Search Results (51,855)

Background/Objectives: Pompia is an ancient, endemic citrus ecotype native to Sardinia (Italy), characterized by distinctive morphology and high content of bioactive compounds. Despite increasing interest, several aspects of this fruit, including its histological characteristics, remain poorly understood. This study aims to address this gap by investigating the anatomical features and spatial distribution of secretory cavities involved in essential oil (EO) production and accumulation, while also evaluating the EO’s chemical profile and associated biological activity. Methods: Pompia peel (flavedo and albedo) was subjected to histological analysis through fixation, dehydration, resin inclusion and sectioning. Sections were stained with 0.05% toluidine blue and observed under a light microscope to measure different parameters of secretory cavities. Essential oil (EO) was obtained from Pompia peel by hydrodistillation and characterized by gas chromatography–mass spectrometry (GC–MS) analysis. The biological activity of Pompia EO was assessed in vitro using NIH/3T3 fibroblasts, where wound-healing was evaluated by scratch assay and anti-senescence effects by β-galactosidase and γH2AX activity. Results: Microscopic analysis of the peel revealed pronounced variability in depth and size of the secretory cavities, along with the presence of lenticel-like structures in the epidermis. GC–MS analysis showed that Pompia EO is dominated by limonene (89%), with minor compounds including myrcene, geranial and neral. In vitro biological assays demonstrated that the EO promotes cell migration in a wound-healing model at concentrations ≥ 12.5 µg/mL and reduces markers of cellular senescence, including β-galactosidase activity and γH2AX foci, in etoposide-induced senescent fibroblasts. Conclusions: Overall, this study provides the first histological characterization of Pompia peel and confirms the bioactive potential of its EO. These findings support future applications in skin regeneration and anti-aging strategies and contribute to the valorization of this underexplored Citrus ecotype. Full article

Hearing loss is often caused by genetic and environmental factors, with inherited mutations responsible for 50–60% of cases. The GJB2 gene, encoding connexin 26, is a major contributor to nonsyndromic sensorineural hearing loss (NSHL) due to its role in cellular communication critical for auditory function. In Taiwan, common deafness-associated genes include GJB2, SLC26A4, OTOF, MYO15A, and MTRNR1, which were similar to those found in other populations. The most common pathogenic genes is GJB2 mutations and the hearing level in children with GJB2 p.V37I/p.V37I or p.V37I/c.235delC was estimated to deteriorate at approximately 1 decibel hearing level (dB HL)/year. We found another common mutation in Taiwan Biobank, GJB2 p.I203T, which were identified in our data and individuals carrying this mutation experienced more severe hearing loss, suggesting a synergistic effect of these mutations on auditory impairment. We suggest GJB2 whole genetic screening is recommended for clinical management and prevention strategies in Taiwan. This study used data from the Taiwan Biobank to analyze allele frequencies of GJB2 gene variants. Predictive software (PolyPhen-2 version 2.2, SIFT for missense variants 6.2.1, MutationTaster Ensembl 112 and Alphamissense CC BY-NC-SA 4.0) assessed the pathogenicity of specific mutations. Additionally, 82 unrelated NSHL patients were screened for mutations in these genes using PCR and DNA sequencing. The study explored the correlation between genetic mutations and the severity of hearing loss in patients. Several common GJB2 mutation sites were identified from the Taiwan Biobank, including GJB2 p.V37I (7.7%), GJB2 p.I203T (6%), GJB2 p.V27I (31%), and GJB2 p.E114G (22%). Bioinformatics analysis classified GJB2 p.I203T as pathogenic, while GJB2 p.V27I and GJB2 p.E114G were considered polymorphisms. Patients with GJB2 p.I203T mutation experienced more severe hearing loss, emphasizing the potential interaction between the gene in auditory impairment. The mutation patterns of GJB2 in the Taiwanese population are similar to other East Asian regions. Although GJB2 mutations represent the predominant genetic cause of hereditary hearing loss, the corresponding mutant proteins exhibit detectable aggregation, particularly at cell–cell junctions, suggesting at least partial trafficking to the plasma membrane. Genetic screening for these mutations—especially GJB2 p.I203T (6%), GJB2 p.V27I (31%), and GJB2 p.E114G (22%)—is essential for the effective diagnosis and management of non-syndromic hearing loss (NSHL) in Taiwan. We found GJB2 p.I203T which were identified in our data and individuals carrying this mutation experienced more severe hearing loss, suggesting a synergistic effect of these mutations on auditory impairment. We suggest whole GJB2 gene sequencing in genetic screening is recommended for clinical management and prevention strategies in Taiwan. These findings have significant clinical and public health implications for the development of preventive and therapeutic strategies. Full article

