Search Results (32,995)

Potentially toxic element (PTE) contamination of urban soils poses long-term ecological and public health risks. Ornamental vegetation is increasingly discussed within green-infrastructure-based risk management. We screened and synthesised 167 field studies (>120 ornamental and horticultural plant species) to characterise the scope, reporting structure and design features of the available phytoremediation-related evidence. Studies assessed a mean of 3.21 elements (SD = 1.37); Pb, Cd and Zn were most frequently investigated (67%), whereas Ni, Cr and B occurred in <10%. Reported element richness differed by setting, averaging 3.8 ± 1.5 in wastewater-affected sites versus 2.6 ± 1.1 in urban parks. Using a study-by-element presence/absence matrix, co-reporting patterns separated three recurrent co-reporting profiles. The first three PCs explained 64.5% of variance (PC1: Pb–Zn–B; PC2: Cu–Ni; PC3: Cd–Cr). Accumulation was reported most often (56.8%), while stabilisation (17.9%) and translocation (25.3%) were less commonly addressed. For public space applications, accumulation-focused plantings require a defined maintenance pathway (pruning/harvest, biomass removal, and safe handling or disposal) to avoid recirculation of metal-bearing material within the urban environment. Sampling focused on aboveground tissues (73.4%) more than roots (28.9%). In multiple regression, environmental type was associated with element richness (Adj. R² = 0.08, p = 0.001). Here, richness is treated as an index of reporting breadth. Overall, the dominant quantitative signals reflect context-dependent reporting and study design patterns. They do not represent harmonised, concentration-based remediation outcomes. These patterns provide an evidence map to support context-aware interpretation and future study standardisation. Full article

Cervical lymph node metastases are major prognostic determinants in head and neck squamous cell carcinoma (HNSCC), and neck dissection (ND) has long been central to regional control. As ND has evolved from radical to selective procedures, immune checkpoint inhibitors (ICIs) have emerged as a fourth treatment pillar, reframing tumor-draining lymph nodes (TDLNs) as active immune organs rather than passive conduits of metastatic spread. This narrative review synthesizes surgical, immunologic, and translational evidence on how ND and cervical irradiation interact with immunotherapy. It also examines the historical development of ND, the immunologic structure and function of cervical TDLNs, and the use of neoadjuvant, perioperative, and recurrent/metastatic immunotherapy in HNSCC. Preclinical and early clinical observations suggest that ablating or heavily irradiating non-involved nodal basins may attenuate ICI efficacy by disrupting antigen presentation, progenitor exhausted CD8⁺ T (Tpex) cell pools, and effector recirculation, supporting the conceptual model of an “immune desert neck.” The review critically appraises timing (pre- versus post-immunotherapy ND), response-adapted or de-escalated surgery, and imaging, tissue-based, and circulating biomarkers to guide individualized management. Current evidence does not support abandoning elective or therapeutic ND, but does highlight the need for biomarker-driven, lymphatic-sparing trials to redefine when ND is essential, modifiable, or potentially avoidable in immunotherapy-treated HNSCC. Full article

Applying a constant external electric field to a semiconductor nanostructure with Wannier–Mott excitons, in which the electron and hole interact via a centrally symmetric Coulomb potential, alters the symmetry of the system. When the electric field is applied parallel to the z-axis, the system exhibits cylindrical symmetry; when the field lies in the $x-y$ plane, the symmetry is broken. These symmetry changes affect the optical properties of the system. We present a theoretical calculation that yields analytical expressions for the optical functions of CdSe Nanoplatelets—reflectivity, transmissivity, and the absorption coefficient—in an external homogeneous electric field. From these, we focus on the absorption coefficient. We consider various configurations, with the external field oriented perpendicular and parallel to the platelet planes. Using the real density matrix approach, we calculate the linear electro-optical functions of CdSe nanoplatelets, taking into account the effect of dielectric confinement on excitonic states. We also discuss the impact of platelet geometry (thickness and lateral dimensions) and applied field strength on the spectrum. Full article

