Search Results (165)

Biostimulants, particularly single amino acids, can increase plant growth and crop quality, gaining significant attention. This study investigates the effects of 10 amino acids via root/foliar application on the growth, quality, taste, and volatile flavor of mini-watermelons and compares the differences between the application methods. Here, we employed electronic noses, electronic tongues, and gas chromatography–ion mobility spectrometry to investigate these effects. Root application excels in fruit growth and pectin accumulation, while foliar application boosts soluble protein and specific nutrients. Specifically, root application (except for Val) significantly increases fruit weight, with Gly being most effective for longitudinal diameter, while most amino acids (except Val/Lys) promote transverse diameter. Pectin content shows bidirectional regulation: root application of Glu/Gly/Lys/Pro/Trp/Val enhances pectin, whereas foliar application inhibits it. For taste indices, most treatments improve soluble solids (except Glu root/Arg-Leu foliar), and Ala/Asp/Glu/Gly reduce titratable acids, optimizing the sugar–acid ratio. Foliar application is more efficient for soluble protein accumulation (Ala/Glu/Gly/Pro/Leu). For nutritional quality, except for Lys, all treatments increase vitamin C and widely promote total phenolics and lycopene, with only minor exceptions, and only Arg foliar application enhances ORAC. Additionally, the results revealed that root-applied lysine and valine greatly raised the levels of hexanal and 2-nonenal, whereas foliar-applied valine significantly increased n-nonanal and (Z)-6-nonenal. Overall, we found that amino acids can considerably improve mini-watermelon production, quality, taste, and antioxidant capacity, providing theoretical and practical references for their widespread use in agriculture. Full article

Background/Objectives: Understanding the molecular interactions between small bioactive compounds and serum albumins is essential for drug development and pharmacokinetics. Noraucuparin, a biphenyl-type phytoalexin with promising pharmacological properties, has shown a strong binding affinity to bovine serum albumin (BSA), a model protein for drug transport. This study aims to elucidate the structural and energetic characteristics of the noraucuparin–BSA complex under physiological and slightly elevated temperatures. Methods: Microsecond-scale molecular dynamics (MD) simulations and Molecular Mechanics Generalized Born Surface Area (MMGBSA)-binding-free energy calculations were performed to investigate the interaction between noraucuparin and BSA at 298 K and 310 K. Conformational flexibility and per-residue energy decomposition analyses were conducted, along with interaction network mapping to assess ligand-induced rearrangements. Results: Noraucuparin preferentially binds to site II of BSA, near the ibuprofen-binding pocket, with stabilization driven by hydrogen bonding and hydrophobic interactions. Binding at 298 K notably increased the structural mobility of BSA, affecting its global conformational dynamics. Key residues, such as Trp213, Arg217, and Leu237, contributed significantly to complex stability, and the ligand induced localized rearrangements in the protein’s intramolecular interaction network. Conclusions: These findings offer insights into the dynamic behavior of the noraucuparin–BSA complex and enhance the understanding of serum albumin–ligand interactions, with potential implications for drug delivery systems. Full article

The tomato leaf miner, Tuta absoluta (Lepidoptera: Gelechiidae), is a destructive pest of Solanaceae crops worldwide. Its olfactory system plays an important role in locating mating partners and recognizing host plants. Understanding its olfactory recognition mechanism, particularly the function of odorant-binding proteins (OBPs), may reveal potential targets for pest management. In this study, we characterized two antenna-specific OBPs, TabsOBP45 and TabsOBP46, which were identified from the T. absoluta genome. Sequence analysis revealed that both TabsOBPs belong to the classic OBP subfamily, which is characterized by the presence of six conserved cysteine residues and an N-terminal signal peptide. Both TabsOBPs showed predominant antennal expression in quantitative real-time PCR (qRT-PCR) assays, suggesting their key roles in olfactory perception. Fluorescence competitive binding assays with a total of 63 tested volatiles revealed that 13 compounds exhibited strong binding affinities (Ki < 22 µM) to TabsOBP45, with the highest binding affinity to β-ionone, β-caryophyllene, terpinolene, and cinnamaldehyde. Nine compounds showed strong binding affinities to TabsOBP46, with the strongest binding to 4-anisaldehyde, 4-methoxybenzaldehyde, cinnamaldehyde, and β-ionone. Molecular docking analysis revealed the key residues involved in β-ionone binding: TabsOBP45 interacted with ILE8, ALA9, PHE12, TRP37, ILE92, PHE94, THR115, and PHE118, while TabsOBP46 interacted with ILE8, PHE12, PHE36, TRP37, ILE92, LEU94, PHE118, and VAL134. These results provide new insights into the olfactory mechanism of T. absoluta and potential molecular targets for the development of olfactory-based pest control strategies. Full article

