Search Results (70)

Micro- and nanoplastics (MNPs) are pervasive in food-contact environments and the human diet, positioning the gastrointestinal (GI) tract as the primary portal of entry and a plausible site of early biological effects. Human exposure is supported by detection of microplastics in stool and colon tissue, and emerging clinical studies report associations between fecal microplastic burden and GI disease states, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). Preclinical studies provide mechanistic plausibility, reporting that ingested MNPs can modulate microbial ecology, alter mucus membrane integrity, increase intestinal permeability through changes in cellular tight junction biology, and induce inflammatory gene expression. These effects can vary by MNP polymer type, particle size/shape, aging state, and exposure dose. Human-relevant experimental platforms increasingly demonstrate size- and concentration-dependent uptake and host responses while revealing substantial inter-individual variability. We synthesize current evidence on dietary sources and key physiochemical properties as they relate to mechanistic pathways connecting MNP exposure to dysbiosis–immune activation–neoplasia axes, in addition to methodological limitations that constrain current clinical utility. Further research including standardized biomonitoring and exposure protocols, environmentally realistic chronic low-dose mixtures, longitudinal human cohorts, and interventional designs that test whether exposure reduction modifies GI inflammation biomarkers and cancer-relevant pathways are critical to clarifying causality. Full article

Background/Objectives: Identifying the source of Staphylococcus aureus bacteremia (SAB) is central to therapeutic management, but data on dental consultation in initially unknown-source SAB are scarce. We characterized its use, timing, and diagnostic yield, and described the underlying clinical findings and management recommendations through structured re-adjudication. Methods: Exploratory retrospective single-center cohort study of adult inpatients with blood-culture-confirmed SAB during 2025, classified at baseline as having an alternative-presumed-source or initially unknown-source SAB. A possible dental focus was defined as a dental condition exhibiting clinical signs of active infection at structured intraoral examination—regardless of whether the active infectious component arose on an acute or, more frequently, on a chronic structural substrate. In the absence of microbiological or molecular confirmation of an odontogenic origin, such findings were interpreted as a possible portal of entry in initially unknown-source patients and as concurrent oral pathology in patients with an alternative-presumed-source. Transesophageal echocardiography (TEE) and infective endocarditis were analyzed as contextual variables; infective endocarditis was extracted as documented by the treating team and was not centrally readjudicated against the modified Duke criteria. Results: Of 72 eligible patients, 53 (73.6%) had an alternative-presumed-source and 19 (26.4%) an initially unknown-source SAB. TEE was performed in 54 (75.0%) and infective endocarditis was diagnosed in nine (12.5%) patients, with similar rates in both subgroups. Dental consultation was requested in 17 patients (23.6%), including six of 19 with initially unknown-source SAB (31.6%); a possible dental focus was identified in five of six consulted unknown-source patients (83.3%; 95% CI 43.6–97.0) versus four of 11 alternative source patients (36.4%). This estimate reflects the yield among consultation-selected patients and is not generalizable to the wider unknown-source population. Cardiac and dental evaluation jointly contributed to source clarification in six of 19 unknown-source patients (31.6%). Structured re-adjudication by a blinded dental specialist showed findings dominated by chronic structural dental disease with active inflammatory components rather than classical acute odontogenic infection; active dental treatment was recommended in 11 of 17 patients (64.7%), including all unknown-source patients. Conclusions: Dental consultation was performed infrequently in SAB, yet among consultation-selected unknown-source patients it frequently identified clinically suspected oral foci and prompted concrete management, complementing echocardiographic evaluation. Given the exploratory single-center design and the absence of microbiological confirmation of an odontogenic origin, these findings should be interpreted as hypothesis-generating and warrant prospective evaluation with predefined dental criteria and linkage to bacteremia-relevant clinical outcomes. Full article