Male pattern baldness (MPB) is a highly prevalent condition with a complex, poorly understood molecular basis that limits therapeutic innovation. This study aimed to bridge the gap between statistical genetic associations and biological function by identifying and prioritizing causal proteins and pathways involved in MPB. Using data from 24,069 men in the UK Biobank, we performed a proteome-wide association study of 2911 plasma proteins with self-reported MPB severity via multivariable ordinal logistic regression, adjusting for age, Body Mass Index (BMI), ethnicity, lifestyle, socioeconomic factors, and testosterone levels. Significant proteins underwent pathway enrichment analysis. Genetic integration included MAGMA for gene-level aggregation and tissue prioritization, transcriptome-wide association studies (TWAS) with GTEx models, conditional fine-mapping, and validation in an independent scalp biopsy transcriptomics dataset (GSE90594). Druggability and pleiotropy were evaluated using databases and phenome-wide association studies. Forty-seven proteins were significantly associated with MPB severity, enriched in pathways involving epidermis development, hair cycle regulation, and cell adhesion. Multi-omic integration prioritized five independent candidate genes: CD38, FGF5, TACSTD2, DPEP1, and PLB1. Transcriptomic validation confirmed differential expression in balding scalp for CD38 (upregulated) and TACSTD2, PLB1 (downregulated). CD38 was identified as druggable with low pleiotropic risks. This study elucidates the molecular architecture of MPB, revealing novel biological pathways beyond canonical androgen signaling. By prioritizing promising non-hormonal targets like CD38, our findings provide a robust, evidence-based framework to guide the development of future therapeutic interventions for this common condition. Full article

Callous–unemotional (CU) traits are characterised by reduced empathy, guilt, and emotional responsiveness, and are strongly linked to atypical socioemotional processing. Eye-tracking research provides a valuable window into these processes by capturing early developing patterns of attention to emotionally salient social cues, particularly facial expressions. This narrative review examines how alterations in gaze behaviour contribute to the emergence of CU traits across neurodevelopmental disorders (NDs), with a focus on autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and conduct disorder (CD). Across studies, elevated CU traits are associated with reduced fixations on the eye region, most consistently in response to fearful faces. ASD is associated with robust eye avoidance, ADHD with inhibitory and attentional control difficulties during face processing, and CD with atypical gaze allocation to negative emotional expressions such as fear and anger. These patterns appear amplified when CU traits co-occur with NDs. Competing explanatory accounts, including aberrant amygdala functioning, oculomotor disinhibition, and hostile attribution biases, each capture aspects of these patterns but fail to provide a unified explanation. Integrating developmental, neurobiological, and environmental perspectives, we propose that CU traits reflect a transdiagnostic developmental construct shaped by early attentional–emotional mechanisms, rather than a disorder-specific identity. Full article

Offspring of hypertensive disorders of pregnancies (HDP) exhibit early-life endothelial dysfunction and have an elevated susceptibility to hypertension during adulthood which is potentially mediated by microRNA (miRNA), a key regulator of gene expression. RNA sequencing showed that miR-196a-5p was significantly upregulated in HUVEC exposed to HDP and may regulate angiogenesis in endothelial cells. Therefore, this study aims to elucidate the role of miR-196a-5p in regulating angiogenesis in HUVEC exposed to HDP. miR-196a-5p expression was validated by stem-loop RT-qPCR. Predicted target genes were identified using four algorithms, miRWalk, miRDB, TargetScan, and DIANA-microT-CDS, focusing on angiogenesis-related genes. Protein expression was confirmed through ELISA. Stem-loop RT-qPCR showed that miR-196a-5p expression was significantly upregulated in HDP HUVEC. Bioinformatic analysis revealed that the PDGFRA gene, a key regulator for angiogenesis, was significantly enriched. Overexpression of miR-196a-5p significantly downregulated PDGFRA, VEGF, and bFGF in HDP HUVEC, whereas its suppression upregulated these genes significantly. The ELISA result confirmed the corresponding changes at the protein level. However, PDGFRA protein levels increased with miR-196a-5p overexpression and decreased with its inhibition. Collectively, the results indicate that miR-196a-5p may have a regulatory effect on PDGFRA, VEGF, and bFGF that is associated with angiogenesis, and the modifications could be beneficial in future epigenetic targeted therapy. Full article