Large-scale blooms of Ulva prolifera severely impact coastal ecosystems and economic development. In addressing Ulva management, the development of high-value utilization approaches for this macroalga remains crucial. Compared to other marine algae, Ulva prolifera exhibits higher protein content with diverse amino acid profiles, and existing studies demonstrate that hydrolyzed Ulva prolifera proteins can yield biologically active peptides with functional potential. Conventional methods for producing bioactive peptides are often cost-intensive. Here, we employed in silico enzymatic hydrolysis to generate small peptides from Ulva prolifera protein. Through computer screening, molecular docking with the Keap1 protein, and molecular dynamics simulations, we identified a potential antioxidant peptide, DWS (Asp-Trp-Ser). Molecular docking and dynamics simulations revealed that DWS forms stable complexes with Keap1 by establishing hydrogen bonds and Pi bonds with conserved amino acid residues (Leu557, Gly558, Ile559, Val604, Val606, and Arg415). In vitro antioxidant assays demonstrated that DWS exhibits potent DPPH and ABTS radical scavenging activities as well as reducing power. Cellular experiments showed that DWS effectively alleviates LPS-induced oxidative stress and inflammation in RAW264.7 macrophages. Full article

Background/Objectives: Inflammatory bowel diseases (IBDs) comprise a group of chronic idiopathic disorders, including ulcerative colitis (UC), Crohn’s disease (CD), and indeterminate colitis (IC). Complex genetic factors, in addition to environmental triggers, have been shown to play a fundamental role in the pathogenesis of IBD, contributing to disease susceptibility. The transition of adolescents with inflammatory bowel disease (IBD) to adult care represents a significant challenge for patients, their families, and healthcare providers. Approximately 25% of individuals with IBD receive a diagnosis before the age of 16, and this population is at increased risk for adverse clinical outcomes. As a result, the transition of care has garnered substantial attention in the scientific and clinical communities over the past decade. This study aims to analyze a cohort of pediatric Sardinian patients with IBD to assess clinical characteristics at diagnosis and at the time of transition and determine potential correlations between NOD2/CARD15 gene variants and HLA class II with the disease phenotype. Methods: From January 2014 to August 2024, we performed an observational, cross-sectional study that included pediatric patients with IBD enrolled in the only pediatric IBD reference center in Sardinia. Data were obtained from the patients’ medical records and from a questionnaire administered at the inclusion visit. In addition, we genotyped a portion of our cohort for the Leu1007fsinsC (SNP13), Gly908Arg (SNP12), and Arg702Trp (SNP8) variants of the NOD2/CARD15 gene, as well as for HLA-DRB1, -DQA1, and -DQB1 class II genes. The obtained results were compared with pediatric data from the national epidemiological IBD registry and existing literature. Results: Seventy-one IBD patients were enrolled (UC 43, CD 28, M 34, F 37). Median age at diagnosis was 12.2 years (IQR 2–17). After a median disease duration of 5 years (IQR: 1–16), only three UC patients experienced proximal extension of proctitis or left-sided colitis, and no CD patients experienced new localizations of disease. Fifteen patients developed extraintestinal manifestations. No significant difference was found in median diagnostic delay (DD) between UC [4 months (IQR: 1–84)] and CD patients [4.5 months (IQR: 1–48)]. At the transition visit, overall, twenty-nine patients (42%) were exposed to one biologic agent (vs. 3% at baseline; p < 0.02); 3 patients (4%) were exposed to two or more biologic agents. 7% of patients (5/71) underwent surgery. By comparing the distribution of NOD2/CARD15 SNPs between pediatric patients and an adult CD population, we found a significant association between gene allelic variants and pediatric onset (p = 0.00048). Our study also revealed a statistically significant association between Sardinian pediatric patients carrying NOD2/CARD15 mutations and early-onset CD (p < 0.009492), along with a stenosing phenotype (p < 0.024) and increased surgical risk (p < 0.026). No significant associations were observed between HLA class II alleles and IBD in our population. Conclusions: Our results provide important insights into the clinical and epidemiological features of the pediatric IBD population. In addition, our study highlights the significant role of NOD2/CARD15 gene polymorphisms in pediatric onset CD. These variants influence the age of onset and disease phenotype, characterized by greater severity and a higher risk of surgical intervention in pediatric patients. Full article

