 124.0 ± 2.5 U/g using olive oil emulsion. Reaction conditions were optimized through a central composite design, evaluating the influence of biocatalyst concentration, temperature, and agitation on ester conversion. The optimal conditions (13.4% CRL-DHP-20, 48.2 °C, and 220.1 rpm) led to 85.4% conversion in 360 min. Additionally, CRL-DHP-20 retained 84% of its initial activity after six reaction cycles, indicating good operational stability. These findings highlight the potential of CRL-DHP-20 as an effective and reusable biocatalyst for green synthesis of flavor esters. Full article

The article presents the synthesis and characterization of double halide perovskites (DHPs) with the nominal composition Cs₂Ag_0.2Na_0.4In_0.6M_0.4Cl₆ (M = Si, Ti, Zr), including photoluminescence (PL), photoluminescence excitation (PLE) spectra measured over a range of temperatures and kinetics of luminescence. The materials were synthesized via a hydrothermal method. The phase purity and elemental composition of the synthesized perovskites were confirmed by X-ray diffraction (XRD), Rietveld refinement, scanning electron microscopy (SEM) equipped with energy-dispersive X-ray spectroscopy (EDS) and elemental analysis, which demonstrated that the samples showed a close match to the target stoichiometry. The PL spectra exhibit a systematic shift toward the lower-energy region with substitution from Si to Zr, correlating with the progressive increase in the ionic radii of the substituting cations. All samples display broad, asymmetric emission bands, characteristic of self-trapped excitonic (STE) states. Temperature-dependent PL measurements reveal a gradual decrease in emission intensity with increasing temperature for all samples. The maximum emission intensity is observed in the range of ~160–200 K, corresponding to optimal conditions for radiative recombination, whereas the lowest intensity is recorded at ~80–100 K, where thermal activation of radiative centers is minimal. An increase in temperature is accompanied by a red shift in the PL bands across all compositions. In the Ti-doped DHP, a pronounced blue shift at low temperatures is observed, which can be attributed to the involvement of Ti³⁺-related electronic states. An analysis of the activation energy of thermal luminescence quenching and the results of time-resolved spectroscopy revealed the activation of thermal processes in the titanium-containing sample and their rapid decay, whereas replacing titanium with silicon leads to more stable luminescence in the crystal under study. Thus, the enhanced luminescence characteristics of double halide perovskites doped with Ti, Si, and Zr highlight their potential for advanced photonic and optoelectronic applications. Full article

China’s rural public open spaces (POS) are largely governed as common-pool resources through self-organized collective arrangements, often regarded as a viable pathway to sustainable commons management. Yet, in practice, these systems remain prone to overuse and under-maintenance, reflecting collective action failures associated with the tragedy of the commons. The governance of rural POS therefore constitutes a complex social–ecological problem shaped by the interplay of institutional rules, biophysical conditions, and user–stakeholder interactions. Taking Taigu District in Shanxi Province—characterized by heterogeneous social–ecological contexts and collective action dilemmas—as the empirical case, this study develops a meso-level baseline model to identify the key conditions (design principles) for sustainable rural POS governance. Adopting an expert-based epistemological approach, 24 specialists in rural governance (scholars, planners, and local administrators) were engaged. Grounded in commons and collective action theories within the Social–Ecological Systems (SES) framework and informed by Transaction Cost Economics (TCE), the study operationalizes a Delphic Hierarchy Process (DHP), combining three rounds of Delphi to establish consensus on governance conditions with the Analytic Hierarchy Process (AHP) to derive their relative weights. The model specifies 14 governance conditions across four interrelated dimensions: ecological (e.g., clearly defined resource boundaries and congruence between resource characteristics and user needs), institutional (e.g., simple and enforceable rules, accessible conflict-resolution mechanisms, accountable monitoring, and calibrated external support), social (e.g., social capital, leadership capacity, clearly defined user boundaries, and group interdependence), and interactional (e.g., resource dependence, equity in benefit distribution, and supply–demand alignment). It further clarifies their relative importance and systemic interdependencies. By operationalizing commons design principles within a meso-level analytical framework, the study advances their empirical application in rural planning and offers five targeted managerial implications to strengthen institutional robustness and the long-term sustainability of self-governed rural POS. Full article

