Search Results (2,022)

The study aimed to evaluate the nutritional contribution of essential elements (Ca, Fe, K, Mg, Zn) and assess health risks associated with potentially toxic elements (Cd, Pb, As, Al, and Sr) in three types of cheese from retail chains and produced by two different producers. One hundred forty-four cheese samples were collected in 12 months. All samples were analyzed using inductively coupled plasma optical emission spectrometry (ICP-OES). The average concentrations of Ca, Fe, K, Mg, Zn, Al and Sr in cheese samples were 4183.87–6227.98 mg/kg, 1.00–1.63 mg/kg, 695.90–884.39 mg/kg, 175.00–255.70 mg/kg, 21.49–27.56 mg/kg, 2.65–5.73 mg/kg and 1.91–5.82, respectively, depending on cheese type and producers. Concentrations of As, Cd and Pb in all analyzed samples were below the limit of detection (LOD). From a nutritional perspective, the analyzed cheeses represented important dietary sources of calcium and zinc, with substantial contributions to recommended daily intakes, particularly under the higher consumption scenario (100 g/day). Magnesium also contributed meaningfully to dietary intake, especially in children, whereas the contributions of iron and potassium remained relatively low in all evaluated consumption scenarios. Health risk assessment was expressed as the percentage of the tolerable daily intake (%TDI) or provisional tolerable weekly intake (%PTWI). Under the higher consumption scenario (100 g/day), children represented the most highly exposed population group, with %PTWI values for aluminum ranging from 0.25 to 9.10% and %TDI values for strontium ranging from 6.92 to 20.00%, depending on cheese type and producer. Overall, the analyzed cheeses showed high nutritional value and low toxicological risk; however, continuous monitoring of potentially toxic elements remains important to ensure food safety. Full article

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive subtype of ALL characterized by unfavorable clinical outcomes. Despite significant progress in deciphering the genetic and epigenetic landscapes of T-ALL, the underlying molecular mechanisms, particularly in non-early T-cell precursor (non-ETP) T-ALL, remain incompletely understood. In this study, functional assays were performed using three well-characterized non-ETP T-ALL cell lines. In vivo therapeutic efficacy was evaluated using non-ETP T-ALL xenograft models. Transcriptomic profiling was performed by RNA sequencing (RNA-seq) followed by bioinformatic analysis. Publicly available clinical datasets from T-ALL patients were mined to analyze survival outcomes. We found that activation of CD40 ligand (CD40LG) or CD28 accelerates cell-cycle progression and enhances the migratory capacity of non-ETP T-ALL cells, with CD40LG uniquely upregulating CXCR4 to mediate bone marrow tropism. Further RNA-seq and functional validation identified Rho GTPase signaling, specifically RhoA/Rac1/Rac2, as a pivotal downstream effector of CD40LG/CD28, leading to therapeutic resistance to PI3K inhibition. Pharmacological blocking RhoA or Rac1 using small-molecule compounds not only induces remarkable cytotoxicity but also sensitizes resistant cells to PI3K inhibitors, both in vitro and in vivo. Clinically, elevated expression of CD40LG, CD28, RHOA, or RAC2 correlates with poor prognosis in non-ETP T-ALL patients. These findings uncover a novel CD40LG/CD28-Rho GTPase axis as a key driver of pathogenesis and a potential therapeutic vulnerability in non-ETP T-ALL, providing a new target for precision intervention and a promising strategy to overcome therapeutic resistance. Full article

