Search Results (172)

Schizophrenia (SCZ) is a debilitating disorder with substantial societal and economic impacts. The clinical high risk of psychosis (CHR-P) state generally precedes the onset of SCZ, offering a window for early intervention. However, treatment guidelines for CHR-P individuals remain contentious, particularly regarding antipsychotic (AP) medications. Although several studies have examined the effects of APs on reducing the risk of conversion to psychosis, the novelty of this narrative review lies in its focus on differentiating APs’ effects on positive and negative symptoms, as well as cognitive functioning, in CHR-P individuals. Evidence suggests that APs may be cautiously recommended for attenuated positive symptoms to stabilize individuals for psychological interventions, but their use in treating negative symptoms is generally discouraged due to limited efficacy and potential side effects. Similarly, the effects of APs on cognitive abilities remain underexplored, with results indicating a lack of significant neurocognitive outcomes. In conclusion, APs’ use in CHR-P patients requires careful consideration due to limited evidence and potential adverse effects. Future research should focus on individual symptom domains and treatment modalities to optimize outcomes in this critical population. Until then, a cautious approach emphasizing non-pharmacological interventions is advisable. 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

Long- or post-COVID-19 syndrome, which is also designated by WHO as Post COVID-19 Condition (PCC), is characterized by the persistent symptoms that remain after recovery from SARS-CoV-2 infection. A worldwide consortium of Long COVID-19 Host Genetics Initiative (Long COVID-19 HGI) identified an SNP rs9367106 (G>C; chr6:41,515,652, GRCh38, p = 1.76 × 10⁻¹⁰, OR = 1.63, 95% CI: 1.40–1.89) that is associated with PCC. Unraveling the functional significance of this SNP is of prime importance to understanding the development of the PCC phenotypes and their therapy. Here, in Silico, I explored how the risk allele of this SNP alters the functional mechanisms and molecular pathways leading to the development of PCC phenotypes. Bioinformatic methods include physical interactions using HI-C and Chia-PET analysis, Transcription Factors (TFs) binding ability, RNA structure modeling, epigenetic, and pathway analysis. This SNP resides within two long RNA genes, LINC01276 and FOXP4-AS1, and is located at ~31 kb upstream of a transcription factor FOXP4. This DNA region, including this SNP, physically interacts with FOXP4-AS1 and FOXP4, implying that this regulatory SNP could alter the normal cellular function of FOXP4-AS1 and FOXP4. Furthermore, rs9367106 is in eQTL with the FOXP4 gene in lung tissue. rs9367106 carrying DNA sequences act as distant enhancers and bind with several transcription factors (TFs) including YY1, PPAR-α, IK-1, GR-α, and AP2αA. The G>C transition extensively modifies the RNA structure that may affect the TF bindings and enhancer functions to alter the interactions and functions of these RNA molecules. This SNP also includes an ALU/SINE sequence and alteration of which by the G>C transition may prevent IFIH1/MDA5 activation, leading to suppression of host innate immune responses. LINC01276 targets the MED20 gene that expresses mostly in brain tissues, associated with sleep disorders and basal ganglia abnormalities similar to some of the symptoms of PCC phenotypes. Taken together, G>C transition of rs9367601 may likely alter the function of all three genes to explain the molecular basis of developing the long-term symptomatic abnormalities in the lungs and brain observed after COVID-19 recovery. Full article

Overweight and obese individuals show lower mortality rates or better prognoses than those of normal weight in a variety of diseases, a phenomenon called the “obesity paradox”. An inverse association of adiposity with atherosclerosis has been observed in both humans and mice. To dissect phenotypic and genetic connections between the traits, 154 female and 145 male F2 mice were generated from an intercross between BALB/cJ and LP/J apolipoprotein E-deficient mice and fed a Western diet for 12 weeks. Atherosclerotic lesion size in the aortic root, body weight, plasma lipids, and glucose were measured, and genotyping was performed on miniMUGA SNP arrays. Quantitative trait locus (QTL) analyses on all F2 mice with sex as a covariate revealed four significant QTLs on chromosomes (Chr) 3, 6, 13, and 15 for atherosclerosis and three significant QTLs on Chr2, 7, and 15 for body weight. Chr15 QTL for atherosclerosis overlapped with one for body weight near 36 Mb. After adjusting for variation in body weight, Chr15 atherosclerosis QTL was downgraded from significant to suggestive linkage. Body weight was inversely correlated with atherosclerotic lesion sizes and accounted for more variance than a single other risk factor for atherosclerosis among F2 mice. Analysis of public data collected from two backcross cohorts revealed strong correlations between body weight and fat mass in adult mice (r ≥ 0.93; p ≤ 1.6 × 10⁻¹³⁶). Thus, the obesity paradox in atherosclerosis is partially attributable to shared genetic components that have an opposite effect on adiposity and atherosclerosis. Full article