Novel brominated flame retardants (NBFRs), including 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), are emerging endocrine-disrupting chemicals, though their direct effects on female gamete maturation remain insufficiently characterized. In this study, we used a refined zebrafish oocyte in vitro maturation (IVM) model integrating germinal vesicle breakdown (GVBD) assessment with real-time, image-based oocyte diameter quantification. The workflow incorporated donor-condition optimization and diameter-based quality control during sorting. Oocytes from donors 4 to 5 months post-fertilization (mpf) showed more consistent diameter dynamics at the dish level than those from donors 3 to 4 mpf. Mixed-sex co-housing was associated with higher GVBD and larger Δdiameter than separated housing, although this comparison should be considered preliminary. Under DHP induction, BTBPE (1–1000 nM) consistently suppressed GVBD and attenuated maturation-associated diameter increases, with a non-monotonic-like response pattern. These findings indicate that BTBPE impairs oocyte maturation competence in vitro and supports real-time morphometric tracking as a practical QC component for zebrafish IVM workflows. Full article

The polyamine metabolic pathway, an evolutionarily conserved nexus integrating nutrient sensing, translation control, and cellular proliferation, is fundamentally rewired in cancer. Melanoma, a malignancy of melanocytes notorious for its metastatic propensity and therapy resistance, exhibits a profound dependency on this pathway, extending beyond mere polyamine abundance to the specialized function of their derivative, hypusine. This review synthesizes cutting-edge insights into the deoxyhypusine synthase (DHPS)/eukaryotic initiation factor 5A (eIF5A) hypusination circuit as a critical amplifier of oncogenic signaling in melanoma. We dissect its role as a translational rheostat for pro-tumorigenic proteomes, a driver of phenotypic plasticity underpinning invasion and vasculogenic mimicry, and a modulator of the immunosuppressive tumor microenvironment. Moving beyond the classical inhibitor GC7, we explore the emergence of novel allosteric DHPS inhibitors with compelling preclinical efficacy. Finally, we propose a paradigm shift: targeting the DHPS/eIF5A axis represents a strategy to disrupt the “non-oncogene addiction” of melanoma—its reliance on hyperactive translation and adaptive survival mechanisms—offering a promising avenue alongside targeted therapies and immunotherapies. Full article

Amphiphilic cationic lipids based on the 1,4-dihydropyridine (1,4-DHP) scaffold represent a versatile platform for the development of self-assembling delivery systems. In this work, a series of ten new amphiphilic 1,4-DHP derivatives bearing branched ester substituents at the 3,5-positions and quaternized cationic groups at the 2,6-positions were designed and synthesized. The effect of branched ester chain length and branching on nanoparticle formation was investigated. The self-assembling properties of the synthesized amphiphiles were evaluated by dynamic light scattering using an ethanol injection method. All compounds formed positively charged nanoparticles with hydrodynamic diameters ranging from 52 to 439 nm and polydispersity index from 0.194 to 0.452. Amphiphiles 14b–17b with 2-hexyldecyl substituents formed smaller particles, with an average diameter below 100 nm. Several derivatives exhibited good stability over a 14-day storage period at room temperature. To clarify structure–property relationships, lipophilicity (AlogP), polar surface area (PSA), and pK_a values were calculated using Schrödinger computational tools. The compounds displayed high lipophilicity AlogP 8.98–19.32, while PSA values remained within a narrow range. The calculated pK_a values ranged from 7.20 to 10.99. The results demonstrate that both the length and architecture of branched ester chains significantly influence nanoparticle size, homogeneity, and stability, highlighting branched-chain 1,4-DHP amphiphiles as promising synthetic lipid candidates for further development of delivery systems after evaluation of biological properties. Full article

