TMK4-mediated FIP37 phosphorylation regulates auxin-triggered N6-methyladenosine modification of auxin biosynthetic genes in Arabidopsis.

The dynamics of N6-methyladenosine (m6A) mRNA modification are tightly controlled by the m6A methyltransferase complex and demethylases. Here, we find that auxin treatment alters m6A modification on auxin-responsive genes. Mechanically, TRANSMEMBRANE KINASE 4 (TMK4), a component of the auxin signaling pathway, interacts with and phosphorylates FKBP12-INTERACTING PROTEIN 37 (FIP37), a core component of the m6A methyltransferase complex, in an auxin-dependent manner. Phosphorylation of FIP37 enhances its interaction with RNA, thereby increasing m6A modification on its target genes, such as NITRILASE 1 (NIT1), a gene involved in indole-3-acetic acid (IAA) biosynthesis. 1-Naphthalacetic acid (NAA) treatment accelerates the mRNA decay of NIT1, in a TMK4- and FIP37-dependent manner, which leads to inhibition of auxin biosynthesis. Our findings identify a regulatory mechanism by which auxin modulates m6A modification through the phosphorylation of FIP37, ultimately affecting mRNA stability and auxin biosynthesis in plants.

UV-B Radiation Exhibited Tissue-Specific Regulation of Isoflavone Biosynthesis in Soybean Cell Suspension Cultures.

Isoflavones, a class of substances with high biological activity, are abundant in soybeans. This study investigated isoflavone biosynthesis in soybean cell suspension cultures under UV-B radiation. UV-B radiation enhanced the transcription level and activity of key enzymes involved in isoflavone synthesis in cell suspension cultures. As a result, the isoflavone contents significantly increased by 19.80% and 91.21% in hypocotyl and cotyledon suspension cultures compared with the control, respectively. Meanwhile, a significant difference was observed in the composition of isoflavones between soybean hypocotyl and cotyledon suspension cultures. Genistin was only detected in hypocotyl suspension cultures, whereas glycitin, daidzein, and genistein accumulated in cotyledon suspension cultures. Therefore, UV-B radiation exhibited tissue-specific regulation of isoflavone biosynthesis in soybean cell suspension cultures. The combination of suspension cultures and abiotic stress provides a novel technological approach to isoflavone accumulation.

Effects of protein-glutaminase on the properties of glutinous rice flour, paste, and gel food: Based on the interactions between the deamidated protein and starch.

In the present study, protein-glutaminase (PG) from Chryseobacterium proteolyticum was applied to improve the processing properties of glutinous rice flour (GRF). After PG modification, the degree of deamidation of glutinous rice protein (GRP) reached 13.6% at 2.0 h, with smaller particle size and decreased zeta potential. The interaction of GRP with starch in PG-modified GRF (PM-GRF) was changed, exhibiting in protein aggregates decreasing and exposure of starch on the surface of GRF. Compared with unmodified GRF (UM-GRF), the solubility and turbidity of PM-GRF were both increased. The rheological properties reflected that the viscosity of PM-GRF paste was increased, and the freeze-thaw stability was also enhanced. Moreover, the textural characteristics showed that the hardness of PM-GRF balls remarkably reduced and the springiness increased. These results indicate that deamidation by PG could be an efficient method for improving characteristics of GRP and GRF.

A conserved GRAS-domain transcriptional regulator links meristem indeterminacy to sex determination in Ceratopteris gametophytes.

