Search Results (527)

CaMK4, a calcium/calmodulin-dependent protein kinase, is an important mediator of cellular signal transduction, yet its role in the regulation of skeletal muscle satellite cells (MuSCs) in goats has remained unclear. In this study, CaMK4 overexpression and knockdown models were established, and integrated transcriptomic and proteomic analyses were performed to systematically elucidate its regulatory network. CaMK4 overexpression altered key pathways associated with cell proliferation and muscle development, including cAMP, PI3K-Akt, and actin cytoskeleton regulation, while proteomic data highlighted calcium signaling and JAK-STAT pathways. Conversely, CaMK4 knockdown enhanced MuSC proliferation by upregulating cell cycle-related genes and proteins. Integrated analyses further identified that Galectin-9 (LGALS9), Collagen triple helix repeat containing-1 (CTHRC1), Hyaluronan Synthase 1 (HAS1), and L-Threonine Dehydrogenase (TDH) may serve as potential key nodes regulating cell cycle, apoptosis, and metabolic control. This suggests a regulatory role for CaMK4. Collectively, these findings provide a mechanistic framework for understanding CaMK4 function in ruminant muscle development and may offer insights for improving goat muscle growth, meat quality traits, and production efficiency. Full article

As a typical heavy metal pollutant, cadmium (Cd) poses significant threats to ecosystems and human health. Giant duckweed (Spirodela polyrhiza), a small aquatic plant characterized by rapid growth and efficient heavy metal accumulation, holds great promise for phytoremediation. However, the mechanisms by which S. polyrhiza enriches Cd—particularly the contributions of its surface-associated microbiota—remain poorly understood. In this study, S. polyrhiza fronds were exposed to 0, 1, and 10 μM Cd, and we observed a concentration-dependent increase in the abundance of epiphytic microorganisms on the frond surfaces. High-throughput 16S rRNA gene sequencing revealed that Cd stress significantly altered the diversity of the frond-epiphytic bacterial community. Notably, the relative abundances of the genera Herbaspirillum, Enterobacter, and Pantoea increased significantly with rising Cd concentrations. Functional prediction using PICRUSt2 indicated enrichment under Cd stress of specific traits—such as the nitrate/nitrite transporter NarK, signal transduction mechanisms, and ion channel proteins—suggesting these taxa may actively participate in Cd uptake and tolerance. Together, our results reveal a synergistic S. polyrhiza–microbiome response to Cd and identify taxa/functions as targets and biomarkers for microbe-augmented remediation. Full article

Joint diseases represent a significant health burden due to their high prevalence and morbidity, yet current treatments fail to provide comprehensive and long-term relief for all patients. In this context, adeno-associated virus (AAV) gene therapy has emerged as a promising approach, offering advantages such as prolonged efficacy and minimal immunogenicity. AAV has been extensively studied for various medical conditions, with some applications successfully implemented in patient treatments. Currently, a few clinical trials utilizing AAV have been completed for treating arthritis. However, challenges such as transduction efficiency, off-targets, and preexisting immune responses persist. This review provides an overview of the current paradigms of treatment with regard to joint diseases, elaborates on the AAV delivery barriers related to application in treating joint diseases, and discusses strategies to improve gene therapy efficacy, including AAV capsid engineering, small molecule-assisted AAV delivery, optimizing tissue-specific or inflammation-inducible promoters, as well as strategies to mitigate immune responses to AAV. Full article

