Search Results (14)

2-Phenylethanol (2-PE) is a key aromatic alcohol contributing to the rose-like odor in brewed wines, primarily synthesized by yeast metabolism with a typical yield of less than 100 mg/L. To enhance the 2-PE content in brewed wines, this study used CRISPR-Cas9 gene editing technology to delete the ARO8 gene (encoding aromatic transaminase I) in Saccharomyces cerevisiae SY. The single-factor experiments were performed to optimize the fermentation process, and the 2-PE content in the brewed wine was measured by high-performance liquid chromatography. The results demonstrated that the 2-PE content in whisky fermented by the SY-A8 was 0.73 g/L, increasing 23.73% compared to SY. The fermentation conditions of SY-A8 were optimized through single-factor experiments and the Box–Behnken design. The optimal conditions were a sugar concentration of 46.30 g/L, a fermentation time of 6 days, and an L-phenylalanine concentration of 1.43 g/L. The high 2-phenylethanol aroma whisky was brewed with a higher 2-phenylethanol content of 3.68 g/L in a 1 L fermenter at the optimal conditions. In conclusion, the modification of Saccharomyces cerevisiae by CRISPR-Cas9 gene editing combined with fermentation process optimization provides an effective technical strategy for improving the 2-PE content in whisky, thereby providing a research perspective for the flavor enhancement of whisky and other brewed wines. Full article

Background/Objectives: The use of the drug delivery system is notable for the systemic improvement of low orally bioavailable compounds, such as the bioactive phenolic acid, syringic acid. Innovative techniques are employed to enhance the performance of certain drug delivery systems. In connection with our previously reported journal with the use of MIL-100(Fe) as a drug carrier for syringic acid, this study utilized a mixed-linker synthesis of syringic acid and trimesic acid and characterized the properties in comparison with the unmodified MIL-100(Fe) through a solid solution approach. Methods: Modified MIL-100(Fe) was synthesized by substituting different molar concentrations of syringic acid for trimesic acid through de novo synthesis. Simple impregnation of syringic acid was carried out at 12, 24, 36, and 48 h and at 1:1 and 1:2 molar ratios of MIL-100(Fe) to syringic acid. Characterization was performed via PXRD, FTIR, BET, SEM, and DLS. In vivo studies included acute oral toxicity testing (OECD 425) and bioavailability assessment in Sprague Dawley rats. Results: The optimized amount of syringic acid to be substituted for trimesic acid is 0.10 mmol, as confirmed by the value of the PXRD. Optimized drug loading of 66.85 ± 0.004% was achieved using a 1:2 ratio of syringic acid to MIL-100(Fe)-10% over 36 h. Structural modifications were confirmed via FTIR, specifically through shifts at 1239.2 cm⁻¹, while TGA demonstrated thermal stability up to approximately 350 °C. Morphological analysis by SEM showed octahedral particles (210.70 ± 1.23 nm), and a decrease in BET surface area post-loading verified successful encapsulation. While in vitro release was media-dependent, toxicity studies at 2000 mg/kg showed no adverse effects; notably, SGOT and SGPT levels decreased, though BUN and creatinine levels rose. Compared to pure oral syringic acid, the SYA@MIL-100(Fe)-10% formulation demonstrated a 5.09-fold increase in relative bioavailability. Furthermore, it outperformed intraperitoneal administration of the drug by 1.65-fold. Conclusions: Modification of MIL-100(Fe) by incorporating syringic acid into the framework as a substituted organic linker indicates that SYA@MIL-100(Fe)-10% is a safe and effective delivery system for syringic acid, enhancing oral bioavailability. To the best of our knowledge, this is the first study to investigate the mixed-linker synthesis of MIL-100(Fe) by utilizing syringic acid as a structural co-ligand, rather than solely as an encapsulated guest. While MIL-100(Fe) has been extensively employed as a carrier for various therapeutics, this research uniquely integrates the active agent into the framework lattice itself to modulate porosity and loading capacity, subsequently evaluating its systemic performance in an in vivo model. Full article