Amaranthus palmeri is a highly problematic agricultural weed due to its rapid growth, high seed production, and strong tendency to develop herbicide resistance. In Spain, the initial colonization of A. palmeri began in 2007, when populations were detected at various locations in the province of Lleida (Catalonia). Since then, new infestations have been reported in other regions of the country, primarily infesting maize fields. Although resistance to glyphosate or to acetolactate synthase (ALS) inhibitors has been documented in several populations from Catalonia and Extremadura, little is known about the resistance profile of populations from Aragon. The main objective of this study was to characterize the putative resistance of five populations from Aragon to 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) inhibitors (glyphosate) and ALS inhibitors (nicosulfuron and imazamox). Sensitivity to both mechanisms of action was measured by root growth in vertical plates and shikimate accumulation for glyphosate. Target-site resistance was evaluated by analyzing EPSPS and ALS gene copy numbers and ALS gene mutations. The populations showed high variability, with no multiple resistance detected. The Bujaraloz population showed moderate resistance to glyphosate due to EPSPS gene amplification. In three populations, mutations in the ALS gene conferring resistance were detected. The Trp574Leu mutation was detected in approximately half of the individuals from the Albelda, Tamarite de Litera, and Caspe populations. In the latter, the Pro197Thr mutation was also present. This study reveals significant genetic variability within each population and provides evidence for the spread of herbicide resistance across different regions of Spain. Full article

Antimicrobial resistance (AMR) is a global health threat, with methicillin-resistant Staphylococcus aureus (MRSA) being one of the major resistant pathogens. This study reports the isolation of a novel mangrove-derived bacterium, Virgibacillus chiguensis FN33, as identified through genome analysis and the discovery of a new anionic antimicrobial peptide (AMP) exhibiting anti-MRSA activity. The AMP was composed of 23 amino acids, which were elucidated as NH₃-Glu-Gly-Gly-Cys-Gly-Val-Asp-Thr-Trp-Gly-Cys-Leu-Thr-Pro-Cys-His-Cys-Asp-Leu-Phe-Cys-Thr-Thr-COOH. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for MRSA were 8 µg/mL and 16 µg/mL, respectively. FN33 AMP induced cell membrane permeabilization, suggesting a membrane-disrupting mechanism. The AMP remained stable at 30–40 °C but lost activity at higher temperatures and following exposure to proteases, surfactants, and extreme pH. All-atom molecular dynamics simulations showed that the AMP adopts a β-sheet structure upon membrane interaction. These findings suggest that Virgibacillus chiguensis FN33 is a promising source of novel antibacterial agents against MRSA, supporting alternative strategies for drug-resistant infections. Full article

