Search Results (123)

Understanding the soil–plant transfer of both essential and non-essential elements is crucial for evaluating the crop nutritional quality, environmental interactions, and food safety. This study delivered a multiyear and multielement assessment under field conditions of the element uptake, translocation, and accumulation in raspberry (Rubus idaeus L.), based on data collected over two growing seasons (2024–2025) in two contrasting Romanian agroecosystems. Two commercial cultivars (Opal and Delniwa) were investigated under fertilized and unfertilized conditions. The concentrations of essential macroelements such as Ca, Mg, Na, and K, as well as trace elements (Li and Sr), were determined in soils and fruits using ICP-OES and AAS. The soil–fruit transfer was quantified through the transfer factor, assisted by a robust statistical framework which integrated spatial–temporal variability and non-parametric analysis. The results highlighted two contrasting accumulation regimes. The essential macroelements revealed a dynamic uptake pattern driven by the physiological demand, soil availability, and fertilization. K exhibited the highest transfer capacity, while Ca had a restricted translocation to the fruits, due to the intrinsic transport limitations. On the other hand, Li and Sr revealed a constrained accumulation, characterized by low concentrations, weak responsiveness to fertilization, and a strong dependence on the soil geochemical background and interannual dilution processes. The spatial variability between the cultivation sites and year-to-year changes in the dilution intensity was evidenced as the dominant driver of the transfer efficiency, while the varietal differences had a secondary but detectable role, mainly for the Ca–Sr discrimination. Overall, the results evidenced that the multielement accumulation in the raspberries was governed by the interplay between the soil geochemistry, physiological transport constraints, and environmental variability. Furthermore, the research provided a field-based, multiyear evidence supporting improved soil management, cultivar selection, as well as the strategies that may increase the fruit nutritional quality while minimizing the trace element risks. Full article

Background/Objectives: To date, limited focus has been given to the possible contribution of attachment theory to the comprehension of how paranoia and conspiracy beliefs may develop. Our study aimed to examine the potential mediating effects of the different adult attachment styles on the relationship between childhood trauma and paranoid/conspiracy thinking. Methods: This is a cross-sectional study that was conducted during September–January 2025 among Tunisian young adults (aged 18–35 years) from the general population. The Child Abuse Self Report Scale (CASRS-12), the Relationship Questionnaire (RQ), the eight-item Green et al., Paranoid Thoughts Scale (GPTS-8), and the Generic Conspiracist Beliefs Scale-5 (GCB-5) were administered to participants. Results: After controlling for potential confounders, analyses showed that secure attachment partially mediated the link between childhood trauma and paranoia (indirect effect: Beta = 0.001; Boot SE = 0.001) and conspiracy beliefs (indirect effect: Beta = 0.024; Boot SE = 0.01). On the other hand, preoccupied attachment acted as a significant mediator in the relationship between childhood trauma and paranoid thinking (indirect effect: Beta = 0.001; Boot SE = 0.001). In all these models, greater childhood trauma was directly related to higher paranoia and/or conspiracy thinking. Conclusions: Findings suggest that interventions and policies aimed at promoting a more secure attachment and addressing insecure attachment representations are likely to be effective in diminishing paranoia and conspiracy beliefs, especially for victims of childhood adversity. Full article