Most land plants alternate between generations of sexual gametophytes and asexual sporophytes. Unlike seed plants, fern gametophytes are free living and grow independently of their sporophytes. In homosporous ferns such as Ceratopteris, gametophytes derived from genetically identical spores exhibit sexual dimorphism, developing as either males or hermaphrodites. Males lack meristems and promote cell differentiation into sperm-producing antheridia. In contrast, hermaphrodites initiate multicellular meristems that stay undifferentiated, sustain cell division and prothallus expansion, and drive the formation of egg-producing archegonia. Once initiating the meristem, hermaphrodites secrete the pheromone antheridiogen, which triggers neighboring slower-growing gametophytes to develop as males, while the hermaphrodites themselves remain insensitive to antheridiogen. This strategy promotes outcrossing and prevents all individuals in the colony from becoming males. This study reveals that an evolutionarily conserved GRAS-domain transcriptional regulator (CrHAM), directly repressed by Ceratopteris microRNA171 (CrmiR171), promotes meristem development in Ceratopteris gametophytes and determines the male-to-hermaphrodite ratio in the colony. CrHAM preferentially accumulates within the meristems of hermaphrodites but is excluded from differentiated antheridia. CrHAM sustains meristem proliferation and cell division through conserved hormone pathways. In the meantime, CrHAM inhibits the antheridiogen-induced conversion of hermaphrodites to males by suppressing the male program expression and preventing meristem cells from differentiating into sperm-producing antheridia. This finding establishes a connection between meristem indeterminacy and sex determination in ferns, suggesting both conserved and diversified roles of meristem regulators in land plants.

High-throughput screening unveils nitazoxanide as a potent PRRSV inhibitor by targeting NMRAL1.

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ's role in augmenting the sensitivity of the IFN-ß pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ's effectiveness.

Electron Spin Broken-Symmetry of Fe-Co Diatomic Pairs to Promote Kinetics of Bifunctional Oxygen Electrocatalysis for Zinc-Air Batteries.

Designing bifunctional catalysts to reduce the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) reaction barriers while accelerating the reaction kinetics is perceived to be a promising strategy to improve the performance of Zinc-air batteries. Unsymmetric configuration in single-atom catalysts has attracted attention due to its unique advantages in regulating electron orbitals. In this work, a seesaw effect in unsymmetric Fe-Co bimetallic monoatomic configurations is proposed, which can effectively improve the OER/ORR bifunctional activity of the catalyst. Compared with the symmetrical model of Fe-Co, a strong charge polarization between Co and Fe atoms in the unsymmetric model is detected, in whom the spin-down electrons around Co atoms are much higher than those spin-up electrons. The seesaw effect occurred between Co atoms and Fe atoms, resulting in a negative shift of the d-band center, which means that the adsorption of oxygen intermediates is weakened and more conducive to their dissociation. The optimized reaction kinetics of the catalyst leads to excellent performance in ZABs, with a peak power density of 215 mW cm-2 and stable cycling for >1300 h and >4000 cycles. Flexible Zinc-air batteries have also gained excellent performance to demonstrate their potential in the field of flexible wearables.

Synergistic enhancement of anthocyanin stability and techno-functionality of colored wheat during the steamed bread processing by selectively hydrolyzed soy protein.

To improve the stability of anthocyanins and techno-functionality of purple and blue wheat, the selectively hydrolyzed soy protein (reduced glycinin, RG) and ß-conglycinin (7S) were prepared and their enhanced effects were comparatively investigated. The anthocyanins in purple wheat showed higher stability compared to that of the blue wheat during breadmaking. The cyanidin-3-O-glucoside and cyanidin-3-O-rutincoside in purple wheat and delphinidin-3-O-rutinoside and delphinidin-3-O-glucoside in blue wheat were better preserved by RG. Addition of RG and 7S enhanced the quality of steamed bread made from colored and common wheat, with RG exhibited a more prominent effect. RG and 7S suppressed the gelatinization of starch and improved the thermal stability. Both RG and 7S promoted the unfolding process of gluten proteins and facilitated the subsequent crosslinking of glutenins and gliadins by disulfide bonds. Polymerization of α- and γ-gliadin into glutenin were more evidently promoted by RG, which contributed to the improved steamed bread quality.

Human NMO-IgG Induced Different Pathological and Immunological Changes in the CNS and Peripheral Tissues of Mice.

