Search Results (2,262)

Seafood contamination by heavy metals is a growing public health concern, particularly in regions like Tunisia where seafood is a major dietary component. This study assessed concentrations of cadmium (Cd), copper (Cu), lead (Pb), and zinc (Zn) in the muscle tissue of the red shrimp Parapenaeus longirostris, collected in 2023 from four coastal regions: Bizerte, Monastir, Kerkennah, and Gabes. Metal analysis was conducted using flame atomic absorption spectroscopy. This species was chosen due to its ecological and economic importance. The study sites were chosen based on their differing levels of industrial, urban, and agricultural influence, providing a representative overview of regional contamination patterns. Mean concentrations were 1.04 µg/g for Zn, 0.59 µg/g for Cu, 1.56 µg/g for Pb, and 0.21 µg/g for Cd (dry weight). Pb was the most prevalent metal across sites. Statistically significant variation was observed only for Cu (p = 0.0334). All metal concentrations were below international safety limits set by FAO/WHO and the European Union. Compared to similar studies, the levels reported were similar or slightly lower. Human health risk was evaluated using target hazard quotient (THQ), hazard index (HI), and cancer risk (CR) values. For adults, THQ ranged from 5.44 × 10⁻⁶ to 8.43 × 10⁻⁴, while for children it ranged from 2.40 × 10⁻⁵ to 3.72 × 10⁻³. HI values were also well below 1, indicating negligible non-carcinogenic risk. CR values for Cd and Pb in both adults and children fell within the acceptable risk range (10⁻⁶ to <10⁻⁴), suggesting no significant carcinogenic concern. This study provides the first field-based dataset on metal contamination in P. longirostris from Tunisia, contributing valuable insights for seafood safety monitoring and public health protection. Full article

Background/Objectives: While ocular albinism (OA) is usually associated with reduced vision, nystagmus, and foveal hypoplasia, there is phenotypic variability in iris and fundus hypopigmentation. Hemizygous pathogenic/likely pathogenic (P/LP) variants in GPR143 at X: 151.56–151.59 have been shown in the literature to be associated with OA. The purpose of this study was to report the case of a Hispanic male with X-linked inherited OA associated with a hemizygous GPR143 variant and to review the literature relating to genotype–phenotype associations with GPR143 and OA. Methods: After consent to an IRB-approved protocol, a 14-year-old Hispanic male patient with OA and his parents underwent whole genome sequencing (WGS) in 2023. Two maternal uncles with nystagmus underwent targeted variant testing in 2024. A literature review of reported GPR143 variants was completed. Results: A male with reduced visual acuity, infantile-onset nystagmus, foveal hypoplasia, and iris hypopigmentation was identified to have the variant GPR143, c.455+3A>G, which was also present in his mother and two affected maternal uncles. This variant has been previously identified in other Hispanic patients of Mexican descent. Additionally, 127 variants were identified in the literature and reported to be associated with OA. All patients had reduced visual acuity (average 0.71 ± 0.23 logMAR), 99% had nystagmus, 97% foveal hypoplasia, 79% fundus hypopigmentation, and 71% iris hypopigmentation. Of those patients with reported optotype best corrected visual acuity (BCVA), eight (9%) had VA from 20/25 to 20/40, 24 (24%) had VA from 20/50 to 20/80, and 63 (67%) had VA from 20/100 to 20/200. The most frequent type of variant was missense (31%, n = 39). Frameshift and nonsense variants were associated with the lowest rates of iris hypopigmentation (50% [n = 11] and 44% [n = 8], respectively; p = 0.0068). Conclusions: This case represents phenotypic variability of GPR143-associated OA and highlights the importance of repeat genetic testing and independent analyses of test results for accurate variant classification, particularly in non-White and Hispanic patients. Further studies in more diverse populations are needed to better develop genotype–phenotype associations for GPR143-associated OA. Full article