This study investigated the levels of four polycyclic aromatic hydrocarbons (BaA, CHR, BbF, and BaP) in 11 types of 100 commercially available tea products using gas chromatography–mass spectrometry (GC-MS), and also evaluated potential dietary risks, toxic equivalency (TEQ), and margin of exposure (MOE). Method validation demonstrated strong linearity of the calibration curves for all four PAHs (R² > 0.99) over a concentration range of 1–20 μg/kg. The LOD for the four PAHs ranged from 0.0610 to 0.1534 μg/kg in the solid matrix and from 0.0035 to 0.0064 μg/kg in the liquid matrix, with corresponding LOQ ranging from 0.1849 to 0.4648 μg/kg in the solid matrix and from 0.0107 to 0.0194 μg/kg in the liquid matrix. All recovery rates were within the acceptable range, demonstrating satisfactory performance, and both intraday and interday accuracy and precision were within acceptable limits, meeting international validation criteria. Among the samples, yerba mate tea (33.58 μg/kg), herbal tea (24.05 μg/kg), and oolong tea (23.21 μg/kg) showed the highest Σ4PAH concentrations. Based on these results, TEQ_BaP and MOE values were calculated for the positive samples. All three teas with detectable PAHs exhibited MOE values above 10,000, indicating a low level of potential carcinogenic risk. However, the presence of PAHs in certain tea types highlights the importance of ongoing monitoring, regulatory oversight, and risk communication to ensure consumer safety. Full article

In response to the growing genetic uniformity within wheat populations, developing efficient wheat–alien translocation strategies has become critically important. We observed that several offspring of the common wheat (Triticum aestivum L.)–wild emmer (Triticum turgidum L. var. dicoccoides) chromosome arm substitution line (CASL4AL) exhibited stunted growth, including significantly reduced plant height, spike length, spikelet number, and stem width compared to normal plants. Integrative transcriptomic analyses (RNA-Seq and BSR-Seq) revealed a statistically significant depletion (p < 0.01) of single nucleotide polymorphisms (SNPs) on chromosome 4B in compromised plants. Chromosome association analysis of differentially expressed genes (DEGs, up- or downregulated) revealed that downregulated genes were predominantly located on chromosome 4B. The 1244 downregulated DEGs on Chr4B were employed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and RNA metabolic processes, DNA repair, and transport systems were significantly enriched by GO analysis; however, only the mRNA surveillance pathway was enriched by KEGG enrichment. Molecular marker profiling showed a complete absence of target amplification in the critical 0–155 Mb region of chromosome 4B in all weak plants. Pearson’s correlation coefficients confirmed significant associations (p < 0.01) between 4B-specific amplification and weak phenotypes. These results demonstrate that 4B segmental deletions drive weak phenotypes in CASL4AL progeny, and provide experimental evidence for chromosome deletions induced in wild emmer chromosome substitution lines. This study highlights the potential of wild emmer as a valuable tool for generating chromosomal variations in wheat breeding programs. Full article

Background: Clinical High Risk for Psychosis (CHR-P) is a psychopathological condition requiring early prevention, particularly in adolescence. Methods: We enrolled 151 patients to assess the potential of the Rorschach Performance Assessment System (R-PAS) in predicting the course of CHR-P and transitions to psychosis. Adolescents with DSM-5 Attenuated Psychotic Symptoms (APS) at baseline were compared with those diagnosed with Early-Onset Psychosis (EOP) and those with other conditions (non-APS). We also examined whether antipsychotics influenced patients’ performance in the R-PAS. Finally, we analyzed correlations between DSM-5 diagnoses at one-year follow-up and baseline R-PAS indexes. Results: APS and EOP patients exhibited similar R-PAS profiles, with APS showing greater impairments in specific Perception and Thinking Problem indexes. Antipsychotic use did not confound results. A distinct R-PAS profile emerged for individuals at risk of psychosis after one year, with the most significant alterations in the Self and Other Representation and the Stress and Distress domains. Conclusions: This study highlights the R-PAS as a valuable tool for early psychosis risk detection and prevention strategies. Targeted, person-centered interventions (i.e., psychotherapy, mindfulness, and relaxation techniques) are recommended to address vulnerabilities. Integrating psychological assessment into early intervention frameworks may enhance outcomes and improve patients and families’ quality of life. Full article

