Search Results (2,600)

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article

In this study, an artificially simulated enhanced UV-B radiation treatment of 96 kJ/m²·d⁻¹ was applied with natural sunlight as the control. By observing changes in biological tissue damage, peroxidase (POD) enzyme activity, and hormone content, combined with transcriptome analysis and quantitative fluorescence PCR validation, this study preliminarily elucidated the physiological mechanisms of plant-specific peroxidase (POD) in responding to enhanced UV-B radiation stress. Enhanced UV-B treatment significantly inhibited biological tissue growth, particularly during the rapid growth stage. At this stage, the treatment exhibited higher malondialdehyde (MDA) content, indicating increased oxidative stress due to the accumulation of reactive oxygen species (ROS). Despite the inhibition in growth, the treatment showed improvements in the accumulation of organic nutrients as well as the contents of abscisic acid (ABA), salicylic acid (SA), and methyl jasmonate (MeJA). Additionally, an increase in POD activity and lignin content was observed in the treatment, especially during the middle period of the rapid growth period. Transcriptome analysis revealed that two POD multigene family members, LOC123198833 and LOC123225298, were significantly upregulated under enhanced UV-B radiation, which was further validated through qPCR. In general, enhanced UV-B radiation triggered a defence response in biological tissue by upregulating POD genes, which can effectively help to scavenge excess ROS. Full article

High semen quality is vital for reproductive success in the swine industry; however, seasonal fluctuations often compromise this quality. The molecular mechanism underlying these seasonal effects on semen quality remains largely unclear. This study employed untargeted metabolomic profiling of boar seminal plasma (SP) to identify metabolites and metabolic pathways associated with semen quality during the summer and winter months. Semen samples were collected from mature Duroc boars at a commercial boar stud and classified as Passed or Failed based on motility and morphology. SP from five samples per group was analyzed using ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS). In total, 373 metabolites were detected in positive ion mode and 478 in negative ion mode. Several differentially expressed metabolites (DEMs) were identified, including ergothioneine, indole-3-methyl acetate, and avocadyne in the summer, as well as LysoPC, dopamine, and betaine in the winter. These metabolites are associated with key sperm functions, including energy metabolism, antioxidant defense, and capacitation. KEGG pathway analysis indicated enrichment in starch and sucrose metabolism, pyrimidine metabolism, and amino acid metabolism across the seasons. Overall, the results reveal that SP metabolomic profiles vary with the season, thereby influencing semen quality. The identified metabolites may serve as potential biomarkers for assessing semen quality and enhancing reproductive efficiency in swine production. Full article

The growing demand for sustainable plant-based dairy alternatives has spurred interest in valorizing agro-industrial byproducts like hazelnut cake, a protein-rich byproduct of oil extraction. This study developed formulations for vegan ice cream using unfermented (HIC) and Aspergillus oryzae-fermented hazelnut cake (FHIC), comparing their physicochemical, functional, and sensory properties to conventional dairy ice cream (DIC). Solid-state fermentation (72 h, 30 °C) enhanced the cake’s bioactive properties, and ice creams were characterized for composition, texture, rheology, melting behavior, antioxidant activity, and enzyme inhibition pre- and post-in vitro digestion. The results indicate that FHIC had higher protein content (64.64% vs. 58.02% in HIC) and unique volatiles (e.g., benzaldehyde and 3-methyl-1-butanol). While DIC exhibited superior overrun (15.39% vs. 4.01–7.00% in vegan samples) and slower melting, FHIC demonstrated significantly higher post-digestion antioxidant activity (4.73 μmol TE/g DPPH vs. 1.44 in DIC) and angiotensin-converting enzyme (ACE) inhibition (4.85–7.42%). Sensory evaluation ranked DIC highest for overall acceptability, with FHIC perceived as polarizing due to pronounced flavors. Despite textural challenges, HIC and FHIC offered nutritional advantages, including 18–30% lower calories and enhanced bioactive compounds. This study highlights fermentation as a viable strategy to upcycle hazelnut byproducts into functional vegan ice creams, although the optimization of texture and flavor is needed for broader consumer acceptance. Full article

