Search Results (387)

Background/Objectives: Sodium glucose co-transporter 2 inhibitors (SGLT2is) have demonstrated a reduction in heart failure (HF) hospitalizations in HF patients and decreased recurrence of atrial fibrillation (AF), including in those who have undergone catheter ablation (CA). The effects of SGLT2i are likely due to suppression of the renin–angiotensin–aldosterone system, reduction in oxidative stress with subsequent improvement in myocardial efficiency, and attenuation of cardiac remodeling. We aim to present the effects of SGLT2i on AF recurrence in patients who have undergone CA for AF. Methods: This is a systematic review and meta-analysis of randomized controlled trials (RCTs) and retrospective studies evaluating the effect of SGLT2i on AF recurrence following CA compared with non-SGLT2i. The primary outcome was the recurrence of AF by the final follow-up reported in each study. Secondary outcomes include AF recurrence by the first follow-up within 12 to 24 months and follow-up intervals (6, 12, 18, 24, and 36 to 42 months) post-ablation, multivariate risk of AF recurrence, and the effect on left atrial diameter (LAD) (less than 45 mm vs. greater than or equal to 45 mm). For risk of bias (ROB) analysis, the NIH ROB and Cochrane ROB2 tool were used. All statistical, heterogeneity, and sensitivity analyses were conducted using Cochrane Review Manager. A random-effect model was employed for all pooled statistical analyses. Results: A total of nine studies, two RCTs and seven retrospective studies, were included (N = 6874) for the primary outcome. Compared to non-SGLT2i (N = 3693), SGLT2i (N = 3181) significantly decreased AF recurrence by the final follow-up (OR = 0.62; 95% CI: 0.45–0.85; p = 0.008). For secondary outcomes, SGLT2i significantly reduced AF recurrence by the first follow-up within 12 to 24 months post-ablation (OR = 0.58; p = 0.0001) and by the different follow-up periods, 6-month (OR = 0.53; p = 0.02), 12-month (OR = 0.56; p = 0.0001), 18-month (OR = 0.55; p = 0.01), and 24-month (OR = 0.60; p = 0.12) follow-up periods. On the other hand, by 36 to 42 months, SGLT2i was associated with increased risk of AF recurrence (OR = 1.41; p = 0.004). Conclusions: We conclude that SGLT2i demonstrated a reduction in AF recurrence following CA, particularly by 12 to 18 months post-ablation. Full article

Given the global economic importance of citrus and growing threats from climate change and soil degradation, this study investigated how arbuscular mycorrhizal (AM) fungi (Funneliformis mosseae, Fm, formerly Glomus mosseae; Diversispora versiformis, Dv, formerly Glomus versiforme) and endophytic fungus Serendipita indica (Si, formerly Piriformospora indica) differentially enhance spring shoot growth, nutrient acquisition, phytohormone profiles, and expression patterns of Fe/Mg transporter genes in two citrus cultivars (‘Beni-Madonna’ and ‘Lane Late’). Si achieved higher root colonization than AM fungi (Fm/Dv) in both cultivars, with peak colonization observed in September. Fungal inoculation differentially enhanced spring shoot growth and leaf gas exchange, with Fm and Dv demonstrating cultivar-specific effects, while Si consistently increased shoot number across cultivars but showed limited gas exchange influence in ‘Lane Late’. In ‘Beni-Madonna’, AM fungi broadly enhanced auxins/cytokinins, while Si specifically increased indole-3-acetic acid and dihydrozeatin but reduced N⁶-isopentenyladenine; ‘Lane Late’ showed comprehensive hormone upregulation by all fungi except Si’s dihydrozeatin suppression. AM fungi enhanced Ca, Mg, and Mn in ‘Beni-Madonna’ and P, S, Zn, and B in ‘Lane Late’, while Si increased Fe and Zn in the former and P, S, and B in the latter. Fungal symbionts differentially regulated Fe/Mg transporter genes in a cultivar-specific manner. In ‘Beni-Madonna’, Fm upregulated key Fe transporters (CsFRO1, CsHA1, and CsIRT1) while Si broadly enhanced all Fe transporters, correlating with increased leaf Fe levels; Fm specifically induced CsMGT2 and CsMGT8, showing strong association with Mg accumulation. ‘Lane Late’ exhibited distinct responses, with Si comprehensively activating both Fe (CsFRO1, CsHA1-2, and CsIRT1-2) and Mg (CsMGT6/8) transporter genes, while Dv showing minimal effects. These findings demonstrate that fungal symbionts differentially regulate citrus growth and nutrient homeostasis in a cultivar-dependent manner, highlighting the importance of host genotype-specific fungal partnerships for sustainable citrus production. Full article

