Search Results (748)

Background/Objectives: Virus-like particle (VLP) vaccines based on human papillomavirus (HPV) L1 proteins have high efficacy for preventing cervical cancer and other HPV-associated diseases. The production yields of commercial HPV VLPs remain suboptimal. We aimed to improve HPV VLP production efficiency using a hyper-expression vector system for the expression of L1 proteins of four major HPV serotypes—HPV 6, 11, 16, and 18. Methods: HPV L1 proteins were expressed in Trichoplusia ni (Hi5) insect cells via a hyper-expression baculovirus vector system. Following cell lysis using a microfluidizer, VLPs were purified through a two-step chromatographic process. Particle morphology was characterized using transmission electron microscopy and dynamic light scattering. Immunogenicity was evaluated using a murine model; mice received three intramuscular injections of the purified quadrivalent VLPs. The resulting IgG and neutralizing antibody responses were compared with those elicited by the commercial quadrivalent vaccine, Gardasil. Results: The L1 proteins from HPV 6, 11, 16, and 18 were successfully expressed at high levels in Hi5 cells, forming uniformly sized VLPs with hydrodynamic diameters of 50–60 nm. The average production yield of the quadrivalent VLPs exceeded 40 mg/L, an improvement over conventional yields. The candidate VLPs elicited strong HPV-specific IgG and neutralizing antibody responses in mice, comparable to those induced by Gardasil. Conclusions: The hyper-expression baculovirus vector system enables high-yield production of HPV L1 VLPs with desirable structural and immunogenic properties. This approach holds promise for the cost-effective and scalable manufacturing of next-generation HPV VLP vaccines, facilitating broader global access to HPV immunization. Full article

Background/Objectives: In children, gastroesophageal reflux disease (GERD) may lead to epithelial barrier dysfunction and the release of thymic stromal lymphopoietin (TSLP), interleukin-25 (IL-25), interleukin-33 (IL-33) and periostin, known as alarmins. These cytokines are associated with type 2 inflammation and may contribute to respiratory and allergic conditions. The main purpose of this study is to evaluate serum concentrations of TSLP, IL-25, IL-33, and periostin in children with and without GERD and to assess their relationships with bronchial hyperresponsiveness (BHR) and sensitization to inhaled allergens. Methods: The study included 93 children aged 7–17 years. GERD was diagnosed based on 24-h esophageal pH impedance monitoring. Serum levels of TSLP, IL-25, IL-33, and periostin were measured using enzyme-linked immunosorbent assay (ELISA). It should be noted that the assay used does not distinguish between TSLP isoforms, which represents a limitation of the study. BHR was assessed via a methacholine challenge test, and allergen sensitization was determined using skin prick tests and allergen-specific immunoglobulin E (asIgE). Results: Serum TSLP levels were significantly higher in children with GERD compared to those without, whereas IL-25, IL-33 and periostin did not differ notably between groups. Periostin was associated with the degree of sensitization to inhalant allergens, but no significant links were found between cytokine levels and bronchial hyperresponsiveness. Conclusions: Significantly higher TSLP levels were noted in children with GERD than in those without. Hence, TSLP may have a potential role as a biomarker of epithelial immune activation in pediatric GERD. In addition, periostin was associated with sensitization to inhalant allergens, although it did not differentiate between children with and without GERD. Full article

Gulf cities have embarked on ambitious public transport infrastructure initiatives in recent decades to foster more livable and sustainable cities. This investigation explores the interpretations and implementation of Transit-Oriented Development (TOD) principles in two prototypical urban districts: Doha’s West Bay, Qatar, and Riyadh’s King Abdullah Financial District (KAFD), Saudi Arabia. By following a comparative case study approach, the study explores how retrofitted (West Bay) and purpose-built (KAFD) TOD configurations fare regarding land use mix, density, connectivity, transit access, and environmental responsiveness. The comparative methodology was selected to specifically capture the spatial, climatic, and socio-economic complexities of TOD implementation in hyper-arid urban environments. Based on qualitative evidence from stakeholder interviews, spatial assessments, and geospatial indicators—such as metro access buffers, building shape compactness, and TOD proximity classification—the investigation reflects both common challenges and localized adaptations in hot-desert Urbanism. It emerges that, while benefiting from integrated planning and multimodal connectivity, KAFD’s pedestrian realm is delimited by climatic constraints and inactive active transport networks. West Bay, on the other hand, features fragmented public spaces and low TOD cohesion because of automotive planning heritages. However, it holds potential for retrofit through infill development and tactical Urbanism. The results provide transferable insights that can inform TOD strategies in other Gulf and international contexts facing similar sustainability and mobility challenges. By finalizing strategic recommendations for urban livability improvement through context-adaptive TOD approaches in Gulf cities, the study contributes to the wider discussion of sustainable Urbanism in rapidly changing environments and supplies a reproducible assessment frame for future TOD planning. This study contributes new knowledge by advancing a context-adaptive TOD framework tailored to the unique conditions of hyper-arid Gulf cities. Full article

