Search Results (604)

Cellular components and inflammatory mediators involved in the transmigration of HTLV-1-infected cells across the blood–brain barrier (BBB) are not fully understood. This study proposes a BBB model to identify the immunological mechanisms associated with HTLV-1 pathogenesis. PBMCs from individuals with HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) (n = 4) or HTLV-1-infected individuals without HAM/TSP (n = 4) were isolated. An indirect cell co-culture was performed between human brain microvascular endothelial (hBMEC) cells and neuroblastoma (SH-SY5Y) cells. PBMCs from healthy individuals (n = 4) were used as a negative control, and MT-2 cells were used as a positive control. Supernatants and cells were collected to quantify inflammatory cytokines and assess cell death after 24, 48, and 72 h. Multiple comparisons were performed using the Kruskal–Wallis test, followed by Fisher’s LSD post hoc analysis. We observed that the production of cytokines IL-6, IL-8, IL-1β, TNF, IL-10, and IL-12p70, as well as the rate of neuronal death, was higher in co-cultures mimicking HAM/TSP carriers compared to HTLV-1-infected individuals without HAM/TSP and controls. Our results suggest that the HAM/TSP condition induces the release of IL-6, IL-8, IL-1β, TNF, IL-10, and IL-12p70, along with the infiltration of mononuclear cells, which may lead to neuronal death. Full article

Background/Objectives: DNA2 is a conserved nuclease–helicase that plays a crucial role in DNA replication and repair by responding to replication stress. Previous studies have established the role of DNA2 in Okazaki fragment processing, the recovery of stalled replication forks, and double-strand break repair. This study investigates the role of Drosophila melanogaster Dna2 in response to exogenous DNA damage and replication stress as well as during developmental stages involving intensive DNA replication. Methods: We used the Drosophila mutant alleles, Dna2^D1 and Dna2^D2, which differ in the presence of the helicase 1A domain, to assess sensitivity to mutagens that cause various types of replication stress and DNA damage. We examined reproductive fitness through Mendelian ratio calculations, fecundity, egg viability assays, and assessed DNA damage via immunostaining of ovarian germaria. Lifespan assays were also conducted to examine adult survival. Results: Dna2 mutants demonstrated significant sensitivity to replication stress induced by MMS, hydroxyurea, topotecan, and nitrogen mustard. Dna2^lS/S1 mutants exhibited higher survival than Dna2^lS/D2 upon exposure to topotecan and bleomycin, suggesting a possible helicase-specific role in damage response. Mutants exhibited decreased fecundity, reduced egg viability, and elevated DNA damage in mitotically active germline cells. Adult lifespan was not reduced in Dna2 mutants, implying potential compensatory stress-response mechanisms. Conclusions: Our findings support a requirement of Dna2 in managing replication stress during critical developmental phases in Drosophila. These insights clarify the nuanced contributions of the nuclease and helicase domains of DNA2, suggesting potential domain-specific functions in genomic stability and repair mechanisms. This work provides a foundation that will enable future researchers to further dissect the complex roles of DNA2 in replication and repair pathways. Full article

Lumpy skin disease (LSD) is an invasive infectious disease caused by the lumpy skin disease virus (LSDV), which is detrimental to the production of cattle. LSDV encodes about 156 proteins, most of whose functions are still unknown. In this study, we found that the ORF137 protein was identified as one of the strongest inhibitors of IFN-β and ISG expression, determining LSDV ORF137 as a negative regulator of interferon (IFN) β signaling. Further evidence suggests that ORF137 interacts with the signal transduction factor IRF3 and inhibits the activation of IFN-β signaling by reducing Phospho-IRF3 (p-IRF3). Further investigation indicated that overexpression of ORF137 in BMEC could significantly inhibit the transcription of IFN-β and ISGs, thereby promoting the replication of LSDV. More importantly, through homologous recombination, we deleted the ORF137 gene from the LSDV/FJ/CHA/2021 strain and constructed the recombinant strain LSDV-ΔORF137-EGFP. Compared with the parental strain, LSDV-ΔORF137-EGFP showed a weakened effect on inhibiting the transcription of IFN-β and ISGs and a reduced replication level in infected MDBK cells. In summary, ORF137 facilitates LSDV replication by targeting IRF3 to inhibit IFN-β signaling. Our findings reveal a new mechanism by which LSDV suppresses the host antiviral response, which may facilitate the development of attenuated live vaccines for LSDV. Full article