Vicia unijuga, an important forage legume on China’s Qinghai–Tibetan Plateau, exhibited dark-brown sunken lesions on their stems at the Qingyang Experimental Station of Lanzhou University. The fungus isolated from the diseased tissues was identified as Colletotrichum tofieldiae via a multi-locus phylogeny (ITS-ACT-Tub2-CHS-1-GADPH-HIS3). The pathogenicity was confirmed by Koch’s postulates. The inoculated plants showed significantly reduced (p < 0.05) growth parameters (height, root length, and biomass), photosynthetic indices (net rate, transpiration, and stomatal conductance), and nutritional quality (crude protein, crude fat, crude ash, and crude fiber) compared to the controls. C. tofieldiae additionally infected six legume species (V. sativa, Medicago sativa, Onobrychis viciifolia, Astragalus adsurgens, Trifolium pratense, and T. repens). Optimal in vitro growth occurred on oatmeal agar (mycelium) and cornmeal agar (spores), with D-sucrose and D-peptone as the best carbon and nitrogen sources. This first report of C. tofieldiae causing V. unijuga anthracnose advances the understanding of legume anthracnose pathogens. Full article

The present study aims to investigate the multi-year effects (5 years) of individualized whole-body vibration (WBV) on locomotion, postural control, and handgrip strength in a 68-year-old man with relapse remitting multiple sclerosis (PwRRMS). The dose–response relationship induced by a single session was quantified by determining the surface electromyographic activity (sEMG) of the participant. The participant wore an orthosis to limit the lack of foot dorsiflexion in the weakest limb during walking in daily life. The gait alteration during walking was assessed at 1, 2 and 3 km/h (without the orthosis) through angle–angle diagrams by quantifying the area, perimeter and shape of the loops, and the sEMG of leg muscles was recorded in both limbs. The evaluation of postural control was conducted during upright standing by quantifying the displacement of the center of pressure (CoP). The handgrip strength was assessed by measuring the force–time profile synchronized with the sEMG activity of upper arm muscles. The participant improved his ability to walk at higher speeds (2–3 km/h) without the orthosis. There were greater improvements in the area and perimeter of angle–angle diagrams for the weakest limb (Δ = 36–51%). The sEMG activity of the shank muscles increased at all speeds, particularly in the tibialis anterior of weakest limbs (Δ = 10–68%). The CoP displacement during upright standing decreased (Δ = 40–60%), whereas the handgrip strength increased (Δ = 32% average). Over the 5-year period of intervention, the individualized WBV improved locomotion, postural control and handgrip strength without side effects. Future studies should consider the possibility of implementing an individualized WBV in PwRRMS. Full article

New approach methodologies (NAMs), including microphysiological systems (MPSs), can recapitulate structural and functional complexities of organs. Vanoxerine was reported to induce cardiac adverse events, including torsade de points (TdP), in a Phase III clinical trial. Despite earlier nonclinical animal models and Phase I–II clinical trials, events of QT prolongation or proarrhythmia were not observed. Here, we utilized cardiac NAMs to evaluate the functional consequences of vanoxerine treatment on human cardiac excitation–contraction coupling. The cardiac MPS used in this study was a microfabricated fluidic culture platform with human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) capable of evaluating voltage, intracellular calcium handling, and contractility. Likewise, the hiPSC-CM comprehensive in vitro proarrhythmia assay (CiPA) was employed based on multielectrode array (MEA). Vanoxerine treatment delayed repolarization in a concentration-dependent manner and induced proarrhythmic events in both NAM platforms. The complex cardiac MPS displayed a frequency-dependent vanoxerine response such that EADs were eliminated at a faster pacing rate (1.5 Hz). Moreover, exposure analysis revealed a 99% vanoxerine loss in the cardiac MPS. TdP risk analysis demonstrated high to intermediate TdP risk at clinically relevant concentrations of vanoxerine and frequency-independent EAD events in the hiPSC-CM CiPA model. These findings demonstrate that nonclinical cardiac NAMs can recapitulate clinical outcomes, including detection of vanoxerine-induced delayed repolarization and proarrhythmic effects. Moreover, this work provides a foundation to evaluate the safety and efficacy of novel compounds to reduce the dependence on animal studies. Full article

