Search Results (104)

The matrix metalloproteinase (MMP) family includes several membrane-bound enzymes. Membrane-type 5 matrix metalloproteinase (MT5-MMP) is unique amongst the MMP family in being primarily expressed in the brain and during development. It is proposed to contribute to synaptic plasticity and is implicated in several pathologies, including multiple cancers and Alzheimer’s disease. In cancer, MT5-MMP expression has been correlated to cancer progression, but a distinct mechanistic role has yet to be uncovered. In Alzheimer’s disease, MT5-MMP exhibits pro-amyloidogenic activity, functioning as an η-secretase that cleaves amyloid precursor protein (APP), ultimately generating two synaptotoxic fragments, Aη-α and Aη-β. Several intracellular binding partners for MT5-MMP have been identified, and of these, N4BP2L1, EIG121, BIN1, or TMX3 binding to MT5-MMP results in a significant increase in MT5-MMP η-secretase activity. Beyond direct effects on APP, MT5-MMP may also facilitate APP trafficking to endosomal/lysosomal compartments and enhance proinflammatory responses. Overall, the substrate profile of MT5-MMP has not been well defined, and selective inhibitors of MT5-MMP have not been described. These advances will be needed for further consideration of MT5-MMP as a therapeutic target in Alzheimer’s disease and other pathologies. Full article

The red plant phenotype of R1 cotton is a genetic marker produced by light-induced anthocyanin accumulation. GhPAP1D controls this trait. There are two 228 bp tandem repeats upstream of GhPAP1D in R1 cotton. In this study, GUS staining assays in transgenic Arabidopsis thaliana (L.) Heynh. demonstrated that tandem repeats in the GhPAP1D promoter-enhanced transcriptional activity. GhPAP1D is a homolog of A. thaliana AtPAP1. AtPAP1’s expression is regulated by photomorphogenesis-related transcription factors such as AtHY5 and AtBBXs. We identified the homologs of A. thaliana AtHY5, AtBBX21, and AtBBX24 in R1 cotton, designated as GhHY5, GhBBX21, and GhBBX24, respectively. Y1H assays confirmed that GhHY5, GhBBX21, and GhBBX24 each bound to the GhPAP1D promoter. Dual-luciferase reporter assays revealed that GhHY5 weakly activated the promoter activity of GhPAP1D. Heterologous expression assays in A. thaliana indicated that GhBBX21 promoted anthocyanin accumulation, whereas GhBBX24 had the opposite effect. Dual-luciferase assays showed GhBBX21 activated GhPAP1D transcription, while GhBBX24 repressed it. Further study indicated that GhHY5 did not enhance GhBBX21-mediated transcriptional activation of GhPAP1D but alleviates GhBBX24-induced repression. Together, our results demonstrate that GhBBX21 and GhBBX24 antagonistically regulate anthocyanin accumulation in R1 cotton under GhHY5 mediation, providing insights into light-responsive anthocyanin biosynthesis in cotton. Full article

Recurrent bacterial cystitis in women can lead to interstitial cystitis or bladder pain syndrome (IC/BPS). Activation of Toll-like receptor 4 (TLR4) by LPS can upregulate signaling of the pro-inflammatory receptor p75^NTR. The aim of the presented study was to assess whether p75^NTR antagonist THX-B can modulate LPS-mediated inflammation in bladder cells. In vitro expression and LPS-activation of p75^NTR were confirmed in urothelial (URO) and smooth muscle (SMC) cells. In UROs, p75^NTR antagonism abolished the LPS-elicited rise in membrane-bound and soluble TNF-α. However, it could not prevent LPS-induced rise in phosphorylated ERK nor decrease in phosphorylated p38MAPK, nor the increase in iNOS and nitric oxide (NO) content. On the other hand, in SMCs, LPS increased phosphorylation of JNK, nuclear translocation of NF-κB, and association of TRAF6 to p75^NTR, outcomes prevented by p75^NTR antagonism. In UROs, LPS decreased the expression of tight junction proteins, ZO-1 and occludin, with the latter rescued by p75^NTR antagonism. Intraurethral instillation of LPS increased inflammation in the lamina propria, activation of JNK, and contractile activity of bladder tissue. Alternatively, intraperitoneal THX-B injections prevented LPS-induced inflammation but not enhanced muscle contraction. Our results suggest that inhibition of p75^NTR could help in reducing bladder symptoms during cystitis. Full article