Although the anticaries properties of phosphate-based compounds have been extensively investigated in recent years, their potential cytotoxic effects remain underexplored. This study evaluated the cytotoxicity of solutions containing sodium trimetaphosphate (TMP), sodium hexametaphosphate (HMP), or calcium glycerophosphate (CaGP). NIH/3T3 fibroblasts were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum and maintained at 37 °C, 100% humidity, and 5% CO₂. The cells were seeded in 96-well plates at a density of 10⁴ cells per well and incubated for 24 h. Subsequently, different dilutions of 10% TMP, HMP, or CaGP solutions were applied to the cells. Cell viability was assessed at 24/48 h using the MTT assay. The data were subjected to two-way ANOVA and Fisher’s LSD test. Spearman’s rank correlation was performed. HMP dilutions led to significantly lower cell viability compared to the other compounds, regardless of the incubation period. TMP maintained higher cell viability from 1/8 dilution onwards, regardless of the incubation time. For CaGP, an increase in cell viability was observed at 1/8 dilution after 24 h. In conclusion, TMP and CaGP demonstrated reduced cytotoxicity at higher dilutions compared to HMP, suggesting their potential as promising candidates for the development of novel biomaterials. Full article

Schizophrenia is a highly polygenic disease, and several genetic variants associated with the disease converge on altered synaptic homeostasis. In particular, the gene encoding complement component 4 (C4) showed the strongest association with schizophrenia, and this protein is involved in complement-dependent and microglia-mediated synaptic pruning. As a matter of fact, microglia are overactive in schizophrenia, and reduced synaptic arborization, especially in the prefrontal cortex (PFC), is an established hallmark of schizophrenia, likely associated with gray matter loss, cortical thinning, hypofrontality, and deficit syndrome. The recent development of a new radioligand targeting the synaptic vesicle glycoprotein 2A (SV2A) demonstrated in vivo lower synaptic density at the PFC level in individuals with schizophrenia, corroborating the synaptic hypothesis of thedisease first proposed by Feinberg in 1982. Interestingly, robust preclinical evidence (in vitro and animal models) showed the ability of psychedelics to promote neuroplasticity and synaptogenesis, potentially counteracting the excessive synaptic loss, restoring volume loss, and possibly explaining improvements in negative and cognitive symptoms described by old clinical studies. Overall, microdoses should be explored first as a possible treatment in a selected sample of patients affected by deficit schizophrenia, followed by low and full doses if encouraging results were to emerge. Full article

Turfgrass provides significant functional, environmental, recreational and aesthetic benefits; however, its high management inputs raise sustainability concerns due to intensive irrigation, fertilization and mowing. The aim of this study is to evaluate whether adopting a new mowing technology can support or enhance current low-input strategies in turfgrass management, such as reducing synthetic fertilization and deficit irrigation. This study was conducted from September 2023 to October 2024 at the Centre for Research on Turfgrass for Environment and Sports (CeRTES) in Pisa, Italy. Two turf compositions, pure tall fescue and tall fescue–microclover mixture, were managed using an autonomous mower operating daily at three mowing heights, 20, 40 and 60 mm. Turf quality, color, the NDVI, weed cover, leaf morphology, and clover presence were assessed throughout the growing season, including a drought and recovery period. The experimental design consisted of a two-factor split-plot randomized complete block design with four replications, and the statistical approach used was two-way and one-way ANOVAs with Fisher’s LSD at p = 0.05. The results of the study indicated that, under conditions where an autonomous mower was set to operate on a daily basis, the selected mowing height had minimal influence on drought response or recovery when water availability was a limiting factor. Furthermore, when subjected to the lowest mowing heights, the legume species included in the turfgrass mix demonstrated strong resilience, maintaining its presence and performance. In addition, when mowing with a high mowing frequency and at low mowing heights, the overall quality of the turfgrass appeared enhanced. These results serve as an important starting point for considering autonomous mowing technology as an innovative strategy in advancing toward turf management systems that prioritize sustainability and efficient use of resources. Full article