Cervical neuroendocrine carcinoma (NECC) is a rare but highly aggressive cervical malignancy, accounting for approximately 1% of invasive cervical cancers. Diagnosis is challenging because NECC overlaps morphologically with other poorly differentiated cervical and metastatic tumors, may show crush artifact in small biopsies, and can display variable expression of conventional neuroendocrine markers. This narrative review provides a practical synthesis of the histopathological, immunohistochemical, molecular, and clinical features of NECC, with emphasis on diagnostic pitfalls and differential diagnosis. Recent English-language literature on cervical neuroendocrine carcinoma was reviewed and qualitatively integrated, focusing on morphology, immunohistochemistry, HPV association, molecular alterations, prognosis, and management-relevant diagnostic issues. Accurate diagnosis requires integration of morphology, epithelial differentiation, neuroendocrine marker expression, HPV-related context, and clinic-radiological correlation. Useful markers include broad-spectrum cytokeratins, synaptophysin, chromogranin A, CD56, INSM1, p16, and Ki-67, with additional markers selected according to the differential diagnosis. Diffuse block-type p16 expression and high-risk HPV detection support a cervical HPV-associated origin but are not specific for neuroendocrine differentiation. Molecular studies show frequent association with HPV18 and recurrent alterations involving PI3K/AKT, RAS/MAPK, and TP53-related pathways, although these findings remain insufficiently validated for routine prognostic or therapeutic stratification. NECC requires early recognition and a multimodal diagnostic approach because of its aggressive behavior and poor prognosis. A practical, stepwise integration of morphology, immunohistochemistry, molecular findings, and clinical–radiological data may improve diagnostic consistency and support multidisciplinary management. Full article

Expansin-like A (EXLA) proteins belong to one of the four main families within the expansin superfamily, a group of plant proteins essential for cell wall loosening. Here, we report, for the first time, the purification of a novel EXLA, named cpEXLA, from canihua seeds. cpEXLA (yield ~0.16 mg per 100 g of seeds) is a 29 kDa glycoprotein with a high melting temperature (Tm of 86.75 ± 1.06 °C). Elucidation of its primary structure reveals that the mature protein consists of 246 amino acids, ten of which are cysteine residues forming five disulphide bridges. Structural studies based on 3D model prediction reveal the presence of N- and C-terminal domains, which are typical of EXLAs and rich in β-sheets, as confirmed by circular dichroism (CD) spectroscopy. Furthermore, comparative analysis of amino acid sequences between cpEXLA and 219 similar EXLAs, retrieved from dicotyledonous genomes and transcriptomes, identified eighteen invariant amino acid residues: eleven in the N-terminal domain and seven in the C-terminal domain. Finally, phylogenetic analysis of EXLAs in dicotyledonous species shows a close relationship with other EXLAs from the Amaranthaceae family, confirming that EXLA proteins are highly conserved among dicotyledonous plants. Overall, cpEXLA represents an intriguing native tool for studying cell wall evolution and the functional role of EXLAs. Full article

Urban soil contamination by potentially toxic elements (PTEs) is a recognized health concern in densely populated urban environments. Through a systematic meta-analysis of 91 peer-reviewed studies (2000–2025) reporting 12,174 sampling sites in capital and core cities, we characterized regional patterns in the spatiotemporal dynamics and health risks of eight PTEs across two well-represented continental subsets (Asia, k = 18–36 per element; Europe, k = 11–23 per element) with comparative reference to the Americas, Africa, and Oceania. Given the uneven geographic distribution of qualifying primary studies, continental comparisons should be interpreted as hypothesis-generating: Asia (k = 18–36 per element) and Europe (k = 11–23 per element) provide the statistically robust core of the synthesis, while results for the Americas (k = 3–7 for several elements), Africa (k = 4–15), and Oceania (k = 2) are presented as illustrative rather than statistically representative. Pooled concentrations followed Zn (138.59) > Pb (56.97) > Cr (54.26) > Cu (47.00) > Ni (31.94) > As (8.56) > Hg (3.13) > Cd (1.23) mg·kg⁻¹. Within the well-represented Asian and European subsets, Asian cities showed the most severe enrichment of As, Cd, Cr, and Hg (I_geo > 4 in hotspots such as Kathmandu I_geo (Cd) = 7.06 and Jinan I_geo (Hg) = 5.27), whereas European centres exhibited substantial legacy Pb accumulation (pooled mean 87.69 mg·kg⁻¹). A reproducible pollution gradient was identified across functional zones: industrial > transportation ≥ residential > commercial > agricultural > urban green areas. The deterministic non-carcinogenic Hazard Index (HI = 1.49) for children in Asia exceeded the safe threshold (HI > 1), driven primarily by As and Cr exposure via incidental soil-and-dust ingestion. Monte Carlo probabilistic assessment (N = 10,000) confirmed elevated cumulative non-carcinogenic risk at the median of the exposure distribution for children in the data-rich Asian (P50 = 1.55; P(HI > 1) = 81.9%) and European (P50 = 1.28; P(HI > 1) = 69.8%) subsets, with adults in both subsets remaining well below the safety threshold (P(HI > 1) = 0.0%). Temporal analysis revealed a decoupling between economic growth and PTE accumulation in long-established cities, together with an inverse Ni–population correlation indicative of strategic resource allocation. For Asian capital and core cities, where the evidence base is strongest (k = 18–36 per element), the present synthesis supports further investigation of risk-based, child-centric soil management as a public-health priority. For European cities (k = 11–23 per element), the same direction of risk is indicated but should be confirmed in regionally focused syntheses. Policy considerations for under-represented regions should await expansion of the primary monitoring base. Full article