Background/Objectives: Plant-derived bioactive compounds like syringic acid, a phenolic acid from the shikimic acid pathway, have shown potential against chronic diseases, including diabetes, cardiovascular disorders, cancer, and cerebral ischemia. However, its poor water solubility and rapid systemic elimination result in low oral bioavailability, limiting therapeutic potential. This study aimed to enhance its oral bioavailability using MIL-100(Fe), a metal–organic framework (MOF) known for high surface area and drug-loading capacity. Methods: MIL-100(Fe) was synthesized using an optimized method and loaded with syringic acid through impregnation at 12, 24, 36, and 48 h. Characterization included PXRD, FTIR, BET, SEM, and DLS. Acute oral toxicity was evaluated following OECD 423 guidelines, and bioavailability was assessed in Sprague Dawley rats. Results: The 1:2 MIL-100(Fe) to syringic acid ratio achieved the highest drug loading at 64.42 ± 0.03% (12 h). PXRD and FTIR confirmed successful loading (notably at 1239.2 cm⁻¹), and TGA indicated thermal stability at ~350 °C. SEM revealed octahedral particles with an average size of 270.67 ± 2.60 nm. BET showed reduced surface area post-loading. In vitro drug release exhibited media-dependent profiles. Toxicity tests indicated no adverse effects at 2000 mg/kg. Oral administration of SYA@MIL-100(Fe) resulted in a 10.997-fold increase in relative bioavailability versus oral syringic acid and a 12.82-fold increase compared to intraperitoneal administration. Conclusions: MIL-100(Fe) is a safe and effective oral carrier for syringic acid, significantly enhancing its bioavailability. This platform shows strong potential for delivering phenolic compounds in pharmaceutical applications. Full article

Conidiation and stress tolerance are pivotal traits in entomopathogenic fungi, critically influencing their production costs and environmental tolerance. While the transcription factor high-mobility group protein (HMG), characterized by a conserved HMG-box domain, has been extensively studied for its role in sexual development, its functions in entomopathogenic fungi remain largely unexplored. This study employed gene knockout to investigate the role of MaHMG in Metarhizium acridum. The deletion of MaHMG delayed conidiation initiation and caused a highly significant 58% reduction in conidial yield versus that of the wild type (WT) after 15 days. Furthermore, the conidiation pattern on microcycle induction medium (SYA) shifted from microcycle to normal conidiation. The ΔMaHMG mutant exhibited decreased conidial germination rates and markedly reduced tolerance following UV-B irradiation and heat-shock treatments, alongside increased sensitivity to the cell wall perturbant calcofluor white (CFW). RNA-seq analysis during this conidiation shift identified 88 differentially expressed genes (DEGs), with functional annotation implicating their predominant association with hyphal development, cell wall biogenesis, cell cycle progression, and conidiation. In conclusion, MaHMG functions as a critical positive regulator governing both conidiation and stress tolerance in M. acridum, underscoring its fundamental role in fungal biology and potential as a target for enhancing biocontrol agent performance. Full article

Syringic acid (SYA) is a significant phenolic compound with the potential for various biomedical uses, including uses of its hepatoprotective properties. Doxorubicin (DOX) is a drug used in the treatment of several tumors, but its side effects, particularly hepatotoxicity, limit its effectiveness. This study investigated the therapeutic effects of SYA on DOX-induced hepatic injury in rats. Molecular docking studies were performed using AutoDock Vina. Five groups of Sprague–Dawley rats (eight in each group) were studied. Gp1 was a negative control group; Gps2–5 was administered intraperitoneally (i.p.) with DOX at a dosage of 4 mg/kg once a week for a month; and Gp2 was left as a positive control group. Gps3–5 received oral SYA at doses of 25, 50, or 75 mg/kg/day, respectively, for a month. Histopathological, molecular, and biochemical analyses were conducted one month after the last SYA dosages were given. The findings demonstrated that by reversing biochemical changes and reducing oxidative stress and inflammation, SYA therapy considerably reduced DOX-induced hepatotoxicity in rats. These results implied that SYA may lessen the hepatotoxicity that DOX causes in rats. Full article