This study investigated the effects of low-dose 1cp-LSD, a prodrug of LSD, on canine anxiety, while exploring the influence of owner psychopathology on treatment outcomes. Seven dogs exhibiting anxiety-related behaviors were recruited and received 2.5, 5, or 10 µg of 1cp-LSD orally every three days for 30 days. One additional dog, which did not meet clinical criteria for anxiety but whose owner perceived it as anxious, received a placebo (saccharin) as an observational case. Anxiety levels were assessed using validated scales at baseline, post-treatment, and one month after treatment cessation. Owners’ neuroticism and psychopathological dimensions were evaluated using the IPIP and SA-45 scales. Linear regression analyses examined associations between anxiety reduction, administered dose, and owner psychological traits. A significant reduction in separation anxiety scores was observed post-treatment (mean: 11.3 ± 3.0, p = 0.023). Higher 1cp-LSD doses correlated with greater anxiety reduction (B = −1.15, 95% CI = [−2.29, −0.003], p = 0.050). Additionally, higher owner psychoticism scores were associated with smaller improvements in canine anxiety (p = 0.035). Anxiety levels remained low one month after treatment, with significant associations between canine anxiety and the owners’ hostility, interpersonal sensitivity, and paranoid ideation. These findings support the potential role of low-dose serotonergic psychedelics in managing canine anxiety and suggest an association between caregiver psychological traits and treatment outcomes. The sustained reduction in anxiety behaviors also suggests a meaningful and lasting improvement in animal welfare. However, significant results should be interpreted cautiously due to the small sample size. Further blinded, controlled studies are needed to validate these preliminary observations and assess broader applications in veterinary behavioral medicine. Full article

Lumpy skin disease (LSD) is a contagious animal disease caused by the lumpy skin disease virus (LSDV). LSD can be transmitted through direct, indirect and insect vectors, severely impacting global cattle production. To evaluate difference in immune response and gut microbiota of 30 healthy 16–18 months old Angus cattle, treated with live attenuated or inactivated goatpox vaccine virus strains. The cattle were randomly divided into three groups (10 animals per group): Group A—goatpox live attenuated vaccine; Group B—goatpox inactivated vaccine; Group C—control (saline). Blood samples were collected on days 14, 28, 42, and 56 post-vaccination to assess hematological parameters, serum biochemical indices, and antibody levels; rectal feces were collected on day 28 for 16S rRNA analysis of gut microbiota. Results showed that, on day 28, both Group A and Group B reached their peak antibody levels (the log₁₀ value of Group A was 2.6, and that of Group B was 2.7), with about 90% of the cattle in each vaccinated group testing antibody-positive. On day 42, Group B retained 90% seropositivity, whereas Group A declined to 80%. Significantly altered in vaccinated Groups (A and B) compared to controls on days 14 and 28 (p < 0.05). Hematological parameters (PLT, NEUT, and LYM) and serum biochemical indices (AST, TP, and GGT) were elevated early after vaccination but returned to baseline by days 42 and 56.Which returned to control levels by days 42 and 56. On day 28 post-vaccination, Vaccinated cattle showed significantly higher gut microbiome richness and diversity than unvaccinated controls (p < 0.05). At the phylum level, the dominance was observed in Firmicutes and Bacteroidetes: the relative abundances were 62.90% and 29.65% in Group A, 60.84% and 30.13% in Group B, and 49.99% and 39.73% in Group C, respectively. These findings indicate that the inactivated goatpox vaccine elicits a more durable and stable antibody response, maintaining higher specific antibody titers, and induces more pronounced shifts in the gut microbiota community structure at the phylum level compared with the live attenuated vaccine. Full article