Bone densitometry in osteoporosis diagnosis via dual-energy X-ray absorptiometry (DXA) can benefit from advances in imaging detector technology. We devised a compact imaging scanner—DXA4A—using a photon-counting and energy-sensitive Timepix4 hybrid pixel detector (512 × 448 pixels, 55 µm pitch), for areal bone mineral density (aBMD) assessments in the distal radius and tibia in the clinic and for future in-flight astronauts’ bone health assessment. We present the design and Monte Carlo simulations of the scanner. A Timepix4 detector with a 1 mm thick CdTe sensor was tested in the laboratory with X-ray tube sources, acquiring first images of test samples. Monte Carlo simulations were implemented for scanner design and performance prediction, using 50 kVp unfiltered and 100 kVp Sm K-edge filtered spectra. With a digital twin of the scanner and patient wrist, we set up a virtual imaging study and determined the aBMD in the forearm of a patient (0.515 ± 0.048 g/cm²), in agreement with the clinical DXA value (0.571 g/cm² for the total forearm). This study highlights the feasibility of realizing a compact DXA scanner for the distal tibia and radius with spectral capabilities, exploiting Timepix4 hybrid detectors for its peculiar energy sensitivity and photon event timing properties for tissue identification. Full article

This study characterized eleven grape pomace varieties from São Paulo and Rio Grande do Sul (Brazil) in terms of proximate composition, total phenolic content, and the total and bioaccessible fractions of inorganic elements and phenolic compounds. On a dry basis, ash, protein, lipid, and carbohydrate contents ranged from 1.4–2.9%, 6.4–13.5%, 8.6–14.7%, and 72.1–83.6%, respectively. Total phenolic content ranged from 567 to 1843 mg GAE/100 g. The contents of essential elements (Ca, Fe, Zn, Cu, Mg, Mn, P, Na, and K) and trace elements (Al, Co, As, Se, Mo, Cd, Sb, Ba, Hg, and Pb) showed wide variation among the varieties studied. Regarding bioaccessibility, low values were observed for Fe, Zn, and Ca, while significant percentages were detected for Mg (27–30%), Mn (1–14%), P (16–26%), Cu (5.5–13%), Co (29–72%), Al (2–13%), and Ba (ND-9%), as well as levels of bioaccessible phenolic compounds (7–19%). The grape pomaces evaluated in this study presented variable levels of total phenolic compounds and minerals, although the bioaccessible fractions varied among the analyzed elements and compounds. These findings contribute to the characterization of Brazilian grape pomaces and indicate their potential applicability as value-added agro-industrial by-products in food formulations, while highlighting the importance of considering bioaccessibility when assessing their nutritional relevance. Full article