Global warming and anthropogenic climate change are projected to expand the geographic distribution and population abundance of ectothermic species and exacerbate the biological invasion of exotic species. DNA methylation, as a reversible epigenetic modification, could provide a putative link between the phenotypic plasticity of invasive species and environmental temperature variations. We assessed and interpreted the epigenetic mechanisms of invasive and indigenous species’ differential tolerance to thermal stress through the invasive species Bemisia tabaci Mediterranean (MED) and the indigenous species Bemisia tabaci AsiaII3. We examine their thermal tolerance following exposure to heat and cold stress. We found that MED exhibits higher thermal resistance than AsiaII3 under heat stress. The fluorescence-labeled methylation-sensitive amplified polymorphism (F-MSAP) results proved that the increased thermal tolerance in MED is closely related to DNA methylation changes, other than genetic variation. Furthermore, the quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis of DNA methyltransferases (Dnmts) suggested that increased expression of Dnmt3 regulates the higher thermal tolerance of female MED adults. A mechanism is revealed whereby DNA methylation enhances thermal tolerance in invasive species. Our results show that the Dnmt-mediated regulation mechanism is particularly significant for understanding invasive species’ successful invasion and rapid adaptation under global warming, providing new potential targets for controlling invasive species worldwide. Full article

The use of radiosensitizers is a beneficial approach in cancer radiotherapy treatment. However, the enhancement of radiation effects on cancer cells by radiosensitizers involves several different mechanisms, reflecting the chemical nature of the radiosensitizer. G-quadruplex (G4) DNA ligands have emerged in recent years as a potential new class of radiosensitizers binding to specific DNA sequences. Recently, we have shown that the Re(I) tricarbonyl complex PDF-Pz-Re and its pyrazolyl-diamine chelator PDF-Pz, carrying a N-methylated pyridostatin (PDF) derivative, act as G4 binders of various G4-forming DNA and RNA sequences. As described in this contribution, these features prompted us to evaluate PDF-Pz-Re and PDF-Pz as radiosensitizers of prostate cancer PC3 cells submitted to concomitant treatment with Co-60 radiation. The compound RHPS4 was also tested, as this G4 ligand was previously shown to exhibit strong radiosensitizing properties in other cancer cell lines. The assessment of the resulting radiobiological effects, namely through clonogenic cell survival, DNA damage, and ROS production assays, showed that PDF-Pz-Re and PDF-Pz were able to radiosensitize PC3 cells despite being less active than RHPS4. Our results corroborate that G4 DNA ligands are a class of compounds with potential interest as radiosensitizers, deserving further studies to optimize their radiosensitization activity and elucidate the mechanisms of action. Full article

The impact of seasonality on the aroma quality of tea has been documented in various tea types, but not specifically in oolong tea. This study is the first to explore the complex relationships between seasonality, volatile compounds, and aroma quality in oolong tea. Using Headspace Solid-Phase Microextraction Gas Chromatography–Mass Spectrometry (HS-SPME-GC-MS)-based untargeted metabolomics, we analyzed 266 samples of Tieguanyin oolong tea. The data identified linalool, linalool oxides (trans-linalool oxide (furanoid) and trans-linalool oxide (pyranoid)), and their metabolites (diendiol I; hotrienol) as key seasonal discriminants. Four out of the top ten key differential compounds for distinguishing aroma scores were metabolites from fatty acid degradation, namely trans-3-hexenyl butyrate, trans-2-hexenyl hexanoate, hexyl hexanoate, and hexyl 2-methyl butyrate. Approximately one-fifth of the seasonal discriminant volatile compounds were significant in influencing aroma quality. Overall, the impact of seasonality on the aroma quality of finished Tieguanyin oolong tea is marginal. These findings enhance our understanding of the interplay between seasonal variations, volatile composition, and aroma quality in oolong tea. Full article

