Search Results (142)

V. parahaemolyticus has several virulence factors, including thermostable direct hemolysin (TDH), TDH-related hemolysin (TRH), and two separate type III secretion systems (T3SSs), T3SS1 and T3SS2. T3SS1 is responsible for cytotoxicity, primarily through the activity of its effector VP1680. To gain a detailed understanding of the relationship between the amount of effector, its expression timing, and cytotoxicity, a system is required to regulate protein expression levels and timing. In the present study, we developed an effector protein expression system controlled by an arabinose-dependent transcription factor and found that cytotoxicity toward mammalian cells increased in a VP1680-dependent manner. To ensure specific protein degradation, we also established a targeted protein degradation system, including VP0917 (ClpP) and VP0918 (ClpX)-, or VP0917 and VP1014 (ClpA)-mediated degradation of ssrA-tagged proteins (proteins bearing the C-terminal degradation tag encoded by tmRNA). By combining these systems, more than 50% of the targeted protein could be degraded within 20 min. As a byproduct of creating the systems, we obtained an enhanced green fluorescent protein variant that emits strong fluorescence in V. parahaemolyticus. The protein degradation system developed in this study has demonstrated the potential to control intracellular protein levels to a certain extent. Moreover, experimentally controlling intracellular protein levels will allow for a more detailed examination of the relationship between protein quantity and cellular phenotype, potentially overcoming the limitations of the “all-or-nothing” model. Full article

The physiological efficacy of plant-based matrices is often limited because bioactive compounds are sequestered within complex lignocellulosic architectures, restricting their release and downstream activity. Fermentation-driven enzymatic biotransformation can overcome these structural barriers; however, the mechanisms by which fermentation-derived, non-viable functional ingredients (postbiotics) confer benefits remain incompletely defined. Here, we examined whether a postbiotic-rich, co-fermented plant matrix enhances host resilience under metabolic stress and whether such effects are accompanied by a remodeling of gut microbial functional capacity. A functional plant matrix was produced by solid-state co-fermentation using two Lactobacillus plantarum strains selected for complementary lignocellulolytic profiles. Untargeted metabolomics and deep shotgun metagenomic sequencing were integrated with a hydrocortisone-induced murine metabolic stress model to quantify substrate remodeling, host neuroendocrine/behavioral outcomes, and microbiome functional reprogramming. Co-fermentation markedly remodeled the phytochemical landscape, increasing extractable flavonoids and generating distinct metabolite clusters. In vivo, administration of the postbiotic-rich matrix partially normalized stress-responsive neuroendocrine markers (ACTH, TRH, and testosterone) and improved behavioral outcomes in open-field and forced swim assays. These systemic changes were paralleled by a coordinated shift in microbial functional potential, including the enrichment of carbohydrate-active enzyme (CAZyme) families involved in complex polysaccharide utilization (e.g., AA9, GH129, CE14) and attenuation of phosphotransferase system modules and cytochrome P450-related functions. Enzymatic synergy-driven biotransformation yields a postbiotic-rich functional matrix that is associated with a selective remodeling of gut microbiome metabolic potential under stress and concomitant improvement in host physiological resilience. This study underscores microbial functional remodeling as a critical mechanistic interface linking fermentation-modified substrates to host physiological recovery, providing a molecular framework for the development of targeted postbiotic interventions. Full article

Thyroid hormones (THs) are master controllers in the endocrine system and have drawn considerable attention from the research community due to their associations with neurodegenerative diseases as well. In this review article, we present a comprehensive summary of the physiological functions and pathogenic mechanisms of THs in the regulation of several representative neurodegenerative diseases. Our study particularly focuses on Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). AD is the most common cause of dementia, primarily caused by tau protein tangles inside nerve cells and β-amyloid plaques outside, which lead to nerve cell death and brain atrophy. PD is primarily a movement disorder. The degeneration of dopaminergic neurons in the brain impairs the brain’s control over muscle activity. MS is usually considered to be an autoimmune demyelinating disease, but it has been found that MS also presents with secondary neurodegenerative pathology, including axonal loss and neuronal damage. In this review, the effects of TH on the pathogeneses of AD, PD, and MS are discussed in detail, with a focus on the following potential mechanisms: neuroprotection, neurogenesis, oxidative stress, and inflammatory response. In addition, we conduct an in-depth review of the possible clinical applications of TH, TH analogs, and thyrotropin-releasing hormone (TRH) in the treatment of AD, PD, and MS based on recent preclinical and clinical studies. By integrating experimental, clinical, and epidemiological results on the effects of TH on neurodegeneration, the present review constructs a theoretical basis for the involvement of TH in the pathogeneses of these diseases in detail. We believe that this basis will be useful for clinical diagnosis and treatment. Full article