Cyathula officinalis Kuan, a medicinal plant used in traditional medicine, remains underexplored as a source of structurally defined wound-repair polysaccharides. In this study, a water-soluble polysaccharide fraction, CoPS, was isolated from C. officinalis roots and structurally characterized using methylation analysis and 1D/2D NMR spectroscopy. Purified CoPS had a total carbohydrate content of 94.8%, a weight-average molecular weight (M_w) of 7.491 kDa, and a narrow dispersity (M_w/M_n = 1.04). Monosaccharide composition analysis showed that CoPS was mainly composed of fructose and glucose at a molar ratio of 95.60:4.40. Structural analyses identified CoPS as a branched levan-type fructan with a β-(2→6)-linked fructofuranosyl backbone and β-(2→1)-linked branching motifs. CoPS was incorporated into a Carbomer/alginate topical formulation, termed CoPS-CPG, and evaluated in vitro and in vivo. CoPS-CPG showed good cytocompatibility and promoted HaCaT keratinocyte migration, reducing the residual scratch area to 48.10% at 12 h compared with 70.13% in the control group and 65.18% in the vehicle (Blank-CPG) group. In a murine full-thickness excisional wound model, CoPS-CPG reduced the residual wound area to 8.70 ± 1.20% on day 14, compared with 24.83 ± 1.51% in the control group and 14.20 ± 0.72% in the vehicle group. Histological and immunological analyses further indicated improved tissue reconstruction, a reduced inflammatory burden, enhanced CD206-associated macrophage signals, increased CD31-associated vascular structures, improved α-SMA-associated perivascular coverage, and lower late-stage HIF-1α expression. These findings identify CoPS as a structurally defined plant-derived levan-type fructan that supports cutaneous wound repair. Full article

Honey is a natural food product which in traditional production represents a clear example of the “farm-to-table” principle, as it excludes any processing of the original product. This study proposes an analytical approach for determining 30 most frequently determined chemical elements (Ag, Al, As, B, Ba, Bi, Ca, Cd, Co, Cr, Cs, Cu, Ga, In, Fe, K, Li, Mg, Mn, Na, Ni, P, Pb, Rb, S, Se, Sr, Te, V, and Zn) in honey, emphasizing the use of a relatively large sample mass to overcome sample heterogeneity and ensure accurate and reliable results. About 31 linden and 16 rapeseed honey samples from different Bulgarian regions were analyzed. Pollen analysis data showed that pollen content ranged from 30 to 78% for linden and 30 to 93% for rapeseed honey. The results identify a group of elements—K, Ca, Mg, Sr, and Rb—whose concentrations show statistically significant dependence on the floral origin and purity of the honey. Based on these findings, these elements are proposed as potential markers for identifying the botanical origin of honey. Furthermore, macronutrients and micronutrients (P, S, B, Cu, Fe, Mn, and Zn), which are generally subject to homeostatic regulation, as well as micro-elements (Al, As, Cd, Co, Cr, and Pb), which are more strongly influenced by environmental factors, showed limited discriminatory potential and no clear correlation with floral purity and botanical origin. Therefore, they should not be used as criteria when assessing the botanical origin of honey, but rather as indicators of environmental pollution and potential quality or safety concerns. Overall, the research contributes to improving the reliability of botanical classification of honey by combining robust analytical methodology with statistically validated elemental markers, while also distinguishing between natural compositional features and contamination-related signals. Full article

Background/Objectives: Adoptive transfer of allogeneic natural killer (NK) cells represents a promising off-the-shelf immunotherapy for cancer, offering advantages in safety and availability over autologous T cell therapies. However, generating therapeutically sufficient NK cell numbers remains challenging due to their low frequency in blood sources. Engineered feeder cell co-cultures have enabled substantial expansions of NK cells to clinically relevant doses. Methods: We evaluated the plasma cell leukemia-derived ARH-77 cell line as a feeder for ex vivo NK cell expansion from healthy donor peripheral blood mononuclear cells (PBMCs). Unmodified ARH-77 was compared to K562, followed by engineering both lines to co-express B7-H6 (NKp30 ligand), CD137L (4-1BBL), IL-15, and IL-15Rα via sequential lentiviral transduction. PBMCs were co-cultured with irradiated feeders in cytokine-supplemented (IL-2, IL-21, and later IL-15) RPMI-1640 or DMEM/F-12 medium for up to 28 days. Expansion (fold change in CD3⁻CD56⁺ cells), purity, surface receptor expression, and cytotoxicity (against K562 targets) were quantified. Results: Unmodified ARH-77 supported significantly greater NK cell expansion than K562 (model-estimated 681-fold vs. 155-fold at week 4 in RPMI; p = 0.0018), with higher purity but comparable cytotoxicity and receptor profiles. Engineered ARH-77 cells achieved robust expansion in RPMI, comparable to that of engineered K562 cells. In optimized DMEM/F-12 medium, engineered ARH-77 drove superior expansion (up to model-estimated 101,241-fold; 95% CI 46,771–219,146 at week 4), significantly outperforming engineered K562 (4.4-fold greater; 95% CI 1.01 to 18.54; p = 0.0479) while maintaining high purity and equivalent cytotoxicity. Substantial inter-donor variability influenced expansion magnitude, though relative feeder performance remained consistent across donors. Conclusions: Genetically modified ARH-77 feeder cells provide a potent platform for large-scale ex vivo expansion of functional NK cells. Full article