In this work, we used a label-free biosensor that provides optical readouts to perform continuous detection of human interleukin 8 (IL-8), which is especially overexpressed in certain cancers and, thus, could be an effective biomarker for cancer prognosis estimation and therapy evaluation. For this purpose, we engineered a compact, portable, and easy-to-assemble biosensing module device. It combines a fluidic chip for reagent flow, a biosensing chip for signal transduction, and an optical readout head based on fiber optics in a single module. The biosensing chip is based on independent arrays of resonant nanopillar transducer (RNP) networks. We integrated the biosensing chip with the RNPs facing down in a simple and rapidly fabricated polydimethyl siloxane (PDMS) microfluidic chip, with inlet and outlet channels for the sample flowing through the RNPs. The RNPs were vertically oriented from the backside through an optical fiber mounted on a holder head fabricated ad hoc on polytetrafluoroethylene (PTFE). The optical fiber was connected to a visible spectrometer for optical response analysis and consecutive biomolecule detection. We obtained a sensogram showing anti-IL-8 immobilization and the specific recognition of IL-8. This unique portable and easy-to-handle module can be used for biomolecule detection within minutes and is particularly suitable for in-line sensing of physiological and biomimetic organ-on-a-chip systems. Cancer biomarkers’ continuous monitoring arises as an efficient and non-invasive alternative to classical tools (imaging, immunohistology) for determining clinical prognostic factors and therapeutic responses to anticancer drugs. In addition, the multiplexed layout of the optical transducers and the simplicity of the monolithic sensing module yield potential high-throughput screening of a combination of different biomarkers, which, together with other medical exams (such as imaging and/or patient history), could become a cutting-edge technology for further and more accurate diagnosis and prediction of cancer and similar diseases. Full article

Calcium is an essential macronutrient for plant growth and development, and there is an optimal calcium concentration for plant growth. Calcium ion concentration changes create “calcium signals” that regulate plant growth through perception, decoding, transduction, and response processes. However, the mechanisms by which calcium signaling regulates photosynthesis are still not fully understood. In this study, Quercus acutissima seedlings were used to investigate the inhibitory effects of different concentrations of the calcium channel blocker lanthanum chloride (LaCl₃) on photosynthesis and the underlying mechanisms. The results show that increasing LaCl₃ concentration significantly decreased photosynthetic parameters, photosynthetic pigment contents, and photosynthetic product accumulation. Long-term water use efficiency decreased with increasing LaCl₃ concentration, while instantaneous water use efficiency initially increased and then decreased. Structural equation modeling analysis indicated that LaCl₃ concentration was significantly positively correlated with leaf calcium concentration in Quercus acutissima seedlings, while it was significantly negatively correlated with stomatal conductance, carotenoids, and soluble sugar content. The study concludes that LaCl₃ directly inhibits the photosynthetic physiological processes of Quercus acutissima seedlings by blocking calcium signaling, providing insights into the regulatory mechanisms of calcium signaling in plant photosynthesis and a theoretical basis for the cultivation and application of Quercus acutissima under varying environmental conditions. Full article

Cadmium (Cd), a pervasive and highly phytotoxic metal pollutant, poses severe threats to agricultural productivity, ecosystem stability, and human health through its entry into the food chain. Plants have evolved intricate defense mechanisms, among which the strategic manipulation of nutrient elements emerges as a critical physiological and biochemical strategy for mitigating Cd stress. This comprehensive review delves deeply into the multifaceted roles of essential macronutrient elements (nitrogen, phosphorus, potassium, calcium, magnesium, sulfur), essential micronutrient elements (zinc, iron, manganese, copper) and non-essential beneficial elements (silicon, selenium) in modulating plant responses to Cd toxicity. We meticulously dissect the physiological, biochemical, and molecular underpinnings of how these nutrients influence Cd bioavailability in the rhizosphere, Cd uptake and translocation pathways, sequestration and compartmentalization within plant tissues, and the activation of antioxidant defense systems. Nutrient elements exert their influence through diverse mechanisms: competing with Cd for root uptake transporters, promoting the synthesis of complexes that reduce Cd mobility, stabilizing cell walls and plasma membranes to restrict apoplastic flow and symplastic influx, modulating redox homeostasis by enhancing antioxidant enzyme activities and non-enzymatic antioxidant pools, regulating signal transduction pathways, and influencing gene expression profiles related to metal transport, chelation, and detoxification. The complex interactions between nutrients themselves further shape the plant’s capacity to withstand Cd stress. Recent advances elucidating nutrient-mediated epigenetic regulation, microRNA involvement, and the role of nutrient-sensing signaling hubs in Cd responses are critically evaluated. Furthermore, we synthesize the practical implications of nutrient management strategies, including optimized fertilization regimes, selection of nutrient-efficient genotypes, and utilization of nutrient-enriched amendments, for enhancing phytoremediation efficiency and developing low-Cd-accumulating crops, thereby contributing to safer food production and environmental restoration in Cd-contaminated soils. The intricate interplay between plant nutritional status and Cd stress resilience underscores the necessity for a holistic, nutrient-centric approach in managing Cd toxicity in agroecosystems. Full article

