Search Results (821)

Background: The ACE Y215C mutation is a common, functionally damaging missense variant (~1.5% allele frequency) associated with reduced plasma ACE levels and increased Alzheimer’s disease (AD) risk. In CHO and HEK cell models, this mutation caused a ~3–6-fold decrease in ACE surface expression, soluble ACE levels, and ACE enzymatic activity compared to those of wild-type ACE. Methods: Circulating ACE levels and activity were measured in EDTA plasma obtained from 84 carriers of the ACE Y215C mutation using a set of mAbs to the ACE. The mAbs 5B3/1G12 binding ratio was revealed as a sensitive marker for the circulating Y215C ACE mutant. Whole-exome and whole-genome sequencing (WES/WGS) were performed to identify genetic variants potentially modifying circulating ACE levels. In parallel, published sequencing and proteomic data from 35,559 Icelanders participants were analyzed to identify genes influencing ACE shedding. Sequence comparison was performed between carriers with elevated and reduced ACE concentrations to identify the potential protective variants that may compensate for decreased ACE levels due to the Y215C mutation itself. Results: Most carriers of the Y215C ACE mutation demonstrated significantly decreased ACE levels (median is 62% of control ACE levels). However, substantial inter-individual variability was observed in plasma ACE activity among carriers. Comparative sequencing analysis revealed 9648 variants unique to individuals with elevated ACE, mapping to 5779 protein-coding genes and enriched for pathways related to intracellular and transmembrane transport. Conclusions: The presence of the damaging ACE mutation Y215C does not invariably result in low plasma ACE or, likely, elevated AD risk. Therefore, combined blood ACE phenotyping and whole-exome sequencing are recommended to more accurately assess ACE-related AD susceptibility in mutation carriers. Full article

Background: The profound heterogeneity of glioblastoma and the often-limited efficacy of conventional treatments, including arsenic trioxide (ATO), underscore the urgent and critical demand for innovative combination strategies specifically designed to overcome treatment resistance. Methods: We evaluated the therapeutic effects of ATO as a single agent and in combination with the MNK1 inhibitor AUM001 across patient-derived xenograft (PDX) models and investigated molecular determinants of sensitivity and synergy. Our results demonstrated that GBM models resistant to ATO, particularly those of the mesenchymal subtype, are more likely to show synergistic cytotoxicity when AUM001 is added. The combination significantly reduces the frequency of glioblastoma stem cells (GSCs) compared to either drug alone, especially in ATO-resistant models. Results: These observations suggest that targeting the MNK1 pathway in conjunction with ATO is a promising strategy to specifically eradicate GSCs, which are major drivers of GBM recurrence and therapeutic failure. Transcriptomic analyses revealed that ATO sensitivity correlated with activated translation-related pathways and cell cycle processes, while synergistic responses to the combination were driven by distinct molecular signatures in different GBM subtypes. Overall, synergistic response to the combination therapy is more associated with cellular organization, amino acid transmembrane transporter activity, ion channels, extracellular matrix organization and collagen formation. Conclusions: Our findings highlight that specific molecular pathways and their activities, including those involving translation, cell cycle and ion transport, appear to modulate the synergistic efficacy of the ATO and AUM001 combination, thereby offering potential biomarkers for improved patient stratification in future GBM clinical trials of such ATO-based treatments. Full article

High regeneration energy demand remains a critical barrier to the large-scale deployment of ethanolamine-based (MEA-based) CO₂ capture. This study adopts an Al₂O₃ ceramic-membrane heat exchanger (CMHE) to recover both sensible and latent heat from the stripped gas. Experiments confirm that heat and mass transfer within the CMHE follow a coupled mechanism in which capillary condensation governs trans-membrane water transport, while heat conduction through the ceramic membrane dominates heat transfer, which accounts for more than 80%. Guided by this mechanism, systematic structural optimization was conducted. Alumina was identified as the optimal heat exchanger material due to its combined porosity, thermal conductivity, and corrosion resistance. Among the tested pore sizes, CMHE-4 produces the strongest capillary-condensation enhancement, yielding a heat recovery flux (q value) of up to 38.8 MJ/(m² h), which is 4.3% and 304% higher than those of the stainless steel heat exchanger and plastic heat exchanger, respectively. In addition, Length-dependent analyses reveal an inherent trade-off: shorter modules achieved higher q (e.g., 14–42% greater for 200-mm vs. 300-mm CMHE-4), whereas longer modules provide greater total recovered heat (Q). Scale-up experiments demonstrated pronounced non-linear performance amplification, with a 4 times area increase boosting q by only 1.26 times under constant pressure. The techno-economic assessment indicates a simple payback period of ~2.5 months and a significant reduction in net capture cost. Overall, this work establishes key design parameters, validates the governing transport mechanism, and provides a practical, economically grounded framework for implementing high-efficiency CMHEs in MEA-based CO₂ capture. Full article