Background/Objectives: The rapid expansion of targeted therapies has reshaped oncology by exploiting ligand-receptor interactions (LRI) to improve treatment specificity and patient outcomes. However, the data describing these ligands remain fragmented across multiple sources, limiting accessibility for researchers and clinicians. To address this gap, we developed the OncoSolidDB, the first curated and oncology-focused bioinformatics database dedicated to ligands associated with solid malignancies. Methods: OncoSolidDB integrates and harmonizes data from reliable repositories, including ChEMBL, DrugBank and the Anti-Cancer Fund, consolidating curated structural, chemical, pharmacological, and clinical annotations along with standardized identifiers. Results: The database currently encompasses 243 ligands across 15 major solid tumor types including breast, lung, colorectal, melanoma, prostate, gastric, ovarian, cervical, bladder, esophageal, head and neck, thyroid, pancreatic, renal and liver cancer (Hepatocellular Carcinoma, HCC). Each entry is annotated by standardized identifiers (DrugBank, ChEMBL), approval year, chemical structures (SMILES strings, 2D images), and downloadable protein structure files (PDB format). Temporal coverage spans 1953–2025, enabling exploration of historical trends in oncology drug approvals. The database content is suitable for bioinformatics analysis, molecular docking, virtual screening, ligand-based modeling, and drug repurposing studies. Outputs are available through a freely accessible web interface that supports search browsing by cancer type. Conclusions: By consolidating oncology-specific ligand data into a single, structured platform, OncoSolidDB offers a valuable resource for advancing drug discovery, repurposing strategies, and the rational design of next-generation targeted therapies for solid tumors. OncoSolidDB is accessible via our Bioinformatics Research PortalEinstein. Full article

Parabens, a prevalent class of endocrine-disrupting chemicals (EDCs), are ubiquitous in consumer products; however, their role in linking pediatric allergic phenotypes remains poorly understood. This case-control study analyzed paraben levels in urine and indoor dust as proxies for internal and external exposures and investigated their associations with allergic rhinitis only (AR Only), asthma only (AS Only), and comorbidities (AR&AS) among children in Shanghai. The concentrations for each of four paraben compounds were quantitatively measured, and multi-pollutant frameworks—including Bayesian Kernel Machine Regression (BKMR) and Weighted Quantile Sum (WQS) regression—were employed to characterize the mixture exposure and risk. Propylparaben (PrP) was detectable in 100% of urine samples and over 90% of dust samples, and the concentrations ranked the highest out of the four compounds in both samples. Benzylparaben (BzP) was detected in >70% of urine samples and over 50% of dust samples at relatively lower levels. Urinary PrP exhibited significantly positive associations with all phenotypes (OR in 2.18–2.92) and BzP with the AR&AS Comorbidity (OR = 3.55, 95% CI: 1.32–9.55). Dust-borne PrP was associated with AR Only (OR = 2.26, 95% CI: 1.16–4.43), indicating a potential “Portal of Entry” effect via direct nasal deposition. According to BKMR and WQS analyses, urinary PrP and BzP emerged as two primary risk drivers. Using interaction analysis, an additive synergistic effect was observed between urinary PrP and BzP with parental history of allergy, suggesting heightened vulnerability to paraben exposure in genetically predisposed subgroups. In conclusion, children with respiratory allergies were associated with higher exposure to PrP and BzP and exhibited higher susceptibility in those with a parental history of allergy. Full article

Timely labor market monitoring is essential for policy design and operational planning, yet annual reports can mask turning points and subgroup heterogeneity. This paper develops a reproducible monitoring and prediction framework using administrative statistics from the General Organization for Social Insurance (GOSI) in the Saudi Open Data Portal. We document descriptive patterns in formal participation and insurable wages, including age-group dispersion, stable correlation structure, and explicit handling of an anomalous wage release and limited missing wage entries. We then formulate from non-salary administrative descriptors. Under leakage control, Random Forest models achieve accuracy around 0.71 across releases. Most errors are concentrated between adjacent wage bands, which is consistent with threshold discretization of a continuous wage distribution. To support operational deployment, we add out-of-time validation across releases and probabilistic assessment, showing that predictive skill transfers across updates and that calibration improves the reliability of probability scores for monitoring thresholds. Overall, the results indicate that administrative releases contain persistent actionable signals for wage segmentation without salary-derived inputs, supporting forecasting-oriented surveillance and early-warning dashboards. Full article