Heliotropium procumbens, a Boraginaceae species native to Panama, has remained largely unexplored regarding its nitrogen-containing metabolites, including pyrrolizidine alkaloids (PAs). In the current study, a comprehensive phytochemical investigation of its aerial parts is presented using HPLC-DAD-IT-MS, UHPLC–HRMS, and GC-MS primarily to profile its PA composition. A total of twelve PAs and N-oxides (PANOs) were identified, along with two phenolamides—including N¹, N¹⁰-diferuloylspermidine, which is biosynthetically related to PAs—and the distinctive metabolite heliotropamide. The detected PAs included unsaturated necines, primarily monoesters of retronecine and heliotridine, as well as saturated PAs such as a platynecine-type PA and the less commonly encountered triol necines and their N-oxides. Among these, helifoline-N-oxide was isolated and structurally elucidated by NMR spectroscopy for the first time as a natural product. Comparison with the chemodiversity of PAs within the Heliotropium genus revealed a high degree of diversity in H. procumbens, which can be attributed both to the species’ inherent biosynthetic capacity for chemical variation and to the more comprehensive and extensive studies conducted on it, which naturally enrich the apparent diversity observed. This work expands the phytochemical knowledge of H. procumbens and contributes to a broader understanding of PA diversity in the genus, offering new insights into their potential ecological and toxicological significance. Full article

Background/objectives: Prostate cancer (PCa) is the most common cancer among males. Approximately 20–40% of patients with clinically localized PCa will present with a biochemical recurrence after a radical prostatectomy (RP), while some will present with recurrent metastasis. Monitoring the disease post-treatment is crucial for detecting a potential cancer recurrence early. Urinary volatile organic compounds (VOCs) have shown potential to detect PCa. However, their application in disease monitoring remains unexplored. Methods: A total of 165 urine samples were collected from male adults with biopsy-designated PCa-positive results before (n = 55) and after a RP (n = 55), and with biopsy-designated PCa-negative diagnosis (n = 55). The post-RP cohort was subdivided into three groups based on their health status after surgery as recovered healthy, biochemical recurrence, and recurrent metastasis. VOCs in the urine samples were extracted by stir bar sorptive extraction and analyzed using gas chromatography and mass spectrometry. We explored the use of metabolomics and a machine learning algorithm tool to investigate the potential of using VOCs for differentiating PCa diagnoses before and after the RP procedure with different outcomes. Results: Over 100 potential VOCs were identified to differentiate PCa patients before and after a RP, and those with biochemical recurrence and recurrent metastasis. Conclusions: Urinary VOCs are promising biomarkers that could be used to differentiate PCa patients pre- and post-RP. The findings from this research provide preliminary insights and could aid future investigations in developing tools for PCa patients after treatment. The absence of a validation cohort limits the reproducibility and translational impact of these findings; therefore, the results should be considered exploratory and require confirmation in larger, independent cohorts. Full article

Soils act as sources or sinks for three major greenhouse gases (CO₂, CH₄, and N₂O). Approximately 20% of global CO₂ emissions are released from soils through the soil respiration process. Soil respiration (soil CO₂ emission) can account for over 85% of ecosystem respiration. The aim of this study was to compare managed and unmanaged stands of pedunculate oak (Quercus robur L.) in order to investigate the impact of forest management on soil CO₂ emissions. We selected one managed and two unmanaged stands. The first stand (S1) represents a managed middle-aged stand, which is the optimal stage of development. The second stand (S2) belongs to the over-mature stage of development in an old-growth oak forest, while the third stand (S3) belongs to the decay stage of development in an old-growth oak forest. The closed chambers method was used for air sampling and the air samples were analyzed using gas chromatography (GC). Multiple regression models that include soil temperature (ST), soil moisture (SM), and their interaction provide a better explanation for variation in soil CO₂ emission (SCDE) (higher R² values) compared to regression models that only involve two variables (ST and SM). The study showed that SCDE in the decay stage of old-growth forest (S3) was significantly lower (p < 0.001) compared to the other two stands (S1 and S2). S3 is characterized by very low canopy cover and intensive natural regeneration, unlike S1 and S2. However, there were no significant differences in SCDE between the managed middle-aged stand (S1) and the over-mature (old-growth) stand (S2). Over a long-term rotation period in pedunculate oak forests, forest management practices that involve the periodic implementation of moderate silvicultural interventions can be deemed acceptable in terms of maintaining the carbon balance in the soil. Full article