Richter transformation (RT) affects 2–10% of chronic lymphocytic leukemia (CLL) patients, evolving into an aggressive lymphoma—most often diffuse large B-cell lymphoma—with poor prognosis, especially when clonally related to CLL. Key risk factors include unmutated IGHV, TP53 and NOTCH1 mutations, stereotyped B-cell receptors, and complex cytogenetics. This review summarizes RT biology, clinical predictors, and treatment outcomes. Traditional chemoimmunotherapy (e.g., R-CHOP) yields complete response rates around 20–30% and median overall survival of 6–12 months; intensified regimens (R-EPOCH, hyper-CVAD) offer only modest gains. Allogeneic hematopoietic stem cell transplantation is potentially curative but limited to fit patients due to high treatment-related mortality. Emerging therapies now include Bruton’s tyrosine kinase and BCL-2 inhibitors, which achieve partial responses but short progression-free survival. CD19-directed chimeric antigen receptor T-cell therapies produce overall response rates of 60–65%, though relapses remain frequent. Bispecific antibodies (e.g., CD3×CD20 agents epcoritamab and mosunetuzumab) show promising activity and tolerable toxicity in relapsed/refractory RT. Ongoing trials are exploring combinations with checkpoint inhibitors, triplet regimens, and novel targets such as ROR1, CD47, and CDK9. Continued research into optimized induction, consolidation, and innovative immunotherapies is essential to improve outcomes in this biologically distinct, high-risk CLL-related lymphoma. Full article

Background/Objectives: Autism spectrum disorder (ASD) is characterized by qualitative difficulties in interaction and communication, as well as hyper- or hypo-responsivity to sensory input, which can substantially challenge the formation of mother-child attachment. This study aimed to identify attachment levels among mothers of preschool-aged children with ASD and to delineate the attachment processes associated with those levels, with the goal of developing a grounded theory explaining these processes. Methods: A two-step study using methodological triangulation was conducted. In the first quantitative study, the attachment level of 64 mothers of children with ASD, under the age of 7 years in Korea, were measured. And 12 were selected for a second study using the grounded theory method of Strauss & Corbin. Results: A significant attachment difference (t = 4.39, p < 0.001) was found in the pregnancy plan. The core attachment category in mothers of pre-school children with ASD was identified as “keep on going with closing the distance”. Eight stages and four types were found in their attachment process. Conclusions: The results of this suggest that it is necessary to develop a personalized intervention strategy and to provide proper nursing by considering the attachment process and type of mothers of children with ASD. Full article

Background/Objectives: Hormonal contraceptives are widely used, but their effects on respiratory health remain underexplored. This systematic review examined the impact of oral contraceptive pills (OCPs) on pulmonary function, with an emphasis on asthma-related outcomes and underlying mechanisms. Methods: MEDLINE (PubMed), EMBASE (Ovid), CINAHL, AMED, SPORTDiscus, and PEDro were searched from January 2000 to December 2024. Pulmonary outcomes assessed included PEFR, FEV₁, airway hyperresponsiveness, and exhaled nitric oxide levels. Results: Twelve peer-reviewed studies were included. Most studies reported that OCPs do not impair lung function and may even improve respiratory parameters. Women using OCPs showed enhanced peak expiratory flow and reduced symptom variability, particularly in asthma and cystic fibrosis. Potential mechanisms include the stabilization of airway reactivity and modulation of inflammatory pathways. Heterogeneity across study populations and contraceptive types limited a meta-analysis, and few studies stratified outcomes by hormonal composition or comorbidities. Conclusions: Hormonal contraceptives may provide protective or regulatory effects on pulmonary function in specific populations. Larger precision-based studies are needed to clarify mechanisms and guide contraceptive counseling for women with respiratory conditions. Full article