Background/Objectives: The aim of this study was to evaluate the impact of inhomogeneity correction (IC) of dose distribution on the dosimetric and radiobiological efficacy of radiation treatment for heterotopic ossification (HO). Methods: This study involved a retrospective analysis of 21 patients treated using a homogeneous dose distribution plan for hip prophylactic HO. These IC-off plans were evaluated against an IC-on dose distribution plan. Dosimetric and corresponding radiobiological parameters (gEUD, LQ-EUD, LQ, EQD2 for α/β = 3 and 10 Gy) were calculated. These parameters were compared for both treatment plans. Additionally, Monte Carlo simulations were performed using mean and standard deviation values from baseline data to generate 10,000 synthetic datasets, allowing for robust statistical modeling of variability in dose distributions and biological outcomes. Results: The homogeneous (IC-off) plans demonstrated overestimation of dose conformity and uniformity, reflected in lower HI values (0.10 ± 0.05 vs. 0.18 ± 0.05) and higher D_90%–D_98% coverage. Radiobiologically, these plans yielded higher gEUD (7.02 Gy vs. 6.80 Gy) and EQD2 values across all α/β scenarios (e.g., EQD2_{[α/β=3]_gEUD} = 14.07 Gy vs. 13.35 Gy), with statistically significant differences (p < 0.001). Although IC-on plans demonstrated steeper dose gradients (higher GIs), this came at the expense of internal dose variability and potentially compromised biological effectiveness. Conclusions: Our results suggest that plans without IC deliver suboptimal biological effectiveness if continued preferentially in routine HO prophylaxis. With advanced radiation dose calculation algorithms available in all centers, inhomogeneity-corrected doses warrant prospective validation. Full article

High-frequency (h. f.) harmonic distortion (HD) of advanced SiGe heterojunction bipolar transistor (HBT)-based power cells (PwCs), featuring optimized metallization interconnections between individual HBTs, was investigated. Single tone input power (P_in) excitations at 1, 2, 5, and 10 GHz frequencies were employed. The output power (P_out) of the fundamental tone and its harmonics were analyzed in both the frequency and time domains. A rapid increase in the third harmonic of P_out was observed at input powers exceeding −8 dBm for a fundamental frequency of 10 GHz in two different PwC technologies. This increase in the third harmonic was analyzed in terms of nonlinear current waveforms, the nonlinearity of the HBT p-n junction diffusion capacitances, substrate current behavior versus P_in, and avalanche multiplication current. To assess the RF power performance of the PwCs, scalar and vectorial load-pull (LP) measurements were conducted and analyzed. Under matched conditions, the SiGe PwCs demonstrated good linearity, particularly at high frequencies. The key power performance of the PwCs was measured and simulated as follows: input power 1 dB compression point (P_{in_1dB}) of −3 dBm, transducer power gain (G_T) of 15 dB, and power added efficiency (PAE) of 50% at 30 GHz. All measured data were corroborated with simulations using the compact model HiCuM L2. Full article

As a type of distinctive pit on Mars, skylights are entrances to subsurface lava caves. They are very important for studying volcanic activity and potential preserved water ice, and are also considered as potential sites for human extraterrestrial bases in the future. Most skylights are manually identified, which has low efficiency and is highly subjective. Although deep learning methods have recently been used to identify skylights, they face challenges of few effective samples and low identification accuracy. In this article, 151 positive samples and 920 negative samples based on the MRO-HiRISE image data was used to create an initial skylight dataset, which contained few positive samples. To augment the initial dataset, StyleGAN2-ADA was selected to synthesize some positive samples and generated an augmented dataset with 896 samples. On the basis of the augmented skylight dataset, we proposed YOLOv9-Skylight for skylight identification by incorporating Inner-EIoU loss and DySample to enhance localization accuracy and feature extracting ability. Compared with YOLOv9, the P, R, and the F1 of YOLOv9-Skylight were improved by about 9.1%, 2.8%, and 5.6%, respectively. Compared with other mainstream models such as YOLOv5, YOLOv10, Faster R-CNN, Mask R-CNN, and DETR, YOLOv9-Skylight achieved the highest accuracy (F1 = 92.5%), which shows a strong performance in skylight identification. 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