After a just tribute to Guido Barbiellini, we show how the notion of a maximum force ($F_{\max }=c^4/\left(4G\right)\simeq 3\times {10}^{43}$ Newtons) present on the event horizon of a black hole (BH) can be used in conjunction with the Wilson area rule to obtain the surface confinement of the mass of a BH analogous to the surface confinement of quarks. This is then translated into the central result of the paper that PeV scale protons exist on the surface of the Kerr BH residing at our galactic center, a result in complete agreement with the HAWC Collaboration result of a Pevatron at the galactic center. We conjecture that the supermassive BHs present at the center of most galaxies are not born out of a galactic collapse but that they must have been present since the formation of their hosting galaxy. Full article

Background: Regional cerebral blood flow (rCBF) is a putative biomarker for neuropsychiatric disorders, including major depressive disorder (MDD). Methods: Here, we show that rCBF can be predicted from resting-state functional MRI (rsfMRI) at the voxel level while correcting for partial volume averaging (PVA) artifacts. Cortical patterns of MDD-related CBF differences decoded from rsfMRI using a PVA-corrected approach showed excellent agreement with CBF measured using single-photon emission computed tomography (SPECT) and arterial spin labeling (ASL). A support vector machine algorithm was trained to decode cortical voxel-wise CBF from temporal and power-spectral features of voxel-level rsfMRI time series while accounting for PVA. Three datasets, Amish Connectome Project (N = 300; 179 M/121 F, both rsfMRI and ASL data), UK Biobank (N = 8396; 3097 M/5319 F, rsfMRI data), and Amen Clinics Inc. datasets (N = 372: N = 183 M/189 F, SPECT data), were used. Results: PVA-corrected CBF values predicted from rsfMRI showed significant correlation with the whole-brain (r = 0.54, p = 2 × 10⁻⁵) and 31 out of 34 regional (r = 0.33 to 0.59, p < 1.1 × 10⁻³) rCBF measures from 3D ASL. PVA-corrected rCBF values showed significant regional deficits in the UKBB MDD group (Cohen’s d = −0.30 to −0.56, p < 10⁻²⁸), with the strongest effect sizes observed in the frontal and cingulate areas. The regional deficit pattern of MDD-related hypoperfusion showed excellent agreement with CBF deficits observed in the SPECT data (r = 0.74, p = 4.9 × 10⁻⁷). Consistent with previous findings, this new method suggests that perfusion signals can be predicted using voxel-wise rsfMRI signals. Conclusions: CBF values computed from widely available rsfMRI can be used to study the impact of neuropsychiatric disorders such as MDD on cerebral neurophysiology. Full article

The WUSCHEL-related homeobox (WOX) gene family is integral to plant growth and development. Here, we identified 14 CcWOX genes from the Cinnamomum camphora genome and analyzed their phylogeny, conserved features, and expression patterns. Phylogenetic inference grouped CcWOX into the Ancient, Intermediate, and WUS clades, consistent with other plant lineages. Expression profiling across seven tissues/organs, together with qRT-PCR validation, revealed tissue-biased expression for several members (e.g., floral or root enrichment), suggesting gene-specific roles during development. Using AlphaFold3, we predicted monomeric structures for CcWOX proteins and an interface model compatible with an interaction between CcWOX3 and CcLBD33. Consistently, bimolecular fluorescence complementation (BiFC) in Nicotiana benthamiana detected nuclear YFP signals for cEYFP-CcWOX3 + nEYFP-CcLBD33 relative to appropriate negative controls, confirming a physical interaction in plant cells. While these findings support a putative WOX–LBD interaction module in C. camphora, the regulatory functions remain to be established. Overall, this work provides a framework for dissecting the CcWOX family in C. camphora and illustrates how AI-assisted structure prediction can be integrated with cell-based assays to accelerate hypothesis generation in plant developmental biology. Full article