OBJECTIVES: The majority of neuromyelitis optica spectrum disorders (NMOSD) patients are seropositive for aquaporin-4 (AQP4)-specific antibodies [also named neuromyelitis optica immunoglobulin G antibodies (NMO-IgG)]. Although NMO-IgG can induce pathological changes in the central nervous system (CNS), the immunological changes in the CNS and peripheral tissue remain largely unknown. We investigated whether NMO-IgG binds to tissue expressing AQP4 and induces immunological changes in the peripheral tissue and CNS. METHODS: C57BL/6 female mice were assigned into an NMOSD or control group. Pathological and immunological changes in peripheral tissue and CNS were measured by immunostaining and flow cytometry, respectively. Motor impairment was measured by open-field test. RESULTS: We found that NMO-IgG did bind to astrocyte- and AQP4-expressing peripheral tissue, but induced glial fibrillary acidic protein and AQP4 loss only in the CNS. NMO-IgG induced the activation of microglia and modulated microglia polarization toward the classical (M1) phenotype, but did not affect innate or adaptive immune cells in the peripheral immune system, such as macrophages, neutrophils, Th17/Th1, or IL-10-producing B cells. In addition, NMOSD mice showed significantly less total distance traveled and higher immobility time in the open field. CONCLUSIONS: We found that injection of human NMO-IgG led to astrocytopathic lesions with microglial activation in the CNS. However, there were no significant pathological or immunological changes in the peripheral tissues.

Addressing adsorption and catalysis of lithium polysulfide via electronic distribution of molybdenum carbide host.

Heterostructure engineering is considered a crucial strategy to modulate the intrinsic charge transfer behavior of materials, enhance catalytic activity, and optimize sulfur electrochemical processes. However, parsing the role of heterogeneous interface-structure-property relationships in heterostructures is still a key scientific issue to realize the efficient catalytic conversion of polysulfides. Based on this, molybdenum carbide (Mo2C) was successfully partial reduced to molybdenum metal (Mo) via a thermal reduction at high-temperature and the typical Mo-Mo2C-based Mott-Schottky heterostructures were simultaneously constructed, which realized the modulation of the electronic structure of Mo2C and optimized the conversion process of lithium polysulfides (LPS). Compared with single molybdenum carbide, the modulated molybdenum carbide acts as an electron donor with stronger Mo-S bonding strength as well as higher polysulfide adsorption energy, faster Li2S conversion kinetics, and greatly facilitates the adsorption → catalysis process of LPS. As a result, yolk-shell Mo-Mo2C heterostructure (C@Mo-Mo2C) exhibits excellent cycling performance as a sulfur host, with a discharge specific capacity of 488.41 mAh g-1 for C@Mo-Mo2C/S at 4 C and present an excellent high-rate cyclic performance accompanied by capacity decay rate of 0.08 % per cycle after 400 cycles at 2 C. Heterostructure-acting Mo2C electron distribution modulation engineering may contributes to the understanding of the structure-interface-property interaction law in heterostructures and further enables the efficient modulation of the chemical behavior of sulfur.

CD22 blockade aggravates EAE and its role in microglia polarization.

AIMS: Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease. Microglia are reportedly involved in the pathogenesis of MS. However, the key molecules that control the inflammatory activity of microglia in MS have not been identified. METHODS: Experimental autoimmune encephalomyelitis (EAE) mice were randomized into CD22 blockade and control groups. The expression levels of microglial CD22 were measured by flow cytometry, qRT-PCR, and immunofluorescence. The effects of CD22 blockade were examined via in vitro and in vivo studies. RESULTS: We detected increased expression of microglial CD22 in EAE mice. In addition, an in vitro study revealed that lipopolysaccharide upregulated the expression of CD22 in microglia and that CD22 blockade modulated microglial polarization. Moreover, an in vivo study demonstrated that CD22 blockade aggravated EAE in mice and promoted microglial M1 polarization. CONCLUSION: Collectively, our study indicates that CD22 may be protective against EAE and may play a critical role in the maintenance of immune homeostasis in EAE mice.

Novel strategy to raise the content of aglycone isoflavones in soymilk and gel: Effect of germination on the physicochemical properties.