Blue fescue (Festuca glauca) is a widely used ornamental grass worldwide. Drought is an important limiting factor for the growth and development of blue fescue; therefore, cultivating new strains of blue fescue with a strong drought tolerance is of great significance for its production practice. To investigate the drought tolerance mechanism of ds-1, this study subjected both ds-1 and “Festina” to a natural drought treatment and measured their physiological and biochemical indicators. A transcriptomic analysis was also conducted to explore the underlying molecular mechanisms. The results showed that, after the drought treatment, the relative water content (RWC), water use efficiency (WUE), and photosynthetic rate (Pn) of ds-1 leaves were significantly higher than those of “Festina”; in addition, the contents of H₂O₂ and O₂⁻, the relative electrical conductivity (REC), the malondialdehyde (MDA) content, the gas conductance (Gs), and the transpiration rate (Tr) were significantly lower than those of “Festina”. The peroxidase (POD) activity of ds-1 was significantly higher than that of “Festina”, while the superoxide dismutase (SOD) activity of ds-1 was significantly lower than that of “Festina”. The transcriptome data analysis showed that there were a total of 9475 differentially expressed genes (DEGs) between ds-1 and “Festina”. A Venn plot analysis showed 692 DEGs between ds-1—8d vs. “Festina”—8d and ds-1—16d vs. “Festina”—16d. A KEGG enrichment analysis showed that these 692 genes were mainly enriched in 86 pathways, including those related to the photosynthesis antenna protein, plant hormone signal transduction, MAPK signaling, starch and sucrose metabolism, and arginine and proline metabolism. Further screening identified genes that may be associated with drought stress, including PYL, PP2C, SnRK2, ABF, BRI1, JAZ, MYC2, Lhc, and MPK6. The qRT-PCR results indicated that the expression trends of the DEGs were consistent with the transcriptome sequencing results. Our research results can provide a basis for exploring candidate genes for drought tolerance in blue fescue. In addition, our research results provide valuable genetic resources for the development of drought-resistant ornamental grass varieties, which can help reduce water consumption in cities and decrease labor and capital investment. Full article

Background/Objectives: Chimeric Antigen Receptor (CAR)-T cell therapy has demonstrated impressive clinical results against hematological malignancies. However, currently commercialized CAR-T therapies are designed for autologous use, which entails some disadvantages, including high costs, manufacturing delays, complex standardization, and frequent production failures due to patient T cell dysfunction. Moreover, their CARs target one specific antigen, increasing the probability of antigen-negative tumor relapses. To overcome these limitations, we developed a novel NKG2D CAR-T cell therapy for allogeneic use with broad target specificity, as this CAR targets eight different ligands commonly upregulated in both solid and hematological tumors. Additionally, the manufacturing process was optimized to improve the phenotypic characteristics of the final product. Methods: Multiplex CRISPR/Cas9 technology was applied to eliminate the expression of TCR and HLA class I complexes in healthy donor T cells to reduce the risk of graft-versus-host disease and immune rejection, respectively, as well as lentiviral transduction for introducing the second-generation NKG2D-CAR. Moreover, we sought to optimize this manufacturing process by comparing the effect of different culture interleukin supplementations (IL-2, IL-7/IL-15 or IL-7/IL-15/IL-21) on the phenotypic and functional characteristics of the product obtained. Results: Our results showed that the novel CAR-T cells effectively targeted cervicouterine and colorectal cancer cells, and that those manufactured with IL-7/IL-15/IL-21 supplementation showed the most suitable characteristics among the conditions tested, considering genetic modification efficiency, cell proliferation, antitumor activity and proportion of the stem cell memory T cell subset, which is associated with enhanced in vivo CAR-T cell survival, expansion and long-term persistence. Conclusions: In summary, this new prototype of NKG2D CAR-T cell therapy for allogeneic use represents a promising universal treatment for a wide range of tumor types. Full article