This paper investigates the design of optimal low-thrust transfers between relative planar and spatial quasi-satellite orbits (QSOs) in the Earth–Moon system under the Circular Restricted Three-Body Problem (CR3BP). A key contribution is the adaptation of a trajectory optimization framework, previously applied to halo orbit transfers, to accommodate the unique challenges of QSO families, especially the transition between planar and spatial configurations. The method employs a refined beam search strategy to construct diverse initial guess chains, which are then optimized via a successive convexification algorithm tailored for the spatial dynamics of QSOs. Additionally, a linear–quadratic regulator (LQR)-based control scheme is implemented to ensure long-term station-keeping of the final 3D-QSO. Simulation results demonstrate the feasibility of connecting planar and spatial QSOs with minimum-fuel trajectories while maintaining bounded terminal deviations, offering new tools for future Earth–Moon logistics and navigation infrastructure. Key findings include the successful design of low-thrust transfer trajectories between planar QSOs and 1:5 3D-QSOs, with a minimum total $\mathsf{\Delta }V$ of 195.576 m/s over a time of flight (ToF) of 261 days, and a minimum ToF of 41 days with a total $\mathsf{\Delta }V$ of 270.507 m/s. Additionally, the application of LQR control demonstrated the ability to maintain 1:5 3D-QSO families around the Moon with less than 12 mm/s $\mathsf{\Delta }V$ over two months. This research provides valuable insights into the optimization of low-thrust transfer trajectories and the application of advanced control techniques for space missions, particularly those targeting lunar and planetary satellite exploration. Full article

C-terminal-binding proteins (CtBPs) dimerize and function predominantly as transcriptional corepressors by recruiting various chromatin-modifying factors to promoter-bound repressors. Hypotonia, ataxia, developmental delay, and tooth enamel defects syndrome (HADDTS) is a recently discovered neurodevelopmental disorder resulting from a heterozygous missense mutation in CTBP1. It is often associated with the early onset of profound cerebellar atrophy in patients. Allen Institute’s Allen Brain Cell (ABC) atlas of human brain data was used to localize CTBP1 expression in the brain to elucidate the etiology of HADDTS. Based on the ABC atlas, CTBP1 is highly expressed in the upper rhombic lip supercluster, which gives rise to cerebellar cells and provides insights into the cerebellar pathophysiology observed in HADDTS patients. Full article

Interest in ancient wheat species is growing because of their unique agronomic and nutritional qualities, and they could be potential sources of antioxidants. The aim of this research was to determine the total, bound, and free phenolic content (TP, FP, BP), the bound and free phenolic acid (BPA, FPA) content, and the phenolic acid (PA) composition of einkorn and emmer cultivars sourced from a two-year pesticide-free organic variety trial. TPs, FPs, and BPs were analyzed using spectrophotometry, and PAs were determined using HPLC/MS/MS. The results showed that highest mean TP, FP, and BP contents were found in an emmer cultivar, while generally, einkorn varieties had lower phytonutrient values than emmer and bread wheat control. Emmer had the highest TPA, FPA, and BPA contents, followed by control wheat and einkorn landraces. Our gap-filling research was the analysis of the individual PA values in all free and bound fractions. Ferulic acid was the predominant phenolic acid, followed by p-coumaric acid, syringic acid, sinapic acid, and p-hydroxybenzoic acid, whereas salicylic acid and caffeic acid had the lowest concentrations. In the future, we propose to continue this research to gain deeper insights into the changes in phytonutrient properties related to the growing conditions of these cultivars. Full article

This study explores the antioxidant activity and antioxidant mechanism of phenolic compounds (including free (FP), esterified (EP), and bound phenolic (BP)) from Dendrobium fimbriatum Hook (DFH) stems, before and after ultra-high pressure (UHP) treatment. A total of 374 compounds were identified, with 149 showing significant differences in DFH phenolic extracts before and after UHP treatment. UHP treatment significantly increased the total phenolic content (TPC) and total flavonoid content (TFC) and enhanced antioxidant activity in vitro. Particularly, the UEP-DFH, IC₅₀ values in ABTS and DPPH were reduced by 49.6% and 64.1%, respectively. In H₂O₂-treated HepG2 cells, the extracts demonstrated significant cytoprotective effects, including increased cell viability, ROS reduction, and enhanced GSH levels by 17.8% (UFP-DFH) and 12.5% (UEP-DFH). The activities of GS, GCL, GR, GSH-Px, SOD, CAT, NQO1, and HO-1 were also elevated in UHP-treated extracts. DAPI staining indicated that the extracts promoted nuclear Nrf2 expression, particularly UFP-DFH and UEP-DFH. Molecular docking indicated that vanillic acid could competitively bind to the Keap1-Kelch domain, facilitating activation of the antioxidant pathway. Overall, UHP treatment enhanced both extraction efficiency and antioxidant activity, making it a promising method for improving the bioactivity of DFH in the food and functional food industries. Full article

