Search Results (338)

Gestational diabetes mellitus (GDM), a prevalent metabolic disorder in pregnancy, induces maternal hyperglycemia and elevates fetal malformation risks, particularly in craniofacial development. To investigate the underlying mechanisms, we employed zebrafish as a model organism due to its conserved skeletal development pathways with humans. Zebrafish embryos were exposed to 3.5% and 4% high glucose (HG) from 10–80 h post-fertilization (hpf). Through comprehensive analyses including Alcian blue staining, confocal microscopy, and molecular assays, we demonstrated that HG exposure caused significant developmental abnormalities including growth retardation, craniofacial cartilage malformations, and impaired cranial neural crest cells (CNCCs) migration and proliferation. Mechanistically, HG induced reactive oxygen species (ROS) accumulation and oxidative stress while downregulating critical CNCCs markers (dlx2 and tfap2a). These molecular alterations correlated with histomorphological defects in pharyngeal arch cartilage, particularly in ceratohyal formation. Our findings establish that glucose disrupts craniofacial development through oxidative stress-mediated CNCCs dysfunction, providing novel mechanistic insights into GDM-associated skeletal abnormalities and potential therapeutic targets. Full article

Perfluorooctane sulfonate (PFOS) is a representative persistent organic pollutant that exerts toxic effects on aquatic organisms. As an alternative to PFOS, sodium p-perfluorous nonenoxybenzene sulfonate (OBS) has been frequently detected in aquatic environments and human tissues in recent years. However, its toxic effects on aquatic organisms and potential health risks to humans remain unclear. Zebrafish embryos are transparent and amenable to in vivo manipulation and observation. Therefore, in the present study, we investigated its developmental toxicity in zebrafish embryos, with PFOS as the positive control. We exposed zebrafish embryos to different concentrations of OBS (15, 20, and 25 mg/L) and PFOS (15 mg/L) for 2–168 h post fertilization (hpf) and then examined physiological and gene expression changes. At 24 hpf, spontaneous twitches in the 25 mg/L OBS group decreased to (5 ± 0.34)/min. By 48 hpf, the 20 mg/L OBS group’s hatching rate was (47.78 ± 2.22)%, significantly lower than the control. At 72 hpf, heart rates in both the PFOS and OBS groups were elevated, at 82 ± 0.6, 84.5 ± 0.5, 89.4 ± 0.3, and 93.7 ± 0.4, respectively. Similarly to PFOS, OBS induced developmental toxicity in zebrafish embryos. In addition, both OBS and PFOS exposure downregulated the expression level of anti-apoptotic Bcl-2 in zebrafish embryos, with a notable 0.53-fold decrease observed in the 25 mg/L OBS group. Conversely, they upregulated the expression levels of pro-apoptotic Bax, Caspase-3, and Caspase-9, with Caspase-3 expression increasing 1.14-, 1.5-, and 1.7-fold in the 15 mg/L PFOS, 20 mg/L OBS, and 25 mg/L OBS groups, respectively. These OBS- and PFOS-induced changes in gene expression increased apoptosis, suggesting that OBS can induce developmental toxicity in zebrafish embryos, and that its effect is comparable to that of PFOS. Therefore, considering its aquatic toxicity, measures aimed at limiting or remediating OBS pollution in the environment are necessary. Full article

Mosquitoes detect sound with their antennae, which transmit vibrations to mechanosensory neurons in Johnston’s organ. However, their auditory system is exposed to low-frequency noise such as convective and thermal noise, as well as noise induced by flight, which could impair sensitivity. High-pass filters (HPFs) may mitigate this issue by suppressing low-frequency interference before it is transformed into neuronal signals. We investigated HPF mechanisms in Culex pipiens mosquitoes by analyzing the phase–frequency characteristics of the primary sensory neurons in the Johnston’s organ. Electrophysiological recordings from male and female mosquitoes revealed phase shifts consistent with high-pass filtering. Initial modeling suggested a single HPF; however, experimentally obtained phase shifts exceeding –90° required revising the model to include two serially connected HPFs. The results showed that male mosquitoes exhibit stronger low-frequency suppression (~32 dB at 10 Hz) compared to females (~21 dB), with some female neurons showing negligible filtering. The estimated delay in signal transmission was ~7 ms for both sexes. These findings suggest that HPFs enhance noise immunity, particularly in males, whose auditory sensitivity is critical for mating. The diversity in female neuronal tuning may reflect broader auditory functions in addition to mating, such as host detection. This study provides indirect evidence for HPFs in mosquito hearing and highlights sex-specific adaptations in auditory processing. The proposed dual-HPF model improves our understanding of how mosquitoes maintain high auditory sensitivity in noisy environments. Full article