Background and Objectives: Hypocalcemia due to hypoparathyroidism (HypoPTH) is the most common complication following thyroid surgery, typically resulting from iatrogenic removal, tissue damage, or compromised vascularization of the parathyroid glands. Patients with persistent HypoPTH are at risk for long-term complications such as osteoporosis, cardiac dysfunction, and renal impairment. Lifelong regulation of calcium levels is therefore essential to prevent morbidity and mortality associated with these complications. In this study, we aimed to evaluate the functional engraftment efficacy of 3D bioprinted human parathyroid tissue constructs in a xenograft model in vivo. Materials and Methods: Primary cells obtained from freshly excised human parathyroid tissue specimens were isolated and 3D bioprinted using alginate-based bioink. The bioprinted tissue constructs were implanted into CD1 athymic mice. Histopathological evaluation of the grafted constructs was performed at different time points. In addition, surface calcium-sensing receptor (CaSR) expression was assessed by immunofluorescence as an indicator of functional parathyroid tissue engraftment. Results: The presence of CaSR on parathyroid cells within the 3D-printed scaffolds confirmed the persistence of functional parathyroid cells following implantation. In tissue samples obtained during the first, second, and third weeks after implantation, CaSR positivity was consistently observed in the parathyroid cells. However, at the three-month follow-up, the pores within the scaffolds were found to be filled with calcified material and replaced by fibrotic tissue. At this stage, the absence of parathyroid hormone (PTH) expression indicated a loss of functional activity in the grafted biomaterial. Conclusions: Human primary parathyroid cells were successfully isolated, and a functional, hormone-active parathyroid tissue substitute was developed ex vivo using 3D-bioprinted hydrogel scaffolds combined with autologous cells. Although short-term functional engraftment was achieved, long-term graft viability and hormonal activity were limited due to scaffold degradation and fibrosis. These findings indicate the necessity for further improvement in scaffold biocompatibility to enhance the therapeutic potential of 3D-bioprinted parathyroid tissue constructs for in vivo applications. Full article

Introduction: Peripheral blood mononuclear cells (PBMCs) constitute a diverse population of cells involved in adaptive and innate immunity, playing an essential role in pathogen recognition, immune signaling, and immune response modulation. Vitamin D deficiency through the regulation of vitamin D receptor (VDR) and calcium-sensing receptor (CaSR) gene expression could influence the apoptotic functioning of PBMCs, which, despite its importance in the immune response, has not been sufficiently explored. Objectives: This research aimed to detect differences in the mRNA expression of CaSR, VDR, and apoptosis of PBMcs between elderly women with hip fractures and vitamin D deficiency and healthy young women, as well as in older women both at baseline and after administration of calcitriol. Methods: A case–control study involving 44 women (22 and 20, respectively) was conducted. The case group (hip fracture) was administered 2 µg/day of calcitriol for two weeks and a before-and-after comparison was made. The baseline gene expression of VDR and CaSR in PBMCs, as well as the effects of calcitriol on both the VDR/CaSR regulation and PBMC apoptosis, were studied in both groups. Serum bone biomarkers were also assessed. Results: No differences were observed in creatinine and calcium serum levels between the young and elderly osteoporotic women studied. Serum phosphorus and 25-hydroxyvitamin D (25(OH)D) were low in osteoporotic fractured women with vitamin D deficiency. In contrast, intact parathyroid hormone (PTH_1–84) and alkaline phosphatase were high, while no significant difference in calcitriol [l,25(OH)₂D₃] serum levels was observed. In elderly women, serum calcium, phosphorus, alkaline phosphatase, 25(OH)D, and calcitriol remained unchanged after intravenous calcitriol therapy; however, PTH_1–84 decreased after the treatment. In comparison to the young women, the elderly women showed decreased VDR and increased CaSR mRNA expression in PBMCs, as well as higher monocyte apoptosis. Conclusions: Calcitriol administration increased both VDR and CaSR mRNA expression in PBMCs and decreased PBMC apoptosis. Conclusions: The results obtained support the role of the vitamin D endocrine system as a regulator of the immune response and thus may contribute to explaining certain aspects of the immune dysfunction reported in individuals with vitamin D insufficiency. Full article