Alzheimer’s disease (AD), a prevalent neurodegenerative disorder in the elderly, poses significant humanistic and economic burdens worldwide. Previously, we identified Trp-Leu-Pro (WLP), a novel antioxidant peptide derived from the sea squirt (Halocynthia roretzi); however, its effects on AD remained unexplored. In this study, we developed a rapid and efficient method to generate AD cerebral organoids with consistent quality using okadaic acid (OKA) exposure. This study aimed to evaluate the protective effects of WLP on OKA-induced AD pathology in cerebral organoids and elucidate its underlying mechanisms. Our results demonstrated that cerebral organoids exposed to 25 nM OKA successfully recapitulated hallmark AD pathologies, including amyloid-beta (Aβ) plaque deposits, neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau proteins, and neuronal loss. WLP treatment significantly enhanced cell viability, increased the proportion of neuronal progenitor cells, and reduced Aβ plaques and NFTs in OKA-induced cerebral organoids. Furthermore, transcriptomic analysis revealed that the neuroprotective effects of WLP are primarily mediated through the regulation of synapse-related and oxidative stress pathways. These findings highlight the potential of WLP as a promising nutraceutical candidate for AD prevention. Full article

PD-L1 (programmed cell death ligand-1) is a protein located on the surface of regulatory cells. It has an immunosuppressive role as it binds specifically to the protein programmed cell death-1 (PD-1), a checkpoint glycoprotein, present on the surface of immune cells such as T and B lymphocytes. Many tumor cells block the immune response by overexpressing PD-L1 on their surface; therefore, targeting PD-L1 represents a powerful strategy that allows tumor localization. To determine the presence of PD-L1 in cells, the use of ad hoc functionalized peptides that bind to PD-L1 can be exploited. One of them is the peptide CLP002 (Trp-His-Arg-Ser-Tyr-Tyr-Thr-Trp-Asn-Leu-Asn-Thr), which, bound to surface-enhanced Raman scattering (SERS) gold nanostructures via a suitable linker, was shown to be highly effective in recognizing MDA-MB-231 breast cancer cells and, importantly, this recognition can be measured by SERS experiments. To characterize, on a molecular scale, the interaction between PD-L1 and peptide functionalized nanostructures, we performed molecular dynamics (MDs) simulations, studying the features of peptide monolayers bound on gold surfaces in the absence and presence of PD-L1. The results obtained allow us to explain why the nature of the linker plays a fundamental role in the binding and why a peptide carrying the same amino acids as CPL002 but with a different sequence (scrambled) is much less active than CLP002. These results open the way to an in silico evaluation of the key parameters that regulate the binding of PD-L1 useful for cancer recognition. Full article

Hypopituitarism is a condition characterized by the deficiency of several hormones produced by the pituitary gland. Genetic factors play an important role. Variants in the POU1F1 gene are associated with combined pituitary hormone deficiency 1 (CPHD1), which manifests as deficiencies in growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin (PRL). This study aimed to analyze the phenotype, genotype, treatment, and outcomes of Vietnamese patients with deficiency. Six patients from five unrelated families, initially diagnosed with hypopituitarism, were enrolled in this study. Data on physical characteristics, biochemical tests, treatment, outcomes, and follow-up were collected. Exome sequencing and Sanger sequencing were conducted to identify disease-causing variants in five probands and their families. All six patients exhibited anterior pituitary hypoplasia on brain magnetic resonance imaging and presented with TSH, GH, and PRL deficiencies. Exome sequencing identified three variants in the POU1F1 gene: c.428G>A p.(Arg143Gln), c.557T>G p.(Leu186Arg), and c.811C>T p.(Arg271Trp). The c.811C>T p.(Arg271Trp) variant was found in three patients, while c.557T>G p.(Leu186Arg) is a novel variant. Based on the ACMG classification, these variants were categorized as likely pathogenic or pathogenic variants. All patients were definitively diagnosed with CPHD1 caused by POU1F1 variants. All patients received levothyroxine and recombinant human growth hormone (rhGH) replacement therapy, leading to considerable growth. During the first year of treatment, all patients showed excellent growth response, with height increases ranging from 11 to 24 cm. After three years of treatment, two patients achieved normal height. One of the six patients developed scoliosis during treatment, which resolved after a one-year pause in rhGH therapy. Upon resuming treatment, no recurrence of scoliosis was observed. Our findings reveal the importance of early hormone testing and genetic analysis in improving the care and outcomes for patients with combined pituitary hormone deficiency. Full article