The purpose of the study was to characterize the basic structure of nanoparticles (Zein-CS-Cur-Que) embedded in curcumin and quercetin, realize the synergistic antioxidant of dietary polyphenols, and improve the transmembrane transport rate and bioavailability of curcumin. The oral delivery system Zein-CS-Cur-Que developed based on the synergistic encapsulation of curcumin and quercetin using the anti-solvent method with corn alkyd-soluble proteins and sodium caseinate possessed varying nanoparticle sizes (173.96–191.03 nm) and good dispersibility (PDI < 0.17), and relied on electrostatic interactions, hydrogen bonding, and hydrophobic interactions to successfully encapsulate curcumin (94.62%) and quercetin (73.75%). The results showed that Zein-CS-Cur-Que enhanced the stability and antioxidant activity of curcumin, and increased the bioaccessibility (nearly 2-fold) and rate of translocation (nearly 2-fold) of curcumin in the gastrointestinal tract significantly. Therefore, the nanocomposite system developed in this study is crucial for the development of functional foods and dietary supplements, providing effective insights into the synergy of polyphenol interactions. Full article

Transmembrane facilitation of substrates by channels and secondary active transporters results in a defined steady-state concentration ratio across the membrane. Evidence is accumulating that asymmetry in the structural build of the transporters, or interaction with asymmetric partner proteins, can shift the position of the transmembrane equilibrium by biased transport directionality. For instance, the bacterial lactose transporter, LacY, and two amino acid transporters, i.e., the human excitatory amino acid carrier, EAAC1, and the yeast lysine permease, Lyp1, were reported to exhibit distinct transport kinetics in the inward and outward direction by protein-intrinsic properties. A recent example is transport modulation of human monocarboxylate transporters, MCT, by shedding of the extracellular domain of an ancillary protein, basigin. Loss of the domain selectively increases export of lactate from lung cancer cells by a factor of four, contributing to the Warburg effect and malignancy. Further, intrinsic properties of monocarboxylate transporters involving asymmetric affinities of substrate binding, or biased open probabilities were shown to generate preference for one transport direction. Here, we discuss molecular mechanisms and physiological contexts of asymmetric secondary active transmembrane transport. Focus is laid on experimentally established cases, and examples are given in which putative bias in transport directionality may have been overlooked. Full article

The synthesis of the melanin pigment in melanocytes plays a crucial role in protecting the body from ultraviolet radiation. Tyrosinase, a key enzyme in melanogenesis, catalyzes the conversion of tyrosine to melanin in the melanosomes of melanocytes. During melanogenesis, Tyrosinase is abundantly synthesized in the lumen of the endoplasmic reticulum (ER) and subsequently transported from the ER to the melanosomes via the Golgi apparatus. In the present study, we demonstrate that Box B-binding factor 2 human homolog on chromosome 7 (BBF2H7), an ER-resident transmembrane transcription factor that functions as an ER stress sensor, is activated by mild ER stress caused by abundant Tyrosinase synthesis. Activated BBF2H7 enhances COPII-mediated anterograde transport by inducing the expression of Sec23a, which is a COPII component and transcriptional target of BBF2H7. Loss of BBF2H7 attenuates the transport of Tyrosinase, leading to its accumulation in the ER lumen and reduced melanin production. Restoration of BBF2H7 or Sec23a expression in Bbf2h7-deficient melanocytes rescues anterograde transport of Tyrosinase from the ER and melanin pigmentation. Collectively, these findings reveal that the BBF2H7-Sec23a axis is essential for the ER-to-melanosome transport of Tyrosinase and subsequent melanin synthesis. Thus, it may be a prospective therapeutic target for disorders related to melanin pigmentation. Full article