Germination holds the key to nutritional equilibrium in plant grains. In this study, the effect of soybean germination on the processing of soymilk (SM) and glucono-δ-lactone (GDL) induced soymilk gel (SG) was investigated. Germination promoted soybean sprout (SS) growth by activating the energy metabolism system. The energy metabolism was high during the three-day germination and was the most vigorous on the second day of germination. After germination, protein dissolution was improved in SM, and endogenous enzymes produced small molecule proteins. Small molecule proteins were more likely to aggregate to produce SM protein particles. Germination increased the water-holding capacity of SG induced by GDL but weakened the strength. Furthermore, the dynamic fluctuations in isoflavone content were closely monitored throughout the processing of soybean products, including SS, SM, and SG. Although the total amount of isoflavones in SM and SG processed from germinated soybeans decreased, a significant enrichment in the content of aglycone isoflavones was observed. The content of aglycone isoflavones in SG processed from germinated soybeans on the second day of germination was 736.17 ± 28.49 µg/g DW, which was 83.19 % higher than that of the control group. This study demonstrates that germination can enhance the nutritional value of soybean products, providing innovative opportunities for the development of health-promoting soybean-based products.

Ultraflexible electrodes for recording neural activity in the mouse spinal cord during motor behavior.

Implantable electrode arrays are powerful tools for directly interrogating neural circuitry in the brain, but implementing this technology in the spinal cord in behaving animals has been challenging due to the spinal cord's significant motion with respect to the vertebral column during behavior. Consequently, the individual and ensemble activity of spinal neurons processing motor commands remains poorly understood. Here, we demonstrate that custom ultraflexible 1-µm-thick polyimide nanoelectronic threads can conduct laminar recordings of many neuronal units within the lumbar spinal cord of unrestrained, freely moving mice. The extracellular action potentials have high signal-to-noise ratio, exhibit well-isolated feature clusters, and reveal diverse patterns of activity during locomotion. Furthermore, chronic recordings demonstrate the stable tracking of single units and their functional tuning over multiple days. This technology provides a path for elucidating how spinal circuits compute motor actions.

A High-Proton Conductivity All-Biomass Proton Exchange Membrane Enabled by Adenine and Thymine Modified Cellulose Nanofibers.

Nanocellulose fiber materials were considered promising biomaterials due to their excellent biodegradability, biocompatibility, high hydrophilicity, and cost-effectiveness. However, their low proton conductivity significantly limited their application as proton exchange membranes. The methods previously reported to increase their proton conductivity often introduced non-biodegradable groups and compounds, which resulted in the loss of the basic advantages of this natural polymer in terms of biodegradability. In this work, a green and sustainable strategy was developed to prepare cellulose-based proton exchange membranes that could simultaneously meet sustainability and high-performance criteria. Adenine and thymine were introduced onto the surface of tempo-oxidized nanocellulose fibers (TOCNF) to provide many transition sites for proton conduction. Once modified, the proton conductivity of the TOCNF membrane increased by 31.2 times compared to the original membrane, with a specific surface area that had risen from 6.1 m²/g to 86.5 m²/g. The wet strength also increased. This study paved a new path for the preparation of environmentally friendly membrane materials that could replace the commonly used non-degradable ones, highlighting the potential of nanocellulose fiber membrane materials in sustainable applications such as fuel cells, supercapacitors, and solid-state batteries.

Refrigerated storage stimulates isoflavone and γ-aminobutyric acid accumulation in germinated soybeans.

This study aims to investigate the quality changes of germinated soybeans during refrigerated storage (4 °C), with an emphasis on the stimulatory effect of refrigeration on their special functional compounds. After germinating for two days, germinated soybeans were stored at 4 °C for seven days, while the germinated soybeans stored at 25 °C served as control group. The results showed that refrigerated storage significantly affected the physiological changes in germinated soybeans. The weight loss rate, browning rate, malondialdehyde (MDA) content and H2O2 content all decreased dramatically during refrigerated storage compared to the control group. The total phenolic and total flavonoid contents of germinated soybeans under refrigeration exhibited a trend of increasing and then decreasing over time. Additionally, during refrigerated storage, the total isoflavone content reached a peak of 8.72 g/kg on the fifth day, in which the content of daidzein and glycitin increased by 45% and 49% respectively, when compared with the control group. Moreover, the content of γ-aminobutyric acid (GABA) peaked on the first day, and kept a high level during storage. In which, the refrigerated group was 2.35-, 2.88-, 1.67-fold respectively after storage for three to seven days. These results indicated that refrigeration stimulated the biosynthesis of isoflavones and GABA in germinated soybeans during storage. More importantly, there was a sequential difference in the timing of the stimulation of the two functional components under refrigeration.