This study presents the development and optimization of a functional soy sauce fermented with Cordyceps militaris (C. militaris), a medicinal fungus known for its high cordycepin and polysaccharide content. Using C. militaris as the sole starter culture, the process aimed to improve both nutritional and functional properties. Response surface methodology was employed to optimize the entire fermentation process. During the koji stage, temperature, aeration, and inoculum concentration were adjusted to maximize protease activity and cordycepin production. In the fermentation stage, temperature, brine concentration, and water-to-material ratio were optimized to increase amino acid nitrogen and bioactive compound levels. Under optimal conditions (24 °C, 679.60 LPM aeration, 9.6% inoculum for koji; 32 °C, 12% brine, 1.53:1 water-to-material ratio for fermentation), the resulting soy sauce contained 1.14 ± 0.05 g/100 mL amino acid nitrogen and 16.88 ± 0.47 mg/100 mL cordycepin. Compared with traditionally fermented soy sauce, the C. militaris product exhibited a darker color, enhanced umami taste, and a distinct volatile profile featuring linoleic acid, methyl palmitate, and niacinamide. These results demonstrate the feasibility of using C. militaris in soy sauce fermentation and its potential as a novel functional condiment with improved bioactivity and sensory quality. Full article

Low-temperature stress severely limits plant growth and reduces agricultural productivity. Calmodulin-like (CML) proteins are crucial calcium sensors in plant cold responses. Transcriptome analysis of cold-stressed Saussurea involucrata identified seven differentially expressed CML genes. qRT-PCR confirmed that SiCML6 was strongly induced at 4 °C and −2 °C. Bioinformatics analysis showed that SiCML6 encodes a transmembrane protein containing an EF-hand domain. This protein carries a signal peptide and shows the closest phylogenetic relationship to Helianthus annuus CML3. Its promoter contains ABA, methyl jasmonate (MeJA), and cold-response elements. Arabidopsis plants overexpressing SiCML6 showed significantly higher survival rates at −2 °C than wild-type plants. Under freezing stress, SiCML6-overexpressing lines exhibited reduced malondialdehyde content, relative electrolyte leakage, and ROS accumulation (H₂O₂ and O₂⁻), along with increased proline, soluble sugars, soluble proteins, and total antioxidant capacity (T-AOC). SiCML6 elevated the expression of cold-responsive genes CBF3 and COR15a under normal conditions and further upregulated CBF1/2/3 and COR15a at 4 °C. Thus, low temperatures induced SiCML6 expression, which was potentially regulated by ABA/MeJA. SiCML6 enhances freezing tolerance by mitigating oxidative damage through boosted T-AOC and osmoprotectant accumulation while activating the CBF-COR signaling pathway. This gene is a novel target for improving crop cold resistance. Full article

Forty per cent of major depression patients are resistant to antidepressant medication. Thus, it is necessary to search for alternative treatments. Melatonin (N-acetyl-5-hydroxytryptamine) enhances neurogenesis and neuronal survival in the adult mouse hippocampal dentate gyrus. Additionally, melatonin stimulates the activity of Ca²⁺/Calmodulin-dependent Kinase II (CaMKII), promoting dendrite formation and neurogenic processes in human olfactory neuronal precursors and rat organotypic cultures. Similarly, ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, modulates CaMKII activity. Importantly, co-treatment of low doses of ketamine (10⁻⁷ M) in combination with melatonin (10⁻⁷ M) produces additive effects on neurogenic responses in olfactory neuronal precursors. Importantly, enhanced neurogenic responses are produced by conventional antidepressants like ISSRs. The goal of this study was to investigate whether hippocampal CaMKII participates in the signaling pathway elicited by combining doses of melatonin with ketamine acutely administered to mice, 30 min before being subjected to the forced swimming test. The results showed that melatonin, in conjunction with ketamine, significantly enhances CaMKII activation and changes its subcellular distribution in the dentate gyrus of the hippocampus. Remarkably, melatonin causes nuclear translocation of the active form of CaMKII. Luzindole, a non-selective MT₁ and MT₂ receptor antagonist, abolished these effects, suggesting that CaMKII is downstream of the melatonin receptor pathway that causes the antidepressant-like effects. These findings provide molecular insights into the combined effects of melatonin and ketamine on neuronal plasticity-related signaling pathways and pave the way for combating depression using combination therapy. Full article