The geochemical characteristics of reinjection fluids play a crucial role in controlling water–rock interactions and the long-term stability of geothermal reservoirs. This study aims to evaluate how different fluid chemistries affect mineral dissolution–precipitation behavior and ion migration during geothermal reinjection. Five types of reinjection water—including geothermal source water (i.e., formation water from the reservoir), primary and secondary treated waters, and their mixtures—were reacted with carbonate rocks from the Wumishan Formation of the Xiong’an New Area, North China Basin, under reservoir-like conditions (70 °C, 17 MPa). A combination of batch experiments, inverse modeling using PHREEQC, and one-dimensional reactive transport simulations was employed. Results show that fluid pH, ionic strength, and saturation state significantly influence reaction pathways. Alkaline-treated waters enhanced silicate dissolution, increasing Na⁺, K⁺, and Si concentrations, while source water and its mixtures promoted carbonate precipitation, increasing the risk of clogging. Simulations revealed that the early injection stage is the most reactive, with rapid ion front advancement and strong mineral transformations. Reaction-controlled ions such as Ca²⁺ and SO₄²⁻ formed enrichment zones, while conservative ions like Na⁺ and Cl⁻ propagated more uniformly. Moderate alkaline regulation was found to mitigate carbonate scaling and improve silicate reactivity, thereby reducing permeability loss. This integrated approach provides mechanistic understanding and practical guidance for reinjection fluid design in medium-to-deep geothermal systems. Full article

Objectives: This study aimed to elucidate the determinants of interindividual variability in the pharmacokinetics of ibrutinib among healthy Chinese subjects, focusing on the influence of demographic characteristics, dietary conditions, and genetic polymorphisms on CYP enzymes and ABC transporters. Methods: Thirty-two participants were randomly assigned to either a fasting (n = 16) or fed (n = 16) group, each receiving a single 140 mg oral dose of ibrutinib. Plasma concentrations were quantified using a validated UPLC–MS/MS method. Genetic polymorphisms in CYP3A4, CYP3A5, CYP2D6, and ABCG2 were identified by Sanger sequencing. Pharmacokinetic parameters, including apparent clearance (CL/F), maximum plasma concentration (Cmax), area under the plasma concentration–time curve (AUC0-t), and time to maximum concentration (Tmax), were estimated by non-compartmental analysis and statistically evaluated for associations with demographic, dietary, and genetic variables. Results: Food intake significantly affected ibrutinib pharmacokinetics, with postprandial administration resulting in reduced CL/F and increased Cmax and AUC0-t (p < 0.01). Gender differences were also observed, as females exhibited higher CL/F, lower Cmax, and AUC0-t than males (p < 0.05). The CYP2D6 c.100C>T polymorphism significantly decreased CL/F and increased exposure in fasting and male subjects (p < 0.05), but this effect was absent under fed conditions. Conversely, the ABCG2 c.421C>A variant was associated with increased CL/F and decreased AUC0-t (p < 0.05), while other genotypes exerted negligible effects. Conclusions: Ibrutinib pharmacokinetics are significantly modulated by dietary status, gender, and genetic polymorphisms, particularly CYP2D6 c.100C>T and ABCG2 c.421C>A. These findings underscore the importance of integrating pharmacogenetic and physiological factors into individualized dosing strategies to optimize therapeutic efficacy and minimize adverse effects. Full article