Soil cadmium (Cd) pollution has emerged as one of the key environmental issues threatening the safety of agricultural products worldwide, yet clean and low-cost intervention strategies that reduce Cd accumulation in edible crops without disrupting agricultural production remain scarce. Grafting onto tolerant rootstocks represents an emerging clean agronomic technology that achieves in situ Cd risk reduction within a single growing season. However, the molecular mechanisms by which rootstocks regulate scion phenotypes remain poorly understood. MicroRNAs (miRNAs) act as critical long-distance signals in plants, yet their roles in rootstock-mediated growth promotion and Cd reduction remain largely unclear. In this study, we used Solanum torvum as rootstock and purple eggplant (Solanum melongena) as scion to investigate growth, fruit quality, Cd accumulation, and miRNA-mediated regulatory mechanisms. Grafting significantly increased plant height (by 18%), stem diameter (by 12%), and yield without obvious effects on fruit quality. Under Cd stress, the Cd content in grafted eggplant fruits was reduced by 76%, whereas leaf potassium (K), calcium (Ca), and magnesium (Mg) contents were elevated by 21%, 17%, and 10%, respectively. High-throughput sequencing and quantitative real-time polymerase chain reaction identified five key differentially expressed miRNAs, including miR164a and miR166b, four of which were related to Cd stress. Gene Ontology (GO) enrichment analyzes that their target genes were mainly involved in hormone signal transduction and ion transport. Further validation suggested that grafting improved growth and reduced Cd accumulation by regulating genes of the NAC, SPL, and HD-ZIP III families. These results suggested that suitable rootstocks can enhance crop productivity and reduce toxic metal accumulation in edible parts through miRNA-mediated regulation. Full article

This study aimed to identify the distinct intrinsic response potential of γδ T cells from COVID-19 patients with different illness severities, to better understand the implication of these cells in COVID-19 disease. Forty-four COVID patients were enrolled at hospitalization and classified as: moderate without oxygen support (MWO₂; N = 15), moderate with oxygen support (MO₂; N = 15), or severe disease requiring mechanical ventilation (SD; N = 14). γδ T cells were characterized ex vivo, isolated from peripheral blood cells, stimulated in vitro with OKT3 and K562 cells, and evaluated for functional markers by flow cytometry. Ex vivo analysis identified 16.21% of total γδ T cells as Vδ1⁻Vδ2⁻. SD patients presented a lower frequency of TRAIL⁺ and of IL-17-producing Vδ2 cells, as well as lower value of fluorescence intensity values for TNF-α in Vδ2 cells, than MWO₂ patients (p < 0.05). In addition, paired analyses showed a lower frequency of IL-17-producing than CD161⁺ Vδ2 cells in SD patients (p < 0.05). These observations suggest a more restricted response potential of the Vδ2 subset in severe disease, show the impact of general immune dysregulation on these cells, or even suggest some role for IL-17-producing Vδ2 cells in preventing critical symptoms. Full article

