Search Results (552)

Termite guts represent a unique microbial habitat harboring bacteria with potential probiotic properties, owing to their ability to inhibit pathogenic microorganisms. This study investigated the probiotic characteristics of lactic acid bacteria newly isolated from the guts of the termite Termes propinquus, aiming to enhance growth performance and reduce the incidence of foodborne pathogen contamination in the commonly consumed edible two-spotted crickets (Gryllus bimaculatus). In this study, five morphologically different bacteria (TPL-1 to TPL-5) were isolated and respectively identified as Levilactobacillus brevis, Lactiplantibacillus plantarum, Streptococcus anginosus, Companilactobacillus alimentarius, and Aerococcus viridans based on 16S rRNA gene sequences and MALDI-TOF MS. All isolates were evaluated for tolerance to stressful conditions (pH 2.5 and 0.3% bile salts), cell surface properties, antioxidant activity, antimicrobial activity against foodborne pathogens, safety profiles, and adhesion to human colon adenocarcinoma cells (Caco-2 and HT-29). Among them, Lactiplantibacillus plantarum TPL-2 demonstrated the strongest probiotic attributes and was further assessed for anti-adhesion activity against foodborne pathogens and in vivo effects on the crickets. Dietary supplementation with Lb. plantarum TPL-2 significantly improved cricket growth, survival, and gut microbiota homeostasis. These findings point to the prospect of termite-derived lactic acid bacteria as beneficial probiotics for use in biotechnological applications and edible insect farming. Full article

Background: Mitophagy is a critical mitochondrial quality control mechanism that limits neuronal injury following cerebral ischemia/reperfusion injury (CI/RI). Tetramethylpyrazine (TMP), a bioactive alkaloid from Ligusticum chuanxiong Hort., exhibits neuroprotective effects in cerebrovascular disorders. However, whether these effects involve mitophagy regulation remains unclear. Methods: CI/RI was induced using a middle cerebral artery occlusion/reperfusion (MCAO/R) model in mice and an oxygen–glucose deprivation/reoxygenation (OGD/R) model in HT22 cells. Neurological function, infarct volume, mitochondrial function, and mitophagy-related markers were assessed. Pharmacological inhibitors and genetic manipulation of YAP and Parkin were used to investigate underlying mechanisms. Results: TMP treatment significantly reduced infarct volume and improved neurological deficits in MCAO/R mice, accompanied by enhanced mitophagy, as indicated by increased mitochondrial LC3 recruitment and Parkin expression. In OGD/R-injured HT22 cells, TMP promoted mitophagosome and mitolysosome formation, reduced mitochondrial reactive oxygen species, and restored mitochondrial membrane potential. Inhibition of mitophagy with Mdivi-1 attenuated TMP-mediated neuroprotection. Mechanistically, TMP promoted YAP nuclear localization, and inhibition of YAP or silencing of Parkin abolished TMP-induced mitophagy, while Parkin overexpression restored mitophagy under YAP inhibition. Conclusions: TMP alleviates CI/RI by promoting mitophagy through the YAP/Parkin signaling pathway, suggesting mitophagy modulation as a potential therapeutic strategy for ischemic brain injury. Full article

Autoimmune thyroid diseases (AITD) are based on reactivity to thyroid self-antigens, resulting in varying degrees of persistent inflammation and glandular hyperplasia. The aim of this study was to investigate the interplay between angiogenesis, inflammation, and oxidative stress in patients with AITD. The study included patients with AITD, divided into a group with Hashimoto’s thyroiditis (HT) and a group with Graves’ disease (GD), as well as healthy controls. The results showed that subjects with GD had significantly higher concentrations of angiopoietin-2 (Ang-2) compared to those with HT and the healthy controls (p < 0.001). Inflammatory parameters (C-reactive protein (CRP), the systemic inflammatory immune response index (SII), and the CRP/albumin ratio (CRP/alb)) were higher in both AITD groups (p < 0.001). Oxidative stress parameters were more pronounced in AITD, while the activity of antioxidant enzymes was reduced. Ang-2 positively correlated with H₂O₂ (r = 0.394, p = 0.006) and NO (r = 0.519, p = 0.001) in HT, as well as with O₂⁻ (r = 0.232, p = 0.009) and TBARS (r = 0.190, p = 0.038) in GD, while in GD it showed a negative correlation with SOD (r = −0.426, p = 0.012) and CAT (r = −0.534, p = 0.008). Thus, angiogenesis, inflammation, and oxidative stress are interconnected processes in AITD, which may have significance for further understanding of the disease and the development of therapeutic approaches. Full article