Sharp declines in temperature pose a significant risk for mass mortality events in the Chinese soft-shelled turtle (Pelodiscus sinensis). To assess the effects of acute cold stress on intestinal health, turtles were exposed to temperatures of 28 °C (control), 14 °C, and 7 °C for 1, 2, 4, 8, and 16 days. The results showed that acute cold stress at 14 °C and 7 °C induced time-dependent alterations in intestinal morphology and histopathology. The damage was more severe at 7 °C, characterized by inflammatory cell infiltration, lymphoid hyperplasia, and extensive detachment and necrosis across the villi, muscle layer, and submucosa. 16S rDNA sequencing revealed significant shifts in intestinal microbiota composition in the 7 °C group, dominated by Helicobacter and Citrobacter. Transcriptomic analysis identified differentially expressed genes (DEGs) that respond to acute cold stress and are involved in the Toll-like receptor signaling pathway (Tlr2, Tlr4, Tlr5, Tlr7, and Tlr8), the NOD-like receptor signaling pathway (Traf6, Traf2, Casr, Rnasel, Pstpip1, Plcb2, Atg5, and Mfn2), apoptosis (Tuba1c, Ctsz, Ctsb, Kras, Hras, Pik3ca, Bcl2l11, Gadd45a, Pmaip1, Ddit3, and Fos), and the p53 signaling pathway (Serpine1, Sesn2, Ccng2, Igf1, Mdm2, Gadd45a, Pmaip1, and Cdkn1a). Metabolomic profiling highlighted differentially expressed metabolites (DEMs) that cope with acute cold stress, such as organic acids (oxoglutaric acid, L-aspartic acid, fumaric acid, DL-malic acid, and citric acid) and amino acids (including L-lysine, L-homoserine, and allysine). The integrated analysis of DEGs and DEMs underscored three key pathways modulated by acute cold stress: linoleic acid metabolism, neuroactive ligand–receptor interaction, and the FoxO signaling pathway. This study provides a comprehensive evaluation of intestinal health in Chinese soft-shelled turtles under acute cold stress and elucidates the underlying mechanisms. Full article

Calcium ions (Ca²⁺) serve as universal second messengers regulating endocrine, neuronal, and metabolic processes. In children and adolescents, tight calcium signaling control is crucial for growth, hormone homeostasis, neuromuscular function, and neurodevelopment. Disruptions in Ca²⁺-dependent pathways—whether genetic, metabolic, or acquired—underlie a spectrum of pediatric endocrine diseases often presenting with neurological manifestations This review summarizes calcium’s roles in hormone secretion, parathyroid and vitamin D metabolism, and neuronal excitability, and discusses monogenic and metabolic disorders affecting calcium sensing and signaling, including CASR, GNA11, AP2S1, STIM1, and ORAI1 mutations. Diagnostic challenges, therapeutic strategies, and future directions for precision medicine in pediatric neuroendocrinology are highlighted, emphasizing early recognition and improved clinical outcomes. Full article

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by mutations in PKD1 or PKD2 genes, encoding polycystin-1 (PC1) or polycystin-2 (PC2), respectively, characterized by excessive cell proliferation and fluid secretion, resulting in renal cyst formation and growth. PC1 and PC2 form a complex localized on the plasma membrane, endoplasmic reticulum, and primary cilia. PC2 is a non-selective cation channel which, in renal epithelial cells, contributes to calcium transport and signaling. It has been previously shown in renal cells that high external calcium increases whole-cell currents likely mediated by PC2. In this study, we explored the possibility that the Calcium Sensing Receptor (CaSR) is involved in the functional regulation of PC2. To test this hypothesis, human conditionally immortalized Proximal Tubular Epithelial cells, isolated from urine sediments, wt or with stably downregulated PKD1 (PC1KD) or PKD2 (PC2KD) were used. Interestingly, CaSR and PC2 co-immunoprecipitated and Proximity Ligation Assay demonstrated a direct physical interaction at endogenous protein levels. Membrane potential measurements demonstrated that selective CaSR activation, elicited by the calcimimetic R568, caused plasma membrane depolarization, consistent with the modulation of PC2-mediated cation currents, which was significantly lower in PC2KD with respect to wt and PC1KD cells. To conclude, this study provides evidence for a functional coupling of CaSR and PC2, which might be relevant for therapeutic strategies to correct dysregulations occurring in ADPKD. Full article