Background/Objectives: Chamaecyparis pisifera (C. pisifera; family Cupressaceae) is known to have insecticidal and antibacterial activities, but its effects on skin depigmentation-related activities have not been elucidated. Thus, in the present study, we aimed to investigate the anti-hyperpigmentation potential of C. pisifera var. filifera leaf essential oil (CPEO), specially focusing on responses related to melanogenesis and melanin transport, using B16BL6 cells. Methods: CPEO was extracted by steam distillation, and its composition was determined by GC/MS spectrometry. The biological activities of CPEO on B16BL6 melanoma cells were analyzed using the water soluble tetrazolium salt, BrdU incorporation, ELISA, and immunoblotting assays. Results: Twenty-eight components were identified in CPEO. CPEO was noncytotoxic to B16BL6 cells at 1–100 μg/mL and reduced serum-induced proliferation in B16BL6 cells. CPEO significantly inhibited α-MSH-stimulated increases in melanin synthesis and tyrosinase activity in the cells (e.g., at 100 μg/mL CPEO, melanin synthesis: 117.89 ± 0.00% vs. 571.94 ± 0.81% with α-MSH; tyrosinase activity: 73.62 ± 0.00% vs. 322.60 ± 3.10% with α-MSH). CPEO also downregulated the expression levels of melanogenesis-related proteins (MITF, tyrosinase, TRP-1 and -2) and melanosome transport-related proteins (Rab27a, melanophilin, myosin Va) in cells exposed to α-MSH. Moreover, the essential oil increased the phosphorylations of MAPKs (p38, ERK1/2, and JNK) in α-MSH-treated B16BL6 cells. In addition, CPEO reduced the ultraviolet A (UVA) induced increases in α-MSH levels in HaCaT cells. In addition, conditioned medium from HaCaT cells irradiated with UVA (CM-UVA) in the presence of CPEO reduced melanin synthesis and tyrosinase activity in B16BL6 cells (e.g., at CM-UVA with 100 μg/mL CPEO, melanin synthesis: 100.92 ± 0.99% vs. 134.44 ± 0.97% with CM-UVA; tyrosinase activity: 101.02 ± 1.81% vs. 133.77 ± 1.88% with CM-UVA). Conclusions: These findings suggest that CPEO inhibits melanin production (probably through the regulation of MAPKs) and transport-related activities in B16BL6 cells, and that CPEO may serve as a potential natural anti-hyperpigmentation or skin whitening. Full article

Osteoarthritis (OA) lacks disease-modifying therapies, in part because key features of the joint microenvironment remain underappreciated. One such feature is localized acidosis, characterized by sustained reductions in extracellular pH within the cartilage, meniscus, and the osteochondral interface despite near-neutral bulk synovial fluid. We synthesize current evidence on the origins, sensing, and consequences of joint acidosis in OA. Metabolic drivers include hypoxia-biased glycolysis in avascular cartilage, cytokine-driven reprogramming in the synovium, and limits in proton/lactate extrusion (e.g., monocarboxylate transporters (MCTs)), with additional contributions from fixed-charge matrix chemistry and osteoclast-mediated acidification at the osteochondral junction. Acidic niches shift proteolysis toward cathepsins, suppress anabolic control, and trigger chondrocyte stress responses (calcium overload, autophagy, senescence, apoptosis). In the nociceptive axis, protons engage ASIC3 and sensitize TRPV1, linking acidity to pain. Joint cells detect pH through two complementary sensor classes: proton-sensing GPCRs (GPR4, GPR65/TDAG8, GPR68/OGR1, GPR132/G2A), which couple to G_s, G_q/11, and G_12/13 pathways converging on MAPK, NF-κB, CREB, and RhoA/ROCK; and proton-gated ion channels (ASIC1a/3, TRPV1), which convert acidity into electrical and Ca²⁺ signals. Therapeutic implications include inhibition of acid-enabled proteases (e.g., cathepsin K), pharmacologic modulation of pH-sensing receptors (with emerging interest in GPR68 and GPR4), ASIC/TRPV1-targeted analgesia, metabolic control of lactate generation, and pH-responsive intra-articular delivery systems. We outline research priorities for pH-aware clinical phenotyping and imaging, cell-type-resolved signaling maps, and targeted interventions in ‘acidotic OA’ endotypes. Framing acidosis as an actionable component of OA pathogenesis provides a coherent basis for mechanism-anchored, locality-specific disease modification. Full article