Background: Adult neurons in the central nervous system often fail to regenerate after spinal cord injury (SCI). Regenerative gene therapies could potentially promote corticospinal axon regeneration, restoration of motor circuitry, and functional improvement after SCI, but translational methods for targeted gene delivery to corticospinal neurons are needed. AAV2retro is an engineered variant of the adeno-associated virus 2 (AAV2) capsid that demonstrates greatly enhanced retrograde transduction of projection neurons. When injected into spinal gray matter, AAV2retro retrogradely transduces neurons in the sensorimotor cortex that project to the injected spinal level. Methods: We initially hypothesized that injection of AAV2retro into the dorsal column white matter immediately rostral of a mouse cervical spinal injury would target transected axons and broadly transduce both forelimb and hindlimb corticospinal neurons. We tested this hypothesis by comparing four groups of mice treated with AAV2retro carrying the tdTomato reporter gene by (1) injection into intact C4 gray matter, (2) injection into intact C4 dorsal column white matter, (3) injection into C4 gray matter bordering a C5 dorsal column lesion, and (4) injection into C4 dorsal column white matter bordering a C5 dorsal column lesion. Results: After injection of AAV2retro into intact C4 dorsal column white matter, we observed extensive transduction of corticospinal neurons throughout both the forelimb and hindlimb sensorimotor cortical regions, and large numbers of transduced hindlimb corticospinal axons in the lumbar spinal cord. Dorsal column injections did not detectably damage the white matter beyond a narrow injection track. In contrast, after injection of intact C4 gray matter, we observed minimal labeling of neurons in the hindlimb sensorimotor cortex or corticospinal axons in the lumbar spinal cord. Conclusions: We conclude that AAV2retro can enter axons of passage in the dorsal column white matter of the spinal cord, and that injecting the cervical dorsal columns can efficiently target both forelimb and hindlimb corticospinal neurons in mice. This new approach for targeted gene delivery to corticospinal neurons could improve the safety and specificity of regenerative gene therapies for spinal cord injury. Full article

A pluripotent callus is central to genetic transformation in Cinnamomum parthenoxylon; however, the molecular and cellular mechanisms regulating callus formation and subsequent differentiation remain unelucidated, hindering progress in its genetic improvement. This study systematically investigated the dynamic changes during the in vitro regeneration of C. parthenoxylon through morphological observations, physiological assays, and transcriptomic analyses, while comparing differences in callus formation under varying induction conditions to elucidate the mechanism of its high-efficiency regeneration. The results showed that the formation of a pluripotent callus is a critical step in C. parthenoxylon regeneration, characterized by the presence of highly proliferative cell zones. Compared to an ordinary callus (P3C), a pluripotent callus (P3) exhibited higher activities of polyphenol oxidase (PPO) and indole-3-acetic acid oxidase (IAAO), as well as elevated levels of zeatin riboside (ZR) and abscisic acid (ABA). In contrast, P3 showed lower levels of soluble sugars, soluble proteins, malondialdehyde (MDA), indole-3-acetic acid (IAA), and gibberellins (GA), a reduced IAA/ZR ratio, and diminished peroxidase (POD) activity. Weighted gene co-expression network analysis (WGCNA) identified 27 hub transcription factors (TFs) strongly associated with IAA/ZR, primarily from the ERF, bHLH, MYB, WRKY, and C3H families. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed the significant enrichment of differentially expressed genes (DEGs) related to plant hormone signal transduction and cell wall metabolism during pluripotent callus acquisition. Further investigations revealed that five genes encoding a putative indole-3-acetic acid-amido synthetase GH3.1, protein TIFY 10A, a two-component response regulator ARR2-like isoform X2, and xyloglucan endotransglucosylase/hydrolase, likely promoting callus pluripotency by modulating plant hormone signaling and cell wall metabolism, thereby enhancing in vitro regeneration in C. parthenoxylon. In summary, this study provides critical insights into the molecular mechanisms of C. parthenoxylon regeneration and offers valuable germplasm resources for establishing an efficient and stable genetic transformation system via tissue culture. Full article