Tetramethyl bisphenol A (TMBPA), a novel alternative to Bisphenol A, is widely used as an industrial flame retardant and a raw material for tetramethyl polycarbonate plastics. With the increasing use of TMBPA, its aquatic ecological risks remain unclear. Therefore, this study investigated the developmental toxicity of TMBPA using zebrafish (Danio rerio) as a model, exposing embryos to 0.5, 5, 50, and 200 μg/L TMBPA for 120 h. The results showed that treatment with 5, 50, and 200 μg/L TMBPA decreased the hatching rate of zebrafish embryos at 48 h post-fertilization (hpf), while no significant difference was observed at 72 hpf. Meanwhile, TMBPA exposure at all concentrations showed no significant effect on the survival rate. Furthermore, a high concentration of TMBPA (200 μg/L) significantly reduced the total length and suppressed swimming ability in zebrafish larvae. In addition, gene expression analysis revealed impacts on antioxidant system (cat, gpx, mn-sod, keap1, ucp2, nrf2), hypothalamic–pituitary–thyroid (HPT) axis (ttr, ugt1ab, trβ), cardiac developmental (tbx2b, myl7, bmp4, notch1b, amhc), and the hypothalamic–pituitary–adrenal (HPA) axis (pomca and nr3c1). The results indicated that TMBPA exposure adversely disrupted embryo hatching and larval development of zebrafish, accompanied by altering the expression of functional genes in larvae. These results provide further evidence for the potential environmental hazard posed by TMBPA. Full article

As typical environmental hormones, endocrine-disrupting chemicals (EDCs) have become a global environmental health issue of high concern due to their property of interfering with the endocrine systems of organisms. As a commonly used substitute for bisphenol A (BPA), bisphenol E (BPE) has been frequently detected in environmental matrices such as soil and water in recent years. Existing research has unveiled the developmental and reproductive toxicity of BPE; however, only one in vitro cellular experiment has preliminarily indicated potential neurotoxic risks, with its underlying mechanisms remaining largely unelucidated in the current literature. Potential toxic mechanisms and action targets of BPE were predicted using the zebrafish model via network toxicology and molecular docking, with RT-qPCRs being simultaneously applied to uncover neurotoxic effects and associated mechanisms of BPE. A significant decrease (p < 0.05) in the frequency of embryonic spontaneous movements was observed in zebrafish at exposure concentrations ≥ 0.01 mg/L. At 72 hpf and 144 hpf, the larval body length began to shorten significantly from 0.1 mg/L to 1 mg/L, respectively (p < 0.01), accompanied by a reduced neuronal fluorescence intensity and a shortened neural axon length (p < 0.01). By 144 hpf, the motor behavior in zebrafish larvae was inhibited. Through network toxicology and molecular docking, HSP90AB1 was identified as the core target, with the cGMP/PKG signaling pathway determined to be the primary route through which BPE induces neurotoxicity in zebrafish larvae. BPE induces neuronal apoptosis and disrupts neurodevelopment by inhibiting the cGMP/PKG signaling pathway, ultimately suppressing the larval motor behavior. To further validate the experimental outcomes, we measured the expression levels of genes associated with neurodevelopment (elavl3, mbp, gap43, syn2a), serotonergic synaptic signaling (5-ht1ar, 5-ht2ar), the cGMP/PKG pathway (nos3), and apoptosis (caspase-3, caspase-9). These results offer crucial theoretical underpinnings for evaluating the ecological risks of BPE and developing environmental management plans, as well as crucial evidence for a thorough comprehension of the toxic effects and mechanisms of BPE on neurodevelopment in zebrafish larvae. Full article