Palmer amaranth (Amaranthus palmeri S. Watson), native to North America, is one of the most prominent invasive weed species on agricultural land. Acetolactate synthase (ALS)-resistant A. palmeri (Amaranthus palmeri) is widespread, while the research focus on resistance pattern and molecular basis of A. palmeri to imazethapyr is seldom documented in China. An A. palmeri population that survived the recommended rate of imazethapyr was collected in Shandong Province, China. The resistant mechanism and pattern of A. palmeri to imazethapyr was investigated. Dose–response assay showed that the resistant (R) population displayed a high resistance level (292.5-fold) to imazethapyr compared with the susceptible (S) population. Sequence analysis of the ALS gene revealed that nucleotide mutations resulted in three resistance-conferring amino acid substitutions, Pro-197-Ile, Trp-574-Leu, and Ser-653-Asp, in the individual plants of the R population. An in vitro enzyme assay indicated that the ALS was relatively unsusceptible to imazethapyr in the R population, showing a resistance index of 88.6-fold. ALS gene expression and copy number did not confer resistance to imazethapyr in the R population. Pro-197-Ile is the first reported amino acid substitution conferring ALS resistance to A. palmeri. This is the first case of an imazethapyr-resistant A. palmeri biotype in China. Full article

Beckmannia syzigachne is one of the most competitive weeds in winter wheat fields in China. In this study, 120 suspected resistant populations of Beckmannia syzigachne were collected from the Anhui, Hubei, Jiangsu, and Shandong Provinces from 2017 to 2019. In total, 110 populations exhibited different levels of resistance to clodinafop-propargyl, 114 populations expressed different levels of resistance to mesosulfuron-methyl, and 105 populations were resistant to both herbicides at different levels. The resistant weeds were mainly distributed in Anhui and Jiangsu Provinces. The detection results of acetyl coA carboxylase (ACCase) and acetolactate synthase (ALS) genes in the resistant populations indicated that ACCase gene mutations occurred in 97 out of 110 populations resistant to clodinafop-propargyl and ALS gene mutations occurred in 25 out of 114 populations resistant to mesosulfuron-methyl. There were several mutation types, including Ile-1781-Leu, Trp-2027-Cys, Ile-2041-Asn, Ile-2041-Val, Asp-2078-Gly, and Gly-2096-Ala in the ACCase sequence and Pro-197-Ser, Pro-197-Thr, Pro-197-His, Pro-197-Leu, Asp-376-Glu, and Trp-574-Leu in the ALS sequence. Among these mutation types, Pro-197-His, Asp-376-Glu, and Trp-574-Leu in the ALS sequence were the first identified in Beckmannia syzigachne. Full article

Background: The potentiator VX-770 (ivacaftor) has been approved as a monotherapy for over 95 cystic fibrosis (CF)-causing variants associated with gating/conductance defects of the CF transmembrane conductance regulator (CFTR) channel. However, despite its therapeutic success, VX-770 only partially restores CFTR activity for many of these variants, indicating they may benefit from the combination of potentiators exhibiting distinct mechanisms of action (i.e., co-potentiators). We previously identified LSO-24, a hydroxy-1,2,3-triazole-based compound, as a modest potentiator of p.Arg334Trp-CFTR, a variant with a conductance defect for which no modulator therapy is currently approved. Objective/Methods: We synthesized a new set of LSO-24 structure-based compounds, screened their effects on p.Arg334Trp-CFTR activity, and assessed the additivity of hit compounds to VX-770, ABBV-974, ABBV-3067, and apigenin. After validation by electrophysiological assays, the most promising hits were also assessed in cells expressing other variants with defective gating/conductance, namely p.Pro205Ser, p.Ser549Arg, p.Gly551Asp, p.Ser945Leu, and p.Gly1349Asp. Results: We found that five compounds were able to increase p.Arg334Trp-CFTR activity with similar efficacy, but slightly greater potency promoted by LSO-150 and LSO-153 (EC₅₀: 1.01 and 1.26 μM, respectively). These two compounds also displayed a higher rescue of p.Arg334Trp-CFTR activity in combination with VX-770, ABBV-974, and ABBV-3067, but not with apigenin. When tested in cells expressing other CFTR variants, LSO-24 and its derivative LSO-150 increased CFTR activity for the variants p.Ser549Arg, p.Gly551Asp, and p.Ser945Leu with a further effect in combination with VX-770 or ABBV-3067. No potentiator was able to rescue CFTR activity in p.Pro205Ser-expressing cells, while p.Gly1349Asp-CFTR responded to VX-770 and ABBV-3067 but not to LSO-24 or LSO-150. Conclusions: Our data suggest that these new potentiators might share a common mechanism with apigenin, which is conceivably distinct from that of VX-770 and ABBV-3067. The additive rescue of p.Arg334Trp-, p.Ser549Arg-, p.Gly551Asp-, and p.Ser945Leu-CFTR also indicates that these variants could benefit from the development of a co-potentiator therapy. Full article

