Search Results (3,391)

Background/Objectives: Successful discourse relies not only on linguistic but also on prosodic information. Difficulty recognizing emotion conveyed through prosody (receptive affective aprosodia) following right hemisphere stroke (RHS) significantly disrupts communication participation and personal relationships. Growing evidence suggests that damage to white matter in addition to gray matter structures impairs affective prosody recognition. The current study investigates lesion–symptom associations in receptive affective aprosodia during RHS recovery by assessing whether disruptions in distinct white matter structures impact different underlying affective prosody recognition skills. Methods: Twenty-eight adults with RHS underwent neuroimaging and behavioral testing at acute, subacute, and chronic timepoints. Fifty-seven healthy matched controls completed the same behavioral testing, which comprised tasks targeting affective prosody recognition and underlying perceptual, cognitive, and linguistic skills. Linear mixed-effects models and multivariable linear regression were used to assess behavioral performance recovery and lesion–symptom associations. Results: Controls outperformed RHS participants on behavioral tasks earlier in recovery, and RHS participants’ affective prosody recognition significantly improved from acute to chronic testing. Affective prosody and emotional facial expression recognition were affected by external capsule and inferior fronto-occipital fasciculus lesions while sagittal stratum lesions impacted prosodic feature recognition. Accessing semantic representations of emotions implicated the superior longitudinal fasciculus. Conclusions: These findings replicate previously observed associations between right white matter tracts and affective prosody recognition and further identify lesion–symptom associations of underlying prosodic recognition skills throughout recovery. Investigation into prosody’s behavioral components and how they are affected by injury can help further intervention development and planning. Full article

Humulus lupulus L. (hop) is a multipurpose crop valued for its essential role in beer production and for its bioactive compounds with recognized medicinal properties. Otherwise, climate change represents a major challenge to agriculture, particularly impacting the cultivation of crops with stenoecious characteristics, such as hop. This highlights the urgent need to enhance crop resilience to adverse environmental conditions. The phytohormone abscisic acid (ABA) is a key regulator of plant responses to abiotic stress, yet the ABA signaling pathway remains poorly characterized in hop. Harnessing the publicly available hop genomics resources, we identified eight members of the PYRABACTIN RESISTANCE 1 LIKE ABA receptor family (HlPYLs). Phylogenetic and gene structure analyses classified these HlPYLs into the three canonical ABA receptor subfamilies. Furthermore, all eight HlPYLs are likely functional, as suggested by the protein sequence visual analysis. Expression profiling indicates that ABA perception in hop is primarily mediated by the HlPYL1-like and HlPYL8-like subfamilies, while the HlPYL4-like group appears to play a more limited role. Structure modeling and topology predictions of HlPYL1b and HlPYL2 provided insights into their potential functional mechanisms. To assess the physiological relevance of ABA signaling in hop, we evaluated the impact of exogenous ABA application during the ex vitro acclimatization phase. ABA-treated plants exhibited more robust growth, reduced stress symptoms, and improved acclimatization success. These effects were associated with reduced leaf transpiration and enhanced stomatal closure, consistent with ABA-mediated drought tolerance mechanisms. Altogether, this study provides the first comprehensive characterization of ABA receptor components in hop and demonstrates the practical utility of ABA in improving plant performance under ex vitro conditions. These findings lay the groundwork for further functional studies and highlight ABA signaling as a promising target for enhancing stress resilience in hop, with broader implications for sustainable agriculture in the face of climate change. Full article

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease (IBD) that has been associated with overconsumption of calories and lipids, compared to the healthy population, and summer temperatures have been reported to be closely related to the prevalence of UC. To evaluate the effects of dietary and lifestyle factors on UC, a combination of 2.0% dextran sulfate sodium (DSS), a high-fat/high-sugar diet, and exposure to high temperature and humidity was used to construct mouse models of UC. Changes in body weight, disease activity index (DAI) scores, histopathological analysis, serum lipid levels, serum diamine oxidase (DAO), and D-Lactate (D-LA) levels, as well as the expression of inflammatory cytokines and tight junction proteins in colonic tissue, were all assessed to study the impacts of the high-fat/high-sugar diet and high-temperature/high-humidity exposure on the progression of UC. The symptoms observed in the UC mouse model induced by 2.0% DSS alone were similar to those seen in patients with UC, while the high-fat and high-sugar diet, along with humid and hot exposure, exacerbated DSS-induced UC in the mice. This included more severe histopathological damage to the colon tissue, increased expression of pro-inflammatory cytokines (IL-6, IL-17A, and IL-1β), and a more significantly compromised intestinal barrier, characterized by the destruction of ZO-1 and elevated levels of DAO and D-LA. Additionally, the high-fat/high-sugar diet and high-temperature/high-humidity exposure led to further disturbances in glucose and lipid metabolism in the mice, which were not observed in those treated with DSS alone. This study is the first to investigate the effects of a high-fat/high-sugar diet and high-temperature/high-humidity exposure on the progression of UC. Full article