Soil salinization poses a significant constraint to agricultural productivity. However, certain plant growth-promoting bacteria (PGPB) can mitigate salinity stress and enhance crop performance. In this study, a bacterial isolate, R-18, isolated from saline-alkali soil in Ningxia, China, was identified as Enterobacter bugandensis based on 16S rRNA gene sequencing. The isolate was characterized for its morphological, biochemical, and plant growth-promoting traits and was evaluated for its potential to alleviate NaCl-induced stress in maize (Zea mays L.) under hydroponic conditions. Isolate R-18 exhibited halotolerance, surviving at NaCl concentrations ranging from 2.0% to 10.0%, and alkaliphilic adaptation, growing at pH 8.0–11.0. Biochemical assays confirmed it as a Gram-negative bacterium, displaying positive reactions in the Voges–Proskauer (V–P) tests, catalase activity, citrate utilization, fluorescent pigment production, starch hydrolysis, gelatin liquefaction, and ammonia production, while testing negative for the methyl red and cellulose hydrolysis. Notably, isolate R-18 demonstrated multiple plant growth-promoting attributes, including nitrogen fixation, phosphate and potassium solubilization, ACC deaminase activity, and indole-3-acetic acid (IAA) biosynthesis. Under 100 mM NaCl stress, inoculation with isolate R-18 significantly enhanced maize growth, increasing plant height, stem dry weight, root fresh weight, and root dry weight by 20.64%, 47.06%, 34.52%, and 31.25%, respectively. Furthermore, isolate R-18 improved ion homeostasis by elevating the K⁺/Na⁺ ratio in maize tissues. Physiological analyses revealed increased chlorophyll and proline content, alongside reduced malondialdehyde (MDA) levels, indicating mitigated oxidative damage. Antioxidant enzyme activity was modulated, with decreased superoxide dismutase (SOD) and peroxidase (POD) activities but increased catalase (CAT) activity. These findings demonstrated that Enterobacter bugandensis R-18 effectively alleviated NaCl-induced growth inhibition in maize by enhancing osmotic adjustment, reducing oxidative stress, and improving ion balance. Full article

This study evaluated the effects of maternal supplementation with rumen-protected methionine (RPM), alone or combined with rumen-protected choline (RPC) and betaine (RPB), during the periconceptional and prepartum periods on reproductive outcomes and offspring performance in Chios ewes. One hundred synchronized ewes were assigned to three groups—control (no supplementation), M (5.50 g RPM/day), and MCB (3.50 g RPM, 1.60 g RPC, 0.49 g RPB/day)—from day −14 to +14 relative to mating. Blood was collected on days −14, 0, and +14 for ABTS (2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), ferric-reducing ability (FRAP), and malondialdehyde (MDA), on days 18 and 21 for progesterone, and on day 26 for pregnancy-associated glycoprotein (PAG) detection. Thirty days before and up to lambing, the ewes were further divided into C-C, C-M, C-MCB, M-M, M-C, MCB-MCB, and MCB-C subgroups. Embryonic loss did not differ between groups. FRAP was higher (p < 0.001) in MCB ewes, and ABTS was lower (p < 0.05) in M ewes, in the periconceptional period. Offspring in the C-M, C-MCB, M-M, M-C, and MCB-MCB groups had higher birth weights (p < 0.01), along with increased MDA levels (p < 0.05). The results suggest that maternal methyl donor supplementation during early and/or late gestation enhances antioxidant status, supports embryonic development, and increases birth weight. Full article