Chrysomya megacephala, as one of the common blowflies, displays biological characteristics, such as ovoviviparity and carrion-feeding adaptation. Thus, this species is generally considered of significant ecological, medical, and forensic importance. However, without a high-quality pseudo-chromosome genome for C. megacephala, elucidating its evolutionary trajectory proved difficult. Herein, we assembled and analyzed a high-quality chromosome-level genome assembly of the C. megacephala, combined with PacBio HiFi long reads, Hi-C data, and Illumina reads. The pseudo-chromosomes assembly of C. megacephala spans 629.44 Mb, with 97.05% anchored to five chromosomes. Final assembly includes 1056 contigs (N50 = 1.68 Mb), and 97 scaffolds (N50 = 121.37 Mb), achieving 98.90% BUSCO completeness (n = 1367). Gene annotation predicted 17,071 protein-coding genes (95.60% BUSCO completeness), while repeat masking identified 244.26 Mb (38.82%) as repetitive elements. Additionally, 3740 non-coding RNAs were characterized. Gene family analyses resulted in 10,579 gene families, containing 151 gene families that experienced rapid evolution. Comparative genomic analyses showed that the expanded genes are related to reproduction and necrophagous habits. In addition, we annotated the gene family P450s, CCEs, IRs, GRs, and ORs, all of which represent remarkable expansion, playing a crucial role in the mechanism of locating the hosts for forensic insects. Our research establishes a high-quality genome sequence to facilitate subsequent molecular investigations into significant species within forensic entomology. Full article

Three novel Aeromonas phages vB_AerVS_332-Yuliya, vB_AerVM_332-Vera, and vB_AerVM_332-Igor and their host Aeromonas veronii CEMTC7594 were found in the same water + sediments sample collected in a freshwater pond. Complete genome sequencing indicated that vB_AerVS_332-Yuliya (43,584 bp) is a siphophage, whereas vB_AerVM_332-Vera (294,685 bp) and vB_AerVM_332-Igor (237,907 bp) are giant phages. The host strain can grow at temperatures from 5 °C to 37 °C with an optimum of 25–37 °C; siphophage vB_AerVS_332-Yuliya effectively reproduced at temperature ≤ 25 °C, the optimal temperature for giant phage vB_AerVM_332-Igor was 25 °C, and giant phage vB_AerVM_332-Vera infected host cells at 5–10 °C. The genomes of these phages differed significantly from known phages; their level of nucleotide identity and values of intergenomic similarity with the corresponding neighboring phages indicated that each of these phages is a member of a new genus/subfamily. Giant phage vB_AerVM_332-Vera is a member of the proposed Chimallinviridae family, which forms Cluster D of giant phages that possibly evolved from phages with shorter genomes. Giant phage vB_AerVM_332-Igor is part of Cluster E, the known members of which preserve the size of genomes. Phages from Cluster F, containing Aeromonas phages among others, show a gradual decrease and/or increase in genomes during evolution, which indicates different strategies for giant phages. Full article

Background: Riboflavin transporter deficiency type 2 is an ultra-rare, yet treatable, inborn error of metabolism. This autosomal recessive disorder is caused by pathogenic mutations in the SLC52A2 gene leading to progressive ataxia, polyneuropathy, and hearing and visual impairment. The early initiation of riboflavin therapy can prevent or mitigate the complications. To date, only 200 cases have been reported, mostly in consanguineous populations. The p.Gly306Arg founder mutation, identified in patients of Lebanese descent, is the most frequently reported worldwide. It was described in a homozygous state in a total of 21 patients. Therefore, studies characterizing the phenotypic spectrum of this mutation remain scarce. Methods: A retrospective review of charts of patients diagnosed with riboflavin transporter deficiency type 2 at a tertiary-care reference center in Lebanon was performed. Clinical, biochemical, and molecular profiles were analyzed and compared to reported cases in the literature. Results: A total of six patients from three unrelated families were diagnosed between 2018 and 2023. All patients exhibited the homozygous founder mutation, p.Gly306Arg, with variable phenotypes, even among family members. The median age of onset was 3 years. Diagnosis was achieved by exome sequencing at a median age of 5 years, as clinical and biochemical profiles were inconsistently suggestive. The response to riboflavin was variable. One patient treated with high-dose riboflavin recovered his motor function, while the others were stabilized. Conclusions: This study expands the current knowledge of the phenotypic spectrum associated with the p.Gly306Arg mutation in the SLC52A2 gene. Increased awareness among physicians of the common manifestations of this rare disorder is crucial for early diagnosis and treatment. In the absence of a consistent clinical or biochemical phenotype, the use of next-generation sequencing as a first-tier diagnostic test may be considered. Full article