Lung-protective ventilation and other experimental conditions raise arterial carbon dioxide tension (PaCO₂) and alter pH. Short-term benefits are reported in non-infectious settings, whereas infection and/or prolonged exposure are typically harmful. This scoping review systematically maps immune-mediated effects of hypercapnia on innate immunity and alveolar epithelial repair. Scoping review per Levac et al. and PRISMA Extension for Scoping Reviews (Open Science Framework protocol: 10.17605/OSF.IO/WV85T; post hoc). We searched original preclinical studies (in vivo/in vitro) in PubMed, Web of Science, ScienceDirect, Cochrane Reviews, and SciELO (2008–2023). PaCO₂ (mmHg) was prioritized; %Fraction of inspired Carbon Dioxide (%FiCO₂) was recorded when PaCO₂ was unavailable; pH was classified as buffered/unbuffered. Data were organized by context, PaCO₂, and exposure duration; synthesis used heat maps (0–120 h) and a narrative description for >120 h. Mechanistic axes extracted the following: NF-κB (canonical/non-canonical), Bcl-2/Bcl-xL–Beclin-1/autophagy, AMPK/PKA/CaMKKβ/ERK1/2 and ENaC/Na,K-ATPase trafficking, Wnt/β-catenin in AT2 cells, and miR-183/IDH2/ATP. Thirty-five studies met the inclusion criteria. In non-infectious models, a “protective window” emerged, with moderate PaCO₂ and brief exposure (65–95 mmHg; ≤4–6 h), featuring NF-κB attenuation and preserved epithelial ion transport. In infectious models and/or with prolonged exposure or higher PaCO₂, harmful signals predominated: reduced phagocytosis/autophagy (Bcl-2/Bcl-xL–Beclin-1 axis), AMPK/PKA/ERK1/2-mediated internalization of ENaC/Na,K-ATPase, depressed β-catenin signaling in AT2 cells, impaired alveolar fluid clearance, and increased bacterial burden. Chronic exposures (>120 h) reinforced injury. Hypercapnia is a context-, dose-, time-, and pH-dependent double-edged modulator. The safe window is narrow; standardized, parallel reporting of PaCO₂ and pH—with explicit comparisons of buffered vs. unbuffered hypercapnia—is essential to guide clinical translation. Full article

Sustainable management of aquatic ecosystems requires effective strategies to monitor and mitigate microplastic pollution, particularly in vulnerable tidal river systems. Microplastic accumulation in these environments poses significant environmental risks, threatening biodiversity, ecosystem health, and long-term water quality. This study employs a three-dimensional hydrodynamic model (TELEMAC-3D—v8p5) coupled with a Lagrangian particle tracking model (CaMPSim-3D—v1.2.1) to simulate microplastic transport dynamics in the lower Fraser River, British Columbia, Canada. The model incorporates tidal forcing, riverine hydrodynamics, and mixing processes, and was validated with good agreement against observed water levels. This model provides a high-resolution representation of microplastic dispersion under varying release scenarios, including emissions from combined sewer overflows (CSOs) and wastewater treatment plants (WWTPs). A novel approach is proposed to identify microplastic accumulation zones using the OPTICS (Ordering Points to Identify the Clustering Structure) clustering algorithm. Accumulation zone locations remain spatially consistent despite variations in release volume. Persistent clusters occurred near channel constrictions and shoreline segments associated with flow deceleration. These findings demonstrate the robustness of the method and provide a systematic framework for prioritizing high-risk areas, supporting targeted monitoring and informing sustainable estuarine management. Full article