Dementia is a progressive neurodegenerative disease which is characterised by cognitive decline, memory loss, and behavioural changes. Patients suffering from dementia often experience emotional distress, sadness and depression which also impacts the wellbeing of their caregivers. Recent research has explored the potential of psychedelics, such as psilocybin and LSD, when treating various mental health conditions. Psychedelics are known to alter perception, mood and cognition by affecting serotonin receptors in the brain. Studies suggest that psychedelics may be a promising treatment for dementia patients and promote neuroplasticity, reduce neuroinflammation and enhance cognitive flexibility. These effects could potentially lead to a reduction in the progression of neurodegenerative diseases and improve the patients’ quality of life. Additionally, psychedelics might contribute to the prevention of dementia by fostering brain health and resilience against age-related decline. The application of psychedelics in dementia care might pose significant safety and ethical concerns. The present paper provides a narrative review of the existing literature on the use of psychedelics in treatment of dementia and its different types (Alzheimer’s) with the aim to raise awareness on the topic from a critical perspective. Full article

This study aimed to investigate cattle farmer livelihoods that relate to cattle welfare in the region with the newly emerging Lumpy Skin Disease (LSD) in Indonesia. A semi-structured interview survey was conducted with randomly selected cattle farmers (n = 102), in Riau. Cattle were bled for analysis of LSD-post-vaccinal seroconversion. The Sustainable Livelihood Framework (SLF) was used; data on livelihood assets, activities, and outcomes were analysed using Multiple Correspondence Analysis (MCA), two-step clustering, and the radar chart of asset possessions. The survey showed that vaccination and veterinary services covered 82.4% and 90.2% of farms. Seroconversion was detectable in vaccinated (15.0%, n = 173) and in non-vaccinated animals (23.1%, n = 13). Farmers mostly fed only grass to cattle (92.2%), with neither pastoral management nor ad libitum water provision. The MCA and cluster analyses indicated that cattle shelter roofing and flooring and manure disposal were the most important markers of the community’s livelihood. Poverty among cattle farmers was 23.5%. The cluster with lower income per capita had lower quality of shelter roofing and flooring, a lack of regular manure disposal, jobless second children, and the lowest possession of natural and physical assets. Helping to possess natural and physical assets might improve cattle farmers’ well-being and cattle welfare. Full article

A growing body of evidence confirms that non-mutational epigenetic reprogramming constitutes an important hallmark of cancer, contributing to the heterogeneity and phenotypic plasticity observed in cancers. Among the many epigenetic modulators, histone lysine demethylases (KDMs) have emerged as promising targets for pharmacological inhibition in cancer treatment. KDMs were found to be frequently overexpressed and/or hyperactivated in cancer cells, and their inhibition was shown to result in the inhibition of cancer cell growth both in vitro and in vivo. The inhibition of Lysine-specific histone demethylase 1A (LSD1), KDM3, KDM4, KDM5, and KDM6 may affect cell survival, proliferation, motility, and apoptosis induction. Importantly, KDM inhibitors can be used as modulators of anti-cancer immune response and sensitivity to radiation and chemotherapy. This narrative review aims to present the most recent evidence documenting the anti-cancer potential of KDM inhibitors. Full article

This study determined the water-use efficiency for post-weaning growth performance of beef cattle of different frame sizes under intensive production systems. A total of 33 beef cattle weaners of three different frame sizes (small, medium, and large) were randomly allocated individually to metabolic pens. Feed and water were provided ad libitum. The water intake (WI), feed intake (FI), and weight were measured across different feeding phases (starter, grower, and finisher). Water consumption (WC) average daily gain (ADG), weight gain (WG), water intake efficiency (WIE), water footprint per animal (WFP/AU), and WFP/kg were computed. General Linear Model of Statical Analysis software (SAS) version 9.4 was used to analyse the data, and the means were separated using Fisher’s LSD test. The results showed that large-frame beef cattle had significantly higher (p < 0.05) WT_f. (412.73 ± 27.27 kg) and WI (3394.09 ± 156.3 L), but also the largest WFP/AU (4407 ± 197.22 L). The medium-frame cattle achieved the highest ADG (1.48 ± 0.14 kg/day) and a moderate WIE (20.15 ± 2.18 L/kg gain), indicating an optimal trade-off between productivity and water use. The small-frame beef cattle exhibited the best WCE (0.051 ± 0.005 kg/L) and the lowest WFP/AU (3822 ± 197.22 L), highlighting superior water-use adaptability. Pearson’s correlation revealed that WCE was positively associated with ADG (r = 0.499; p < 0.05) and negatively with WIE (r = −0.987; p < 0.05). These findings suggest that medium-frame beef cattle provided a balanced compromise between growth performance and resource efficiency, making them more suitable for sustainable production in water-limited environments. Full article