Light-chain (AL) amyloidosis is a rare and incurable disease, classified under the category of plasma cell neoplasms and other diseases with paraproteins in the 5th Edition of the World Health Organization classification of lymphoid tumors. This entity shares some similarities with multiple myeloma (MM), remarkably a bone marrow infiltration of clonal plasma cells. Moreover, one out of five newly diagnosed cases of AL amyloidosis (NDAL) also fulfills the current diagnostic criteria for MM. A multidisciplinary therapy approach should be established, in which hematological therapy plays a crucial role. Anti-clonal therapy is the basis of hematological therapy, in addition to supportive therapy and emerging anti-fibrils therapy. In recent years, advances in the anti-clonal therapy for MM have progressively transferred to carefully selected patients with systemic AL amyloidosis, significantly improving outcomes in this rapidly changing field. This review aims to critically analyze the comparative evolution and evidence-based approach of anti-clonal therapy in NDAL vs. MM since the introduction of bortezomib. Participation in clinical trials remains the first option to consider in daily clinical practice. Full article

DNA-based cancer vaccines represent a safe and promising immunotherapeutic strategy, but their clinical efficacy is often limited by weak immunogenicity, primarily due to inefficient antigen cross-presentation. To overcome this challenge, the MHC class I trafficking domain (MITD) can be fused to tumor antigens to enhance their intracellular routing in dendritic cells (DCs), thereby promoting the efficiency of cross-presentation. In addition, incorporation of CD4⁺ T cell epitopes, such as PADRE or P2P16, can robustly activate CD4⁺ T cells, further amplifying antitumor immunity. Thus, combining MITD with CD4⁺ epitopes is expected to synergistically improve DNA vaccine potency. Mesothelin (MSLN), a tumor-associated antigen highly expressed in pancreatic cancer, was selected as the target in this study. We designed MSLN-targeted DNA vaccines incorporating MITD together with either PADRE or P2P16. In a Panc02 murine model, the MITD–PADRE construct, a novel design, elicited stronger immune responses and more effective antitumor activity compared to other formulations. To further counteract immunosuppression, we combined the vaccine with gemcitabine, which enhanced therapeutic efficacy. Together, these findings demonstrate that integrating PADRE with MITD in MSLN-targeted DNA vaccines offers a promising combinatorial strategy for advancing pancreatic cancer immunotherapy. Full article

The time evolution of nanoscale structure formation on the surface of CdI₂ crystals grown both from the melt and from the gas phase is investigated. Atomic force microscopy was used to show that, already at the initial stages of exposure to air at room temperature, island-shaped nanostructures form, which subsequently aggregate into nanoclusters as the exposure time increases. Similar nanostructures, including nanopores and nanoclusters, are observed for CdI₂ crystals grown from the gas phase after prolonged exposure to air. Photoluminescence spectroscopy indicates that the formed nanoclusters are consistent with the presence of cadmium hydroxide (Cd(OH)₂) and cadmium oxide (CdO). The formation of nanostructures determines the time evolution of the low-temperature luminescence spectra of CdI₂ crystals. Additional bands with maxima at 1.87 eV and long-wavelength luminescence in the region with a maximum at 1.68 eV appear in the spectral structure. These results highlight the close relationship between surface structural evolution and the time-dependent optical properties of CdI₂. Full article