This study investigates the effects of Bisphenol A (BPA)—a ubiquitous endocrine disruptor—on the swimming behavior of the rotifer Brachionus plicatilis. Across a 0–40 ppm gradient, a biphasic response was observed, with swimming speed peaking at 20 ppm (100.42 ± 12.17 µm/s) and then significantly declining by 43% to 57.58 ± 30.59 µm/s at 40 ppm (Tukey, p < 0.05). Speed–frequency plots revealed co-existing hyper- and hypoactive sub-populations at 10–30 ppm, whereas severe inhibition dominated at 40 ppm. Additionally, temporal analysis confirmed that BPA effects were both concentration- and time-dependent, with the mean speed at 10 ppm declining only slightly over time (slope ≈ −0.8), whereas at 40 ppm, the decrease was an order of magnitude steeper (slope ≈ −16.9). Additionally, BPA exposure also triggered a sharp rise in abrupt turns (582.53 ± 477.55 events) and greater path sinuosity, consistent with neuromuscular disturbance. These findings demonstrate that rotifer locomotion provides an early and sensitive indicator of environmental BPA exposure. Full article

In this preliminary study, the thermoregulatory response in individuals diagnosed with Parkinson’s disease was investigated by infrared thermography. Parkinson’s disease is a complex neurodegenerative disorder primarily known for motor impairments, significantly reducing the quality of life of affected people. However, in most cases, such disease is accompanied or preceded by non-motor symptoms, including autonomic dysfunction. As in the case of neurovegetative dysautonomia, this dysfunction involves a malfunction of the autonomic nervous system, which also plays a key role in thermoregulation. In general, such conditions are not always easy to detect; a valid method could be represented by the vasomotor response of the skin to cold stimuli. In this context, infrared thermography can provide insights into the thermoregulatory patterns associated with autonomic dysfunction, representing a valuable tool for non-invasive assessment of Parkinson’s research. Early biomarkers of the disease can be obtained through changes in skin temperature, allowing for timely intervention and management. The study was conducted on a cohort of 16 subjects (8 patients with Parkinson’s disease and 8 healthy controls), who were monitored with infrared images captured from their hands, following a specific protocol established by a preliminary analysis. Experimental results revealed that thermography can detect focal points and regions exhibiting either hyper- or hypothermia across the skin surface and muscular regions. This capability allows for extracting and categorizing precise medical data, which could inform future research aimed at identifying early markers of the disease. However, as this is a preliminary observational study, no diagnostic claims are made, and further investigations on larger cohorts with controlled comorbidities are needed. Full article

The ileum serves as the primary site for nutrient digestion and absorption in the intestine, with villus height representing a critical indicator of intestinal absorptive capacity. To investigate the regulatory mechanisms underlying ileal villus development, we conducted a feeding trial using crossbred pigs (Duroc × Landrace × Yorkshire) with an initial body weight of 27.74 ± 0.28 kg, stratifying them into high-villus and low-villus groups based on ileal villus height (n = 4). The results revealed 849 differentially RNA-edited genes (REGs) between the two groups, including 472 hyper-edited genes in the low-villus group and 377 in the high-villus group. Functional enrichment analysis showed that these REGs were significantly enriched in inflammation-related pathways, particularly the TNF signaling pathway and IL-17 signaling pathway, with TNF pathway genes exhibiting notably higher editing levels in the high-villus group. Additionally, 46 differentially expressed genes (DEGs) were identified, comprising 22 upregulated in the low-villus group and 24 in the high-villus group, which were similarly enriched in TNF and IL-17 signaling pathways. Integrated quadrant analysis of the RNA editing and transcriptomic profiles demonstrated that pro-inflammatory genes CXCL10 (C-X-C motif chemokine 10), CCL2 (C-C motif chemokine ligand 2), CREB3L2 (CAMP-responsive element-binding protein 3-like 2), and PIK3R1 (Phosphoinositide-3-kinase regulatory subunit 1) were highly expressed in the low-villus group but exhibited significantly lower RNA editing levels compared to the high-villus group. Furthermore, the expression of the inflammation-suppressive RNA editing enzyme APOBEC1 (apolipoprotein B mRNA editing enzyme catalytic subunit 1) showed correlation with villus height (R = 0.81, p < 0.05). Collectively, our findings indicate that RNA editing dynamics influence the variation in ileal villus height within inflammation-associated pathways, particularly the TNF signaling pathway. Enhanced RNA editing of this pathway may mitigate intestinal inflammation and promote healthy ileal villus developments. Full article