The thymus and parathyroid glands share a common embryological origin from the third pharyngeal pouch, yet their potential morphological and functional interconnections remain insufficiently explored. We conducted a comparative study integrating immunohistochemistry (IHC) and SEM on human thymic tissue, parathyroid adenomas, and parathyroid tissue excised during thyroidectomy. IHC staining targeted Thymosin-α1, CaSR, and PTH1R, with semi-quantitative evaluation of staining intensity and distribution. SEM analysis was performed at multiple magnifications to assess stromal organization and microvascular relief. Non-parametric statistical tests (Kruskal–Wallis with Mann–Whitney post hoc comparisons) were applied to clinical and laboratory data across the three cohorts. Scanning electron microscopy (SEM) revealed convergent ultrastructural features between thymus and parathyroid, including reticular stromal meshes and vascular grooves suggestive of comparable microcirculatory organization. IHC demonstrated robust Thymosin expression in thymus, with heterogeneous/apical distribution in parathyroid tissue; CaSR showed strong membranous and cytoplasmic expression in parathyroid, but weak diffuse signal in thymus; PTH1R exhibited low-to-moderate expression in thymus and moderate heterogeneous expression in parathyroid, with apical accentuation in adenomas. Statistical analysis confirmed significant differences in ionized calcium, PTH, and anti-AChR titers among the three cohorts (all p < 0.001), while TSH and calcitonin did not differ significantly. Our findings strengthen the hypothesis of a morpho-functional parathyroid–thymus axis. The robust parathyroid expression of CaSR and PTH1R aligns with established roles in calcium–PTH homeostasis, while the novel detection of Thymosin in parathyroid tissue suggests an expanded functional repertoire. These results highlight a continuum between embryological proximity and adult tissue cross-talk, with potential clinical implications for parathyroid pathology and immune regulation. Full article

Astrocytic calcium signaling is a central mechanism of neuron-glia communication that operates across multiple spatial and temporal scales. Traditionally, research has focused on intracellular Ca²⁺ oscillations that regulate gliotransmitter release, ion homeostasis, and metabolic support. Recent evidence, however, reveals that extracellular calcium ([Ca²⁺]o) is not a passive reservoir but a dynamic signaling mediator capable of influencing neuronal excitability within milliseconds. Through mechanisms such as calcium-sensing receptor (CaSR) activation, ion channel modulation, surface charge effects, and ephaptic coupling, astrocytes emerge as active partners in both slow and rapid modes of communication. This dual perspective reshapes our understanding of brain physiology and disease. Disrupted Ca²⁺ signaling contributes to network instability in epilepsy, synaptic dysfunction in Alzheimer’s and Parkinson’s disease, and impaired maturation in neurodevelopmental disorders. Methodological advances, including Ca²⁺-selective microelectrodes, genetically encoded extracellular indicators, and computational modeling, are beginning to uncover the richness of extracellular Ca²⁺ dynamics, though challenges remain in achieving sufficient spatial and temporal resolution. By integrating classical intracellular pathways with emerging insights into extracellular signaling, this review highlights astrocytes as central architects of the ionic landscape. Recognizing calcium as both an intracellular messenger and an extracellular signaling mediator provides a unifying framework for neuron–glia interactions and opens new avenues for therapeutic intervention. Full article

Reproductive and growth traits are key economic traits in sheep. This study aims to identify key single nucleotide polymorphisms (SNPs) and candidate genes associated with reproductive and growth traits in Tianmu polytocous sheep through a genome-wide association study (GWAS). The findings are expected to provide both a theoretical foundation for molecular breeding in this breed and novel insights into the genetic basis of ovine reproductive and growth performance. This study took 483 adult Tianmu polytocous ewes as the research subjects, collected their lambing records, measured their phenotypic values of growth traits (3 weight and 11 body size traits), and collected their blood samples for whole-genome resequencing to identify SNPs in the Tianmu polytocous sheep genome. The results identified a total of 9,499,019 (3× coverage) and 27,413,216 (30× coverage) high-quality SNPs in the Tianmu polytocous sheep genome. Subsequently, the association analysis between SNPs and reproductive and growth traits was conducted using a mixed linear model. A total of 92, 66, 18, 28, 6, 42, 3, 3, 6, 1, 12, 3, 22, 8, 6, and 3 SNPs were found associated with litter size at first parity, litter size at second parity, litter size at third parity, litter size at fourth parity, birth weight, weaning weight, body height, withers height, body length, head length, head width, cannon bone circumference, forelimb height, chest girth, chest depth, and withers width, respectively. Further, based on SNP annotation, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, candidate genes associated with the reproductive and growth traits were identified. Among these genes, 11 LOC, DEPTOR, GNG12, GRM7, PTH, PTH2R, WWOX, INHA, and NRG3 are candidate genes associated with litter size at first parity or litter size at third parity. These genes are involved in the G protein-coupled receptor signaling pathway, G protein-coupled receptor activity, ovarian tissue development, and hormone secretion. Additionally, TFRC and NTN1 are candidate genes associated with birth weight, while five UGT1A and CASR are candidate genes associated with weaning weight. These candidate genes are primarily involved in lipid metabolism. Finally, the following genes were identified as candidates associated with specific traits: DLG2, TMEM126A, and TMEM126B with body height; DSCAM and SCN8A with body length; BARX1 with cannon bone circumference; four LOC genes with forelimb height; EPHA4 with chest depth; and MRS2 with withers width. Full article