Objectives: To investigate how the FLASH effect modulates radiation response on multiple developmental endpoints of zebrafish embryos under normoxic and hypoxic conditions, after irradiation with proton beams at a conventional and an ultra-high dose rate (UHDR). Methods: Embryos were obtained from adult zebrafish and irradiated with a 228 MeV proton beam 24 h post-fertilization (hpf) at a dose rate of 0.6 and 317 Gy/s. For the hypoxic group, samples were kept inside a hypoxic chamber prior to irradiation, while standard incubation was adopted for the normoxic group. After irradiation, images of single embryos were acquired, and radiation effects on larval length, yolk absorption, pericardial edema, head size, eye size, and spinal curvature were assessed at specific time points. Results: Data indicate a general trend of significantly reduced toxicity after exposure to a UHDR compared to conventional regimes, which is maintained under both normoxic and hypoxic conditions. Differences are significant for the levels of pericardial edema induced by a UHDR versus conventional irradiation in normoxic conditions, and for eye and head size in hypoxic conditions. The toxicity scoring analysis shows a tendency toward a protective effect of the UHDR, which appears to be associated with a lower percentage of embryos in the high score categories. Conclusions: A radioprotective effect at a UHDR is observed both for normoxic (pericardial edema) and hypoxic (head and eye size) conditions. These results suggest that while the UHDR may preserve a potential to reduce radiation-induced damage, its protective effects are endpoint-dependent; the role of oxygenation might also be dependent on the tissue involved. Full article

Nano- (NPs) and microplastics (MPs) are ubiquitous and raising concerns about their toxicity. A popular model for studying acute toxicity is Danio rerio. This study investigated the acute toxicity in FET test of polystyrene nanoparticles (500 nm, nanoPS) at different concentrations (0.01, 0.1, and 0.2 mg/mL), with different surface groups (non-modified, amine, carboxyl) and discuss the toxicological contribution of commercially added compounds. Different behavioural tests were used to investigate the neurotoxicity of nanoPS and sodium azide: coiling assay test, light–dark preference test, and colour preference test. Sodium azide and other preservatives are often present in commercially available NP and MP solutions frequently used in microplastic toxicity tests, but their effects on the results remain largely unknown. In the FET test, nanoPS did not increase mortality or affect the heart rate or body length. A higher hatching rate was observed at 48 hpf. Although nanoPS showed no acute toxicity, behavioural tests revealed subtle neurotoxic effects (changes in colour preference), suggesting a potential impact on neurological function. Additionally, sodium azide exhibited toxicity, indicating that additives may confound toxicity assessments. This highlights the need for careful consideration of preservatives in nanoparticle research to avoid misleading conclusions. Full article

In this paper, we address the problem of intelligent operation of Distribution Static Synchronous Compensators (D-STATCOMs) in power distribution systems to reduce energy losses and CO₂ emissions while improving system operating conditions. In addition, we consider the entire set of constraints inherent in the operation of such networks in an environment with D-STATCOMs. To solve such a problem, we used three master–slave methodologies based on sequential programming methods. In the proposed methodologies, the master stage solves the problem of intelligent D-STATCOM operation using the continuous versions of the Monte Carlo (MC) method, the population-based genetic algorithm (PGA), and the Particle Swarm Optimizer (PSO). The slave stage, for its part, evaluates the solutions proposed by the algorithms to determine their impact on the objective functions and constraints representing the problem. This is accomplished by running an Hourly Power Flow (HPF) based on the method of successive approximations. As test scenarios, we employed the 33- and 69-node radial test systems, considering data on power demand and CO₂ emissions reported for the city of Medellín in Colombia (as documented in the literature). Furthermore, a test system was adapted in this work to the demand characteristics of a feeder located in the city of Talca in Chile. This adaptation involved adjusting the conductors and voltage limits to include a test system with variations in power demand due to seasonal changes throughout the year (spring, winter, autumn, and summer). Demand curves were obtained by analyzing data reported by the local network operator, i.e., Compañía General de Electricidad. To assess the robustness and performance of the proposed optimization approach, each scenario was simulated 100 times. The evaluation metrics included average solution quality, standard deviation, and repeatability. Across all scenarios, the PGA consistently outperformed the other methods tested. Specifically, in the 33-node system, the PGA achieved a 24.646% reduction in energy losses and a 0.9109% reduction in CO₂ emissions compared to the base case. In the 69-node system, reductions reached 26.0823% in energy losses and 0.9784% in CO₂ emissions compared to the base case. Notably, in the case of the Talca feeder—particularly during summer, the most demanding season—the PGA yielded the most significant improvements, reducing energy losses by 33.4902% and CO₂ emissions by 1.2805%. Additionally, an uncertainty analysis was conducted to validate the effectiveness and robustness of the proposed optimization methodology under realistic operating variability. A total of 100 randomized demand profiles for both active and reactive power were evaluated. The results demonstrated the scalability and consistent performance of the proposed strategy, confirming its effectiveness under diverse and practical operating conditions. Full article