In electric vehicles (EVs), the batteries are arranged in the battery pack (BP), which has a small layout space and difficulty in dissipating heat. Therefore, in EVs, the battery thermal management systems (BTMSs) are critical to managing heat to ensure safety and performance, particularly under higher operating temperatures and longer discharge conditions. To solve this problem, in this article, the thermal analysis models of a 3-battery-cell BP were created, including scenarios (1) natural air cooling without a BTMS; (2) natural air cooling with water cooling hybrid BTMS; and (3) forced air cooling plus water cooling composite BTMS. The thermal performances of the pack-level BPs were simulated and analyzed based on computational fluid dynamics (CFD). A variety of boundary conditions and working parameters, such as ambient temperature, inlet coolant flow rate and initial temperature, discharge rate, air flow rate, and initial temperature, were considered. The results show that without a BTMS (Scenario 1), the maximum temperature in the BP rises rapidly and continuously to reach 63.8 °C, much higher than the upper bound of the recommended operating temperature range (ROTR between +20 °C to +35 °C) under the extreme discharge rate of 3 C and even if the discharge rate is 2 C. With a hybrid BTMS (Scenario 2), the maximum temperature in BP rises to about 38.7 °C, slightly above the upper bound of the ROTR. Lowering the coolant (water) initial temperature can effectively lower the temperature up to 5.7 °C in BP, but the water flow rate cannot since the turbulence model. While with a composite BTMS (Scenario 3), the temperature can be further lowered up to 1.5 °C under the extreme discharge rate of 3C, just reaching the upper bound of the ROTR. In addition, lowering the initial coolant temperature or air temperature can effectively decrease the temperatures up to 5.1 and 1.0 °C, respectively, in BP, but the coolant flow rate (due to the turbulence model) and the air flow rate cannot. Finally, the thermal performances of the different battery cells in the BP with different cooling systems and at the different positions of the BP were compared and analyzed. The present work may contribute to the design of BTMSs in the EV industry. Full article

Tartary buckwheat is a nutrient-rich pseudo-cereal whose starch contents, including amylose and amylopectin contents, and their properties hold significant importance for enhancing yield and quality. The granule-bound starch synthase (GBSS) is a key enzyme responsible for the synthesis of amylose, directly determining the amylose content and amylose-to-amylopectin ratio in crops. Although one has already been cloned, the GBSS genes at the genome-wide level have not yet been fully assessed and thoroughly analyzed in Tartary buckwheat. This study comprehensively analyzed the FtGBSSs in Tartary buckwheat. Based on the genome data of Tartary buckwheat, five FtGBSS genes, namely FtGBSS-1 to FtGBSS-5, were identified on three chromosomes, exhibiting about 1800 bp lengths in their CDSs and numerous exons and introns in gene structures. Amino acid analyses revealed high homology in ten GBSS proteins from Tartary buckwheat, rice, maize, and Arabidopsis thaliana, with a specific starch synthase catalytic domain and ten conserved motifs. The Tartary buckwheat GBSS proteins had a closer relationship with GBSS proteins from monocot based on evolutionary relationship analysis. Expression analyses suggested that the FtGBSS genes showed distinct tissue-specific expression patterns in Tartary buckwheat and rice-Tartary buckwheat. Among them, FtGBSS-1, FtGBSS-2, and FtGBSS-4 were higher expressed in the root, stem, or flower, suggesting that they have a role in the amylose synthesis of these tissues. Notably, FtGBSS-3 and FtGBSS-5 were more highly expressed in seeds than in other tissues, suggesting that they have a pivotal role in amylose synthesis of the seeds of Tartary buckwheat. Furthermore, the cis acting elements in the promoters of FtGBSSs and their binding transcription factors (TFs) were investigated. A protein–protein interaction network was constructed and co-expression was analyzed based on the gene expression patterns of the FtGBSSs, and the identified TFs, belonging to bZIP, ERF, bHLH, and MADS-box TF families, were identified within this network, and their expression patterns were significantly correlated to the expression patterns of two seed-specific FtGBSS genes (FtGBSS-3 and FtGBSS-5). Finally, FtGBSS1-5 was successfully transformed into rice through transgenic manipulation, and the FtGBSS1-5 overexpression lines showed an increase in amylose content accompanied by a reduction in amylopectin and total starch contents compared with WT. Overall, this research not only deepens our understanding of the molecular mechanisms of amylose synthesis in Tartary buckwheat, but also provides scientific insights for enhancing crop amylose content and quality through molecular breeding. Full article