Chronic kidney disease (CKD)-associated anemia is a global health concern and is linked to vascular and ocular complications. Hypoxia-inducible factor (HIF) stabilizers, or HIF prolyl hydroxylase inhibitors (PHIs), are promising candidates for the treatment of CKD-associated anemia. Since hypoxia and angiogenesis are involved in eye diseases, this study examined the effects of HIF-PHIs on metabolism and gene expression in retinal pigment epithelium (RPE) cells. Results revealed that PHIs differentially induced angiogenic (VEGFA, ANG) and glycolytic (PDK1, GLUT1) gene expression, with Roxadustat causing the strongest transcriptional changes. However, Roxadustat-induced angiogenic signals did not promote endothelial tube formation. Moreover, it did not induce oxidative stress, inflammation, or significant antioxidant gene responses in ARPE-19 cells. Roxadustat also reduced the inflammatory cytokine response to tumor necrosis factor-α, including IL-6, IL-8, and MCP-1, and did not exacerbate VEGF expression under high-glucose conditions. Overall, Roxadustat triggered complex gene expression changes without promoting inflammation or oxidative stress in RPE cells. Despite these findings, ophthalmologic monitoring is advised during PHI treatment in CKD patients receiving HIF-PHIs. Full article

The recently identified proton-activated chloride (PAC) channel is ubiquitously expressed, and it regulates several proton-sensitive physiological and pathophysiological processes. While the PAC channel is activated by strong acids due to the binding of protons to extracellular binding sites, here, we describe the way in which weak acids inhibit the PAC channel by a mechanism involving a distinct extracellular binding site. Whole-cell patch clamp was performed on wildtype HEK293T cells, PAC-knockout HEK293 cells expressing human (h)PAC mutant constructs, and on hiPSC-derived cardiomyocytes. Proton-induced cytotoxicity was examined in HEK293T cells. Acetic acid inhibited endogenous PAC channels in HEK 293T cells in a reversible, concentration-dependent, and pH-dependent manner. The inhibition of PAC channels was also induced by lactic acid, propionic acid, itaconic acid, and β-hydroxybutyrate. Weak acids also inhibited recombinant wildtype hPAC channels and PAC-like currents in hiPSC-derived cardiomyocytes. Replacement of the extracellular arginine 93 by an alanine (hPAC–Arg93Ala) strongly reduced the inhibition by some weak acids, including arachidonic acid. Although lactic acid inhibited PAC, it did not reduce the proton-induced cytotoxicity examined in wildtype HEK 293 cells. To conclude, weak acids inhibit PAC via an extracellular mechanism involving Arg93. These data warrant further investigations into the regulation of the PAC channel by endogenous weak acids. Full article

Background: Medullary thyroid carcinoma (MTC) has a high rate of local and distant metastases. In particular, the RET protooncogene appears to be the predominant driver mutation for oncogenesis. The German S3 thyroid carcinoma guidelines recommend molecular genetic analysis of the tumour without specifying the site of the tissue sampling. Whether there is difference in RET protooncogene between the primary tumour, lymph node, and distant metastasis has not yet been investigated. However, differences could be important with regard to biopsy localization, and also, thus, the choice of single- or multi-tyrosine-kinase-inhibitor therapy. Methods: In a case of sporadic MTC, Cancer Hotspot panel diagnostics were performed on the primary tumour, lymph node metastasis, and distant metastasis. Mutations were classified using different gene databases, and the different stages of metastasis were compared. Results: RET protooncogene (chr10:43609933, c.1886_1891delTGTGCG, p.Leu629_Asp631delinsHis) was found to be present in the MTC tissue of the primary tumour, lymph node, and distant metastasis in the Cancer Hotspot Panel diagnostic, while the other investigated therapy-relevant mutational profiles were not consistently found. Conclusions: Further longitudinal studies in larger patient cohorts are required to elucidate the role of the RET protooncogene in the metastatic progression of MTC and to determine its impact on the selection of biopsy sites and the subsequent decision-making regarding single- versus multi-tyrosine kinase inhibitor therapy. Full article