Background: CIC-rearranged sarcoma is a rare and aggressive type of undifferentiated round cell tumor characterized by CIC gene fusion, most commonly CIC::DUX4. This study presents a series of eleven cases, highlighting their clinicopathological features. Methods: Pathology records (2019 to 2024) were searched using “sarcoma with CIC”, identifying eleven cases, of which seven referred cases were initially misdiagnosed. Pathological and clinical analysis was conducted. Treatment was dictated upon multidisciplinary panel discussion based on tumor stage. Follow-up data (1–25 months) was available for all patients. Results: The cohort included six males and five females, with a median age of 43 years (range;14–53), with nine in soft tissue and two in bone. Tumor size ranged from 3.5 cm to 20.0 cm (mean: 9.8 cm). Most cases showed sheets of undifferentiated round- to oval-shaped cells. Two cases showed an Ewing-like pattern, and one case showed spindle cells in a fibrotic stroma transitioning to epithelioid cells. Necrosis was present in nine cases, and mitotic count ranged from 2 to 38/ 10HPFs (mean = 14.2). CD99 was positive in (10/11) cases and WT-1 in (6/9). NKX2.2, S100, and MDM2 were positive in rare cases. CIC::DUX4 fusion was detected in four cases. FISH for CIC gene rearrangement was positive in seven cases, two of them confirmed by methylation analysis. Metastasis at diagnosis was common (n = 8), primarily in the lungs, with later metastasis to the brain and bone. At time of final analysis, eight patients died within a median of 10 months (range: 1–19 months), while three were alive, two with stable disease (for a period of 6 and 25 months) and one with progression after 10 months. Significant correlation was seen between overall survival and the presence of metastasis at diagnosis (p value = 0.03). Conclusions: CIC-rearranged sarcomas are rare, high-grade tumors with predilection for soft tissue. Misdiagnosis is frequent, necessitating molecular confirmation. These tumors are treatment-resistant, often present with lung metastasis, and carry a poor prognosis, especially with initial metastasis. Full article

Background: Butylated hydroxyanisole (BHA) has been extensively used in several commercial industries as a preservative. It causes severe cellular and neurological damage affecting the developing fetus and might induce attention deficit hyperactivity disorder (ADHD). Methods: Zebrafish embryos were subjected to five distinct doses of BHA—0.5, 1, 2, 4, and 8 ppb up to 96 h post fertilization (hpf). Hatching rate, heart rate, and body malformations were assessed at 48 hpf, 72 hpf, and 48–96 hpf, respectively. After exposure, apoptotic activity, neurobehavioral evaluation, neurotransmitter assay, and antioxidant activity were assessed at 96 hpf. At 120 hpf, the expression of genes DRD4, COMT, 5-HTR1aa, and BDNF was evaluated by real-time PCR. Results: BHA exposure showed a delay in the hatching rate and a decrease in the heart rate of the embryo when compared with the control. Larvae exhibited developmental deformities such as bent spine, yolk sac, and pericardial edema. A higher density of apoptotic cells was observed in BHA-exposed larvae at 96 hpf. There was a decline in catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and superoxide dismutase (SOD) activity, indicating oxidative stress. There was a significant decrease in Acetylcholinesterase (AChE) activity and serotonin levels with an increase in concentration of BHA, leading to a dose-responsive increase in anxiety and impairment in memory. A significant decrease in gene expression was also observed for DRD4, COMT, 5-HTR1aa, and BDNF. Conclusions: Even at lower concentrations of BHA, zebrafish embryos suffered from developmental toxicity, anxiety, and impaired memory due to a decrease in AChE activity and serotonin levels and altered the expression of the mentioned genes. Full article