Zinc (Zn) is a mineral micronutrient that is essential for plant growth and development. Soil Zn deficiency or excess severely impacts plant health and crop yields. MicroRNAs (miRNAs) play crucial roles in plant responses to abiotic stress, but their roles in Zn homeostasis in important crop bread wheat (Triticum aestivum L.) remain unknown. This study investigated miRNA expression profiles in wheat roots under different Zn supply conditions using high-throughput sequencing. Phenotypic and physiological analyses revealed that high Zn promoted wheat plant growth, while low and excess Zn resulted in wheat plant growth inhibition and oxidative stress. A total of 798 miRNAs (including 70 known and 728 novel miRNAs) were identified; among them, 10 known and 122 novel miRNAs were differentially expressed. Many key miRNAs, such as miR397-5p, miR398, 4D_25791, and 5A_27668, are up-regulated under low Zn but down-regulated under high Zn and excess Zn. Target gene prediction and enrichment analysis revealed that the regulated genes of these miRNAs focused on “zinc ion transmembrane transporter activity”, “divalent inorganic cation transmembrane transporter activity”, and “cellular detoxification” processes in the low Zn vs. CK group. However, “glutathione metabolism” and “ABC transporter” pathways were obviously enriched in high Zn vs. excess Zn conditions, implying their potential functions in alleviating the oxidative damage and Zn efflux caused by Zn toxicity. Together, this study identified key miRNAs that respond to both Zn deficiency and excess Zn in bread wheat, revealing distinct regulatory patterns of the target genes in different Zn supply conditions. These findings provide a new field and valuable candidate miRNAs for molecular breeding aimed at improving zinc’s utilization efficiency in wheat. Full article

Sucrose is a key quality trait in peanuts, yet high-sucrose varieties are scarce. Although sucrose transporters (SUT/SUC) play crucial roles in sucrose transport and accumulation during seed development, systematic analyses in peanuts are limited. This study conducted a genome-wide analysis of the SUC gene family in cultivated peanut (Arachis hypogaea L.). Sixteen AhSUC genes were identified and characterized for genomic distribution, phylogeny, and expression across tissues and developmental stages. The genes are unevenly distributed across the genome with clustered chromosomal localization. All AhSUC proteins contain the conserved sucrose/proton co-transporter domain (IPR005989), exhibit the typical 12 transmembrane α-helical structure of the major facilitator superfamily, are hydrophobic, and predicted to localize to the membrane. Promoter analysis revealed cis-regulatory elements associated with growth, development, light, hormone, and stress responses. Expression profiling showed tissue-specific patterns, with eight AhSUC genes being highly expressed in cotyledons and embryos. Comparative analysis between high-sugar and conventional varieties showed higher expression of AhSUC2, AhSUC9, and AhSUC11 in the high-sugar variety, correlating with increased sucrose accumulation. Functional validation using a sucrose transport-deficient yeast mutant confirmed the sucrose transport activity of these genes. These findings provide insight into sucrose accumulation mechanisms and offer genetic targets for breeding high-sugar peanut varieties. Full article

Urea transporter (UT) proteins are a group of membrane proteins specifically facilitating the transmembrane transport of urea, primarily divided into the UT-A and UT-B subfamilies. Early studies have predominantly focused on their pivotal roles in the mechanism of urine concentration in kidneys. Recently accumulating evidences suggest that UTs are also expressed in the cardiovascular system, particularly in cardiomyocytes and vascular endothelial cells, where they contribute to critical physiological processes such as regulation of cell volume homeostasis, modulation of nitric oxide production, control of myocardial electrophysiological properties, and adaptation to cardiac stress. Importantly, impairments or disruptions in UT activities have been increasingly associated with the pathogenesis and progression of multiple cardiovascular disorders, including hypertension, uremic cardiomyopathy, myocardial hypertrophy, heart failure, cardiac conduction disorders and atherosclerosis, which deepens the understanding of the role of urea metabolism as a key component in cardiovascular homeostasis. This brief review summarizes the distribution and physiological functions of UTs in the cardiovascular system, and evaluates the potential and existing challenges of targeting UTs as a novel therapeutic approach for cardiovascular diseases. Full article