Hexavalent chromium (Cr(VI)) is toxic, carcinogenic, and harmful to biological systems. Common detection methods, such as colorimetry, atomic absorption spectrometry, ion chromatography, and biological systems, can only be used in the laboratory and do not provide real-time feedback. To address these limitations, the current study cloned the ChrB gene, which exhibits high specificity in detecting Cr(VI), and the ChrA gene, which exhibits high Cr(VI) tolerance, into Escherichia coli. This recombinant strain, ChrA–ChrB–E. coli, was integrated into a single-chamber microbial fuel cell for accurate continual monitoring over a wide range of Cr(VI) concentrations. ChrA–ChrB–E. coli thrived in temperatures from 25 °C to 45 °C and pH levels between 5 and 8. Its ability to reduce Cr(VI) remained consistent across Cr(VI) forms, carbon sources, and oxyanions. Cyclic voltammetry was employed to verify the electrical activity of the biosensor. The biosensor exhibited a detection limit of 0.0075 mg/L. Under conditions simulating the regulatory emission limit for Cr(VI) of 0.5 mg/L in industrial wastewater, the biosensor achieved a response time of 20 s during continual operation. When tested with synthetic wastewater containing Cr(VI) concentrations from 0.02 to 150 mg/L, the system exhibited high adaptability and facilitated stable monitoring (relative standard deviation ≤ 2.7%). Additionally, the biosensor’s accuracy (−1.73% to 2.5%) matched that of traditional batch methods, highlighting its suitability for real-time Cr(VI) monitoring in aquatic environments. Full article

One out of every hundred live births present with congenital heart abnormalities caused by the aberrant development of the embryonic cardiovascular system. The conserved zinc finger transcription factor proteins, which include GATA binding protein 5 (GATA5) and GATA binding protein (GATA6) play important roles in embryonic development and their inactivation may result in congenital heart defects (CHDs). In this study, we performed genotypic–phenotypic analyses in two families affected by right-sided CHD diagnosed by echocardiography imaging. Proband A presented with pulmonary valve stenosis, and proband B presented with complex CHD involving the right heart structures. For variant detection, we employed whole-genome single-nucleotide polymorphism (SNP) microarray and family-based whole-exome sequencing (WES) studies. Proband A is a full-term infant who was admitted to the neonatal intensive care unit (NICU) at five days of life for pulmonary valve stenosis (PVS). Genomic studies revealed a normal SNP microarray; however, quad WES analysis identified a novel heterozygous [Chr20:g.61041597C>G (p.Arg237Pro)] variant in the GATA5 gene. Further analysis confirmed that the novel variant was inherited from the mother but was absent in the father and the maternal uncle with a history of heart murmur. Proband B was born prematurely at 35 weeks gestation with a prenatally diagnosed complex CHD. A postnatal evaluation revealed right-sided heart defects including pulmonary atresia with intact ventricular septum (PA/IVS), right ventricular hypoplasia, tricuspid valve hypoplasia, hypoplastic main and bilateral branch pulmonary arteries, and possible coronary sinusoids. Cardiac catheterization yielded anatomy and hemodynamics unfavorable to repair. Hence, heart transplantation was indicated. Upon genomic testing, a normal SNP microarray was observed, while trio WES analysis identified a novel heterozygous [Chr18:c.1757C>T (p.Pro586Leu)] variant in the GATA6 gene. This variant was inherited from the father, who carries a clinical diagnosis of tetralogy of Fallot. These findings provide new insights into novel GATA5/6 variants, elaborate on the genotypic and phenotypic association, and highlight the critical role of GATA5 and GATA6 transcription factors in a wide spectrum of right-sided CHDs. Full article

Background/Objectives: Copy number variations (CNVs) are a significant source of genetic variation and have been shown to influence growth traits in livestock. This study aimed to validate previous CNV candidates within the NSMF gene (XM_015093798.1) and identify novel CNV markers for molecular breeding in sheep. Methods: Using quantitative PCR (qPCR), we genotyped NSMF CNVs (chr3: 586,001–601,000) and assessed their associations with growth traits in three Chinese sheep breeds: Chaka sheep (CKS, n = 312), Hu sheep (HS, n = 67), and Small-tailed Han sheep (STHS, n = 70). Results: Our results revealed significant differences in NSMF CNV genotype frequencies across the three breeds, with the highest proportion of deletions observed in STHS (98.44%) and CKS (90.57%), while HS exhibited a higher frequency of duplications (14.06%). No significant associations were observed between NSMF CNV genotype and CKS growth traits (p-value > 0.05). However, the CNV could markedly affected cannon circumference in HS (p-value = 0.021), with individuals carrying the normal genotype showing a larger cannon circumference. Additionally, a marginally significant association was found between the CNV and body diagonal length in HS (p-value = 0.050). Conclusions: Future investigations employing larger cohorts of Hu sheep are warranted to definitively establish the utility of NSMF CNVs as genetic markers for growth traits in Hu sheep breeding programs. Full article