The FOT is a non-invasive method for assessing respiratory mechanics. It enables the measurement of respiratory system impedance by applying pressure oscillations through a loudspeaker at the subject mouth and then studying its deformation, which is commensurate to the resistance opposed by the respiratory system. The main parameters which can be determined with the FOT are the impedance (Z) and the components of respiratory resistance (Rrs) and reactance (Xrs). The FOT has been predominantly applied to the study of respiratory mechanics for research purposes; however, preclinical experiments and subsequently observational clinical studies have demonstrated that FOT can effectively assess airway obstruction, bronchodilator response, bronchial hyperresponsiveness, and the presence of small airways disease. More recently, studies on the FOT in restrictive lung diseases have also been reported. Nonetheless, international guidelines on the precise applications of the FOT in lung diseases are still lacking. The aim of the review was to describe the technical aspects related to the FOT methodology in clinical practice and to provide a concise state of the art on the applications of the FOT in obstructive and restrictive lung diseases. Full article

Background and Clinical Significance: As a common inflammatory skin disorder, acne vulgaris is classically associated with sebum overproduction, follicular hyper keratinization, and Cutibacterium acnes proliferation. Emerging evidence suggests a link between severe or treatment-resistant acne and metabolic syndrome, characterized by central obesity, insulin resistance, dyslipidemia, and hypertension. This case series aims to explore the clinical overlap between acne and metabolic dysfunction and highlight the relevance of multidisciplinary evaluation. Case Presentation: Three patients with severe acne vulgaris and coexisting metabolic abnormalities were evaluated at a dermatology clinic in Oradea, Romania, between 2023 and 2024. Each patient underwent dermatologic examination, laboratory testing for metabolic and hormonal parameters, and individualized treatment. Management strategies included topical/systemic acne therapies combined with metabolic interventions (lifestyle modifications, metformin (in two cases), and lipid-lowering agents). Case 1 (female, 23) had obesity, insulin resistance, dyslipidemia, and polycystic ovary syndrome (PCOS). Case 2 (male, 19) presented with central obesity and atherogenic dyslipidemia. Case 3 (male, 18) showed insulin resistance, overweight status, and elevated inflammatory markers. All three showed suboptimal response to standard acne treatment. Adjunct metabolic management resulted in partial improvement within 3 months. One patient required isotretinoin after metabolic stabilization. Conclusions: These cases underscore the interplay between acne and metabolic dysfunction. Insulin resistance and systemic inflammation may contribute to therapeutic resistance in acne. Early recognition of metabolic syndrome features in patients with severe acne may improve treatment outcomes. Dermatologists should consider metabolic screening to guide comprehensive, multidisciplinary care. Full article

Reactive oxygen species (ROS) are often seen solely as harmful byproducts of oxidative metabolism, yet evidence reveals their paradoxical roles in both promoting and inhibiting cancer progression. Despite advances, precise context-dependent mechanisms by which ROS modulate oncogenic signaling, therapeutic response, and tumor microenvironment dynamics remain unclear. Specifically, the spatial and temporal aspects of ROS regulation (i.e., the distinct effects of mitochondrial versus cytosolic ROS on the PI3K/Akt and NF-κB pathways, and the differential cellular outcomes driven by acute versus chronic ROS exposure) have been underexplored. Additionally, the specific contributions of ROS-generating enzymes, like NOX isoforms and xanthine oxidase, to tumor microenvironment remodeling and immune modulation remain poorly understood. This review synthesizes current findings with a focus on these critical gaps, offering novel mechanistic insights into the dualistic nature of ROS in cancer biology. By systematically integrating data on ROS source-specific functions and redox-sensitive signaling pathways, the complex interplay between ROS concentration, localization, and persistence is elucidated, revealing how these factors dictate the paradoxical support of tumor progression or induction of cancer cell death. Particular attention is given to antioxidant mechanisms, including NRF2-mediated responses, that may undermine the efficacy of ROS-targeted therapies. Recent breakthroughs in redox biosensors (i.e., redox-sensitive fluorescent proteins, HyPer variants, and peroxiredoxin–FRET constructs) enable precise, real-time ROS imaging across subcellular compartments. Translational advances, including redox-modulating drugs and synthetic lethality strategies targeting glutathione or NADPH dependencies, further highlight actionable vulnerabilities. This refined understanding advances the field by highlighting context-specific vulnerabilities in tumor redox biology and guiding more precise therapeutic strategies. Continued research on redox-regulated signaling and its interplay with inflammation and therapy resistance is essential to unravel ROS dynamics in tumors and develop targeted, context-specific interventions harnessing their dual roles. Full article