Background/Objectives: Xu Chunfu’s Modified Xianglian Pill (XXLP) has been used for centuries in Chinese medicine to treat “diarrhea” and “dysentery,” conditions analogous to modern ulcerative colitis (UC). However, the scientific basis for its efficacy and mechanisms remains unclear. Methods: The chemical composition of XXLP was analyzed via UPLC-ESI-MS/MS. A colitis mouse model was established using DSS, and the therapeutic effects were assessed based on body weight, disease activity index (DAI), colon length, and histopathology. Inflammatory cytokines were measured using ELISA. Proteomic analysis and molecular docking identified key targets, which were validated using LPS-induced HT-29 cells via Western blot (WB), qRT-PCR, immunofluorescence (IF), and transmission electron microscopy (TEM). Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Results: Analysis of XXLP led to the detection of 373 compounds. XXLP significantly improved colitis symptoms, including weight loss and colon shortening, and reduced the concentrations of inflammatory markers IL-1β, IL-18, TNF-α, and IL-6. Proteomics and molecular docking identified NADPH oxidase 2 (NOX2) as a key target of XXLP intervention in mice with colitis. qRT-PCR, WB, IF, and TEM results further confirmed that XXLP effectively suppressed the expression of NOX2 and its associated protein levels. Sequencing analysis of 16S rRNA showed that XXLP significantly increased the relative abundance of beneficial bacterial genera (Muribaculaceae and Ruminococcaceae) while markedly reducing the levels of harmful bacteria (Enterobacteriaceae). Correlation analysis revealed that specific microorganisms were correlated with NOX2-related protein expression and severity of colonic inflammation. Conclusions: XXLP effectively alleviates colitis by suppressing inflammatory responses. Its mechanism involves regulating the NOX2/ROS/mitochondria/NLRP3 axis and altering gut microbiota composition, providing novel insights for colitis treatment. Full article

Surface cracks in integral structures of aircraft pose a significant threat to structural integrity. This paper investigates the three-dimensional propagation behavior and crack-arrest characteristics of surface-initiated cracks in the web of an integral wing spar manufactured from 7050-T7451 aluminum alloy. A three-dimensional finite element model is developed in ANSYS 2024R2 to evaluate the stress intensity factors (SIFs) along the crack front under representative displacement-controlled loading conditions. This paper focuses on comparing the crack-arrest effectiveness of different tear strap configurations by varying their height-to-thickness (H/T) ratios while maintaining a constant mass. The results indicate that surface crack propagation in the spar web is dominated by Mode I (opening mode). Among the investigated designs (H/T = 0.5, 2.0, and 8.0), the configuration with the smallest ratio (H/T = 0.5) exhibits the most effective crack-arrest capability, yielding the lowest crack-driving force as the crack approaches the strap. Furthermore, fatigue life estimates based on Paris’ law illustrate the dependence of remaining service life on the evaluated stress intensity factor evolution. These findings provide a comparative basis for the damage-tolerant design of integral metallic aircraft structures, suggesting that selecting appropriate geometric proportions for crack-arrest features can enhance resistance to surface crack propagation. Full article

To investigate the effects of dietary vitamin C (VC) supplementation at different concentrations (0, 5000, and 15,000 mg/kg) on the growth and feeding performance of sea cucumbers (Apostichopus japonicus), a 60-day feeding trial was conducted. The results demonstrated that supplementation with 5000 mg/kg VC significantly enhanced growth performance, evidenced by a higher specific growth rate and weight gain, along with a shorter feeding initiation time and increased tentacle feeding frequency. Furthermore, the activities of digestive enzymes—including amylase, lipase, and pepsin—were markedly elevated in the intestines of A. japonicus fed 5000 mg/kg VC, accompanied by increased mucus secretion in the oral tentacles. Correspondingly, intestinal 5-hydroxytryptamine (5-HT) levels and the expression of tryptophan hydroxylase (AjTPH) and 5-HT receptor (Aj5-HT4R) genes were significantly upregulated in the same group. In contrast, relatively lower growth performance was observed in the control (0 mg/kg) and high-dose (15,000 mg/kg) VC groups. Histological analysis further revealed that 5000 mg/kg VC increased villus height and width and thickened the intestinal muscle layer. Overall, dietary supplementation with 5000 mg/kg VC enhanced feeding activity, digestive function, and intestinal morphology, thereby promoting growth. However, excessive supplementation (15,000 mg/kg) failed to provide similar benefits and was associated with impaired performance. Full article