Background: Sarcopenia has been associated with poor outcomes in pancreatic cancer (PC). However, published results are heterogeneous in terms of study design, oncological outcomes, and sarcopenia measurements. This meta-analysis aims to evaluate the impact of computed tomography (CT)-based sarcopenia on overall survival (OS) and progression-free survival (PFS) in patients with PC, considering potential confounders such as the CT-based method and thresholds used to define sarcopenia, as well as treatment intention. Methods: We systematically searched databases for observational studies reporting hazard ratios (HRs) for OS and PFS in PC patients stratified by CT-based sarcopenia status. Random-effects models were used to calculate pooled crude and adjusted HRs (cHRs and aHRs, respectively), with subgroup analyses based on sarcopenia measurement methods, cutoff values, sarcopenia prevalence, and treatment intention. Heterogeneity was assessed using the I² and τ² statistics, and publication bias was evaluated using funnel plots and Egger’s test. Results: Data from 48 studies were included. Sarcopenia was significantly associated with worse OS (pooled cHR = 1.58, 95% CI: 1.38–1.82; pooled aHR = 1.39, 95% CI: 1.16–1.66) and worse PFS (pooled cHR = 1.55, 95% CI: 1.29–1.86; pooled aHR = 1.31, 95% CI: 1.11–1.55). Subgroup analyses revealed significantly different, stronger associations in studies using stricter sarcopenia cutoffs (<50 cm²/m² for males) and in patients undergoing curative treatments. Heterogeneity was substantial across analyses (I² > 67%), but with generally low τ² values (0.01–0.25). Egger’s test indicated potential publication bias for OS (p < 0.001), but no significant bias was observed for PFS (p = 0.576). Conclusions: Sarcopenia determined by CT is an independent predictor of poor OS and PFS in PC, but this association varies depending on the cutoff used for its definition as well as on the treatment intention. Therefore, its routine assessment in clinical practice could provide valuable prognostic information, but future research should focus on standardizing sarcopenia assessment methods. Full article

Populus deltoides holds significant ecological and economic importance and is a crucial gene donor for the world’s staple poplar varieties. To select and breed P. deltoides with improved agronomic traits, nine growth and leaf traits were examined in 375 different genotypes, assessing their genetic diversity and performing correlation and comprehensive ranking analyses. Phenotyping results were then utilized to screen a total of 2,009,263 SNP (single nucleotide polymorphism) loci significantly associated with the nine phenotypic traits. A total of 45 SNP loci exhibited significant associations with growth traits based on a general linear model (GLM) analysis. By analyzing the Linkage disequilibrium (LD) block of five SNP loci with significant leaf area and height, we identified five candidate genes related to leaf area and height. Three of the five SNP loci were successfully validated using KASP (kompetitive allele-specific PCR) assays. One loci Chr08_16007979 was closely linked with leaf area, and two loci Chr05_12148738, and Chr05_17106547 were closely linked with height. The developed functional KASP markers offer valuable insights for subsequent further marker-assisted breeding and genetic improvement studies in southern-type poplars. Full article