Managing rutting aggression is critical in sika deer (Cervus nippon) farming. To mitigate rutting aggression in male sika deer, this study evaluated the efficacy, safety, and physiological mechanisms of exogenous progesterone. Twelve sika deer were randomly assigned to either a control group or a treatment group, with behavior monitored for 60 days post-administration. Serum hormones, non-targeted serum metabolomics, biochemical indicators (including reflecting liver and kidney function), and subsequent antler performance were assessed. The treatment group exhibited significantly reduced aggressive and mating behavior throughout the study (p < 0.05). HPG axis hormones (GnRH, LH, FSH, and T) and PRL were significantly reduced throughout the study (p < 0.05), while TRH was elevated, T4 declined, and GH showed time-dependent fluctuations. Differential metabolites were significantly enriched in pathways related to nucleotide metabolism, pyruvate metabolism, and arachidonic acid metabolism. Except for a transient decrease in the ALB/GLB ratio (p < 0.05), no significant changes were observed in other biochemical indicators or antler performance (p > 0.05). This study confirms that exogenous progesterone effectively controls rutting behavior primarily via HPG-axis suppression and multi-system endocrine interactions, without inducing detectable organ toxicity or compromising production, supporting its use as a safe management intervention. Full article

Background and Objectives: Inadvertent perioperative hypothermia is a common and clinically significant complication during laparoscopic surgery, leading to pain, agitation, shivering, and delayed recovery. This randomized controlled trial evaluated the effect of peri-induction active warming with an electric resistive blanket on postoperative pain and agitation—the primary outcomes—compared with passive insulation. Materials and Methods: This study was registered at ClinicalTrials.gov (Identifier: NCT06022926; date of registration: 15 August 2023) prior to the enrollment of the first patient. One hundred and thirty-two American Society of Anesthesiologists I–II adults undergoing laparoscopic cholecystectomy were randomly allocated (1:1) to two groups: one received active warming with a resistive carbon fiber underbody blanket (Group 1), and the other received passive insulation (Group 2). The tympanic core temperature was measured at four perioperative time points (TT1–TT4). Postoperative agitation (Riker Sedation–Agitation Scale, RSAS) and pain (Numerical Rating Scale, NRS) were assessed 20 min after extubation in the post-anesthesia care unit (PACU). Secondary outcomes included intraoperative and postoperative temperature, postoperative shivering, adverse events (bradycardia, tachycardia, hypotension, hypertension, postoperative nausea and vomiting, and respiratory depression), and the PACU length of stay. Results: Baseline core temperatures (TT1) were similar between the groups (36.5 ± 0.55 °C vs. 36.6 ± 0.54 °C; p = 1.00). However, mean core temperatures at TT2, TT3, and TT4 were significantly higher in the active warming group compared with the control group (TT2: 36.7 ± 0.53 °C vs. 36.5 ± 0.54 °C; TT3: 36.6 ± 0.49 °C vs. 36.4 ± 0.54 °C; TT4: 36.6 ± 0.51 °C vs. 36.2 ± 0.52 °C; all p < 0.001). Active warming markedly reduced postoperative agitation (RSAS ≥ 5: 3.1% vs. 19.4%, p = 0.004) and pain (NRS ≥ 4: 15.4% vs. 49.3%, p < 0.001). The incidence of shivering was lower (20.0% vs. 46.3%, p = 0.006), and the PACU stay was shorter (24 [23–28] min vs. 35 [30–40] min, p < 0.001) with active warming. No significant differences in adverse events were observed between groups. Logistic regression identified the intraoperative fentanyl dose as a predictor of agitation and identified shivering and the PACU duration as predictors of pain. Conclusions: Peri-induction active warming effectively maintained normothermia and improved recovery quality by reducing postoperative agitation, pain, shivering, and PACU stays without increasing adverse events. It should be considered a standard component of thermal management in short- and medium-duration laparoscopic surgeries. Full article

Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic–pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. Between February 2021 and November 2025, 1251 patients with long COVID were evaluated, of whom 207 (19%) had relatively low random ACTH or cortisol levels. Ultimately, 16 underwent anterior pituitary stimulation tests and were included. All tests were performed in an inpatient setting without exogenous steroids. Fifteen patients (six women, mean age 35.6 years) underwent corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH) tests. All patients had mild acute COVID-19, eight had ≥2 vaccinations, and the mean interval from infection was 343 days. Frequent symptoms included fatigue (100%), insomnia (66.7%), headache (60.0%), anorexia/nausea (40.0%), and brain fog (40.0%). Mean early-morning cortisol and 24 h urinary free cortisol were 7.5 μg/dL and 41.0 μg/day, respectively. MRI showed an empty sella in one case. Peak hormonal responses were preserved (ΔACTH 247%, ΔTSH 918%, ΔPRL 820%, ΔFSH 187%, ΔLH 1150%); however, peaks were delayed beyond 60 min in ACTH (13%), LH (33%), and FSH (87%). Notably, significantly delayed elevations remained at 120 min in the responses of TSH (4.1-fold), PRL (1.8-fold), LH (9.3-fold), and FSH (2.8-fold), suggesting possible hypothalamic involvement, particularly in the gonadotropin responses. Additionally, serum IGF-I was lowered (−0.70 SD), while GH response (mean peak 35.5 ng/mL) was preserved by growth hormone-releasing peptide (GHRP)-2 stimulation. Low-dose hydrocortisone and testosterone were initiated for three patients. Although direct viral effects and secondary suppression have been proposed, our findings may suggest that, at least in part, the observed response characteristics are consistent with functional secondary hypothalamic dysfunction rather than irreversible primary injury. These findings highlight the need for objective endocrine evaluation before initiating hormone replacements. Full article

Silver tarnishing in museum environments depends on multiple, interacting factors that are not often studied in situ. With the aim of addressing the problem in real-world scenarios, this study presents a one-year assessment at the National Archaeological Museum of Spain, in Madrid, a museum that houses a significant collection of silver objects. Pure Ag coupons were placed in four display cases—two designs with different airtightness—and in an adjacent gallery. Tarnishing was quantified by colorimetry, gravimetry, and galvanostatic reduction, and analyzed in relation to environmental parameters (T/RH) and gaseous pollutants (H₂S, SO₂, HF, HCl, formic and acetic acids), measured with passive samplers. Coupons showed different degrees of tarnish, with annual corrosion rates ranging from IC1 (very low) to IC2 (low), without a straightforward relation to hydrogen sulfide concentrations. Electrochemical profiles and XPS on representative coupons identified Ag₂S as the dominant product, with AgCl and minor Ag₂SO₄ in the coupons exposed outside the airtight cases, indicating different contributions inside and outside the cases. Findings highlight that sulfide concentration is not the sole driver; case airtightness, internal materials, cleaning products used on adjacent areas, and, possibly, other aspects influence silver tarnishing. Full article

Changes in vegetation coverage reflect the status and dynamic processes of ecosystems and serve as a crucial foundation for regional ecological protection. Using Landsat-5 and Sentinel-2 data, this study calculated the vegetation coverage in the Three-River Headwaters (TRH) region from 1990 to 2022 with the pixel dichotomy model, identified land cover changes over the past three decades via a deep neural network, and analyzed the primary influencing factors behind vegetation coverage dynamics. The results indicate that vegetation coverage in TRH has generally increased, as very high vegetation coverage expanded by 10.3%, while very low and low vegetation coverage decreased by 4.2%. Extensive bare land in the western region decreased and transformed into grassland, while the areas of shrubland and forest in the central and eastern TRH areas increased. The areas of grassland, shrubland, and forest increased by 3.7 × 10⁴ km², 2.1 × 10⁴ km², and 4.7 × 10³ km², respectively. Precipitation, elevation, and temperature are the main factors influencing the spatial variation in vegetation coverage. We found that the contributions of the permafrost active layer thickness and precipitation to changes in vegetation coverage are high. Finally, we provide a detailed and timely analysis of recent vegetation distribution and type changes on the Tibetan Plateau, offering a strengthened scientific foundation for monitoring, assessment, and ecological conservation efforts aimed at supporting ecosystem restoration in the region. Full article

Anal cancer is high in men who have sex with men living with human immunodeficiency virus (MSM-LWHIV). This cancer is strongly associated with high-risk human papillomavirus (HR-HPV) infection. Anal cancer screening using cytology and high-resolution anoscopy (HRA) for diagnosis of anal intraepithelial neoplasia requires specialized expertise. Biomarkers for the diagnosis of abnormal anal cells are of interest. Thyrotropin-releasing hormone (TRH) methylation at cg01009664 was detected using a pyrosequencing assay to compare methylation patterns among different anal lesions. Our results demonstrated that TRH methylation was significantly hypermethylated in anal intraepithelial neoplasia (AIN3) (>20%) and AIN1-2 (>10%) but less methylated in normal (<10%) (p < 0.001). TRH gene methylation showed higher sensitivity than the cytology for predicting AIN1+ (75.96% vs. 25.37%, respectively) and AIN2+ (78.95%% vs. 19.23%, respectively). There was no significant correlation between TRH methylation and the percentage of CD4 in patients with HIV (p > 0.05). TRH methylation in anal swabs reflects the presence of anal intraepithelial neoplasia. Methylation analysis showed higher sensitivity than cytology for high-grade lesions and was independent of immune status. These findings support its use as a screening tool to preselect patients for HRA, potentially reducing unnecessary procedures while maintaining diagnostic accuracy. Full article