Background. The STING protein is activated by the second messenger cGAMP to promote the innate immune response against infections. Beyond this role, a chronically overactive STING signaling has been described in several disorders. Patients with severe COVID-19 exhibit a hyper-inflammatory response (the cytokine storm) that is in part mediated by the cGAS-STING pathway. Several STING inhibitors may protect from severe COVID-19 by down-regulating several inflammatory cytokines. This pathway has been implicated in the establishment of an optimal antiviral vaccine response. STING agonists as adjuvants improved the IgG titers against the SARS-CoV-2 Spike protein vaccines. Methods. We investigated the association between two common functional STING1/TMEM173 polymorphisms (rs78233829 C>G/p.Gly230Ala and rs1131769C>T/p.His232Arg) and severe COVID-19 requiring hospitalization. A total of 801 non-vaccinated and 105 fully vaccinated (mRNA vaccine) patients, as well as 300 population controls, were genotyped. Frequencies between the groups were statistically compared. Results. There were no differences for the STING1 variant frequencies between non-vaccinated patients and controls. Vaccinated patients showed a significantly higher frequency of rs78233829 C (230Gly) compared to non-vaccinated patients (CC vs. CG + GG; p = 0.003; OR = 2.13; 1.29–3.50). The two STING1 variants were in strong linkage disequilibrium, with the rs78233829 C haplotypes being significantly more common in the vaccinated (p = 0.02; OR = 1.66; 95%CI = 1.01–2.55). We also studied the LTZFL1 rs67959919 G/A polymorphism that was significantly associated with severe COVID-19 (p < 0.001; OR = 1.83; 95%CI = 1.28–2.63). However, there were no differences between the non-vaccinated and vaccinated patients for this polymorphism. Conclusions. We report a significant association between common functional STING1 polymorphisms and the risk of developing severe COVID-19 among fully vaccinated patients. Full article

Abiotic stress can reprogram the gametophytic pathway; the mechanisms by which floral bud pre-treatment influences microspore embryogenesis initiation remain unclear. In this study, we use bisulfite sequencing, sRNA-seq, and RNA-seq to analyze the dynamic changes in rice microspores under different cold treatment durations. Our results showed that a 10-day cold treatment is essential for CXJ microspore embryogenesis initiation. DNA methylation levels showed a slight change at CG, CHG, and CHH sites under cold treatment. The number of both hyper- and hypomethylated DMRs increased over cold treatment, with more hypermethylated DMRs at 5 and 10 dpt. Hypermethylated DMRs were more frequently in the TSS region compared to hypomethylated DMRs. The proportion of 24 nt sRNAs increased upon cold stress, with more downregulated than upregulated sRNAs at 10 dpt. The number of DMR target DEGs increased from 5 to 10 dpt. Promoter hypomethylation at the CHH site was more frequently associated with DEGs. These outcomes suggested that the RdDM pathway participates in the initiation of rice ME. GO analysis indicated that DMR target DEGs at 10 dpt were enriched in responses to chemical stimuli, biological processes, and stress responses. An auxin-related gene, OsHOX28, was further identified. Its upregulation, potentially mediated by the RdDM pathway, may play a crucial role in the initiation of rice ME. This study provides more information on epigenetic mechanisms during rice ME. Full article

In an era marked by accelerating ecological degradation and widening global inequalities, prevailing patterns of resource extraction and consumption are proving increasingly unsustainable. Driven by hyper-consumption and entrenched linear production models, the global economy continues to exert immense pressure on planetary systems. This communication article calls for a fundamental paradigm shift from the long-standing assumption of resource abundance to a framework of responsible scarcity. Drawing from recent data on material throughput, on the transgression of planetary boundaries, and on the structural and geopolitical disparities underlying global resource use, this article highlights the urgent need to realign natural resource governance with ecological limits and social justice. A conceptual framework is proposed to support this transition, grounded in principles of ecological constraint, functional sufficiency, equity, and long-term resilience. The article concludes by outlining a forward-thinking research and policy agenda aimed at fostering sustainable and just modes of resource utilization in the face of growing environmental and socio-economic challenges. Full article