Alzheimer’s disease (AD) is increasingly recognized as a disorder that extends beyond amyloid-β (Aβ) and tau pathology. To this end, growing evidence suggests that aberrant neuronal cell cycle re-entry (CCR) may contribute to neurodegeneration. To investigate this mechanism, we profiled the expression of 84 cell cycle-related genes in the brains of aged APP/PS1 mice, a widely used transgenic model of AD, and compared them with age-matched non-transgenic littermates. Our analysis revealed 32 differentially expressed genes (DEGs), 8 of which exhibited significant changes (fold change > 2, p < 0.05). Several of these DEGs, including CDC7 and CCNC, displayed consistent dysregulation in human AD brains as assessed using the AMP-AD knowledge portal, supporting their translational relevance. Furthermore, integration with miRNA prediction analyses identified candidate post-transcriptional regulators of these DEGs, highlighting novel layers of regulation. Collectively, our results provide the first systematic overview of cell cycle gene dysregulation in aged APP/PS1 mice, establish cross-species concordance with human AD, and propose miRNA–gene interactions as potential contributors to neuronal vulnerability. These findings underscore the importance of cell cycle pathways in AD pathogenesis and point to new avenues for therapeutic exploration. Full article

The AlimurgITA portal is a user-friendly and effective tool for researching Wild Edible Plants (WEPs). It provides valuable information on alimurgic plant species, aiding conservation and potential applications (agricultural, food, etc.). Users can interact with authors to report errors and contribute to the knowledge base regarding local uses. The authors will update the site every six months to include new data. Currently, the online database contains data on 1116 taxa used in 20 Italian regions: updated scientific name and link to the site Acta Plantarum, family, main synonyms, common name in Italian and regional dialect, chorotype, life form, a map showing the regions where it is known to be used, the part used, how it is used, and the bibliography. From the home page, you can search for taxa by scientific name, and there are pages dedicated to summaries of the entries: scientific name, family, chorotype, life form, method of use, and part used. Additionally, within the FuD WE PIC Project, the AlimurgITA entity list is being integrated with Italian vegetation data from the European Vegetation Archive to model WEPs richness, identify diversity hotspots, and explore the relationship between WEPs diversity and habitat types. Full article

Foot and mouth disease is a contagious viral disease infecting ungulates, with great economic impact on farmers’ income; it is primarily controlled using inactivated vaccines, which have certain limitations, such as short-lived immunity and a lack of mucosal immunity at the portals of virus entry. The present approach aims to exploit the efficiency of chitosan nanoparticle-encapsulated inactivated type ‘O’ FMDV antigen (FMDV-CS-NPs) to induce mucosal and systemic immune responses in a guinea pig animal model through intranasal and intramuscular administration in comparison with the conventional inactivated, mineral oil-adjuvanted vaccine that is administered systemically. In this study, the FMDV-CS-NPs were prepared by ionotropic gelation, followed by incubation; were characterized for their physical properties and in vitro antigen release; and were found to encapsulate a good amount of antigen. The prepared nanoparticles were assessed for their ability to induce humoral and cell-mediated immune responses by SNTs; indirect ELISAs for serum IgG, IgG1, and IgG2; and nasal washing sIgA and lymphocyte proliferation assays. The preparation induced comparatively more measurable sIgA and systemic immune responses with the intranasal and intramuscular routes of administration, respectively, which are attributable to a specific interaction between the positively charged chitosan and the negatively charged mucosal surface and cell membrane. The challenge infection protected 87.5% of the animals in the FMDV-CS-NP I/M group, followed by 77.7% in the FMDV-CS-NP I/N and inactivated vaccine groups. The outcomes of this study in guinea pigs highlight that chitosan nanoparticle-based vaccine formulations could be employed as a promising antigen delivery system for targeted delivery, devoid of any adverse effect, to induce protective immune responses. Full article

Parasitic infections, such as those caused by the myxozoans Myxobolus cerebralis and Tetracapsuloides bryosalmonae, pose major threats to wild and farmed salmonids due to severe tissue damage and impairment of the host immune system. While individual infections have been studied, limited information is available on the host response during co-infection. This study investigated the transcriptomic immune response of rainbow trout (Oncorhynchus mykiss) during single and sequential co-infections with M. cerebralis and T. bryosalmonae using RNA-seq. Trout were exposed to single infections (Mc or Tb) followed by co-infections (Mc⁺ or Tb⁺). Fish were sampled at 31 days post-single infection (1 day post-co-infection). RNA from gill and caudal fin (portal of parasite entry) was sequenced, followed by differentially expressed genes (DEGs) identification and GO and KEGG enrichment. In the caudal fin, Mc⁺ (1 day after co-infection with T. bryosalomne) fish showed mild immune activation with C4B upregulation, while Tb⁺ fish exhibited a stronger response involving IFI44, ISG15, RSAD2, and TLR7 signaling. In gills, Mc⁺ fish showed moderate cytokine-related gene upregulation, while Tb⁺ (1 day after co-infection with M. cerebralis) fish displayed increased expression of humoral response genes (C3, immunoglobulin pathways) but suppression of genes involved in B cell development. These results indicate that the order of infection shapes the outcome of the host immune response, offering candidate targets at the host–pathogen interface. Full article