Background/Objectives: Microhematuria is common in patients with infective endocarditis (IE). The present study aims to assess whether the addition of microhematuria in the 2023 Duke-International Society for Cardiovascular Infectious Diseases (ISCVID) minor immunological criteria could enhance its diagnostic performance. Methods: This retrospective study was conducted at the Lausanne University Hospital, Switzerland (2014–2024). All patients with suspected IE and urinalysis within 24 h from presentation were included. The Endocarditis Team classified episodes as IE or non-IE. Microhematuria was defined as >5 red blood cells per high power field (HPF). Results: Among 801 episodes with suspected IE, 263 (33%) were diagnosed with IE. Microhematuria (>5/HPF) was present in 462 (58%) episodes, with no difference between episodes with and without confirmed IE (61% versus 56%; p = 0.223). Based on the 2023 ISCVID-Duke, minor immunological criteria were present in 42 episodes (5%). By adding microhematuria, 473 (59%) episodes met the minor immunological criteria. Sensitivity of the clinical criteria of the 2023 ISCVID-Duke version without and with hematuria was calculated at 75% (69–80%) and 86% (81–90%), respectively. Specificity was at 52% (48–57%) and 40% (36–45%), respectively. Among episodes with suspected IE, microhematuria was associated with female sex, enterococcal bacteremia, sepsis or septic shock, acute kidney injury, non-cerebral embolic events, and bone and joint infection. Conclusions: Microhematuria was frequent among patients with suspected IE, but it was not associated with the diagnosis of IE. The addition of microhematuria in the 2023 ISCVID-Duke minor immunological criteria did not enhance the overall performance of the criteria. Full article

The presence of pesticides in surface waters has been widely reported worldwide and represents a significant problem that raises concerns on local, regional, national, and international scales. Among these, metolachlor is one of the most widely used herbicides to control annual grasses and broadleaf weeds in various crops. Despite the existing research, data on the effects of metolachlor on the nervous system of fishes, remain limited. The present study aims to investigate the impact of metolachlor during embryonic development on the formation of the nervous system and the subsequent inflammatory response in zebrafish (Danio rerio), focusing specifically on larvae at 24 h post-fertilization (hpf). To achieve this, transgenic zebrafish lines marking neuronal populations Tg(Hu:GFP), glial cells Tg(gfap:GFP), and circulating macrophages Tg(mpeg:GFP) were employed. Following exposure to sub-lethal doses of metolachlor, we observed a significant decrease in GPF-positive cells marking the neuronal population, accompanied by an increase in apoptotic cells within the brain region. Additionally, treated embryos exhibited a marked neuroinflammatory response, characterized by astrogliosis and the specific accumulation of microglia/macrophage-positive cells in the head region. In situ hybridization and real-time PCR analyses revealed a significant downregulation of the neurogenin-1 (ngn1) transcript and a noticeable upregulation of the pro-inflammatory cytokine interleukin-1 beta (il1b). Our findings contribute to the growing body of evidence suggesting that metolachlor, even at early developmental stages, can have detrimental effects on both the formation of the nervous system and the regulation of immune responses. Full article

The present work proposes a novel fractional-order multifunction filter topology in current-mode (CM), which is designed based on the Modified Current Feedback Operational Amplifier (MCFOA). The proposed design simultaneously generates fractional-order low-pass (FO-LPF), high-pass (FO-HPF), and band-pass (FO-BPF) outputs while utilizing an optimized set of essential active and passive elements, thereby ensuring simplicity, cost efficiency, and compatibility with integrated circuits (ICs). The fractional-order feature allows precise control over the transition slope between the passband and the stopband, enhancing design flexibility. PSpice simulations validated the filter’s theoretical performance, confirming a 1 kHz cut-off frequency, making it suitable for VLF applications such as military communication and submarine navigation. Monte Carlo analyses demonstrate robustness against parameter variations, while a low THD, a wide dynamic range, and low power consumption highlight its efficiency for high-precision, low-power applications. This work offers a practical and adaptable approach to fractional-order circuit design, with significant potential in communication, control, and biomedical systems. Full article