Background: Finasteride, a 5α-reductase inhibitor commonly prescribed for androgenetic alopecia, has been linked to persistent adverse effects after discontinuation, known as post-finasteride syndrome (PFS). Symptoms include neurological, psychiatric, sexual, and gastrointestinal disturbances. Emerging evidence suggests that PFS may involve disruption of sex steroid homeostasis, neuroactive steroid deficiency (notably allopregnanolone, ALLO), and gut–brain axis alterations. Objective: This study aimed to investigate the effects of finasteride withdrawal (FW) in a rat model and evaluate the potential protective effects of ALLO on gut and hypothalamic inflammation. Methods: Adult male Sprague Dawley rats were treated with finasteride for 20 days, followed by one month of drug withdrawal. A subgroup received ALLO treatment during the withdrawal. Histological, molecular, and biochemical analyses were performed on the colon and hypothalamus. Gut microbiota-derived metabolites and markers of neuroinflammation and blood–brain barrier (BBB) integrity were also assessed. Results: At FW, rats exhibited significant colonic inflammation, including a 4.3-fold increase in Mφ1 levels (p < 0.001), a 2.31-fold decrease in butyrate concentration (p < 0.01), and elevated hypothalamic GFAP and Iba-1 protein expression (+360%, p < 0.01 and +100%, p < 0.01, respectively). ALLO treatment rescued these parameters in both the colon and hypothalamus but only partially restored mucosal and BBB structural integrity, as well as the NF-κB/PPARγ pathway. Conclusions: This preclinical study shows that FW causes inflammation in both the gut and hypothalamus in rats. ALLO treatment helped reduce several of these effects. These results suggest ALLO could have a protective role and have potential as a treatment for PFS patients. Full article

Background/Objectives: Pituitary apoplexy (PA) is a rare medical emergency characterized by the sudden onset of symptoms resulting from hemorrhage and/or infarction within the pituitary gland. Precipitating factors include the use of dopamine agonists (DAs), whose main indication is the treatment of prolactin (PRL)-secreting pituitary neuroendocrine tumors (PitNETs), but which can also be considered in non-functioning PitNETs. Here we report a case of PA in a patient taking cabergoline for a non-functioning PitNET, followed by a review of the literature focusing on the cases of PA associated with the use of DAs. Methods: A review of the literature was performed, searching Pubmed for other clinical cases of PA associated with the use of DAs, from inception to March 2025. Results: We found 43 cases of PA associated with the use of DAs. All the patients had secreting tumors: 86% were classified as PRL-secreting PitNETs, 7% were classified as GH-secreting PitNETs, and 4.6% included a mixed PRL/GH-secreting PitNET and a TSH-secreting PitNET. By contrast, here we present a case of PA in a non-functioning PitNET during cabergoline therapy. Our patient was managed conservatively and endocrine function recovered spontaneously. In our case, cabergoline might have promoted PA, which is consistent with the reported efficacy of cabergoline in inducing tumor shrinkage of non-functioning PitNETs that express dopamine 2 receptors, including silent PIT1 and SF1 or NULL tumors. Conclusions: Our case confirms cabergoline efficacy in non-functioning PitNETs and sheds light on a possible complication of its use. Patients, particularly those with large tumors, should be closely monitored for this occurrence. Full article