Simultaneous Localization and Mapping (SLAM) is a fundamental technique in mobile robotics, enabling autonomous navigation and environmental reconstruction. However, dynamic elements in real-world scenes—such as walking pedestrians, moving vehicles, and swinging doors—often degrade SLAM performance by introducing unreliable features that cause localization errors. In this paper, we define dynamic regions as areas in the scene containing moving objects, and dynamic features as the visual features extracted from these regions that may adversely affect localization accuracy. Inspired by biological perception strategies that integrate semantic awareness and geometric cues, we propose Instance-level Point-Line SLAM (IPL-SLAM), a robust visual SLAM framework for dynamic environments. The system employs YOLOv8-based instance segmentation to detect potential dynamic regions and construct semantic priors, while simultaneously extracting point and line features using Oriented FAST (Features from Accelerated Segment Test) and Rotated BRIEF (Binary Robust Independent Elementary Features), collectively known as ORB, and Line Segment Detector (LSD) algorithms. Motion consistency checks and angular deviation analysis are applied to filter dynamic features, and pose optimization is conducted using an adaptive-weight error function. A static semantic point cloud map is further constructed to enhance scene understanding. Experimental results on the TUM RGB-D dataset demonstrate that IPL-SLAM significantly outperforms existing dynamic SLAM systems—including DS-SLAM and ORB-SLAM2—in terms of trajectory accuracy and robustness in complex indoor environments. Full article

Lumpy skin disease (LSD) poses a significant transboundary threat to livestock health and productivity, especially in regions where vector-borne transmission is a major driver of spread. Environmental and climatic factors are recognized as critical determinants of LSD transmission dynamics. This study aimed to model the environmental suitability for LSD across Thailand using a maximum-entropy approach. Outbreak data from 2021 to 2023 were analyzed alongside bioclimatic variables, land cover, normalized difference vegetation index (NDVI), and cattle population density. The model produced an area under the curve (AUC) value of 0.699 (~0.70), indicating moderate predictive performance. Based on variable contribution, land cover (65%), cattle density (25%), and NDVI (3%) were identified as the most influential predictors of environmental suitability for LSD. The resulting risk map identified central and northeastern Thailand as the most suitable regions for disease occurrence. These findings provide valuable insights to support risk-based surveillance, improve veterinary resource allocation, and enhance early warning systems for effective LSD prevention and control in Thailand. Full article

Numerous individuals suffer from mental health issues including depression and anxiety, resulting in substantial societal burden. Data suggests individuals are choosing to self-medicate with Novel Psychoactive Substances (NPS); however, this phenomenon is poorly understood. We aimed to investigate which NPS are being used to self-medicate, evaluate their perceived effectiveness and examine influencing factors. Data from respondents (n = 274) (Mean Age [SD] = 29.8 ± 9.1, Male = 71%, Female = 18%, non-binary 5%) were collected via an online survey, with five participants (male = 2; nonbinary = 3) undertaking further semi-structured interviews and the data examined using a Framework analysis. NPS used included bromazolam, etizolam, clonazolam, 1P-LSD and 2-FDCK. Individuals perceived self-medication to be more effective than conventional treatment (p < 0.001). A Framework analysis identified the following themes surrounding mood and anxiety disorder self-medication: (1) depression being chronic, treatment resistant and often comorbid; (2) individuals attempting to mimic existing treatments; (3) individuals having high levels of pharmacological knowledge; (4) difficulties in controlling benzodiazepine self-medication. This study brings important insight into self-medication practices with NPSs, adding to data demonstrating an increase in bromazolam use. Data suggests self-medication follows conventional treatment and, therefore, we outline the importance of affordable emerging treatment options for depression and anxiety. Full article