Giardiasis, caused by Giardia duodenalis, is a common gastrointestinal infection. This study aimed to evaluate the effects of Hedera helix leaf extract (HLE) and HLE-loaded chitosan nanoparticles (HLE-CsNPs) against Giardia duodenalis isolates from individuals with gastrointestinal issues, using an experimental rat model. Stool samples from 147 participants were analyzed for Giardia duodenalis, with positive samples further characterized by nested PCR-RFLP, revealing a 4.8% prevalence, all belonging to assemblage B. Ten groups of male albino rats were used to evaluate the antigiardial activity of various treatments. This included five non-infected groups [one untreated and four treated with HLE, HLE-CsNPs, CsNPs, and metronidazole (MTZ)] and five infected groups [one untreated and four similarly treated]. Treatment efficacy was assessed using parasite counts, intestinal histopathology, CD117 immunohistochemistry, and markers of liver and kidney function. HLE-CsNPs markedly reduced Giardia cysts by 88.8%, approaching the 99.2% reduction achieved by MTZ, while also improving intestinal architecture and reducing inflammation. Importantly, HLE and HLE-CsNPs provided superior protection for the liver and kidneys compared to MTZ. In conclusion, HLE-CsNPs exhibited significant antigiardial activity and organ protection in rats, suggesting a potential alternative treatment for Giardia duodenalis isolated from individuals with gastrointestinal issues. Full article

Gene delivery/administration and, in particular, small interfering RNA (siRNA) delivery represent a therapeutic challenge, though very effective carriers have yet to be identified. Cyclodextrins (CDs) are cyclic oligosaccharides with unique host–guest inclusion capabilities, widely recognized in the pharmaceutical field for their ability to enhance drug solubility and bioavailability. Their excellent biocompatibility and chemical versatility make them powerful building blocks for the design of supramolecular nanovectors (NVs). Thanks to their facility of functionalization, CDs are highly versatile and have found numerous applications across various fields. In this context, CD-based NVs are currently explored as non-viral agents to transport and release siRNA. Recent studies suggest that self-assembled NVs based on CDs can improve the transfection and safety of siRNA delivery. This review provides a comprehensive overview of the most recent advances in the design of NVs based on CDs and their use for siRNA delivery, discussing the role played by structural differences and chemical functionalization in the context of encapsulation and release. Full article

Background/Objectives: Vaccines targeting melanoma antigens can elicit CD8⁺ T cell responses, but a growing body of work suggests CD4⁺ T cells also play a role in tumor control. Induction of CD4⁺ cells may also support B cells in producing tumor antigen-specific antibodies (Abs). We investigated Abs induced by vaccination with a cocktail of six class II MHC-restricted melanoma peptides (6MHP) and the effect of adjuvant type on Ab isotypes. We hypothesized that the vaccines would induce Abs that respond to different epitopes on individual peptides and that IgG isotype distribution varies with different vaccine adjuvants. Methods: Sera from patients who received a 6MHP vaccine were evaluated with enzyme-linked immunosorbent assays to map epitopes for polyclonal Ab responses to synthetic melanoma peptides. IgG isotypes of Ab responses to 6MHP were assessed in patients who received one of four adjuvants (Incomplete Freund’s Adjuvant (IFA) alone, IFA + polyICLC, IFA + systemic metronomic cyclophosphamide (mCy), or IFA + polyICLC + systemic mCy) to characterize IgG isotype distribution. Results: Epitope mapping revealed that at least 50% of patients had responses to two or more epitopes on the same peptide, suggesting polyclonal Ab responses. Serum evaluation for IgG isotypes showed predominant induction of IgG1 and IgG3. Mean total IgG was highest when IFA and polyICLC were used in combination. Patients who received TLR3 agonist polyICLC had significantly higher concentrations of total IgG, IgG1, and IgG3 compared to patients who did not receive polyICLC. Conclusions: Vaccine-induced Abs may respond to multiple epitopes within the same peptide, warranting further studies into their ability to facilitate antigen uptake and presentation through the formation of large immune complexes. The findings also show that adding polyICLC to IFA can significantly enhance Ab responses. Collectively, this work underscores the immunologic potential of peptide-induced Abs and the importance of adjuvant selection in cancer vaccine design. Full article