Background and Objectives: Inherited disorders of calcium metabolism are rare pediatric conditions with diverse manifestations, including seizures, growth impairment, and renal or skeletal complications. Precise molecular diagnosis is crucial for effective management and informed genetic counseling. This study aimed to develop a systematic diagnostic approach, broaden the mutational spectrum, and characterize initial clinical features. Material and Methods: We retrospectively analyzed 13 pediatric cases at a tertiary center in southern Taiwan (2020–2025). Clinical, biochemical, and imaging data were reviewed. Genetic testing followed a tiered strategy to identify copy number variations and single-nucleotide variants. Variants were classified according to the ACMG/AMP guidelines and assessed by in silico tools. Results: The pediatric cohort (8 males, 5 females) had a median diagnostic age of 2 years and a mean follow-up of 7.7 years. Hypoparathyroidism was most common (n = 7), followed by PTH resistance (n = 3), hyperparathyroidism (n = 1), calcipenic rickets (n = 1), and syndromic hypercalcemia (n = 1). Genetic diagnoses were established in 12 children and one parent, involving CASR, GNAS, PRKAR1A, CYP27B1, and KMT2D. Two novel variants were identified (CASR p.Val836Ile and GNAS c.719-30A>T). Phenotypic heterogeneity included incomplete penetrance in autosomal dominant hypocalcemia and variable multisystem involvement in syndromic cases. Conclusions: A stepwise genetic testing strategy achieved a high diagnostic yield in pediatric calcium metabolism disorders. The discovery of novel and population-specific variants expands the mutational spectrum, supporting precision medicine in pediatric endocrinology. Full article

A novel long-lasting luminescent composite material based on the (Ca,Sr)-Al-O system was synthesized using a solution combustion method. (Ca,Sr)₃Al₂O₆ is the primary phase, with SrAl₂O₄ as a controllable secondary phase. Compared to conventional single-phase SrAl₂O₄ phosphors, the introduction of a calcium-rich hexaaluminate matrix creates additional defects and a specific trap distribution at the composite interface, significantly improving carrier storage and release efficiency. Eu²⁺ + Nd³⁺ synergistic doping enables precise control of the trap depth and number. Under 365 nm excitation, Eu²⁺ emission is located at ~515 nm, with Nd³⁺ acting as an effective trap center. Under optimal firing conditions at 700 °C (Eu²⁺ = 0.02, Nd³⁺ = 0.003), the afterglow lifetime exceeds 30 s. Furthermore, The (Ca,Sr)₃Al₂O₆ host stabilizes the lattice and optimizes defect states, while synergizing with the SrAl₂O₄ secondary phase to improve the afterglow performance. This composite phosphor exhibits excellent dual-mode anti-counterfeiting properties: long-lasting green emission under 365 nm excitation and transient blue-violet emission under 254 nm excitation. Based on this, a screen-printing ink was prepared using the phosphor and ethanol + PVB, enabling high-resolution QR code printing. Pattern recognition and code verification can be performed both in the UV on and off states, demonstrating its great potential in high-security anti-counterfeiting applications. Compared to traditional single-phase SrAl₂O₄ systems, this study for the first time constructed a composite trap engineering of the (Ca,Sr)₃Al₂O₆ primary phase and the SrAl₂O₄ secondary phase, achieving the integration of dual-mode anti-counterfeiting functionality with a high-resolution QR code fluorescent ink. Full article