CD9 protein belongs to a family of proteins called tetraspanins, so named for their four-transmembrane-spanning architectures. These proteins are located in domains in the plasmatic membrane, called tetraspanin-enriched microdomains (TEMs). Several proteases and cellular receptors for virus entry cluster into TEMs, suggesting that TEMs are preferred virus entry portals. Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates virus attachment and entry into cells by binding to human angiotensin-converting enzyme 2 (ACE-2). In addition, the secretory, type-I membrane-bound SARS-CoV-2 S protein is synthesized as a precursor (proS) that undergoes posttranslational cleavages by host cell proteases, such as furin and TMPRSS2. Moreover, it has been shown that neuropilin-1 (NRP1), which is known to bind furin-cleaved substrates, potentiates SARS-CoV-2 infectivity. Our results indicate that CD9 facilitates SARS-CoV-2 infection. In addition, we show how knocking out CD9 leads to a decrease in the expression of NRP1, a protein that improves SARS-CoV-2 infection. Furthermore, we show that CD9 colocalizes with ACE-2, NRP1, furin, and TMPRSS2 at the plasma membrane; that the absence of CD9 decreases the expression of these proteins on the plasma membrane CD9-enriched microdomains, and that CD9 interacts with ACE2. In conclusion, our data suggest that CD9 facilitates SARS-CoV-2 infection and that CD9 brings together different host proteins involved in SARS-CoV-2 attachment and entry into host cells, such as ACE2, NRP1, furin, and TMPRSS2. Importantly, the fact that a blocking antibody targeting CD9 can effectively reduce SARS-CoV-2 titers highlights not only the mechanistic role of CD9 in viral entry but also offers translational potential, suggesting that tetraspanin-targeting antibodies could be developed as therapeutic agents against SARS-CoV-2 and possibly other coronaviruses, with meaningful implications for clinical intervention. Full article

In vivo dosimetry (IVD) is a vital component of modern radiotherapy, ensuring accurate and safe delivery of radiation doses to patients by measuring dose parameters during treatment. This paper provides a comprehensive overview of IVD, covering its fundamental principles, historical development, and the technologies used in clinical practice. Key techniques, including thermoluminescent dosimeters (TLDs), optically stimulated luminescent dosimeters (OSLDs), diodes, metal-oxide-semiconductor field-effect transistors (MOSFETs), and electronic portal imaging devices (EPIDs), are discussed, highlighting their clinical applications, advantages, and limitations. The role of IVD in external beam radiotherapy, brachytherapy, and pediatric treatments is emphasized, particularly its contributions to quality assurance, treatment validation, and error mitigation. Challenges such as measurement uncertainties, technical constraints, and integration into clinical workflows are explored, along with potential solutions and emerging innovations. The paper also addresses future perspectives, including advancements in artificial intelligence, adaptive radiotherapy, and personalized dosimetry systems. This entry underscores the critical role of IVD in enhancing the precision and reliability of radiotherapy, advocating for ongoing research and technological development. Full article