This study aimed to elucidate the physiological, biochemical, and transcriptional regulatory responses of potato plants to iron deficiency stress. Two potato varieties were selected for analysis: 05P (high tuber iron content) and CI5 (low tuber iron content). Tissue culture seedlings of both varieties were subjected to iron deficiency, and the effects on stem length, root length, fresh weight, soluble sugar and protein contents, as well as the activities of superoxide dismutase (SOD), peroxidase (POD), malondialdehyde (MDA), and leaf chlorophyll content (SPAD) values were evaluated. Additionally, the impact of iron deficiency on zinc (Zn), magnesium (Mg), calcium (Ca), manganese (Mn), and copper (Cu) concentrations in different tissues were analyzed. Transcriptomic sequencing and quantitative real-time PCR (qRT-PCR) were performed on various seedling tissues. The results showed that iron deficiency significantly inhibited seedling growth and development, resulting in reduced plant height and fresh weight, increased root length, decreased leaf SPAD content, and elevated soluble sugar and protein concentration. SOD, POD, and MDA activities were also significantly increased. Elemental analysis revealed that iron deficiency enhanced the uptake and accumulation of Zn, Mg, Ca, Mn, and Cu across different tissues. Transcriptomic analysis identified differentially expressed genes (DEGs) significantly enriched in pathways related to photosynthesis, carbon metabolism, and ribosome function in roots, stems, and leaves. Iron deficiency induced the upregulation of H⁺-ATPase genes in roots (PGSC0003DMG400004101, PGSC0003DMG400033034), acidifying the rhizosphere to increase active iron availability. Subsequently, this was followed by the upregulation of FRO genes (PGSC0003DMG400000184, PGSC0003DMG400010125, PGSC0003DMG401009494, PGSC0003DMG401018223), which reduce Fe³⁺ to Fe²⁺, and activation of IRT genes, facilitating Fe²⁺ transport to various tissues. Iron deficiency also reduced SPAD content in leaves, negatively impacting photosynthesis and overall plant growth. In response, the osmotic regulation and antioxidant defense systems were activated, enabling the plant to mitigate iron deficiency stress. Additionally, the absorption and accumulation of other metal ions were enhanced, likely as a compensatory mechanism for iron scarcity. At the transcriptional level, iron deficiency induced the expression of genes involved in metal absorption and transport, as well as those related to photosynthesis, carbon metabolism, and ribosomal function, thereby supporting iron homeostasis and maintaining metabolic balance under stress conditions. Full article

Calcium (Ca) is one of the most important elements determining vegetable yield, but the driving factors that regulate microbial community structure, microbial network system stability, and metabolic pathways along the soil Ca gradient remain unclear. In this work, the relationship between soil physicochemical properties and bacterial and fungal communities was investigated under distinct Ca gradients in well-established Chinese cabbage fields located in Shijiazhuang, Hebei Province, China, with sites named Group 1 (G1), Group 2 (G2), and Group 3 (G3) from lowest to highest along the soil Ca gradient. This study demonstrated that Ca exerts dual effects by modulating pH, electrical conductivity (EC), and soil organic carbon (SOC) dynamics, enhancing bacterial diversity while reinforcing fungal network stability through distinct metabolic adaptations. Bacterial networks showed reduced stability despite increased diversity, perhaps linked to the downregulation of ATP-binding cassette (ABC) transporters. Notably, Fe-Mn oxides counteracted Ca influences through selective nutrient adsorption, creating antagonistic selection pressures. Under calcium stress, both Ca and total P (TP) emerge as key drivers of microbial community restructuring, with fungal networks exhibiting significantly greater stability compared to their bacterial counterparts. This study bridges the knowledge gap in the driving mechanisms of microbial communities under soil Ca stress and provides a theoretical basis for improving vegetable yields, with implications for soil management in Ca-rich ecosystems. Full article

The cytosolic pH (pH_i) of mammalian cells is tightly maintained at values ~7.2. Cytoplasmic acidosis (pH_i < 6.8) occurs when the intracellular proton concentration ([H⁺]_i) exceeds the buffering capacity of the cytosol and transport processes to extrude protons are exhausted. During intracellular acidosis, the contractility of cardiac and skeletal muscle cells is strongly reduced, often at sufficient Ca²⁺ levels. A contraction of striated muscle is achieved when the intracellular calcium (Ca²⁺) concentration rises above resting levels. The amplitude and kinetics of Ca²⁺ signals are controlled by Ca²⁺ handling proteins and force is generated if Ca²⁺ ions interact with contractile filaments of the sarcomere. Some aspects of this phenomenon, such as the biochemical origin of excessive protons in working muscle cells and molecular interactions of protons with Ca²⁺ handling proteins or contractile filaments, are not yet fully understood. This review summarizes our current understanding of how striated muscle cells handle Ca²⁺ and H⁺ and how a rise in [H⁺]_i may interfere with Ca²⁺ signaling in the working skeletal muscle (fatigue) or during ischemic events in cardiac muscle. Finally, we briefly address experimental strategies to measure Ca²⁺ signaling at different pH values with fluorescent probes and highlight their limitations. Full article