This study investigated the effect of KOH activation on biochar, with a focus on how porosity and potassium content influence microwave-assisted catalytic biodiesel production, using experimental design approaches. Activated biochar was synthesized from oat hull waste through KOH activation, followed by pyrolysis under controlled conditions. The biochar was characterized through chemical, morphological, and physical analyses, and its catalytic performance in converting used waste cooking oil (WCO) into biodiesel was evaluated using methanol as the acyl acceptor and microwave irradiation to optimize the reaction via experimental design. Results revealed that increasing the KOH/biomass ratio significantly enhanced the specific surface area (SSA) of the catalyst, achieving a maximum SSA of 637.28 m²/g under optimal pyrolysis conditions: 600 °C for 3 h with a KOH/biomass ratio of 2. A maximum fatty acid methyl ester (FAME) yield of 100% was achieved within 1 min of microwave-assisted reaction using an optimized catalyst dosage of 2.5%, a WCO/MeOH molar ratio of 1/12, and a reaction temperature of 150 °C, with the catalyst being successfully recycled across three cycles. An economic and energy evaluation estimated a catalyst production cost of USD 176.97/kg and a biodiesel production cost of USD 8.9/kg of FAMEs. This research provides a straightforward and cost-effective approach for biofuel production. Full article

Background/Objectives: Holy basil (Ocimum tenuiflorum L.) essential oil exhibits antioxidant, antimicrobial, and anesthetic activities, mainly due to eugenol, methyl eugenol, and β-caryophyllene. However, its clinical application is limited by poor water solubility, instability, and low bioavailability. This study developed and compared two delivery systems, self-nanoemulsifying drug delivery systems (SNEDDS) and microemulsions (ME), to enhance their stability and fish anesthetic efficacy. Methods: The optimized SNEDDS (25% basil oil, 8.33% coconut oil, 54.76% Tween 80, 11.91% PEG 400) and ME (12% basil oil, 32% Tween 80, 4% sorbitol, 12% ethanol, 40% water) were characterized for droplet size, PDI, zeta potential, pH, and viscosity. Stability was evaluated by monitoring droplet size and PDI over time and by determining the retention of eugenol, methyl eugenol, and β-caryophyllene after storage at 45 °C. Fish anesthetic efficacy was tested in koi carp (Cyprinus carpio var. koi). Results: SNEDDS maintained a small droplet size (~22.78 ± 1.99 nm) and low PDI (0.188 ± 0.088 at day 60), while ME showed significant size enlargement (up to 177.10 ± 47.50 nm) and high PDI (>0.5). After 90 days at 45 °C, SNEDDS retained 94.45% eugenol, 94.08% methyl eugenol, and 88.55% β-caryophyllene, while ME preserved 104.76%, 103.53%, and 94.47%, respectively. In vivo testing showed that SNEDDS achieved faster anesthesia (114.70 ± 24.80 s at 120 ppm) and shorter recovery (379.60 ± 15.61 s) than ME (134.90 ± 4.70 s; 473.80 ± 16.94 s). Ethanol failed to induce anesthesia at 40 ppm and performed poorly compared to SNEDDS and ME at other concentrations (p < 0.0001). Conclusions: SNEDDS demonstrated superior physical stability and fish anesthetic performance compared to ME. These findings support SNEDDS as a promising formulation for delivering holy basil essential oil in biomedical and aquaculture applications. Full article

Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT). Key histone modifiers, including KLF5, EZH2, and the demethylases KDM4/6, regulate osteoclastogenic signaling pathways and the transition between metastatic dormancy and reactivation. Simultaneously, SWI/SNF chromatin remodelers such as BRG1 and BRM reconfigure enhancer–promoter interactions that promote bone tropism. Non-coding RNAs, including miRNAs, lncRNAs, and circRNAs (e.g., miR-34a, NORAD, circIKBKB), circulate via exosomes to modulate the RANKL/OPG axis, thereby conditioning the bone microenvironment and fostering the formation of a pre-metastatic niche. These mechanistic insights have accelerated the development of epigenetic therapies. DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling. Inhibitors targeting EZH2, BET proteins, and KDM1A are now advancing through early-phase clinical trials, often in combination with bisphosphonates or immune checkpoint inhibitors. Moreover, novel approaches such as CRISPR/dCas9-based epigenome editing and RNA-targeted therapies offer locus-specific reprogramming potential. Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases. Full article