Insect pathogenic fungi have shown great potential in agricultural pest control. Conidiation is crucial for the survival of filamentous fungi, and dispersal occurs through two methods: normal conidiation, where conidia differentiate from mycelium, and microcycle conidiation, which involves conidial budding. The conidiation process is related to cell separation. The forkhead box gene Sep1 in Schizosaccharomyces pombe plays a crucial role in cell separation. Nevertheless, the function of Sep1 has not been clarified in filamentous fungi. Here, MaSep1, the homolog of Sep1 in Metarhizium acridum, was identified and subjected to functional analysis. The findings revealed that conidial germination of the MaSep1-deletion strain (ΔMaSep1) was accelerated and the time for 50% germination rate of conidial was shortened by 1 h, while the conidial production of ΔMaSep1 was considerably reduced. The resistances to heat shock and UV-B irradiation of ΔMaSep1 were enhanced, and the expression of some genes involved in DNA damage repair and heat shock response was significantly increased in ΔMaSep1. The disruption of MaSep1 had no effect on the virulence of M. acridum. Interestingly, ΔMaSep1 conducted the normal conidiation on the microcycle conidiation medium, SYA. Furthermore, 127 DEGs were identified by RNA-Seq between the wild-type and ΔMaSep1 strains during microcycle conidiation, proving that MaSep1 mediated the conidiation pattern shift by governing some genes associated with conidiation, cell division, and cell wall formation. Full article

This research introduces the NeuRaiSya (Neural Railway System Application), an innovative railway signaling system integrating deep learning for passenger analysis. The objectives of this research are to simulate the NeuRaiSya and evaluate its effectiveness using the GreatSPN tool (graphical editor for Petri nets). GreatSPN facilitates evaluations of system behavior, ensuring safety and efficiency. Five models were designed and simulated using the Petri nets model, including the Dynamics of Train Departure model, Train Operations with Passenger Counting model, Timestamp Data Collection model, Train Speed and Location model, and Train Related-Issues model. Through simulations and modeling using Petri nets, the study demonstrates the feasibility of the proposed NeuRaiSya system. The results highlight its potential in enhancing railway operations, ensuring passenger safety, and maintaining service quality amidst the evolving railway landscape in the Philippines. Full article

Semantic segmentation of remote sensing images (RSIs) is pivotal for numerous applications in urban planning, agricultural monitoring, and environmental conservation. However, traditional approaches have primarily emphasized learning within the spatial domain, which frequently leads to less than optimal discrimination of features. Considering the inherent spectral qualities of RSIs, it is essential to bolster these representations by incorporating the spectral context in conjunction with spatial information to improve discriminative capacity. In this paper, we introduce the spectral–spatial context-boosted network (SSCBNet), an innovative network designed to enhance the accuracy semantic segmentation in RSIs. SSCBNet integrates synergetic attention (SYA) layers and cross-fusion modules (CFMs) to harness both spectral and spatial information, addressing the intrinsic complexities of urban and natural landscapes within RSIs. Extensive experiments on the ISPRS Potsdam and LoveDA datasets reveal that SSCBNet surpasses existing state-of-the-art models, achieving remarkable results in $F_1$-scores, overall accuracy (OA), and mean intersection over union (mIoU). Ablation studies confirm the significant contribution of SYA layers and CFMs to the model’s performance, emphasizing the effectiveness of these components in capturing detailed contextual cues. Full article