Tomato yellow leaf curl virus (TYLCV) is a highly destructive pathogen of global tomato crops. The open reading frame (ORF) of TYLCV V2 contains two initiation codons (ATG1/V2-1 and ATG2/V2-2), producing distinct protein isoforms. Using custom antibodies, we confirmed V2-1 and V2-2 expression in infected Nicotiana benthamiana and tomato plants. Deletion mutants revealed their specialized roles: V2-1 was indispensable for viral replication and systemic spread—its loss severely reduced pathogenicity and genome accumulation. V2-2 acted as an auxiliary factor, and its deletion attenuated symptoms but kept the virus infection. Host-specific effects were observed—V2-1 deletion led to lower viral DNA/coat protein levels in N. benthamiana than in tomato, suggesting host-dependent regulation. Mutant viruses declined progressively in tomato, indicating host defense clearance. Heterologous co-expression of both isoforms via potato virus X induced systemic necrosis in N. benthamiana, demonstrating functional synergy between isoforms. Both initiation codons were essential for V2-mediated suppression of transcriptional gene silencing (TGS) and post-transcriptional gene silencing (PTGS). This study uncovers the mechanistic divergence of V2 isoforms in TYLCV infection, highlighting their collaborative roles in virulence and host manipulation. The findings advance understanding of geminivirus coding complexity and offer potential targets for resistance strategies. Full article

Accurately screening fathers for perinatal mental health problems requires well-validated screening instruments that assess the expression of paternal perinatal mental distress. This study aimed to identify and describe the psychometric properties of perinatal mental health screening instruments administered to paternal cohorts within the past two decades. A scoping review was conducted following Arksey and O’Malley’s scoping review framework and is reported in line with the PRISMA-ScR guidelines. A systematic search of Embase, PsycINFO, Medline, and ProQuest databases identified peer-reviewed literature published within the past 20 years that implemented a screening instrument for fathers’ perinatal mental health within the first 12 months of their child’s birth. Twenty-eight instruments used to screen fathers’ perinatal mental health were identified across 36 studies. The instruments most frequently assessed symptoms of depression. Only five were explicitly developed for fathers and while these instruments produced promising results, further evaluation is necessary before they can be considered a superior screening method compared to existing instruments. Full article

Soybean mosaic virus (SMV) causes systemic infections in soybean plants, leading to chlorotic mosaic and significant yield losses. In Argentina, during the 1990s, three isolates were collected in Marcos Juárez (MJ), Manfredi (M), and Northwestern Argentina (NOA), along with the “Planta Vinosa” (PV) isolate, which causes severe necrosis in some cultivars. These isolates were freeze-dried and stored at −70 °C for several years. They were recovered by mechanical inoculation and biologically, molecularly, and physiologically characterized for the first time. Three of the four isolates showed low genetic divergence in the P1, CI, and CP genes. Although SMV-NOA and SMV-PV had high nucleotide sequence identity, they differed in pathogenicity, seed mottling, and transmission efficiency by seeds or aphids. SMV-NOA caused early changes in photosystem II quantum efficiency (ɸPSII) and malondialdehyde (MDA) content before symptom expression (BS). After symptom development (LS), SMV-M significantly increased MDA, total soluble sugars, and starch compared to the other isolates. Thus, early changes in ɸPSII and sugars may influence late viral symptoms. Likewise, SMV-MJ induced more severe symptoms in the susceptible Davis cultivar than in Don Mario 4800. Therefore, our results demonstrate genomic, biological, and physiological differences among SMV isolates and variable interactions of SMV-MJ with two soybean cultivars. Full article

Background: Canine parvovirus (CPV) is a highly pathogenic virus that predominantly affects puppies, with mortality rates exceeding 70%. Although commercial multivalent live attenuated vaccines (MLV) are widely employed, their efficacy is often compromised by maternal antibody interference. Consequently, the development of novel vaccines remains imperative for effective CPV control. Methods: Recombinant CPV VP2 protein (rVP2) and canine interlukine 12 protein (rcIL-12) were expressed using the Bac-to-Bac baculovirus expression system and the biological activity of these proteins was assessed through hemagglutination, Cell Counting Kit-8 (CCK8) and IFN-γ induction assays. The combined immunoenhancement effect of rVP2 and rcIL-12 protein was evaluated in puppies. Results: Both rVP2 and rcIL-12 were successfully expressed and purified, exhibiting confirmed antigenicity, immunogenicity, and bioactivity. Co-administration of rVP2 with rcIL-12 elicited higher neutralizing antibody titer (6–7 times higher), complete challenge protection efficiency (no clinical symptoms and tissue and organ lesions), fewer viral shedding (decreasing significantly 8-day post challenge) and superior viral blockade (lower viral load in the organism) compared to rVP2 alone. Conclusions: Our findings demonstrate that rVP2 co-administered with rcIL-12 induces robust protective immunity in puppies and significantly mitigated the inhibitory effects of maternal antibodies. This represents a promising strategy for enabling earlier vaccination in puppies and rational design of CPV subunit vaccines. Full article