Polyhalogenated carbazoles (PHCZs) are emerging persistent organic pollutants that have attracted widespread attention due to their environmental occurrence and potential ecological risks. 1-Bromo-3,6-dichlorocarbazole (1-B-36-CCZ), which is a typical homolog of PHCZs produced as a byproduct in the dye industry, has been widely detected in various environmental media. In this study, we employed an integrated approach using an in vivo zebrafish model and network toxicology methods to systematically evaluate the vascular developmental toxicity of 1-B-36-CCZ and elucidate its underlying mechanisms. The experimental results revealed that the 96 h-LC₅₀ of 1-B-36-CCZ in zebrafish larvae was 4.52 mg/L. Sublethal exposures (0.045–45 μg/L) significantly induced an increase in heart rate (p < 0.05) and an enlargement of the pericardial edema area (p < 0.01). Using Tg(flk:eGFP) transgenic zebrafish embryos to assess vascular toxicity at concentrations of 0, 0.045, 0.45, 4.5, and 45 μg/L, we observed that 1-B-36-CCZ exposure significantly reduced the length and anastomosis rate of intersegmental vessels (ISVs) at 30 hpf, and inhibited the development of the common cardinal vein (CCV) at 48 and 72 hpf as well as the subintestinal vessel (SIV) at 72 hpf. Quantitative PCR (qPCR) analysis further revealed that the expression of key angiogenic genes (flk, kdr, and vegfa) was significantly downregulated, thus corroborating the phenotypic observations. Moreover, a “compound–target–pathway” network model predicted that SRC kinase is a key molecular target for 1-B-36-CCZ action. Enrichment analysis of target protein-coding genes and verapamil replication experiments indicated that 1-B-36-CCZ may cause damage to early vascular development in zebrafish larvae by altering intracellular calcium ion content through the activation of the SRC-mediated calcium ion signaling pathway. This study provides new experimental evidence for elucidating the toxic mechanisms of PHCZ-type pollutants and offers a theoretical basis for environmental health risk assessments. Full article

Background/Objectives: The consumption of highly processed foods (HPFs) is increasing on a global scale, and these foods have been associated with non-communicable diseases (NCDs). In particular, the consumption of HPFs has been associated with the intensification of inflammatory responses, with these foods being implicated in the exacerbation of chronic inflammatory conditions. Conversely, ultra-processed foods (UPFs) have been indicated as a possible factor in the pathogenesis of inflammatory bowel disease (IBD), particularly Crohn’s disease (CD). Methods: From October 2023 to October 2024, 275 patients with IBD were screened at a tertiary referral center. This study’s control cohort comprises 101 individuals from the local population. All study participants answered a questionnaire asking about the participants’ sex, body type and weight, height, age, marital status, employment, and other sociodemographic information. All subjects had to complete a food frequency questionnaire (FFQ) and the German version of the Screening Questionnaire of Highly Processed Food Consumption (sQ-HPF). IBD patients answered questions about their disease course and history as well as objective parameters of inflammation have been collected. Results: The sQ-HPF (%) showed significant differences (p < 0.001; g = −0.5) between the IBD cohort and the control group, suggesting higher HPF consumption within the IBD cohort. A subsequent analysis of the IBD cohort found no significant difference by disease type (Crohn’s disease: p = 0.441; g = −0.1; ulcerative colitis: p = 0.170; g = −0.3) or sex (women: p = 0.219; g = 0.2; men: p = 0.522; g = 0.1), but men with colitis did show higher HPF% compared to women with the same diagnosis. Spearman’s rho revealed no significant correlation between fecal calprotectin and HPF% in men with CD (p = 0.155, r = 0.191) or women with CD (p = 0.836, r = 0.026), and no correlation in men with UC (p = 0.707, r = 0.057) or women with UC (p = 0.560, r = −0.099). IBD health-related quality of life showed a significant positive correlation with HPF consumption in CD men (p = 0.026, r = 0.278), but not in CD women (p = 0.539, r = 0.075). No significant correlations between HPF consumption and health-related quality of life have been found in UC (men: p = 0.663, r = −0.064; women: p = 0.445, r = 0.121). Conclusions: The German version of the sQ-HPF is a reliable tool for rapid screening of habitual HPF% consumption in IBD patients. The findings of this analysis indicate a clear deviation from the recommended nutritional regimens for IBD, emphasizing the imperative for further investigation and the potential development of interventions to address these dietary discrepancies, with the ultimate goal of optimizing health outcomes for these patients. Full article