Background: Breast cancer (BC) is the most common cancer and the leading cause of cancer death in women. Hereditary BC risk accounts for 25% of all cases. Pathological variants in known BC precursor genes explain only about 30% of hereditary BC cases, while the underlying genetic factors in most families remain unknown. Identifying hereditary cancer risk factors will help improve genetic counseling, cancer prevention, and cancer care. Methods: Here, we used whole-exome sequencing (WES) to identify genetic variants in 105 Vietnamese patients with BC and 50 healthy women. BC-associated variants were screened by the Franklin software and the criteria of the American College of Medical Genetics and Genomics (ACMG) and evaluated based on in silico analysis. Results: In total, 56 variants were identified in 37 genes associated with BC, including ACVR1B, APC, AR, ARFGEF1, ATM, ATR, BARD1, BLM, BRCA1, BRCA2, CASP8, CASR, CHD8, CTNNB1, ESR1, FAN1, FGFR2, HMMR, KLLN, LZTR1, MCPH1, MLH1, MSH2, MSH3, MSH6, NF1, PMS2, PRKN, RAD54L, RB1CC1, RECQL, SLC22A18, SLX4, SPTBN1, TP53, WRN, and XRCC3 in 41 patients. Among them, 12 variants were novel, and 10 variants were assessed as pathogenic/likely pathogenic by ACMG and ClinVar. Variants of uncertain significance (VUS) were evaluated using in silico prediction software to predict whether they are likely to cause the disease in patients. Conclusions: This is the first WES study to identify BC-associated genetic variants in Vietnamese patients, providing a comprehensive database of BC susceptibility gene variants. We suggest using WES as a tool to identify genetic variants in BC patients for risk prediction and treatment guidance. Full article

Purpose: This study investigates the role of CASR gene polymorphisms (A986S, R990G, Q1011E) in PHPT genetic susceptibility and its clinical variability. The aim is to evaluate the prevalence of these polymorphisms in patients with sporadic PHPT and their impact on clinical course, biochemistry, and histological features. Methods: 106 patients underwent clinical and anamnestic evaluations, focusing on major PHPT complications, as well as biochemical analyses of blood and urine. Genetic testing was conducted for CASR gene polymorphisms. Histological data were available for 68 patients who underwent parathyroidectomy. Results: The sample included 83 women and 23 men; mean age at diagnosis was 54.5 years. 55 patients carried CASR gene polymorphisms, while 51 were wild-type. Prevalence rates of polymorphisms were consistent with data for the Caucasian population, with A986S being the most common (31%). No significant associations were found between polymorphisms and increased levels of ionized calcium or other blood phospho-calcium metabolism parameters. However, 24-h urinary calcium levels were higher in patients with polymorphisms (p = 0.0185), particularly in those older than 50 years (p = 0.030) and with the A986S variant. Hypercalciuria was predictive of CASR polymorphism presence (OR = 2.76, p = 0.003). No significant association with PHPT complications, such as renal calculi or bone involvement, was confirmed. Histological data revealed no clear links between polymorphisms and more aggressive variants. Conclusions: CASR gene polymorphisms are associated with hypercalciuria but do not significantly influence age of onset or clinical phenotype in PHPT. Genetic analysis may be useful in selected cases to better understand individual clinical profiles. Full article

Background/Objectives: Social worry may appear in preadolescence, causing it to persist in the future, such that adolescents become more avoidant of situations in which they are evaluated by others. Many previous studies have shown that approximately 4% of preadolescent children suffer from high levels of social worry, which may lead to other problems in the future. It is important to take necessary precautions to explore this worry and take the necessary measures to address it. This study aimed to do so by extracting the psychometric properties of the Social Worries Questionnaire (SWQ) for preadolescence in Arab countries. Methods: The sample consisted of 269 children aged 8–12 years. The SWQ, Spence Child Anxiety Scale (SCAS), Child Abuse Self-Reporting Scale (CASRS-12), and Arabic version of the Children’s Depression Inventory (AVCDI) were administered via various social media. Results: Confirmatory factor analysis was used, and the one-factor model showed that the scale consists of 14 items. The results also indicated evidence of discriminant validity, and that the internal consistency was acceptable. For reliability, the test–retest results showed that the value was appropriate. Conclusions: This scale could be valuable in detecting worry in preadolescent children and providing them with therapeutic and psychological services. Full article