Background/Objectives: As the prevalence of depression and the use of antidepressants have risen steadily in the last decade, new treatment options are needed. Aloysia gratissima var. gratissima ethanol extract has previously shown antidepressant-like activity, and the present study was conducted to identify the active fraction and clarify the possible mechanisms of action. Methods: Tail suspension (TST) and forced swimming (FST) behavioral tests were performed, and possible mechanisms of action were elucidated using serotonergic, dopaminergic, adrenergic, and GABAergic system antagonists. UPLC-DAD-MS analyses were performed to identify compounds in active fractions, and molecular docking studies were carried out to determine the binding affinities of these compounds to serotonergic and dopaminergic receptors (5-HT_1A, 5-HT_2A, 5-HT₃, and D₂R). Results: Ethyl acetate and butanol fractions were found to decrease immobility time in FST. The reduction in immobility time during the FST caused by the ethyl acetate fraction was reversed by pretreating mice with WAY100635 (5-HT_1A antagonist), ketanserin (a 5-HT_2A antagonist, ondansetron (5-HT₃ antagonist), or haloperidol (D₂ antagonist). UPLC-DAD-MS analysis revealed a similar composition for the ethyl acetate and butanol fractions of A. gratissima var. gratissima. Pharmacokinetic predictions suggest that only a few of the identified compounds have the potential to permeate the blood–brain barrier, and molecular docking simulations showed that compounds such as 13-oxooctadecadienoic acid, ferulic acid, and coumaric acid have binding affinities to the druggable site of serotonergic and dopaminergic receptors. Conclusions: These results suggest that the Agg ethyl acetate fraction possesses antidepressant-like activities, altering dopaminergic and serotonergic system functions. Computational simulations also suggest that some of the identified compounds have binding affinities to the 5-HT_1A, 5-HT_2A, 5-HT₃, and D₂R receptors. Full article

Human breast milk harbors commensal lactic acid bacteria with probiotic potential, and microbial fermentation may enhance the bioactivity of plant-derived exosome-like nanovesicles (EVs); this study evaluated whether L. plantarum BMSE-HMP251 isolated from breast milk could safely ferment Hordeum vulgare L. and improve the anti-inflammatory activity of derived EVs. BMSE-HMP251 was identified by 16S rRNA sequencing and characterized by biochemical, safety, and genomic analyses. EVs derived from Hordeum vulgare L. extract and BMSE-HMP251-fermented broth were evaluated for physicochemical properties, antioxidant activity, cytotoxicity, and anti-inflammatory activity in LPS-stimulated HT-29 and RAW 264.7 cells. EVs derived from Hordeum vulgare L. fermentation exhibited a distinct size distribution and significantly enhanced bioactivity, including higher DPPH radical scavenging activity and greater suppression of nitric oxide production and proinflammatory cytokine (TNF-α and IL-1β) mRNA expression, compared with EVs from unfermented extracts. These effects were observed following fermentation with the human breast milk-derived strain L. plantarum BMSE-HMP251, which showed species-consistent phenotypic and genomic characteristics and no safety concerns. Overall, fermentation markedly enhances the anti-inflammatory potential of plant-derived EVs, supporting fermentation as a safe and effective strategy to improve their functional value. Full article