Optic neuritis is an inflammatory demyelinating disease of the optic nerve that often occurs in multiple sclerosis (MS) patients. Sixty percent of patients develop some level of permanent visual loss due to retinal ganglion cell (RGC) damage following optic neuritis, with no known treatment to prevent this loss. Prior studies showed that MP201, a prodrug of 2,4-dinitrophenol (DNP) administered in the experimental autoimmune encephalitis (EAE) mouse model of MS attenuated optic neuritis with preserved vision, increased retinal ganglion cell (RGC) survival, decreased axon loss, and reduced demyelination. Oral administration of MP201, which converts to active form DNP after entry in the portal vein, decreases mitochondrial-derived reactive oxygen species (ROS) and restores calcium homeostasis, which are both implicated in many neurodegenerative diseases. Due to the established therapeutic benefits of prodrug MP201 in EAE mice, we hypothesized that administration of DNP itself may also have significant potential for therapeutic effects. Here, effects of varying doses of DNP treatment in EAE mice were assessed by the extent of spinal cord paralysis, optokinetic response (OKR), RGC survival, and optic nerve demyelination and inflammation. Results show that daily oral doses of 5-10 mg/kg DNP initiated after onset of EAE can significantly reduce spinal cord paralysis, a marker of the EAE MS-like disease, by day 42 after disease induction. DNP treatment significantly reduces RGC loss induced by optic neuritis in EAE mice; however, effects of DNP do not significantly improve visual function, or optic nerve demyelination and inflammation. Current studies show DNP treatment promotes increased RGC survival, but continued inflammation and demyelination likely reduce visual function, suggesting future studies examining combination therapy of DNP with anti-inflammatory agents may be warranted. Full article

Due to the poor stability of the roof and floor of the roadway in the 3-1 coal seam of Chahasu Coal Mine, traditional gob-side entry retaining (GER) methods fail to meet the production safety requirements. To address this, a GER technology using paste backfill was proposed. This study reveals the stability mechanism of the surrounding rock in GER with paste backfill through theoretical analysis, numerical simulation, and industrial experiments. First, theoretical analysis was conducted to determine the overburden movement characteristics under varying backfill ratios. Uniaxial compressive tests on the paste material demonstrated that its bearing capacity reaches a relatively stable state after 14–28 days of curing. Second, numerical simulations were performed to study the deformation patterns of the surrounding rock and mine pressure characteristics under backfill ratios of 65%, 75%, 85%, and 95%. The Strain-Softening model was used to calibrate the backfill material parameters. The results showed that as the backfill ratio increased, the support provided by the backfill material improved, leading to enhanced bearing capacity of the overlying strata, reduced mine pressure intensity, significantly decreased deformation of the roadway, and substantially improved stability of the surrounding rock. Third, under a backfill ratio of 95%, the evolution of the abutment stress during face advancement was investigated. It was found that as the working face advanced, the backfill material and the overlying strata gradually formed a stable composite structure, with the abutment stress in the mining area stabilizing over time. Finally, to address the issue of insufficient initial strength and limited support capacity of the paste backfill material, a comprehensive control system for surrounding rock stability was proposed. This system integrates a basic bolt-mesh-cable support structure with localized reinforcement using portal hydraulic supports. Field industrial practices demonstrated that after applying this comprehensive control technology, the convergence of roof and floor was approximately 190 mm and the convergence of two ribs was about 140 mm, effectively ensuring the stability of surrounding rock in GER with paste backfill working face. Full article

This paper is a theoretical exploration that works through a global Indigenous consciousness. As a critically reflexive story work and auto-ethnographic contemplation it begins by confronting a presumed genealogy in a post-apocalyptic world of coloniality through a global Indigenous lens. Extending beyond racially legalised genealogical ancestry, the metaphysics of indigeneity in the context of Western modernity can be re-positioned as a metaphor of past future human-being-ness or person/people-hood. Global Indigeneity and Indigenous metaphysics are framed as a portal and entry beyond coloniality through fugitive sociality and subversive relationality. Confronting the tensions of colonially purist and racially essentialist categories of indigenous identity, lineages of the post-post-apocalyptic world are forming in the enduring social connections embodied in an Indigenous genealogical consciousness of the present. Full article

Hepatitis E virus (HEV) infection is typically a self-limiting, acute illness that spreads through the gastrointestinal tract but replicates in the liver. However, chronic infections are possible in immunocompromised individuals. The HEV virion has two shapes: exosome-like membrane-associated quasi-enveloped virions (eHEV) found in circulating blood or in the supernatant of infected cell cultures and non-enveloped virions (“naked”) found in infected hosts’ feces and bile to mediate inter-host transmission. Although HEV is mainly spread via enteric routes, it is unclear how it penetrates the gut wall to reach the portal bloodstream. Both virion types are infectious, but they infect cells in different ways. To develop personalized treatment/prevention strategies and reduce HEV impact on public health, it is necessary to decipher the entry mechanism for both virion types using robust cell culture and animal models. The contemporary knowledge of the cell entry mechanism for these two HEV virions as possible therapeutic target candidates is summarized in this narrative review. Full article