Background: Empagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, improves outcomes in heart failure (HF) patients, yet inter-individual variability in response remains unclear. Genetic variants in Brain-Derived Neurotrophic Factor BDNF (rs6265) and ATPase Sarcoplasmic/Endoplasmic Reticulum Ca²⁺ Transporting 2 ATP2A2 (rs1860561) may influence the treatment efficacy. Objective: To assess the association of BDNF and ATP2A2 polymorphisms with the response to low-dose empagliflozin (10 mg) in Pakistani patients with heart failure and a reduced ejection fraction (HFrEF). Methods: In this prospective study, 120 HF patients with an ejection fraction of 25–45% who had been on stable standard heart failure therapy for at least 3 months were initiated on 10 mg of empagliflozin. The brain natriuretic peptide (BNP) and LVEF left ventricular ejection fraction (LVEF) were assessed at 6 and 12 months. Genotyping for rs6265 and rs1860561 was performed via Sanger sequencing. A response was defined as a ≥5% EF increase or ≥20% BNP reduction. Associations were analyzed using chi-square and logistic regression. Results: Among 99 genotyped patients, BDNF T allele carriers (CT/TT) had a significantly lower EF (p = 0.028) and BNP (p < 0.001) response. The CC genotype was associated with improved outcomes (BNP OR: 7.70; EF OR: 5.97). For ATP2A2, the GG genotype showed a strong association with EF improvement (OR: 5.97; p = 0.001), with no BNP association. Variant allele frequencies were higher among Punjabis and Kashmiris than Pathans. Conclusions: BDNF rs6265 and ATP2A2 rs1860561 polymorphisms appear to influence the individual response to empagliflozin in HFrEF patients. These findings underscore the potential of pharmacogenetic profiling to guide personalized therapy and optimize treatment outcomes in heart failure. Full article

Low-salinity waterflooding (LSWF) enhances oil recovery at low cost in carbonate reservoirs, but its effectiveness requires the precise control of injected water chemistry and interaction with reservoir minerals. This study specifically investigates carbonated low-salinity waterflooding (CLSWF), where dissolved ${\mathrm{CO}}_2$ modulates geochemical processes. This study develops an integrated transport model coupling geochemical surface complexation modeling (SCM) with multiphase compositional dynamics to quantify wettability alteration during CLSWF. The framework combines PHREEQC-based equilibrium calculations of the Total Bond Product (TBP)—a wettability indicator derived from oil–calcite ionic bridging—with Corey-type relative permeability interpolation, resolved via COMSOL Multiphysics. Core flooding simulations, compared with experimental data from calcite systems at 100 ${}^{\circ }\mathrm{C}$ and 220 bar, reveal that magnesium ([${\mathrm{Mg}}^{2+}$]) and sulfate ([${\mathrm{SO}}_4^{2-}$]) concentrations modulate the TBP, reducing oil–rock adhesion under controlled low-salinity conditions. Parametric analysis demonstrates that acidic crude oils (TAN higher than 1 $\mathrm{m}$$\mathrm{g}$ KOH/$\mathrm{g}$) exhibit TBP values approximately $2.5 \mathrm{times}$ higher than those of sweet crudes, due to carboxylate–calcite bridging, while pH elevation (higher than 7.5) amplifies wettability shifts by promoting deprotonated ${\mathrm{-COO}}^{-}$ interactions. The model further identifies synergistic effects between ([${\mathrm{Mg}}^{2+}$]) (ranging from 50 to 200 mmol/kgw) and ([${\mathrm{SO}}_4^{2-}$]) (higher than 500 mmol/kgw), which reduce (${\mathrm{Ca}}^{2+}$)-mediated oil adhesion through competitive mineral surface binding. By correlating TBP with fractional flow dynamics, this framework could support the optimization of injection strategies in carbonate reservoirs, suggesting that ion-specific adjustments are more effective than bulk salinity reduction. Full article