Gastrodiae Rhizoma (tianma, TM), a traditional medicine that has food and medicine homology, faces controversy over retaining its epidermis (tianma pi, TP) during processing due to unclear phytochemical value. This study presents the first integrated approach combining GC–IMS, UHPLC–MS, and Caenorhabditis elegans (C. elegans) aging models to compare TP with the tuber core (tianma xin, TX). The results include the following: (1) A total of forty-seven volatile compounds were identified by GC–IMS, including 12 key aroma substances via relative odor activity value (ROAV ≥ 1), of which seven ((Z)-4-heptenal, β-citronellol, hexanal, 1-pentanol, 1-octen-3-one, 2-methylpropanol, and 2-butanone) were enriched in TP. (2) Non-targeted metabolomics revealed 1025 metabolites via UHPLC–MS, highlighting phenylpropanoid biosynthesis as the primary differential pathway (p < 0.05). Phenylpropanoids and polyketides exhibited predominant enrichment in TP (|log2FC| > 2, VIP > 1, p < 0.01). (3) In C. elegans models, TP outperformed TX in pharyngeal pumping (4.16%, p < 0.05), while both extended stress-resistant lifespan (p < 0.01). In conclusion, TP plays an essential role in establishing the characteristic odor profile of TM and retaining bioactive components, particularly phenylpropanoids. Preserving TP during processing optimally maintains the distinctive aroma profile and pharmacological value of TM, which provides valuable guidance for industrial utilization. Full article

Background/Objectives: Aristolochia ringens, a medicinal plant widely used in traditional medicine, has shown potential therapeutic applications. This study aimed to investigate the anticancer mechanism of action of its crude extract against human colorectal adenocarcinoma cells (Caco-2 and HT-29). Methods: Cell viability was assessed using the MTT assay to determine IC₅₀ values. Immunofluorescence microscopy was used to examine nuclear morphology and microtubule integrity. Flow cytometry with PI staining was used for cell cycle analysis and Annexin V-FITC/PI staining for apoptosis detection. Mitochondrial membrane potential was evaluated using JC-1 dye. Bioactivity-guided fractionation was performed via HPLC, and GC–MS was used to profile active constituents. Results: The extract exhibited dose-dependent cytotoxicity with IC₅₀ values below 30 µg/mL in colon adenocarcinoma cell lines. Treated Caco-2 cells showed nuclear shrinkage and disrupted microtubules. PI-based flow cytometry revealed G₁ phase arrest, and Annexin V-FITC/PI staining indicated enhanced late apoptosis. JC-1 staining demonstrated mitochondrial depolarization. HPLC fractionation identified fractions 2 and 3 as active, and preliminary GC–MS analysis tentatively annotated the presence of alkaloids, sesquiterpenes/diterpenes, and steroidal compounds. Conclusions: A. ringens exerts anticancer effects through a mitochondria-mediated apoptotic pathway, involving G₁ checkpoint arrest and cytoskeletal disruption. These findings provide the first integrated cellular and mechanistic evidence of its anticancer potential in colorectal cancer, supporting its promise as a source of novel therapeutic lead compounds. Full article