Triple negative breast cancer (TNBC) is a type of breast cancer associated with early metastasis, poor prognosis, high relapse rates, and mortality. Previously, we demonstrated that SYA013, a selective σ2RL, could inhibit cell proliferation, suppress migration, reduce invasion, and induce mitochondria-mediated apoptosis in MDA-MB-231 cell lines, although we were unable to demonstrate the direct involvement of sigma receptors. This study aimed to determine the anticancer properties and mechanisms of action of SYA014, [4-(4-(4-chlorophenyl)-1,4-diazepan-1-yl)-1-(4-fluorophenyl)butan-1-one oxime], an oxime analogue of SYA013, the contribution of its sigma-2 receptor (σ2R) binding, and its possible synergistic use with cisplatin to improve anticancer properties in two TNBC cell lines, MDA-MB-231 (Caucasian) and MDA-MB-468 (Black). In the present investigation, we have shown that SYA014 displays anticancer properties against cell proliferation, survival, metastasis and apoptosis in the two TNBC cell lines. Furthermore, a mechanistic investigation was conducted to identify the apoptotic pathway by which SYA014 induces cell death in MDA-MB-231 cells. Since SYA014 has a higher binding affinity for σ2R compared to σ1R, we tested the role of σ2R on the antiproliferative property of SYA014 with a σ2R blockade. We also attempted to evaluate the combination effect of SYA014 with cisplatin in TNBC cells. Full article

Entomopathogenic fungi are promising biocontrol agents of insect-mediated crop damage. Microcycle conidiation has shown great potential in enhancing the conidial yield and quality of entomopathogenic fungi. Homologs of Cts1, an endochitinase of Saccharomyces cerevisiae, participate in cell separation in several fungal spp. and may contribute to the morphological differences that occur during the shift to microcycle conidiation. However, the precise functions of Cts1 in entomopathogenic fungi remain unclear. Herein, the endochitinase gene, MaCts1, was characterized in the model entomopathogen, Metarhizium acridum. A loss of function line for MaCts1 led to a delay of 1 h in the median germination time, a 28% reduction in conidial yield and significant defects in fungal resistances to UV-irradiation (18%) and heat-shock (15%), while fungal tolerances to cell wall stressors, oxidative and hyperosmotic stresses and virulence remained unchanged. The MaCts1-disruption strain displayed typical conidiation on the microcycle conidiation induction medium, SYA. In contrast, deletion of key genes in the morphogenesis-related NDR kinase network (MOR pathway)/regulation of Ace2 and morphogenesis (RAM pathway) did not affect the SYA-induction of microcycle conidiation. This indicates that MaCts1 makes contributions to the microcycle conidiation, which may not be dependent on the MOR/RAM pathway in M. acridum. Full article

Zinc finger proteins are an important class of multifunctional regulators. Here, the roles of a C2H2 zinc finger protein MaNCP1 (Metarhizium acridum nitrate-related conidiation pattern shift regulatory factor 1) in nitrogen utilization and conidiation were explored in the entomopathogenic fungus M. acridum. The results showed that MaNCP1-disruption mutant (ΔMaNCP1) impaired the ability to utilize nitrate, ammonium and glutamine and reduced the expression of nitrate assimilation-related genes, suggesting that MaNCP1 was involved in governing nitrogen utilization. In addition, the conidial yield of the ΔMaNCP1 strain, cultured on the microcycle conidiation medium (SYA), was significantly decreased, which could be restored or even enhanced than that of the WT strain through increasing the nitrate content in SYA medium. Further study showed that MaAreA, a core regulator in the nitrogen catabolism repression (NCR) pathway, was a downstream target gene of MaNCP1. Screening the differential expression genes between WT and ΔMaNCP1 strains revealed that the conidial yield of M. acridum regulated by nitrate might be related to NCR pathway on SYA medium. It could be concluded that MaNCP1 contributes to the nitrate assimilation and conidiation, which will provide further insights into the relationship between the nitrogen utilization and conidiation in fungi. Full article