Recent years have provided numerous reports on the mechanisms of action of psychiatric medications (antidepressants, antipsychotics, mood stabilizers, and antidementia drugs) that directly inhibit the growth of cancer cells, as well as on their indirect effects on the psyche and immune system, and their supportive effects on chemotherapeutic agents. The mechanisms of the anticancer activity of psychiatric drugs include inhibition of dopamine and N-methyl-D-aspartate receptors that work via signaling pathways (PI3K/AKT/mTOR/NF-κB, ERK, Wnt/ß-catenin, and bcl2), metabolic pathways (ornithine decarboxylase, intracellular cholesterol transport, lysosomal enzymes, and glycolysis), autophagy, Ca²⁺-dependent signaling cascades, and various other proteins (actin-related protein complex, sirtuin 1, p21, p53, etc.). The anticancer potential of psychiatric drugs seems to be extremely broad, and the most extensive anticancer literature has been reported on antidepressants (fluoxetine, amitriptyline, imipramine, mirtazapine, and St John’s Wort) and antipsychotics (chlorpromazine, pimozide, thioridazine, and trifluoperazine). Among mood stabilizers, lithium and valproates have the largest body of literature. Among antidementia drugs, memantine has documented anticancer effects, while there is limited evidence for galantamine. Of the new psychiatric substances, the antipsychotic drug brexpiprazole and the antidepressant vortioxetine have a very interesting body of literature regarding glioblastoma, based on in vitro and in vivo animal survival studies. Their use in brain tumors and metastases is particularly compelling, as these substances readily cross the blood–brain barrier (BBB). Moreover, the synergistic effect of psychiatric drugs with traditional cancer treatment seems to be extremely important in the fight against chemo- and radio-resistance of tumors. Although there are some studies describing the possible carcinogenic effects of psychiatric drugs in animals, the anticancer effect seems to be extremely significant, especially in combination treatment with radio/chemotherapy. The emerging evidence supporting the anticancer properties of psychiatric drugs presents an exciting frontier in oncology. The anticancer properties of psychiatric drugs may prove particularly useful in the period between chemotherapy and radiotherapy sessions to maintain the tumor-inhibitory effect. While further research is necessary to elucidate the mechanisms, clinical implications, dose-dependence of the effect, and clear guidelines for the use of psychiatric medications in cancer therapy, the potential for these commonly prescribed medications to contribute to cancer treatment enhances their value in the management of patients facing the dual challenges of mental health and cancer. Full article

Glucosamine (GlcN) is a high-value compound with significant health applications. GlcN is widely used in the food and health industry as a food additive or functional food. The development of a green, efficient, and safe method for GlcN production is of great significance due to the complexity of traditional production methods, environmental pollution, and sensitization of raw materials. In this study, Saccharomyces cerevisiae genes PFK1, PDB1, GNA1, ISR1, and PCM1 were knocked out using the Clustered Regularly Interspaced Short Palindromic Repeats Cas9 (CRISPR-Cas9) method. In addition, three key enzyme genes, glucosamine-6-phosphate deaminase GlmD, glucosamine-6-phosphate phosphatase GlmP, and ammonium transporter AMT1, were introduced to construct engineered strains for GlcN synthesis in the presence of high-concentration inorganic ammonium ions. The results indicated that S. cerevisiae HPG5 with GlmD, GlmP, and AMT1 integration and simultaneous deletion of PFK1, PDB1, GNA1, PCM1, and ISR1 achieved the highest GlcN yield (1.95 ± 0.02 g/L) during fermentation with 10 g/L (NH₄)₂SO₄, which was 2.47-fold higher than the control. The conversion rate of glucose to GlcN in HPG5 was 9.75% in liquid YPD medium containing 20 g/L of glucose and 10 g/L of (NH₄)₂SO₄. Thus, the results indicated that S. cerevisiae HPG5 could effectively produce GlcN in the presence of high-concentration ammonium sulphate. This study provides a promising alternative, S. cerevisiae HPG5, for GlcN production. Full article