A Novel Nanofiber Hydrogel Adhesive Based on Carboxymethyl Cellulose Modified by Adenine and Thymine.

Natural polymer-based adhesive hydrogels have garnered significant interest for their outstanding strength and versatile applications, in addition to being eco-friendly. However, the adhesive capabilities of purely natural products are suboptimal, which hampers their practical use. To address this, we engineered carboxymethyl cellulose (CMC) surfaces with complementary bases, adenine (A) and thymine (T), to facilitate the self-assembly of adhesive hydrogels (CMC-AT) with a nanofiber configuration. Impressively, the shear adhesive strength reached up to 6.49 MPa with a mere 2% adhesive concentration. Building upon this innovation, we conducted a comparative analysis of the shear adhesion properties between CMC and CMC-AT hydrogel adhesives when applied to delignified and non-delignified wood chips. We examined the interplay between the adhesives and the substrate, as well as the role of mechanical interlocking in overall adhesion performance. Our findings offer a fresh perspective on the development of new biodegradable polymer hydrogel adhesives.

Comparative Outcomes of Intravenous, Intranasal, and Intracerebroventricular Transplantation of Human Neural Stem Cells in Mice Model of Ischemic Stroke.

BACKGROUND: Transplantation of neural stem cells improves ischemic stroke outcomes in rodent models and is currently in the clinical test stage. However, the optimal delivery route to achieve improved efficacy remains undetermined. OBJECTIVE: This study aims to evaluate three more clinically feasible delivery routes: intravenous (IV), intranasal (IN), and intracerebroventricular (ICV). We compared the therapeutic efficacies of the three routes of transplanting human neural stem cells (hNSCs) into mice with permanent middle cerebral artery obstruction (pMCAO). METHODS: Behavioral tests and cresyl violet staining were used to evaluate the therapeutic efficacies of functional recovery and lesion volumes. The expression of proinflammatory cytokines and neurotrophic factors was measured by real-time PCR. The distribution and differentiation of hNSCs were determined by immunofluorescence staining. The effect on endogenous neurogenesis and astrocyte function were determined by immunofluorescence staining and western blot. RESULTS: hNSC transplantation using the three routes improved behavioral outcomes and reduced lesion volumes; IV transplantation of hNSCs results in earlier efficacy and improves the inflammatory microenvironment. The long-term distribution and differentiation of transplanted hNSCs in the peri-infarct areas can only be evaluated using ICV delivery. IV and ICV transplantation of hNSCs promote neurogenesis and modulate the dual function of astrocytes in the peri-infarct areas. CONCLUSION: IV and IN delivery is suitable for repeated administration of hNSCs to achieve improved prognosis. Comparatively, ICV transplantation provides long-term efficacy at lower doses and fewer administration times.

Apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) promotes stress granule formation via YBX1 phosphorylation in ovarian cancer.