In our previous studies, methylated CpG oligodeoxynucleotides (ODN) derived from Bifidobacterium longum subsp. infantis have demonstrated immunomodulatory effects through the induction of regulatory T cells (Tregs). To define the structural determinants underlying this effect, we synthesized four CpG ODNs varying in methylation degree, CpG motif placement, and backbone length. These include (1) ODN-A (2m-V1), a 20-nucleotide CpG oligodeoxynucleotide incorporating two 5-methylcytosines at positions 4 and 12 within centrally placed CpG motifs; (2) ODN-B (um-V2), a 20-nucleotide CpG oligodeoxynucleotide with a backbone structure identical to ODN-A but unmethylated; (3) ODN-C (2m’-V3), a 20-nucleotide CpG oligodeoxynucleotide with a backbone structure identical to ODN-A, but with two 5-methylcytosines shifted to positions 7 and 15; (4) ODN-D (3m-V4), a 27-nucleotide CpG oligodeoxynucleotide with an extended backbone structure, this time with three 5-methylcytosines at positions 3, 11, and 19. Using a murine model of an OVA-induced allergy, we show that methylated ODN-A (2m-V1) and ODN-D (3m-V4) markedly reduce serum anti-OVA IgE, clinical symptoms, eosinophilic infiltration, and Th2/Th17 responses, while promoting splenic Treg expansion and IL-10 production. In contrast, unmethylated ODN-B (um-V2) and a positionally altered methylated ODN-C (2m’-V3) both failed to suppress allergic inflammation, and, in contrast, enhanced the Th2/Th17 response and induced robust in vitro Toll-like receptors TLR7/8/9 expression in native splenocytes. These findings suggest that both methylation and motif architecture critically influence the immunologic profile of CpG ODNs. Our results provide mechanistic insights into CpG ODN structure/function relationships and support the therapeutic potential of select methylated sequences for restoring immune tolerance in allergic diseases. Full article

Perfluorononanoic acid (PFNA) is a ubiquitous persistent environmental pollutant, and several studies have found significant links between atopic dermatitis (AD) and prenatal exposure to PFNA. However, the relationship between PFNA and AD remains unclear. In this study, 2,4-dinitrochlorobenzene (DNCB)-treated female BALB/c mice were used as AD models to investigate the effects of PFNA and its potential mechanisms. These mice were topically applied with 5 mg/kg PFNA per day for 15 days. The results demonstrated that PFNA significantly increased AD lesion severity and clinical symptoms, including dermatitis score, ear thickness, and epidermal thickness. In addition, PFNA also increased the serum IgE level, splenic atrophy, and upregulated the expression of TNF-α, IL-6, and IL-1β, genes that are associated with skin inflammatory factors. In addition, Western blot results showed that PFNA treatment upregulated the expression of p-JNK protein. Additionally, cellular experiments indicated that RAW264.7 macrophages and mouse brain microvascular endothelial (bEnd.3) cells treated with PFNA at concentrations of 0.01–100 μM for 72 h showed no changes in cell viability. However, 100 μM PFNA upregulated the mRNA expression levels of the pro-inflammatory cytokines IL-1β and IL-6, as well as the protein expression of p-JNK, in RAW264.7 cells induced with 1 mg/mL LPS for 2 h. Similarly, PFNA increased TNF-α and IL-6 mRNA expression and p-JNK protein expression in bEnd.3 cells stimulated with 20 ng/mL TNF-α for 0.5 h. Based on these findings, we can conclude that PFNA may aggravate atopic dermatitis by promoting inflammation. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder marked by relapsing episodes of gastrointestinal inflammation, potentially causing severe symptoms. These unpredictable acute episodes, paired with chronic disabilities, such as fatigue and malabsorption, and extensive pharmacological and surgical treatments, can severely impact patients’ quality of life. This study aimed to assess which aspects of the patients’ lives IBD impacts, and how IBD patients perceive their disease. Methods: All IBD patients who had an appointment in our tertiary centre from 10 October 2022 to 21 February 2023, were invited to complete anonymous questionnaires. The questionnaires used were IBDQ-32, WPAI, and IBD Disk, all designed specifically to assess the IBD patients’ quality of life. Results: The questionnaires were completed by a total of 159 participants, 51% of whom were males, 47.9% who had UC, and 49.4% who had been or were currently treated with biologics. There was no statistically significant difference in the answers from patients with CD compared to UC, as well as those treated with conventional therapies compared to those with advanced options. Most of them considered their health to be good, but only a few (12.8%) claimed, with absolute certainty, that their health was at the level of healthy individuals, and only 13 (8.3%) claimed their health was excellent. A total of 95 (60.1%) participants expressed at least minor limitations when performing strenuous activities, but lighter forms of activities were not affected as much by the disease. A significant portion (48.7%) of the participants believed they were exposed to more stress than others, and their current pharmacological therapy was the cause of fear in 26.5%. A total of 119 (75.3%) participants believed that the disease affected their lives at least mildly during remission. Conclusions: Our study showed that IBD patients have diminished quality of life, not only in the periods of active disease but also during clinical remission. The decline in quality of life was not solely attributed to physical symptoms, as previously thought. Other factors, such as mental health issues, were found to impact quality of life as well. We firmly believe that restoring quality of life should be emphasised in guidelines as one of the most important therapeutic goals. 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