A series of multi-parameter, multi-layer observations was conducted to study possible electromagnetic precursors associated with the M 6.7 earthquake that struck Iburi, Hokkaido, Japan, at 18:07:59 UT on 5 September 2018. The most significant observation is seismogenic lower-ionospheric perturbations in the propagation anomalies of sub-ionospheric VLF/LF signals recorded in Japan and Russia. Other substantial observations include the GIM-TEC irregularities, the intensification of stratospheric atmospheric gravity waves (AGWs), and the satellite and ground monitoring of air temperature (T), relative humidity (RH), atmospheric chemical potential (ACP), and surface latent heat flux (SLHF). We have found that there were very remarkable VLF/LF anomalies indicative of lower-ionospheric perturbations observed on 4 and 5 September just before the EQ date and even after it from the observations in Japan and Russia. In particular, the anomaly was detected for a particular propagation path from the JJY transmitter (Fukushima) to a VLF station at Wakkanai one day before the EQ, i.e., on 4 September, and is objectively confirmed by machine/deep learning analysis. An anomaly in TEC occurred only on 5 September, but it is unclear whether it is related to a pre-EQ effect or a minor geomagnetic storm. We attempted to determine whether any seismo-related atmospheric gravity wave (AGW) activity occurred in the stratosphere. Although numerous anomalies were detected, they are most likely associated with convective weather phenomena, including a typhoon. Finally, the Earth’s surface parameters based on satellite monitoring seem to indicate some anomalies from 29 August to 3, 4, and 5 September, a few days prior to EQ data, but the ground-based observation close to the EQ epicenter has indicated a clear T/RH and ACP on 2 September with fair weather, but no significant data on subsequent days because of severe meteorological activities. By integrating multi-layer observations, the LAIC (lithosphere–atmosphere–ionosphere coupling) process for the Hokkaido earthquake appears to follow a slow diffusion-type channel, where ionospheric perturbations arise a few days after ground thermal anomalies. This study also provides integrated evidence linking concurrent lower-ionospheric, atmospheric, and surface thermal anomalies, emphasizing the diagnostic value of such multi-parameter observations in understanding EQ-associated precursor signatures. Full article

Neuropeptide Y (NPY) is a small signalling molecule produced by neurons through the cleavage of a precursor protein. It generally binds to and activates G protein-coupled receptors to modulate complex homeostatic processes and behaviours in animals. Mammals provide definitive proof of the role of NPY in the thyroid axis, but in reptiles, this link is unclear. We demonstrate that the thyroid axis responds to NPY administration in a dose-dependent manner, with a reduction in plasma TRH and TSH concentrations, and an increase in plasma T₃ and T₄ levels 2 and 24 h after administration, suggesting that NPY may activate the thyroid axis. This increase in thyroid hormones is supported by morphological findings in the thyroid gland, which show clear signs of stimulation demonstrated by a dose-dependent increase in the height of the follicular epithelium and the presence of numerous resorption vacuoles. Moreover, we investigated the 5-T₄ ORD (type II) Monodeiodinase activity at the hepatic level, showing that NPY increased hepatic T₃ levels and decreased hepatic T₄ levels, and suggesting an alternative mode of signalling by NPY on peripheral biosynthesis of thyroid hormones. Our study helps to address the current lack of research in the field of endocrinology concerning the effects of NPY on metabolism and thyroid function. Full article

Background and Objectives: Left ventricular diastolic dysfunction (LVDD) is a known precursor of heart failure with preserved ejection fraction (HFpEF), particularly in patients with metabolic comorbidities. Acute coronary syndrome (ACS) and percutaneous coronary interventions (PCI) may exacerbate LVDD via systemic inflammation. This study aimed to explore the association between post-procedural systemic inflammation and the severity of diastolic dysfunction in patients with ACS and metabolic comorbidities. Materials and Methods: A retrospective observational study was conducted in 181 patients with ACS who underwent PCI. Inflammatory markers (leukocytes, neutrophils, and C-reactive protein [CRP]) measured at 24–48 h post-intervention were analyzed in relation to diastolic dysfunction, assessed by echocardiography. Multivariable ordinal logistic regression and correlation analyses were performed. Results: CRP showed a non-significant trend toward association with more advanced diastolic dysfunction (p = 0.081). Hypertension had a positive but nonsignificant coefficient. Other metabolic comorbidities (diabetes, dyslipidemia, and obesity) were not significantly associated. The correlation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin was exploratory. NT-proBNP was the only marker significantly correlated with high-sensitivity troponin (TrHS) at 48 h, indicating a link between myocardial injury and wall stress. Conclusions: CRP may be weakly associated with the severity of diastolic dysfunction post-PCI. However, classical metabolic comorbidities were not independently predictive. Post-PCI inflammation showed only modest, non-significant trends toward diastolic impairment, warranting confirmation in larger prospective studies. Full article