Background: Leber’s hereditary optic neuropathy (LHON) is the most common mitochondrial disorder and an inherited optic neuropathy. Recently, two different LHON inheritance types have been discovered: mitochondrially inherited LHON (mtLHON) and autosomal recessive LHON (arLHON). Our case report is the first diagnosed case of arLHON in a patient of Lithuanian descent and confirms the DnaJ Heat Shock Protein Family (Hsp40) Member C30 (DNAJC30) c.152A>G p.(Tyr51Cys) founder variant. Case Presentation: A 34-year-old Lithuanian man complained of headache and sudden, painless loss of central vision in his right eye. On examination, the visual acuity of the right and left eyes was 0.1 and 1.0, respectively. Visual-field examination revealed a central scotoma in the right eye, and visual evoked potentials (VEPs) showed prolonged latency in both eyes. Optical coherence tomography showed thickening of the retinal nerve fiber layer in the upper quadrant of the optic disk in the left eye. Magnetic resonance imaging of the head showed evidence of optic nerve inflammation in the right eye. Blood tests were within normal range and showed no signs of inflammation. Retrobulbar neuritis of the right eye was suspected, and the patient was treated with steroids, which did not improve visual acuity. He later developed visual loss in the left eye as well. A genetic origin of the optic neuropathy was suspected, and a complete mitochondrial DNA analysis was performed, but it did not reveal any pathologic mutations. Over time, the visual acuity of both eyes slowly deteriorated, and the retinal nerve fiber layer (RNFL) thinning of the optic disks progressed. A multidisciplinary team of specialists concluded that vasculitis or infectious disease was unlikely to be the cause of the vision loss, and a genetic cause for the disease was still suspected, although a first-stage genetic test did not yield the diagnosis. Thirty-three months after disease onset, whole-exome sequencing revealed a pathogenic variant in the DNAJC30 gene, leading to the diagnosis of arLHON. Treatment with Idebenone was started 35 months after the onset of the disease, resulting in no significant worsening of the patient’s condition. Conclusion: This case highlights the importance of considering arLHON as a possible diagnosis for patients with optic neuropathy, because the phenotype of arLHON appears to be identical to that of mtLHON and cannot be distinguished by clinicians. Full article

Aim: To investigate the synergistic effects of exercise training and Brassica oleracea var. italica (broccoli sprout) supplementation on Apolipoprotein A-I, B-100, and J levels in men with Type 2 diabetes mellitus (T2DM). Methods: Forty-four males with T2DM were randomly assigned to four groups: Control (CG), Supplement (SG), Training (TG), and Training + Supplement (TSG) groups. Participants in the supplement groups (SG and TSG) received 10 g of broccoli supplement after meals for 12 weeks, while those in the training groups (TG and TSG) participated in a structured exercise program (resistance and aerobic), performed three times per week for 12 weeks, at intensities of 60–70% one-repetition maximum (1RM) for resistance training and 60–70% peak oxygen uptake (VO_2peak) for aerobic training. Results: Circulating levels of apolipoproteins improved after 12 weeks in the TSG, TG, and SG groups. However, the TSG group exhibited the most pronounced improvements across metabolic and lipoprotein markers, reflecting an additive effect of both interventions. Specifically, the TSG group demonstrated absolute reductions in ApoB-100 (−48.30 ± 7.20 mg/dL) and ApoJ (−44.05 ± 5.76 mg/dL), along with an increase in ApoA-I (+44.92 ± 6.05 mg/dL). Main effect analysis revealed that exercise training elicited the most substantial improvements across metabolic and lipoprotein markers, with large effect sizes for glucose (η²p = 0.787), insulin (η²p = 0.640), HOMA-IR (η²p = 0.856), ApoA-I (η²p = 0.685), ApoB-100 (η²p = 0.774), ApoJ (η²p = 0.848), and HDL-C (η²p = 0.535). Supplementation showed moderate effects, particularly on HOMA-IR (η²p = 0.370), ApoA-I (η²p = 0.383), and ApoB-100 (η²p = 0.334), supporting an additive but exercise-dominant benefit. The combined intervention group (TSG) showed the most pronounced improvements across all measured outcomes, with large effect sizes for ApoA-I (η²p = 0.883), glucose (η²p = 0.946), insulin (η²p = 0.881), HOMA-IR (η²p = 0.904), and ApoJ (η²p = 0.852). Conclusions: The effects of combining training and broccoli sprout supplementation on apolipoprotein levels are likely to result from the activation of two separate pathways, one from training and the other from supplementation. This dual-modality intervention could serve as an effective complementary strategy in managing metabolic and cardiovascular risk factors for individuals with T2DM. However, the magnitude of change induced by the combination of exercise training and broccoli supplementation was largely driven by the training component, with supplementation providing complementary but less consistent benefits. Full article