Objectives: To characterize urodynamic findings after lower-level spinal cord injury (LSCI) and to evaluate a new pressure-based classification framework—the bladder–sphincter dyscoordination syndrome (BSDS)—for describing voiding patterns. We also introduce a descriptive “neurogenic bladder outlet obstruction” (NBOO) phenotype for straining-dependent voiding difficulty. Methods: We retrospectively analyzed the first urodynamic studies (December 2020–August 2024) in 81 men with LSCI (injury at T10 or below). Key urodynamic measures included detrusor and intravesical pressures during filling and voiding, bladder volumes (first desire to void and capacity), compliance, maximum flow rate (Q_max), post-void residual (PVR), voiding efficiency, and the ratio of detrusor to abdominal pressure rise (ΔPdet/ΔPabd). We compared cases with detrusor overactivity (DO) versus those without DO. Among those with voiding discoordination, we distinguished classical detrusor–sphincter dyssynergia (DSD) from a proposed NBOO phenotype (characterized by abdominal straining pressure ≥ 40 cmH₂O, detrusor pressure < 20 cmH₂O, incomplete emptying, and no anatomic obstruction). We further classified discoordination cases using the BSDS framework into four subtypes—dual high-pressure (DHP), detrusor-muscle predominant (DMP), dual low-pressure (DLP), and abdominal-pressure predominant (APP)—based on reference pressure thresholds (detrusor 20 cmH₂O; abdominal 40 cmH₂O). Results: Patients with DO (43.2%) showed significantly higher detrusor pressures during filling (at first desire to void and at capacity) and a lower first desire volume than non-DO patients, while maximum capacity was similar (p = 0.105). During voiding, DO cases had lower PVR and higher emptying rates, although the detrusor-vs-abdominal pressure contribution (ΔPdet/ΔPabd) was comparable between groups. Among 63 patients with voiding discoordination, 32 (50.8%) met NBOO criteria; these NBOO cases exhibited lower detrusor and intravesical voiding pressures but worse emptying (higher PVR) compared to classical DSD cases. Overall, 76 of 81 patients (93.8%) fit within the BSDS classification—distributed as 22 DHP, 13 DMP, 15 DLP, and 26 APP patterns. Conclusions: The BSDS framework (and the NBOO descriptor when conventional indices cannot be applied) offers a novel way to describe voiding patterns after LSCI. It links urodynamic observations to potential management strategies (by identifying whether the bladder or outlet is the primary issue). Prospective studies are needed to validate this framework against outcomes such as upper tract integrity, continence, and dependence on catheterization. Full article

Objectives: As widely used first-line antihypertensive drugs, dihydropyridine calcium channel blockers (DHP-CCBs) have relatively few studies comparing their adverse reactions based on real-world data. This study aims to identify and compare the potential adverse drug reaction (ADR) signals of four DHP-CCBs (amlodipine, felodipine, nicardipine, and nifedipine) through the US Food and Drug Administration Adverse Event Reporting System (FAERS), providing a reference for further drug safety assessment and clinical medication risk awareness. Methods: Adverse event reports from medical professionals (Q3 2014–Q4 2024) were analyzed using signal detection methods, including reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and the Medicines and Healthcare Products Regulatory Agency (MHRA) methods. Risk signals for the four DHP-CCBs were compared with both the full database and the DHP-CCBs background. For high-risk signals in amlodipine, multivariate logistic regression was used for validation. The analysis reveals distinct ADR profiles for the four DHP-CCBs. Results: Amlodipine is strongly linked to suicide-related risks, confirmed by logistic regression. Nicardipine and nifedipine show significant risks for pregnancy-related events, such as premature delivery and exposure during pregnancy. Nicardipine is also associated with hyponatremia, hyperkalemia, and lactic acidosis. These adverse events are not yet included in the FDA labeling for any of the DHP-CCBs. Although palpitations and angioedema are listed for felodipine, their signal strength is much higher compared to the other DHP-CCBs. Conclusions: The ADR risk profiles of the four DHP-CCBs differ significantly. This study identified several high-risk adverse events not included in current labels. Clinical use should consider each drug’s risk profile and patient-specific factors, with particular attention to serious risk signals. For pregnant and postpartum women, the benefits and risks of using nicardipine and nifedipine should be carefully evaluated. Full article