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and is a leading cause of cervical, anal, penile, and oropharyngeal cancers. This review summarizes the epidemiology of HPV and the immunogenicity, clinical efficacy, and current HPV vaccination recommendations among people living with HIV (PLWH). PLWH experience a disproportionate burden of HPV-related infection and HPV-related malignancies. Although HPV vaccines have been shown to be highly effective, vaccination coverage among PLWH remains suboptimal, particularly in low- and middle-income countries. Barriers to vaccination include extended dosing schedules, limited awareness of the vaccine, and misinformation. Evidence indicates HPV vaccines are safe and induce a robust antibody response in PLWH, especially among individuals with higher CD4+ cell counts and viral suppression on antiretroviral therapy. However, evidence for reduction in clinical HPV-related disease in this population remains limited. Ongoing research is aimed at optimizing the HPV vaccination schedule for PLWH and expanding vaccination in older, high-risk subgroups. Integrating HPV vaccination into HIV care is essential to reduce HPV-related morbidity and mortality in PLWH. Full article

Background: Ovarian cancer (OC) remains the most common cause of gynecological cancer-related death, and about 70% of these deaths are from advanced high-grade serous ovarian cancer (HGSOC). Cysteine-rich secretory protein 3 (CRISP3) is related to various human diseases; however, the roles and mechanisms of CRISP3 in HGSOC remain unclear. Methods: The clinical significance of CRISP3 in patients with OC was analyzed using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. CRISP3 expression in OC tissues was validated by RNA-sequencing (RNA-seq), quantitative PCR, and immunohistochemistry. Furthermore, we explored the effect of CRISP3 expression modulation on the biological behavior of HGSOC through CCK-8, EdU, and Transwell assays in vitro, and the differences in CRISP3 during the progression of HGSOC in vivo. We utilized RNA-seq, GSEA and Western blotting to detect CRISP3’s regulatory mechanisms. Finally, we employed data from the IMvigor210 cohort and TCGA to assess the correlation of CRISP3 with clinical response to immunotherapy, and the landscape of immune cell infiltration. Results: CRISP3 expression was markedly reduced in HGSOC. In vitro studies demonstrated that CRISP3 knockdown significantly enhanced proliferation, migration, and invasion of HGSOC cells, whereas its overexpression suppressed these malignant phenotypes. Moreover, CRISP3 expression was found to be downregulated during OC progression in vivo. Mechanistically, CRISP3 acted as a tumor suppressor through the PI3K/AKT signaling pathway to inhibit the progression and metastasis of HGSOC. Additionally, we observed an association between CRISP3 expression and CD8⁺ T cell, macrophage, neutrophil and Th1 cell infiltration. Conclusions: We demonstrate that CRISP3 suppresses tumorigenesis in HGSOC by regulating the PI3K/AKT pathway, and that alterations in its expression correlate with disease progression, supporting its utility as a biomarker. Full article

Natural Killer (NK) cell-based immunotherapy relies on CD16-mediated Antibody-Dependent Cellular Cytotoxicity (ADCC), yet the ovarian tumor microenvironment (TME) severely compromises this function via Transforming Growth Factor-beta (TGF-β). This study investigated the molecular mechanisms driving this suppression and evaluated a bi-specific Chimeric Antigen Receptor (CAR) strategy to overcome this hurdle. Primary PBNK cells exposed to TGF-β showed sustained canonical SMAD2 phosphorylation, accompanied by a marked reduction in activating receptors such as CD16 and NKG2D and an increase in exhaustion markers such as PD-1. Functionally, these phenotypic alterations led to failed infiltration and cytotoxicity in vitro and within ovarian cancer-derived spheroids. To overcome this limitation, we engineered NK-92 cells with a bi-specific CAR-targeting Folate Receptor Alpha (FRα) and CD16. While TGF-β typically impairs NK cell function, our armed CAR-NK cells successfully infiltrated tumoroids and synergized with Trastuzumab to induce potent ADCC-mediated lysis. Our findings define the TGF-β/SMAD2 axis as a central driver of NK cell dysfunction in ovarian cancer and demonstrate that bi-specific CAR-NK platforms offer a robust therapeutic solution to bypass TME-induced suppression and restore antibody-mediated tumor suppression. Full article