Pseudomonas plecoglossicida JUIM01 is an industrial 2-keto-d-gluconate (2KGA)-producing strain. However, its regulation mechanism of 2KGA metabolism remains to be clarified. Among other reported Pseudomonas species, the 2-ketogluconate utilization operon (kgu operon) plays key roles in 2KGA catabolism. In this study, the structural genes of the kgu operon and its promoter in P. plecoglossicida JUIM01 were identified using reverse transcription PCR and lacZ reporter gene fusion. The results showed the kgu operon in P. plecoglossicida was composed of four structural genes: kguE, kguK, kguT, and kguD. The ptxS gene located upstream of kguE was excluded from the kgu operon. Then, the knockout and corresponding complementation strains of kguE, kguK, kguT, and kguD were constructed, respectively, to prove the kgu operon was involved in 2KGA catabolism of P. plecoglossicida. The knockout stains, especially JUIM01ΔkguE, showed potential as industrial production strains for 2KGA. Moreover, the transcriptional regulation mechanism of PtxS on the kgu operon was elucidated using multiple methods. In P. plecoglossicida, the LacI-family transcription regulator PtxS could recognize a 14 bp palindrome (5′-TGAAACCGGTTTCA-3′) within the promoter region of the kgu operon and specifically bind to a 26 bp region where the palindrome was located. As the binding sites overlapped with the transcription start site of the kgu operon, the binding of PtxS possibly hindered the binding of RNA polymerase, thus repressing the transcription of the kgu operon and further regulating 2KGA catabolism. 2KGA bound to PtxS as an effector to dissociate it from the kgu operon promoter region, so as to relieve the transcription repression. The results will provide strategies for improving the product accumulation in 2KGA industrial production and theoretical bases for the construction of a Pseudomonas chassis. Full article

Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) were used to study the effects of heat treatments and water removal by freeze-drying after different time intervals (6, 12, 24, 48, and 72 h) on the molecular structure of potato tubers. SEM images show structural differences between raw (RP), microwaved (MP), and boiled potato (BP). MP showed a cracked structure. BP was able to re-associate into a granule-like structure after 6 h of freeze-dying, whereas RP had dried granules within a porous matrix after 24 h of freeze-drying. These results are consistent with the moisture content and FTIR results for MP and BP, which demonstrated dried spectra after 6 h of freeze-drying and relatively coincided with RP results after 24 h of freeze-drying. Additionally, three types of hydrogen bonds have been characterized between water and starch, and the prevalence of water very weakly bound to starch has also been detected. The relative crystallinity (RC) was increased by thermal treatment, whereby microwaving recorded the highest value. A comparison of the FTIR and XRD results indicated that freeze-drying treatment overcomes heat effects to generate an integral starch molecule. Full article

Seeking food-derived antioxidants and inhibitors of α-glucosidase and α-amylase has been recognized as an effective way for managing diabetes. Coffee silver skin (CSS) is rich in phenolic compounds, which may be potential agents as antioxidants and for α-glucosidase and α-amylase inhibition. But whether phenolics in different forms show similar bioactivity remains unknown. In this study, phenolic compounds in CSS were extracted as free phenolics (FPs), esterified phenolics (EPs), and bound phenolics (BPs). The phenolic profiles and antioxidant activities of them were investigated. Their inhibitory effects on α-glucosidase and α-amylase were analyzed, and the inhibitory mechanisms were elucidated by molecular docking and molecular dynamic simulation. Results showed that FPs exhibited the best antioxidant ability and inhibitory effects on α-glucosidase and α-amylase. A total of 17 compounds were identified in FPs with 3-caffeoylquinic acid, 4-feruloylquinic acid, and dicaffeoylquinic acids as the dominant ones. Typical phenolics in FPs could bind to α-glucosidase and α-amylase through hydrogen bonds and form hydrophobic interaction with several key amino acid residues. In addition, 3,4-dicaffeoylquinic acid and 3-caffeoylquinic acid might be the principal components that account for the inhibitory effect of FPs on α-glucosidase. The results of this study may provide some scientific support for CSS utilization as a health-beneficial component in functional food development for type 2 diabetes mellitus management. Full article