This paper is about poetry and pilgrimage in Tembilahan, Indragiri Hilir, where Abdurrahman Siddiq, a prominent alim who lived in the late nineteenth and early twentieth century, is buried. In addition to his treatises on theology, mysticism, and ethics, Abdurrahman Siddiq is also renowned for his contribution to Islamic literature in Sumatra. He is a famous Islamic scholar and is respected in Indragiri Hilir for his spiritual messages delivered in the form of sya’ir (poetry). Malay Muslims have preserved the saint’s legacy through the act of pilgrimage and various cultural events and festivals. This paper argues that the recitation of Abdurrahman Siddiq’s poems during the pilgrimage to Tembilahan and Islamic festivals shows how Malay Muslims honor their respected saint. Full article

Background and Objectives: Alpha-1 antitrypsin is a serine protease inhibitor that demonstrates an array of immunomodulatory functions. Individuals with the genetic condition of alpha-1 antitrypsin deficiency (AATD) are at increased risk of early onset emphysematous lung disease. This lung disease is partly driven by neutrophil mediated lung destruction in an environment of low AAT. As peripheral neutrophil hyper-responsiveness in AATD leads to excessive degranulation and increased migration to the airways, we examined the expression of the membrane voltage-gated proton channel-1 (HVCN1), which is integrally linked to neutrophil function. The objectives of this study were to evaluate altered HVCN1 in AATD neutrophils, serine protease-dependent degradation of HVCN1, and to investigate the ability of serum AAT to control HVCN1 expression. Materials and Methods: Circulating neutrophils were purified from AATD patients (n = 20), AATD patients receiving AAT augmentation therapy (n = 3) and healthy controls (n = 20). HVCN1 neutrophil expression was assessed by flow cytometry and Western blot analysis. Neutrophil membrane bound elastase was measured by fluorescence resonance energy transfer. Results: In this study we demonstrated that HVCN1 protein is under-expressed in AATD neutrophils (p = 0.02), suggesting a link between reduced HVCN1 expression and AAT deficiency. We have demonstrated that HVCN1 undergoes significant proteolytic degradation in activated neutrophils (p < 0.0001), primarily due to neutrophil elastase activity (p = 0.0004). In addition, the treatment of AATD individuals with AAT augmentation therapy increased neutrophil plasma membrane HVCN1 expression (p = 0.01). Conclusions: Our results demonstrate reduced levels of HVCN1 in peripheral blood neutrophils that may influence the neutrophil-dominated immune response in the AATD airways and highlights the role of antiprotease treatment and specifically AAT augmentation therapy in protecting neutrophil membrane expression of HVCN1. Full article

(1) Carthamus Tinctorius L. (safflower) is extensively used in traditional herbal medicine. (2) The aim of this study was to investigate the bioactive properties of polyphenol extracts from flowers of Carthamus Tinctorius (CT) cultivated in Italy. We also evaluated the properties of two bioactive water-soluble flavonoid compounds, hydroxy safflor yellow A (HSYA) and safflor yellow A (SYA), contained in Carthamus Tinctorius petals. (3) The total polyphenol content was 3.5 ± 0.2 g gallic acid equivalent (GAE)/100 g, flavonoids content was 330 ± 23 mg catechin equivalent (CE)/100 g in the flowers. The extract showed a high antioxidant activity evaluated by oxygen radical absorbance capacity (ORAC) and 2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assays. In addition, flower extract, SYA, and HSYA were able to reduce the susceptibility of low-density lipoprotein to copper-induced lipid peroxidation. In order to investigate the bioactive properties of flower extract, SYA, and HSYA we also studied their modulatory effect of oxidative stress on human dermal fibroblasts (HuDe) oxidized by tert-butyl hydroperoxide (t-BOOH). The CT extract at concentrations ranging from 0.01–20 μg GAE/mL of polyphenols, exerted a protective effect against t-BOOH triggered oxidative stress. At higher concentration the extract exerted a pro-oxidant effect. Similar results have been obtained using HSYA and SYA. (4) These results demonstrate a biphasic effect exerted by HSYA, SYA, and flower extracts on oxidative stress. Full article