Given the critical role of manganese (Mn) as an essential micronutrient in wheat growth and development and the high efficiency of foliar fertilization in optimizing nutrient uptake and improving crop quality, this study aimed to elucidate the regulatory effects of exogenous manganese sulfate application on wheat grain yield and carotenoid accumulation. Methods: Field experiments were conducted from 2022 to 2024 at the Shuitou Experimental Station of the Cotton Research Institute, Shanxi Agricultural University (35°11′ N, 111°05′ E), using the wheat cultivar ‘Jinmai 110’. Foliar applications of manganese sulfate were administered at concentrations of 0.5 g/kg, 1.0 g/kg, and 1.5 g/kg, with water serving as the control (CTRL). Spraying was conducted on the upper canopy during the flowering and grain-filling stages, applied every 7 days for a total of three times. Samples for transcriptomic analysis were collected within 24 h of the final application. At maturity, yield-related traits and grain carotenoid contents were assessed. Results: Foliar application of 1.0 g/kg MnSO₄ significantly enhanced both grain yield and carotenoid content in wheat. Transcriptome sequencing revealed that treatment with 1.0 g/kg manganese sulfate (M2) resulted in 4761 differentially expressed genes (DEGs), including 2933 upregulated and 1828 downregulated genes, relative to CTRL. Gene Ontology (GO) analysis showed that in the M2 vs. CTRL comparison, 819 GO terms were significantly enriched among upregulated DEGs and 630 among downregulated DEGs. Specifically, upregulated genes were associated with 427 biological process terms and 299 cellular component terms, while downregulated genes were linked to 361 biological processes and 211 cellular components. Enriched functions primarily included cellular processes, metabolic processes, catalytic activity, and binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed 809 annotations for upregulated DEGs and 330 for downregulated DEGs, mainly related to photosynthesis, carotenoid biosynthesis, phenylpropanoid biosynthesis, and plant hormone signal transduction. In total, 43,395 alternative splicing (AS) events were identified from 17,165 genes, including 445 upregulated and 319 downregulated AS events, primarily enriched in photosynthesis and plant hormone-related pathways. Conclusion: Foliar application of manganese sulfate significantly modulates gene expression in wheat grains, thereby improving both yield and carotenoid accumulation. Key biological processes affected include photosynthesis, plant hormone signal transduction, and the carotenoid biosynthetic pathway. The interactions among these regulatory networks constitute a complex molecular mechanism through which exogenous Mn influences agronomic traits. These findings provide mechanistic insights and practical implications for enhancing wheat productivity and nutritional quality through foliar manganese application. Full article

Phosphorus is an essential nutrient for maize growth and development, and its deficiency can significantly inhibit plant growth, leading to reduced yield and quality. To elucidate the genetic mechanisms underlying low phosphorus tolerance in maize, this study utilized a panel of 257 maize inbred lines and conducted controlled experiments under low phosphorus (LP) and normal phosphorus (CK) conditions in artificial climate chambers. Through genome-wide association study (GWAS), a total of 46 SNP loci significantly associated with low phosphorus tolerance were detected, and 74 candidate genes were predicted. To further investigate, the low-phosphorus tolerant material CML422 and the phosphorus-sensitive material CIMBL90 were selected for transcriptome sequencing, which identified a total of 7232 differentially expressed genes (DEGs). KEGG enrichment analysis revealed that these genes were significantly enriched in key pathways such as plant hormone signal transduction, MAPK signaling pathway, and starch and sucrose metabolism, suggesting that maize responds to low phosphorus stress through the coordinated regulation of multiple pathways. By integrating GWAS and transcriptome data, 18 co-localized genes were screened, ultimately identifying 10 candidate genes closely associated with low phosphorus tolerance during the maize seedling stage, which are potentially involved in regulating growth and development under phosphorus stress. This study preliminarily elucidates the molecular mechanisms underlying low phosphorus tolerance in maize through multi-omics analysis, providing both a theoretical basis and genetic resources for breeding new maize varieties with high phosphorus use efficiency. Full article