Inverse synthetic aperture radar (ISAR) imaging techniques are frequently used in target classification and recognition applications, due to its capability to produce high-resolution images for moving targets. In order to meet the demand of ISAR imaging for electromagnetic calculation with high efficiency and accuracy, a novel accelerated shooting and bouncing ray (SBR) method is presented by combining a Graphics Processing Unit (GPU) and Bounding Volume Hierarchies (BVH) tree structure. To overcome the problem of unfocused images by a Fourier-based ISAR procedure under wide-angle and wide-bandwidth conditions, an efficient parallel back projection (BP) imaging algorithm is developed by utilizing the GPU acceleration technique. The presented GPU-accelerated SBR is validated by comparison with the RL-GO method in commercial software FEKO v2020. For ISAR images, it is clearly indicated that strong scattering centers as well as target profiles can be observed under large observation azimuth angles, $\Delta \phi =90°$, and wide bandwidths, 3 GHz. It is also indicated that ISAR imaging is heavily sensitive to observation angles. In addition, obvious sidelobes can be observed, due to the phase history of the electromagnetic wave being distorted resulting from multipole scattering. Simulation results confirm the feasibility and efficiency of our scheme by combining GPU-accelerated SBR with the BP algorithm for fast ISAR imaging simulation under wide-angle and wide-bandwidth conditions. Full article

Iron in soil exists in various valence states and is prone to changes with alterations in soil environmental conditions. Its migration and transformation are crucial for soil formation and understanding soil evolution. This study focuses on Quaternary red soils found in woodland, sparse forest grassland, grassland, and cultivated land located in the semi-humid region of the middle temperate zone. For comparison, buried Quaternary red soil was also examined. A soil reconstruction model was used to quantitatively calculate the variation of different forms of iron in order to analyze various forms of iron composition, migration, and transformation within the soil profile, as well as the evolutionary traits of Quaternary red soils influenced by diverse land use activities. This study found that after exposure and use, iron from the topsoil of buried Quaternary red soil migrated to the subsoil, altering the iron distribution. Free iron and crystalline oxides decreased in the topsoil but increased in specific subsoil layers, with woodland and grassland showing the most significant changes. Silicate-bound iron pooled in the soil weathered to form free iron under different land uses, and poorly crystalline iron oxides transformed into crystalline oxides, with grassland exhibiting the highest transformation intensity. Conversion processes predominated over iron migration in the Quaternary red soils. The evolution of Quaternary red soils can be divided into three stages, marked by changes in iron composition and crystallization due to anthropogenic land use activities. Initially, during 140−94 ka BP, iron composition was stable. Then, between 94–24 ka BP, plant decomposition formed iron–metal complexes, releasing and crystallizing poorly crystalline iron oxides. Finally, from 24 ka BP to the present, anthropogenic activities intensified, increasing the formation and conversion rates of these oxides. This study quantifies iron migration and transformation in Quaternary red soils, providing insights for sustainable soil management, especially in regions where human activities have accelerated iron evolution. Based on these findings, the following policy recommendations are proposed: implement sustainable land use practices, encourage land management strategies that preserve natural vegetation, promote research on soil management techniques, develop and implement regulatory policies, and support educational programs to maintain the health and stability of Quaternary red soils, particularly in regions prone to accelerated iron evolution due to anthropogenic activities. Full article

Cellobionic acid (CBA) can be obtained through the oxidation of cellobiose, the monomer of cellulose. CBA serves as a plant-based alternative to its stereoisomer lactobionic acid, which is used in the pharmaceutical, cosmetic, and food industries. Gluconobacter oxydans is a well-established whole-cell biocatalyst with membrane-bound dehydrogenases (mDH) for regio-specific oxidations. As G. oxydans wildtype cells show low cellobiose oxidation activities, the glucose mDH from Pseudomonas taetrolens was overexpressed in G. oxydans BP9, a multi mDH deletion strain. Whole-cell biotransformation studies were performed with resting cells of the engineered G. oxydans in stirred tank bioreactors. Initial biomass specific cellobionate formation rates increased with increasing cellobiose concentrations up to 190 g L⁻¹, and were constant until the solubility limit. The maximal volumetric CBA formation rates and the oxygen uptake rates increased linearly with the concentration of engineered G. oxydans. This enables the estimation of the maximum biocatalyst concentration limited by the maximum oxygen transfer rate of any bioreactor. Thus, 5.2 g L⁻¹ G. oxydans was sufficient to produce 502 g L⁻¹ CBA with >99% yield in a simple aerobic batch process. The highly concentrated CBA will reduce downstream processing costs considerably after cell separation. Full article