Osteoarthritis (OA) is the most common chronic arthropathy worldwide. OA synovitis is a common feature that predicts the development and progression of symptoms and joint damage. Although the OA synovium is a target for novel therapies, the development of ex vivo models remains an area requiring further research. We aim to develop a 3D tissue explant culture model of human OA synovium that preserves the architecture and cellular heterogeneity of the original tissue in vitro. We derived tissue explant models from seven patients with OA and followed the culture for up to 10 days, assessing their morphology and cellular composition by immunohistochemistry (IHC) and flow cytometry, respectively. IHC analysis of explant cultures showed that tissue integrity and viability were maintained in our in vitro system. Furthermore, cellular heterogeneity was essentially unchanged when considering CD4⁺ T cells, CD8⁺ T cells, and myeloid fractions in our model. No significant variation was observed in the CD90⁺ and CD90^-CD55⁺ fractions, which also maintained an activated state as indicated by high levels of FAP expression. An ex vivo OA synovial tissue explant model can maintain pathological tissue integrity for 10 days in culture. This simple and reliable culture system may be useful for analyzing the pathogenesis of OA disease and for the development and testing of therapeutic drugs. Full article

Early biomarkers are needed to predict the long-term persistence of rheumatical symptoms in patients infected with Chikungunya virus (CHIKV). This nested case-control study aimed to assess immunological factors during the early phases of CHIKV infection to predict the risk of post-CHIK chronic rheumatism (pCHIK-CR) in adult patients of two prospective cohorts. We evaluated 46 febrile patients (median age: 33.5 years; IQR: 19 years; women: 50.0%) with CHIKV infection confirmed during the 2014–2015 outbreak in Santander, Colombia. The participants were classified by a rheumatologist as either cases (pCHIK-CR) or controls (WoRM, without rheumatical manifestations). We quantified serum levels of IL-4, IL-6, IL-8/CXCL-8, IL-27, CCL-2, CXCL-9, CXCL-10, and IgG using Luminex and ELISA assays during the acute and subacute phases of infection. Then, we evaluated the association of these immune factors with the case-control status using piecewise logistic regression adjusted for age and sex. There were non-linear associations between IL-8/CXCL-8, CXCL-9, and CXCL-10 with pCHIK-CR. Increases in the levels of IL-8/CXCL-8 (<35.7 pg/mL), CXCL-9 (≥6000 pg/mL), and CXCL-10 (≥36,800 pg/mL) were significantly associated with a reduced risk of pCHIK-CR (adjusted ORs: 0.85, 0.96, and 0.94, respectively). These results suggest that increases in IL-8/CXCL-8, CXCL-9, and CXCL-10 levels, measured in the early stages of CHIKV infection, may predict a chronic disease risk. This suggests the possibility that an early and strong immune response could contribute to enhancing CHIKV control and potentially reduce the risk of persistent joint symptoms. Given their expression patterns and timing, these three immune factors may be considered promising biomarker candidates for assessing the risk of chronic rheumatologic disease. These findings should be considered as exploratory and validated in additional cohort studies. Full article