Malaria in pregnancy remains a major driver of poor maternal and neonatal health outcomes in sub-Saharan Africa. For decades, intermittent preventive treatment in pregnancy (IPTp), with sulphadoxine-pyrimethamine (SP), has mitigated malaria-associated health risks, but concerns have been raised regarding accumulated Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutations on the efficacy of SP. Western Kenya, including Busia County, is a high malaria transmission setting where molecular surveillance of dhfr and dhps mutations remains limited. This study assessed the prevalence and haplotype structure of dhfr and dhps mutations in P. falciparum isolates from Busia County, Kenya. A total of 66 samples of P. falciparum isolates collected from patients attending Matayos Sub-County Hospital between November 2024 and January 2025 were analysed. PCR amplification and Sanger sequencing targeted dhfr codons C50R, N51I, C59R, S108N/T, I164L, and dhps codons I431V, S436A/F, A437G, K540E, A581G, and A613S/T to determine mutation frequencies, haplotypes, and combined dhps and dhfr haplotype profiles. High frequencies of dhfr and dhps mutations were observed across the parasite isolates. The most common dhfr substitutions included N51I (85.2%) and C59R (75.4%), while S108N (32.8%) and S108T (19.7%) were detected at lower frequencies. Dhfr haplotypes identified included N51I + C59R, N51I + C59R + S108N, and a N51I + C59R + S108T + I164L variant. The I164L mutation was detected at a frequency of 18.0% and was observed exclusively on a non-canonical S108T background (19.7%). Dhps haplotypes were dominated by A437G (92.3%), K540E (40%) alone, and the A437G + K540E double mutant. Combined dhfr and dhps haplotype analyses revealed circulation of classical dhfr triple-mutant (N51I + C59R + S108N) backgrounds with dhps A437G. Quintuple haplotypes (dhfr N51I + C59R + S108T + I164L with dhps A437G) and rare complex haplotypes incorporating both I164L and K540E or I164L and S436F were also detected. These findings indicate the persistence and circulation of both canonical and non-canonical dhfr and dhps haplotypes in P. falciparum isolates from Busia County. This study highlights the need for continuous molecular and phenotypic surveillance to clarify the functional and epidemiological significance of parasites carrying S108T and I164L mutations, and to inform IPT policy. Full article

Background: Amidst escalating global challenges such as antimicrobial resistance and post-COVID therapeutic gaps, dihydropyrimidines (DHPs) and their thione derivatives have emerged as a highly promising scaffold for drug development. This systematic review aims to consolidate recent advancements (2020–2025) and evaluate the synthetic innovation, structure–activity relationships (SAR), and preclinical potential of these compounds. Methods: A systematic review was conducted according to PRISMA guidelines, searching multiple electronic databases (Scopus, PubMed, Web of Science). Sixty original studies from 2020 to 2025 meeting predefined inclusion criteria were selected for data extraction and qualitative synthesis. Results: The analysis reveals a surge in publications (over 300% since 2020). Key structural modifications, such as N-methylation to improve bioavailability and specific substitutions at C4/C5 positions, significantly enhance biological potency, yielding strong inhibitory effects against viral proteases and cancer cell lines. Notable compounds include the apoptosis inducer LaSOM 65 and multitarget Ru(II)–Biginelli hybrids. Conclusions: This review affirms the timeliness and translational potential of the DHP scaffold. The field shows bright prospects for advancing to phase I trials by 2030, urging intensified exploration to unlock novel pharmaceuticals from this versatile chemotype. Full article

Indane-1,3-dione and 1,4-dihydropyridine (1,4-DHP) scaffolds are of significant interest in medicinal chemistry. Herein, we report the synthesis characterization of a new lipid-like indane-1,3-dione–1,4-DHP betaine, 2-(3′,5′-bis((dodecyloxy)carbonyl)-2′,6′-dimethyl-1′,4′-dihydro-[3,4′-bipyridin]-1-ium-1-yl)-1,3-dioxo-2,3-dihydro-1H-inden-2-ide (3). Compound 3 was synthesized from 2,2-dicyanomethylideneindan-1,3-dione (1) oxide and a didodecyl-substituted 1,4-DHP derivative 2 and characterized by UV–Vis spectroscopy, ¹H-NMR, ¹³C-NMR, and HRMS. The obtained results demonstrate a promising strategy for the design of delivery agents, exploiting the lipid-like properties of the synthesized betaine. Full article