This article presents the general method of QR decomposition of $r$-qubit operations, $r\ge 3$, by means of quantum signal-induced heap transformations (QsiHT). These are quantum analogues of discrete signal-induced heap transformations, which are generated by given signals and paths, or orders, of processing the data. The case of the 5-qubit operations is described in detail, and a recurrent form of calculation of all 5-qubit QsiHTs from the 4-qubit QsiHTs is given. For that, roadmaps and quantum circuits are presented for all 31 5-point QsiHTs that are used in the QR decomposition. New roadmaps, namely the schemes with paths for performing basic operations on qubits, and corresponding quantum circuits, are also described for the 4- and 3-qubit transformations. All QsiHTs use fast paths, which allow us to calculate the QR decomposition only on disjoint bit planes. As a result, we build the quantum circuits for 5- and more-qubit operations without permutations, only elementary rotations. Unitary operations with real numbers are considered. In the general case, the method of compositing all the roadmaps and quantum schemes for the calculation of any $r$-qubit operation by only ${(2}^r-1)2^{r-1}$ elementary rotations is described. Full article

Anthropogenic CO₂ emissions drive ocean acidification through changes in the carbonate system, lowering seawater pH. In contrast, salinity variations arise from physical processes such as freshwater fluxes and circulation. This study reports the preparation and Harned cell characterization of three equimolal TRIS buffer solutions (0.01 mol·kg⁻¹, 0.025 mol·kg⁻¹, and 0.04 mol·kg⁻¹) in artificial seawater (ASW) matrices with practical salinities of 35 and 50 and temperatures of 20 °C, 25 °C, and 30 °C. Determined pH_T values achieved expanded uncertainties ($U_{{\mathrm{p}\mathrm{H}}_{\mathrm{T}}}$ ≤ 0.006), meeting Global Ocean Acidification Observing Network (GOA-ON) “climate” quality standards. Absolute salinity (S_A) was concurrently measured via density (TEOS-10), revealing systematic deviations from practical salinity due to TRIS content. A nonlinear regression model was developed to predict pH_T as a function of salinity, temperature, and TRIS molality, with r² = 0.99998. These results provide a robust dataset for developing Certified Reference Materials (CRMs) for pH_T calibration under climate-relevant high-salinity environments at different temperature conditions, offering a practical tool for high-accuracy calibration in variable marine conditions. Full article

Background: Hashimoto’s thyroiditis (HT) is a prevalent autoimmune disorder, often diagnosed late due to its asymptomatic or nonspecific presentation. Emerging evidence suggests that gut-derived lipopolysaccharides (LPS) may contribute to autoimmune activation. Objective: The primary objective of this study was to assess circulating LPS concentrations and dietary patterns in patients with Hashimoto’s thyroiditis compared to healthy controls. Methods: A hospital-based case–control study was conducted involving 105 HT patients and 25 healthy controls. Serum LPS concentrations, thyroid hormone profiles, and autoantibody levels were assessed. Dietary patterns were evaluated using the validated KomPAN questionnaire. Results: HT patients exhibited significantly higher serum LPS levels, particularly those with elevated anti-TPO and TRAB antibodies. A positive correlation was found between LPS and the fT3/fT4 ratio (r = 0.247, p = 0.006), and a negative correlation with fT4 (r = −0.314, p < 0.001). Dietary analysis revealed lower Pro-Healthy Diet Index scores in HT patients (3.94 vs. 5.34, p = 0.001), with increased consumption of processed foods and reduced intake of whole grains and oats. Conclusions: Elevated levels of lipopolysaccharides (LPS) and unhealthy dietary patterns may play a role in the development of thyroid autoimmunity. Taken together, these observations are consistent with a multifactorial model that potentially involves gut barrier dysfunction, endotoxemia, and nutritional factors in HT pathogenesis. Full article

In this work, we discuss a method for the QR-factorization of $N\times N$ matrices where $N\ge 3$ which is based on transformations which are called discrete signal-induced heap transformations (DsiHTs). These transformations are generated by given signals and can be composed by elementary rotations. The data processing order, or the path of the transformations, is an important characteristic of it, and the correct choice of such paths can lead to a significant reduction in the operation when calculating the factorization for large matrices. Such paths are called fast paths of the $N$-point DsiHTs, and they define sparse matrices with more zero coefficients than when calculating QR-factorization in the traditional path, that is, when processing data in the natural order $x_0,x_1,x_2,\dots$. For example, in the first stage of the factorization of a 512 $\times$ 512 matrix, a matrix is used with 257,024 zero coefficients out of a total of 262,144 coefficients when using the fast paths. For comparison, the calculations in the natural order require a 512 $\times$ 512 matrix with only 130,305 zero coefficients at this stage. The Householder reflection matrix has no zero coefficients. The number of multiplication operations for the QR-factorization by the fast DsiHTs is more than 40 times smaller than when using the Householder reflections and 20 times smaller when using DsiHTs with the natural paths. Examples with the 4 × 4, 5 × 5, and 8 × 8 matrices are described in detail. The concept of complex DsiHT with fast paths is also described and applied in the QR-factorization of complex square matrices. An example of the QR-factorization of a 256 $\times$ 256 complex matrix is also described and compared with the method of Householder reflections which is used in programming language MATLAB R2024b. Full article