In birds, light can penetrate the cranial bones and reach deep brain regions, where non-visual photoreceptors, especially in the hypothalamus, detect spectral and photoperiodic cues. Alongside retinal photoreception, deep-brain light sensing contributes to circadian entrainment and regulates melatonin secretion by the pineal gland. These light-driven pathways modulate endocrine activity, playing a key role in muscle development. This review explores how monochromatic light-emitting diode (LED) illumination, particularly green and blue wavelengths, affects the somatotropic axis (growth hormone-releasing hormone [GHRH]-growth hormone [GH]-insulin-like growth factor 1 [IGF-1]), the gonadal axis (gonadotropin-releasing hormone [GnRH]-luteinizing hormone [LH]/follicle-stimulating hormone [FSH]-sex steroids [testosterone, estrogen, progesterone]), the thyroid axis (thyrotropin-releasing hormone [TRH]-thyroid-stimulating hormone [TSH]-thyroxine [T₄]/triiodothyronine [T₃]), and the hypothalamic-pituitary-adrenal (HPA) axis (corticotropin-releasing hormone [CRH]-adrenocorticotropic hormone [ACTH]-corticosterone). Green light enhances early-stage muscle growth via GHRH and IGF-1 upregulation, while blue light supports later myogenic activity and oxidative balance. Light schedules also influence melatonin dynamics, which in turn modulate endocrine axis responsiveness to photic cues. Furthermore, variations in photoperiod and exposure to artificial lights at night (ALAN) affect thyroid activity and HPA axis reactivity, influencing metabolism, thermoregulation, and stress resilience. Together, ocular and intracranial photoreception form a complex network that links environmental light to hormonal regulation and muscle growth. These insights support the strategic use of LED lighting to optimize broiler performance and welfare. Full article

In this article, we provide a study of the energy calibration model used for Timepix-type detectors. The Timepix detectors, operating in Time-over-Threshold mode, measure information that needs to be mapped into the corresponding energies using a non-linear function. We consider three iterative algorithms, Gradient-Descent, Gauss–Newton and Levenberg–Marquardt algorithm, which we modify according to the calibration model constraints to perform better in terms of the convergence properties. Moreover, based on the variable projection method, we suggest a partial linearization of the calibration problem and provide results for this novel method. Full article

Background/Objectives: Breast cancer is a leading cause of cancer-related mortality among women worldwide. Small nucleolar RNAs (snoRNAs) represent a class of non-coding RNAs with potential as novel biomarkers applicable to improve diagnostic and prognostic applications. Methods: We performed a comprehensive evaluation of the snoRNA-related gene expression by qPCR using benign and tumor tissue samples associated with invasive breast carcinomas of no special type (NST). Selected candidate snoRNAs, i.e., SCARNA2, SCARNA3, SNORD15B, SNORD94, SNORA68, and SNHG1, along with RNU2-1 snRNA, were further validated and their associations with clinicopathological parameters were examined. External datasets and plasma samples were used for additional validation. Results: SCARNA2 was identified as the most promising snoRNA biomarker candidate, showing a positive association with better progression-free survival (PFS) in our data (13.3-month survival difference between low- and high-expression groups) and with both PFS and overall survival in external RNA-seq datasets. SNORD94, SNORD15B, SCARNA3, and RNU2-1 snRNA were also indicated as putative tumor suppressors. SNORD94 was associated with better progression-free survival (PFS) in our data as well (12.4-month survival difference between low- and high expression groups). Greater downregulation in the low-expression tumor subgroup compared to benign samples further supports the prognostic potential of SCARNA2 and SNORD94. Evidence for SNHG1 and SNORA68 as putative oncogenes was less conclusive. Conclusions: Several small nucleolar RNAs were found to be dysregulated in breast cancer specimens, supporting their further evaluation as potential biomarkers. In particular, SCARNA2, SNORD94, SNORD15B, SCARNA3, and RNU2-1 snRNA merit further investigation to determine their clinical relevance and biological roles in breast cancer. Full article