Δ¹-Pyrroline-5-carboxylate reductase (EC 1.5.1.2; called ProC in most bacteria) is an enzyme of central metabolism that catalyzes the last step of the proline biosynthetic pathways, namely the NADPH-dependent reduction of pyrroline-5-carboxylate (P5C) to L-proline (L-Pro). The enzyme, however, is also active towards other substrates, and these reactions might have physiological relevance. Herein, the substrate versatility of ProC from Escherichia coli was explored as follows. We initially characterized the reverse reaction carried out by ProC, i.e., the formation of P5C from L-Pro. This reaction was easily measurable at pH 10, allowing the determination of the kinetic parameters. Under the same conditions, we then tested the ability of ProC to oxidize a number of L-Pro analogs, confirming that ProC reacts most effectively with analogs containing a simple five-membered ring such as L-thioproline (THP) and 3,4-dehydro-L-proline (DHP). Larger substrates such as L-pipecolate (PIP) reacted with lower efficiency, and the four-membered ring analog, L-azetidine-2-carboxylate (A2C) showed no detectable reactivity and behaved as a weak inhibitor of the ProC reaction. To interpret these results, we built a structural model of ProC and employed this model for a docking analysis of L-Pro and of its analogs. This approach highlighted the presence of a peculiar “three-point interaction”, in which the L-Pro carboxylate and amino groups form hydrogen bonds with conserved residues in the binding site, while the substrate ring stacks with the nicotinamide ring of NADP⁺. The L-Pro analogs tried to preserve as much as possible these critical interactions for a correct positioning and a favorable binding. The possibility of an inherent multifunctionality of ProC was further explored by examining the genomic context of the proC gene in a large number of bacterial species. Full article

1,4-Dihydropyridines (1,4-DHPs) are privileged heterocycles with broad relevance in medicinal chemistry and redox-related applications. However, conventional Hantzsch syntheses typically require prolonged thermal heating and often suffer from limited efficiency and regioselectivity. Herein, we report a sustainable and efficient microwave-assisted protocol for the synthesis of 1,4-DHPs, employing phosphotungstic acid (HPW) as a heteropolyacid catalyst in PEG-400 as a green reaction medium. The multicomponent cyclocondensation proceeds rapidly under microwave irradiation, affording the desired 1,4-DHP derivatives in good to excellent yields within short reaction times. Compared with classical acid-catalyzed conditions, the HPW/PEG-400 system markedly enhances regioselectivity toward the 1,4-DHP framework while simultaneously reducing energy input. Moreover, the catalytic system exhibits good recyclability, underscoring its potential as a practical and environmentally responsible platform for the synthesis of bioactive 1,4-dihydropyridine scaffolds. Full article

Background/Objectives: Recent reports have demonstrated the antiparasitic activity of 1,4-dihydropyridine (1,4-DHPs). This study aimed to assess the in vitro antischistosomal activity of 24 1,4-DHPs against Schistosoma mansoni adult worms. Methods: Sixteen hexahydroquinolines (1–16) and eight Hantzsch esters (17–24) previously obtained through a multicomponent Hantzsch reaction were tested in vitro against Schistosoma mansoni adult worms. In silico studies with the most active compounds were also carried out. Results: Among the tested compounds, the Hantzsch esters 20 (diethyl 4-(4-bromophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) and 21 (diethyl 4-(3-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) provided the lowest IC₅₀ (15.2 and 13.1 µM, respectively) and the highest selectivity for this parasite (SI = 2.31 and >4.59, respectively). Conclusions: Docking studies revealed that compound 21 has a high affinity for the S. mansoni target (PDB ID: 6UY4). Furthermore, ADMET predictions indicated that compound 21 meets the drug-likeness criteria without violating any Lipinski, Veber, or Egan’s rules. Full article