Polyhydroxybutyrate (PHB), as a biodegradable and green polymer, holds significant potential for replacing traditional petroleum-based plastics. However, its production efficiency and cost remain bottlenecks limiting large-scale application. In recent years, hybrid systems constructed from photosensitive nanomaterials and microorganisms have provided a novel pathway for enhancing PHB synthesis efficiency. These systems augment the supply of intracellular reducing power through efficient photo-generated electron injection, thereby driving microbial carbon fixation and PHB anabolic metabolism. This review systematically summarizes the mechanisms and performance of various types of photosensitive materials (including g-C₃N₄, CdS, polymer dots, etc.) in regulating PHB synthesis in microorganisms, such as Cupriavidus necator H16. It focuses on the influence of material composition, structure, energy band characteristics, and their interfacial interactions with microorganisms on electron transfer efficiency and biocompatibility. Furthermore, the article outlines the current challenges faced by these hybrid systems in key energy and mass transfer processes, including light energy conversion, transmembrane electron transport, and NADPH regeneration. It also prospects the design principles of novel bio-inspired multi-level heterojunction materials and their application potential in constructing efficient “material microbe” collaborative synthesis systems. This review aims to provide a material-level theoretical foundation and design strategies for developing high-performance and sustainable light-driven biomanufacturing technologies for PHB. Full article

Annual wild soybean is characterized by a high protein content. To elucidate the genetic basis, this study utilized a chromosome segment substitution line population (177 lines) constructed with cultivated soybean NN1138-2 as the recipient and wild soybean N24852 as the donor. Phenotypic analyses across three environments revealed significant variation in protein content ranging from 42.86% to 49.08%, with a high heritability of 0.70, indicating strong genetic control. Through high-throughput sequencing, six wild segments associated with high protein content were detected on chromosomes 3, 6, 9, 15, and 20, with phenotypic variation explained (PVE) by individual segments ranged from 3.58% to 22.46%, with segments on chromosomes 9, 15, and 20 as large-effect segments with PVE > 10%. All wild segments exhibited positive additive effects (0.42–1.09%), consistent with the characteristic of a high protein content in wild soybean. Compared with previous studies, five segments overlapped with reported loci, while qPro6.1 on chromosome 6 was a novel discovery. Integration of genomic and transcriptomic data identified 10 genes involved in nucleic acid binding, transmembrane protein transport, and amino acid synthesis pathway, with homologs validated in soybean, rice, and rapeseed. This research deepens the understanding of wild soybean’s high protein and offers new gene resources for breeding high-protein cultivated soybean. Full article

Extracellular vesicles (EVs) secreted by Fusarium oxysporum play an important role in the process of its infestation of the host, but the in vitro research system for EVs of F. oxysporum (Fo-EVs) has not yet been improved, and the mechanism of its action remains unclear. In this study, particle size distribution, particle concentration, number of particles per unit of protein, number of particles per unit of mycelial biomass, and concentration of contaminated proteins were used as indicators to evaluate the yield and purity of Fo-EVs. The optimal method for Fo-EV preparation and extraction was screened by comparing liquid culture, solid culture, and solid culture with enzymatic cell wall hydrolysis. The optimal system for Fo-EVs separation and purification was screened by a pairwise combination of three primary methods (Ultracentrifugation (UC), Ultrafiltration (UF), and Polyethylene glycol precipitation method (PEG)) and two secondary methods (Size-exclusion chromatography (SEC) and Aqueous two-phase system (ATPS)), respectively. The protein composition was identified via mass spectrometry technology, followed by GO annotation and GO enrichment analysis using whole-genome proteins as the background. Based on these steps, a Fo-EV protein library was constructed to reveal Fo-EV’s most active biological functions. The results showed that solid culture combined with the UC-SEC method could effectively enrich Fo-EVs with a typical cup-shaped membrane structure. The obtained Fo-EVs had an average particle size of 253.50 nm, a main peak value of 200.60 nm, a particle concentration of 2.04 × 10¹⁰ particles/mL, and a particle number per unit protein of 1.09 × 10⁸ particles/μg, which were significantly superior to those of other combined methods. Through proteomic analysis, 1931 proteins enriched in Fo-EVs were identified, among which 350 contained signal peptides and 375 had transmembrane domains. GO enrichment analysis revealed that these proteins were mainly involved in cell wall synthesis, vesicle transport, and pathogenicity-related metabolic pathways. Additionally, 9 potential fungal EV markers, including Hsp70, Rho GTPase family, and SNARE proteins, were screened. This study constructed an isolation system and a marker database for Fo-EVs, providing a methodological and theoretical basis for in-depth analysis of the biological functions of Fo-EVs. Full article