APE1 is an essential gene involved in DNA damage repair, the redox regulation of transcriptional factors (TFs) and RNA processing. APE1 overexpression is common in cancers and correlates with poor patient survival. Stress granules (SGs) are phase-separated cytoplasmic assemblies that cells form in response to environmental stresses. Precise regulation of SGs is pivotal to cell survival, whereas their dysregulation is increasingly linked to diseases. Whether APE1 engages in modulating SG dynamics is worthy of investigation. In this study, we demonstrate that APE1 colocalizes with SGs and promotes their formation. Through phosphoproteome profiling, we discover that APE1 significantly alters the phosphorylation landscape of ovarian cancer cells, particularly the phosphoprofile of SG proteins. Notably, APE1 promotes the phosphorylation of Y-Box binding protein 1 (YBX1) at S174 and S176, leading to enhanced SG formation and cell survival. Moreover, expression of the phosphomutant YBX1 S174/176E mimicking hyperphosphorylation in APE1-knockdown cells recovered the impaired SG formation. These findings shed light on the functional importance of APE1 in SG regulation and highlight the importance of YBX1 phosphorylation in SG dynamics.

Antifreeze Polysaccharides from Wheat Bran: The Structural Characterization and Antifreeze Mechanism.

Exploring a novel natural cryoprotectant and understanding its antifreeze mechanism allows the rational design of future sustainable antifreeze analogues. In this study, various antifreeze polysaccharides were isolated from wheat bran, and the antifreeze activity was comparatively studied in relation to the molecular structure. The antifreeze mechanism was further revealed based on the interactions of polysaccharides and water molecules through dynamic simulation analysis. The antifreeze polysaccharides showed distinct ice recrystallization inhibition activity, and structural analysis suggested that the polysaccharides were arabinoxylan, featuring a xylan backbone with a majority of Araf and minor fractions of Manp, Galp, and Glcp involved in the side chain. The antifreeze arabinoxylan, characterized by lower molecular weight, less branching, and more flexible conformation, could weaken the hydrogen bonding of the surrounding water molecules more evidently, thus retarding the transformation of water molecules into the ordered ice structure.

Clinical outcomes of peripheral nerve interfaces for rehabilitation in paralysis and amputation: a literature review.

Peripheral nerve interfaces (PNIs) are electrical systems designed to integrate with peripheral nerves in patients, such as following central nervous system (CNS) injuries to augment or replace CNS control and restore function. We review the literature for clinical trials and studies containing clinical outcome measures to explore the utility of human applications of PNIs. We discuss the various types of electrodes currently used for PNI systems and their functionalities and limitations. We discuss important design characteristics of PNI systems, including biocompatibility, resolution and specificity, efficacy, and longevity, to highlight their importance in the current and future development of PNIs. The clinical outcomes of PNI systems are also discussed. Finally, we review relevant PNI clinical trials that were conducted, up to the present date, to restore the sensory and motor function of upper or lower limbs in amputees, spinal cord injury patients, or intact individuals and describe their significant findings. This review highlights the current progress in the field of PNIs and serves as a foundation for future development and application of PNI systems.

Metabolomics Analysis of Different Quinoa Cultivars Based on UPLC-ZenoTOF-MS/MS and Investigation into Their Antioxidant Characteristics.

In recent years, quinoa, as a nutritious and sustainable food material, has gained increasing popularity worldwide. To investigate the diversity of nutritional characteristics among different quinoa cultivars and explore their potential health benefits, metabolites of five quinoa cultivars (QL-1, SJ-1, SJ-2, KL-1 and KL-2) were compared by non-targeted metabolomics analysis based on UPLC-ZenoTOF-MS/MS in this study. A total of 248 metabolites across 13 categories were identified. Although the metabolite compositions were generally similar among the different quinoa cultivars, significant variations existed in their respective metabolite contents. Among the identified metabolites, amino acids/peptides, nucleosides, saponins and phenolic acids were the most abundant. Notably, SJ-1 exhibited the most distinct metabolite profile when compared to the other cultivars. Amino acids/peptides and nucleosides were found to be crucial factors contributing to the unique metabolite profile of SJ-1. Collectively, these aforementioned metabolites accounted for a substantial 60% of the total metabolites observed in each quinoa variety. Additionally, a correlation between the DPPH radical scavenging activity and the free phenolic content of quinoa was observed. Variations in phenolic content resulted in different antioxidant capacities among the quinoa cultivars, and SJ-1 exhibited lower phenolic levels and weaker antioxidant activity than the others. These results can provide important information for the development of quinoa resources.