Background: The study presents a detailed examination and follow-up of a Slovenian patient with an Leber Hereditary Optic Neuropathy (LHON)-like phenotype and bilateral optic neuropathy in whom genetic analysis identified a novel variant MT-CYB:m.15309T>C (Ile188Thr). Methods: We provide detailed analysis of the clinical examinations of a male patient with bilateral optic neuropathy from the acute stage to 8 years of follow-up. Complete ophthalmological exam, electrophysiology and optical coherence tomography (OCT) segmentation were performed. The genotype analysis was performed with a complete screening of the mitochondrial genome. Furthermore, proteomic analysis of the protein structure and function was performed to assess the pathogenicity of a novel variant of unknown significance. Mitochondrial function analysis of the patient’s peripheral blood mononuclear cells (PBMCs) was performed with the objective of evaluating the mutation effect on mitochondrial function using flow cytometry and high-resolution respirometry. Results: The patient had a profound consecutive bilateral visual loss at 19 years of age due to optic neuropathy with characteristics of LHON; however, unlike patients with typical LHON, the patient experienced a fluctuation in visual function and significant late recovery. He had a total of three visual acuity deteriorations and improvements in the left eye, with concomitant visual loss in the right eye and a final visual acuity drop reaching nadir 9 months after onset. The visual loss was characterized by centrocecal scotoma, abnormal color vision and abnormal VEP, while deterioration of PERG N95 followed with a lag of several months. The OCT examination showed retinal nerve fiber layer thinning matching disease progression. Following a two-year period of legal blindness, the patient’s visual function started to improve, and over the course of 5 years, it reached 0.5 and 0.7 Snellen (0.3 and 0.15 LogMAR) visual acuity (VA). Mitochondrial sequencing identified a presumably pathogenic variant m.15309T>C in the MT-CYB gene at 65% heteroplasmy, belonging to haplogroup K. Mitochondrial function assessment of the patient’s PBMCs showed a lower respiration rate, an increase in reactive oxygen species production and the presence of mitochondrial depolarization, compared to an age- and sex-matched healthy control’s PBMCs. Conclusions: A novel variant in the MT-CYB:m.15309T>C (Ile188Thr) gene was identified in a patient with optic nerve damage and the LHON phenotype without any additional systemic features and atypical presentation of the disease with late onset of visual function recovery. The pathogenicity of the variant is supported by proteomic analysis and the mitochondrial dysfunction observed in the patient’s PBMCs. Full article

Five representatives of a novel type of di(hydroperoxy)alkane adducts of phosphine oxides have been synthesized and fully characterized, including their solubility in organic solvents. The phosphine oxide Cy₃PO (1) has been used in combination with the corresponding aldehydes to create the adducts Cy₃PO·(HOO)₂CHCH₃ (2), Cy₃PO·(HOO)₂CHCH₂CH₃ (3), Cy₃PO·(HOO)₂CH(CH₂)₂CH₃ (4), Cy₃PO·(HOO)₂CH(CH₂)₃CH₃ (5), and Cy₃PO·(HOO)₂CH(CH₂)₇CH₃ (6). All adducts crystallize easily and contain the peroxide and phosphine oxide hydrogen-bonded in 1:1 ratios. The single crystal X-ray structures of 2–6 and their unique features are discussed. The ³¹P NMR spectra of the adducts 2–6 show downfield-shifted signals as compared to Cy₃PO. In the IR spectra, the ν(P=O) wavenumbers of the adducts have smaller values than the neat phosphine oxide. All spectroscopic results of 2–6 show that the P=O bond is weakened by hydrogen-bonding to the di(hydroperoxy)alkane moieties. Adduct 6 selectively oxidizes PPh₃ to OPPh₃ within minutes, and nonanal is reformed in the process. The easy synthesis, handling, and administration of these stable, solid, and soluble peroxides with well-defined composition will have a positive impact on synthetic chemistry. Full article

Background: The present study aimed to evaluate the potential synergy between pharmaceutical formulations containing Bixa orellana L. (granulated—CHR OR and injectable nanodispersion—CHR IN) in conjunction with a cannabidiol (CBD)-rich extract of Cannabis sativa L. (CSE) on experimental pain models in Wistar rats. Methods: Chemical analysis was performed using gas chromatography (GC-MS). The pain tests employed were acetic acid-induced writhing (injection i.p. of 0.9% acetic acid), formalin (solution 1%), hot plate (55 ± 0.5 °C), and cold-water tail withdrawal tests. Results: Chemical analyses by chromatography confirmed that the oil from B. orellana is rich in δ-tocotrienol (72.0 ± 1.0%), while the oil from Cannabis sativa highlighted the presence of cannabidiol (CBD). The results from the experimental pain tests indicated that the combined administration of formulations containing Bixa orellana and C. sativa, such as the granulated CHR OR (400 mg/kg, orally) with CSE (40 mg/kg, orally) or the nanodispersion CHR IN (10 mg/kg, intramuscularly) with CSE (40 mg/kg, orally), demonstrated significant results (p < 0.001) in pain reduction. Although the formulations containing Bixa orellana extract showed statistical significance in the tests when used in isolation, their effects were inferior compared to the combined use with CSE or the isolated use of CSE. These findings suggest that combining formulations containing extracts of these plant species may represent a viable therapeutic option, considering the synergistic action in reducing pain under the experimental conditions employed. Conclusions: these results imply that combining the phytocomplexes present in B. orellana and C. sativa may be a promising approach for pain treatment. Full article