Aquaporins (AQPs) facilitate transmembrane transport of water and small solutes, critically influencing plant growth, development, and stress adaptation. However, tea plant AQPs (CsAQPs) remain incompletely characterized genome-wide. In this study, 61 CsAQPs were identified from the tea plant genome and could be classified into five subfamilies. The bioinformatics characteristics, including phylogenetic relationships, gene structures, chromosomal locations, conserved motifs, promoter cis-acting elements, and three-dimensional protein structure, were systematically investigated. Additionally, the expression patterns of CsAQPs in tea plants in response to abiotic and biotic stresses were comprehensively explored based on transcriptome data and qRT-PCR, suggesting that CsAQPs were closely associated with the tea plant responding to environmental adaptation. Notably, the functions of CsPIPs in response to drought and salt, as well as potential H₂O₂ transporters and their subcellular localization, were investigated in yeast. Collectively, our study delivers a complete genomic and evolutionary dissection of the CsAQPs gene family in the tea plant, providing valuable insights into their diverse functions for further investigation. Full article

Nanoplastics are ubiquitous in aquatic environments, and elucidating their bioaccumulation behavior is essential for assessing toxicity and trophic transfer risks. While most studies focus on nanoplastics properties (e.g., type, size, surface charge), the influence of organismal growth stage remains unclear. Through bioaccumulation kinetic experiments with 10 mg/L polystyrene nanoplastics (PSNPs), this study found that Tetrahymena thermophila (T. thermophila) in the lag phase (cell density 4 × 10⁴ cells/mL) exhibited the highest uptake rate of nanoplastics, 1.2–5.8 times that of the exponential phase (1–5 × 10⁵ cells/mL) and 7.7 times that of the stationary phase (>5 × 10⁵ cells/mL). Lag phase cells also had a larger specific surface area (0.319 vs. 0.271/0.269 μm⁻¹), supporting their heightened uptake capacity. Under PSNP exposure, exponential and stationary phase cells showed significantly elevated reactive oxygen species (ROS) levels, accompanied by downregulated superoxide dismutase (SOD) and stable catalase (CAT) activity, indicating impaired antioxidant defense and potential redirection of energy toward stress mitigation. Consistent with efficient internalization, confocal imaging revealed clear PSNP colocalization within food vacuoles of lag period cells. Proteomic and transcriptomic analysis further confirmed the upregulation of carrier proteins, FAD/FMN oxidoreductases, and pathways associated with cellular components (membrane and organelle membrane) and molecular functions (transporter activity and transmembrane transporter activity) in lag-phase T. thermophila. Collectively, these findings provide a molecular-level understanding of the multi-phase-dependent bioaccumulation of PSNPs, offering critical insights for assessing the environmental risks of polystyrene nanoplastics in dynamic aquatic ecosystems. Full article

Background/Objectives: Previous studies have demonstrated an association between migraine headache and temporomandibular joint disorders (TMDs), with a higher prevalence of TMD symptoms in patients with migraine. Methods: In this study, we conducted RNA sequencing to identify differentially expressed genes (DEGs) in the spinal trigeminal nucleus caudalis of mice with migraine-like pain and/or myogenic TMD. Results: We observed 204 upregulated and 274 downregulated genes in the comorbid migraine and TMD group compared to the control group. We identified 15 ferroptosis-related DEGs enriched in the pathways of neurodegeneration, cellular homeostasis, interleukin signaling, and pain response. Gene Ontology analysis highlighted the involvement of neuroinflammatory response and monoamine transmembrane transporter activity, while Gene Set Enrichment analysis showed enrichment in chemokine signaling, cell cycle, and calcium signaling pathways. Immune infiltration analysis identified M0 macrophages, immature dendritic cells, neutrophils, and eosinophils as key responders. Hub genes in the protein–protein interaction network included Gm7536, Rpl17, Rpl22l1, Rpl14, Rps8, Rps29, Rpl35, Gm4889, Gm11808, Rps27rt, Rps12-ps3, Rpl10-ps3, Gm9843, Oas1c, Il1b, and Serpine1, indicating their synergistic roles in such orofacial pain comorbidity. Conclusions: Our results suggest that the comorbid migraine and TMD can regulate gene expressions involving ferroptosis and immune cell responses and the identified DEGs could be targeted to develop novel therapies for this painful comorbidity. Full article