Atherosclerosis (AS) is a major driver of acute cardiovascular events, yet the mechanisms by which exercise stabilizes atherosclerotic plaque remain poorly understood. This study investigated the protective effects of a 12-week treadmill exercise training on plaque stability and macrophage autophagy in ApoE^−/− mice fed an atherogenic diet. Exercise significantly decreased the serum pro-inflammatory cytokine (tumor necrosis factor-α) and increased the anti-inflammatory (interleukin-10) mediator in AS mice. Histopathology analysis revealed that exercise improved plaque stability through reduced necrotic core size, increased fibrous cap thickness, and increased collagen content. These improvements were accompanied by decreased lipid accumulation, MMP-9 expression, and macrophage infiltration (CD11b) within the plaque. Mechanistically, exercise activated plaque autophagy, evidenced by increased LC3B fluorescence, elevated LC3II/I ratio, restoration of Beclin-1, and degradation of p62. Notably, exercise-induced autophagy is specific to plaque-resident macrophages, as demonstrated by strong colocalization of LC3B and CD11b fluorescent signals (Pearson’s correlation coefficient = 0.56). Furthermore, exercise restored fibroblast growth factor 21 (FGF21) levels in both circulation and plaque while concurrently suppressing downstream PI3K/Akt/mTOR signaling. Collectively, these findings demonstrated that exercise promotes plaque stability by reducing lipid accumulation, macrophage infiltration, MMP-9 expression, and activation of FGF21. This protection is likely mediated by the activation of macrophage autophagy, specific to plaque-resident macrophages, indicating the cardioprotective benefits of aerobic exercise against AS. Full article

Under the background of global climate change and China’s “carbon peak and carbon neutrality” strategy, it is of great significance to assess the carbon sink benefits of urban park plant communities. This study took 20 plant community plots of 20 m × 20 m (400 m²) in Tientsin Water Park as the research object. Carbon sequestration capacity was characterized by carbon stock (CS) and annual carbon sequestration (ACS), and six community structure indicators were quantified: Vegetation Coverage (VC), Canopy Density (CD), Three-Dimensional Green Volume (3DGV), Tree-to-Shrub Ratio (TSR), Vertical Complexity (CV), and Number of Individuals (N). Spearman correlation analysis, principal component analysis, and regression analysis were adopted, and K-means clustering was introduced to identify vegetation structure–function groups, thereby exploring the statistical correlations between these structural characteristic indicators and carbon sink capacity indicators (CS and ACS). The results showed that (1) VC, CD, and 3DGV were significantly positively correlated with CS, suggesting that these factors may be more conducive to long-term carbon pool accumulation; (2) N was significantly positively correlated with ACS, and a nonlinear decreasing trend was observed in the current observation data; (3) the influence of TSR and CV on carbon storage and sequestration also showed a nonlinear correlation. Based on the above correlation findings, the community combinations with higher carbon sink performance in this case were screened out. And suggestions for low-carbon configuration of plant communities, centered on optimizing canopy structure, configuring high-carbon-sequestration tree species, and regulating reasonable density, were proposed, which can be used as a reference for forming hypotheses in subsequent confirmatory studies. Full article

In most ratiometric electrochemiluminescence (ECL) sensors, the utilization of different co-reactants for anodic and cathodic ECL luminophores, along with a broad potential scanning range, restricts their practical applications. Herein, we first reported dual-cathodic potential-resolved ECL from nitrogen/sulfur-codoped carbon dots (N,S-CDs) and mercaptopropionic acid-functionalized copper nanoclusters (MPA-Cu NCs) using their common co-reactant K₂S₂O₈ within a potential range of 0 to −2 V, and developed a ratiometric ECL biosensor for miRNA-155 analysis. Initially, the ECL peak of MPA-Cu NCs at approximately −2 V on the electrode was quenched through resonance energy transfer (RET) by methylene blue. Subsequently, trace target miRNA-155 was converted into abundant output DNA via a DNA walker mechanism. In the presence of Pb²⁺, partial DNA was cleaved to remove methylene blue, thereby restoring the ECL intensity of MPA-Cu NCs. Furthermore, the cleaved DNA fragments sparked rolling circle amplification (RCA), which ultimately facilitated the loading of N,S-CDs onto the electrode surface, generating an ECL peak at approximately −1 V. As the concentration of miRNA-155 increased, both ECL signals rose simultaneously but with different magnitudes. The fabricated ratiometric ECL sensor achieved a linear detection range for miRNA-155 from 10 aM to 0.1 nM, with a limit of detection of 2.91 aM. Overall, this study offers a new strategy for constructing dual-cathodic ratiometric ECL biosensors and provides a promising approach for early disease diagnosis. Full article