Buchnera aphidicola, an obligate endosymbiont of most aphid species, can influence aphids’ host adaptability through amino acid metabolism, potentially mediating biotype differentiation. However, its role in the biotype differentiation of Sitobion avenae remains unclear. To address this issue, six S. avenae biotypes were tested in this study. Buchnera abundance varied among biotypes fed on different wheat/barley varieties (i.e., Zhong 4 wumang, 186-TM12-34; Dulihuang, Zaoshu No.3, Xiyin No.2). The reduction in Buchnera abundance through antibiotic (rifampicin) treatment altered the virulence of five S. avenae biotypes. Based on transcriptome analysis, the differential expression of three genes (i.e., LeuB, TrpE, and IlvD) related to leucine, tryptophan, isoleucine, and valine metabolism was detected between different biotypes. Principal component analysis showed that leucine and tryptophan deficiencies most significantly impacted nymph development duration and aphid fecundity. Additionally, a neighbor-joining phylogenetic tree indicated the genetic differentiation of Buchnera among different biotypes. These results suggest Buchnera-mediated amino acid metabolism is correlated with biotype differentiation in S. avenae, although the precise mechanisms by which Buchnera influences this differentiation require further investigation. This study can offer a theoretical basis for the development of resistant crops, leading to the sustainable control of this aphid and reduced reliance on chemical insecticides. Full article

Background/Objectives: This study investigated the potential of green algae-derived carotenoids as natural inhibitors of the proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of cholesterol metabolism. PCSK9 promotes the degradation of low-density lipoprotein receptors (LDLR), thereby increasing blood cholesterol levels and elevating the risk of cardiovascular diseases. Methods/Results: We screened the pharmacophore fit score of 27 carotenoids with PCSK9 and identified 14 that were analyzed for binding affinity and molecular interactions. Astaxanthin, siphonaxanthin, and prasinoxanthin were identified as the top candidates, demonstrating strong binding affinity (−10.5, −10.3, and −9.4 Kcal/mol, respectively) and stable interactions with several known key residues within the active site of PCSK9, including Pro-331, Arg-357, Cys-358, Val-359, Asp-360, Ile-416, Leu-436, Thr-437, Pro-438, Leu-440, Arg-458, Val-460, Trp-461, Arg-476, Cys-477, Ala-478, Ala-649, Val-650, and Asp-651. Density functional theory analysis confirmed the stability of astaxanthin and its favorable electronic properties, suggesting its potential as an effective inhibitor. Molecular dynamics simulations of the PCSK9–astaxanthin complex revealed sustained structural stability and key interactions critical for maintaining the functional integrity of the protein. Conclusions: These findings provide evidence that specific carotenoids, particularly astaxanthin, may offer a cost-effective alternative to existing PCSK9 inhibitors, providing a potential approach for managing cholesterol levels and reducing cardiovascular risk. Pre-clinical and clinical validations are required to confirm the therapeutic potential of these compounds. Full article