Background: Three-dimensional (3D) cancer models are currently essential tools in high-throughput screening (HTS), serving as a bridge between in vitro and in vivo approaches during drug development. Even though spheroids offer many advantages over 2D cultures, analyzing 3D cultures with heterogeneous morphology remains challenging due to the lack of standardized visualization techniques and multiparameter analysis. Methods: In this work, an optimized CellProfiler pipeline and a Python algorithm for weighting morphological features are used to visualize, extract, and analyze morphological data from spheroids derived from colorectal and pancreatic cancer cell lines with diverse morphologies (HCT116, LoVo, PANC-1, and CFPAC-1). Results: We developed a feature weighting process that combines multiple morphological parameters into a single metric using principal component analysis (PCA). There is a strong correlation between this process and a standard Alamar Blue proliferation assay (r = 0.89, ρ = 0.91, p < 0.001). Using this method, we were able to ascertain the IC₅₀ values of substances that did not produce results in cell lines with heterogeneous morphology (LoVo and CFPAC-1) using a standard proliferation assay. Conclusions: By removing the need for tracer dyes, the resulting methodology may lower costs while accelerating preclinical drug development through informative multiparameter analysis of compound efficacy. Full article

Constipation is a common gastrointestinal disorder that seriously affects quality of life and is associated with multiple secondary complications. Barley leaves (BLs) have been suggested as potential functional foods for constipation prevention. Here, we investigated the preventive effects of common barley leaves (CBLs) and hulless barley leaves (HBLs) in a loperamide-induced constipation model in C57BL/6 mice. Both BLs improved stool parameters and gastrointestinal transit. Notably, high-dose HBLs increased stool weight to 263.84 ± 66.70 mg and stool amount to 250.20 ± 66.88 pellets, which were 12.7 and 11.1 times higher than those in the model group, respectively. BLs also modulated gut motility-related hormones (MTL, SP, Gas, SS, and VIP) and normalized colonic AQP3, AQP4, and 5-HT₄R expression levels. Furthermore, BLs enhanced SCFAs production and modulated gut microbiota by increasing Bacteroides abundance and decreasing Akkermansia abundance. CBLs and HBLs also exhibited distinct mechanisms. High-dose CBLs affected SERT expression, whereas HBLs uniquely decreased Alistipes abundance and increased SCFA production. These findings suggest that BLs may help prevent loperamide-induced constipation in mice by modulating the gut barrier and microbiota. Future studies should identify key active components and validate efficacy in longer-term and clinical studies. Full article

The renin–angiotensin–aldosterone system (RAAS) is essential for controlling blood pressure and maintaining fluid balance, driving significant structural changes throughout the cardiovascular system, including the heart and blood vessels. As a result, the RAAS is a key therapeutic target for various chronic cardiovascular diseases, ranging from arterial hypertension (AH) to heart failure (HF). In this review, one of our objectives is to describe the new evidence over the last 4 years regarding the RAAS. Moreover, we pay attention to the structure and function of the angiotensin II type 1 receptor (AT1R) and its role in hypertension, as well as define its active site. Later, we discuss the most potent, selective inhibitors of AT1 receptors, based on in vitro and in vivo experiments, from 2020 to 2024. Large peptide molecules, small non-peptide-like molecules, and sartan derivatives are analyzed. The low IC₅₀ values of the entities that do not resemble sartans showcase the vast chemical space that can be explored for the creation of more potent antihypertensive medications. We have also employed computational chemistry tools in order to identify key molecular interactions between the compounds of the literature studied in order to elucidate the underlying reasons why these different molecules exhibit variations in their binding energies and overall potency. Full article