Natural lignocellulosic fibers (NLFs) replacing synthetic fibers have been used as reinforcement in polymer matrix composites. In this work, a lesser-known NLF endemic to the Amazon region, the envira fiber (Bocageopsis multiflora), was analyzed for its basic physical, thermochemical, morphological, and mechanical characteristics. In addition, epoxy matrix composites with 10, 20, 30, and 40 vol% of continuous and aligned envira fibers were evaluated by Fourier transform infrared spectroscopy (FTIR) and tensile tests. The results were statistically compared by ANOVA and Tukey’s test. The density found for the envira fiber was 0.23 g/cm³. The crystallinity index and microfibrilar angle obtained were 69.5% and 7.07°, respectively. Fiber thermal stability was found up to around 210 °C. FTIR confirmed the presence of functional groups characteristic of NLFs. Morphological analysis by SEM revealed that the envira fiber displayed fine bundles of fibrils and a rough surface along its length. The average strength value of the envira fiber was found to be 62 MPa. FTIR analysis of the composites confirmed the presence of the main constituents of the epoxy resin and NLFs. The tensile strength results indicated that the envira fiber addition increased the strength of the composites up to 40 vol%. The analysis of the fracture region revealed brittle aspects. These results indicate that envira fibers present potential reinforcement for polymer matrix composites and can be used in engineering applications, favored by their lightness and cost-effectiveness. Full article

Visual grounding for remote sensing (RSVG) is the task of localizing the referred object in remote sensing (RS) images by parsing free-form language descriptions. However, RSVG faces the challenge of low detection accuracy due to unbalanced multi-scale grounding capabilities, where large objects have more prominent grounding accuracy than small objects. Based on Faster R-CNN, we propose Faster R-CNN in Visual Grounding for Remote Sensing (FR-RSVG), a two-stage method for grounding RS objects. Building on this foundation, to enhance the ability to ground multi-scale objects, we propose Faster R-CNN with Adaptive Vision-Language Fusion (FR-AVLF), which introduces a layered Adaptive Vision-Language Fusion (AVLF) module. Specifically, this method can adaptively fuse deep or shallow visual features according to the input text (e.g., location-related or object characteristic descriptions), thereby optimizing semantic feature representation and improving grounding accuracy for objects of different scales. Given that RSVG is essentially an expanded form of RS object detection, and considering the knowledge the model acquired in prior RS object detection tasks, we propose Faster R-CNN with Adaptive Vision-Language Fusion Pretrained (FR-AVLF_PRE). To further enhance model performance, we propose Faster R-CNN with Cascaded Hierarchical Attention Grounding and Multi-Level Adaptive Vision-Language Fusion Pretrained (FR-CHAGAVLF_PRE), which introduces a cascaded hierarchical attention grounding mechanism, employs a more advanced language encoder, and improves upon AVLF by proposing Multi-Level AVLF, significantly improving localization accuracy in complex scenarios. Extensive experiments on the DIOR-RSVG dataset demonstrate that our model surpasses most existing advanced models. To validate the generalization capability of our model, we conducted zero-shot inference experiments on shared categories between DIOR-RSVG and both Complex Description DIOR-RSVG (DIOR-RSVG-C) and OPT-RSVG datasets, achieving performance superior to most existing models. Full article

The use of non-Saccharomyces species is gaining momentum in modern winemaking as part of broader efforts to reduce chemical inputs and adapt to climate-driven challenges. In this study, Furmint grapes were harvested at two distinct ripeness levels: an early harvest with healthy berries and a late harvest that included botrytized fruit. Two oenological protocols were compared: a conventional sulphur dioxide-based protocol and an alternative bioprotection-oriented approach that minimized SO₂ additions. Bioprotection was carried out using Metschnikowia pulcherrima, followed by sequential inoculation with Torulaspora delbrueckii and Saccharomyces cerevisiae. Grape-derived tannins (from skin and seed) were also added to inhibit oxidative enzymes such as laccase. Fermentation was monitored using standard analytical techniques, with volatile aroma profiles characterized by HS-SPME-GC-MS. Results showed that harvest timing and botrytization strongly influenced the chemical composition of the wines. Moreover, the treatment protocol had a marked effect on the final sensory profile. Wines produced with the bioprotection-oriented protocol displayed enhanced aromatic complexity, particularly through higher concentrations of esters and higher alcohols. Overall, the alternative protocol involving M. pulcherrima-based bioprotection resulted in wines with more pronounced floral and fruity notes, supporting its potential as a viable strategy for producing expressive wines under evolving climatic conditions. Full article