Optimal sensing devices exhibit a combination of key performance attributes, including an extensive detection limit, exceptional selectivity, high sensitivity, consistent repeatability, precise measurement, and rapid response times with efficient analyte flow. In recent years, biosensing platforms incorporating nanoscale materials have garnered considerable attention due to their diverse applications across various scientific and technological domains. The integration of nanoparticles (NPs) in biosensor design primarily bridges the dimensional gap between the signal transduction element and the biological recognition component, both of which operate at nanometer scales. The synergistic combination of NPs with electrochemical techniques has facilitated the development of biosensors characterized by enhanced sensitivity and superior analyte discrimination capabilities. This comprehensive analysis examines the evolution and recent advancements in nanomaterial (NM)-based biosensors, encompassing an extensive array of nanostructures. These consists of one-dimensional nanostructures including carbon nanotubes (CNTs), nanowires (NWs), nanorods (NRs), and quantum dots (QDs), as well as noble metal and metal and metal oxide nanoparticles (NPs). The article examines how advancements in biosensing techniques across a range of applications have been fueled by the growth of nanotechnology. Researchers have significantly improved biosensor performance parameters by utilizing the distinct physiochemical properties of these NMs. The developments have increased the potential uses of nanobiosensors in a wide range of fields, from food safety and biodefense to medical diagnostics and environmental monitoring. The continuous developments in NM-based biosensors are the result of the integration of several scientific areas, such as analytical chemistry, materials science, and biotechnology. This interdisciplinary approach continues to drive innovations in sensor design, signal amplification strategies, and data analysis techniques, ultimately leading to more sophisticated and capable biosensing platforms. As the field progresses, challenges related to the scalability, reproducibility, and long-term stability of nanobiosensors are being addressed through innovative fabrication methods and surface modification techniques. These efforts aim to translate the promising results observed in laboratory settings into practical, commercially viable biosensing devices that can address real-world analytical challenges across various sectors. Full article

Beef production is an important component of the world’s food supply, with production being near 59 million tons in 2023 (USDA, 2023). Enhancing our understanding of the factors influencing metabolism will lead to improvements in production efficiency. Using RNA-seq and WGCNA of longissimus muscle samples, gene expression and metabolic pathway analyses were performed to examine relationships with ultrasound and body mass variables. In this study, body weight (BW), ultrasound back fat (BF), ultrasound muscle depth (MD), and body condition score (BCS) were traits recorded for 18 cull beef cows. As expected, all production-related traits monitored (WT, BF, MD, and BCS) in this study exhibited a positive correlation with each other. Large-scale transcriptome analyses were performed using RNA extracted from longissimus dorsi muscles. Weighted correlation network analysis (WGCNA) was employed to associate changes in traits with gene expression. In WGCNA, the dark-green module demonstrated a positive correlation (cor) with all traits, with the highest observed for BF (cor = 0.45, p = 0.07) and MD (cor = 0.45, p = 0.07). Functional analysis of the dark-green module highlighted olfactory transduction (p = 0.03) and RNA processing as significantly correlated (p = 0.08) with production traits. Additionally, the hematopoietic cell lineage pathway was reported as the most significant negative correlation with muscle depth (cor = −0.71, p = 0.001). We identified four hub genes (i.e., SEPTIN9, NONO, CCDC88C, and CACNA2D3) showing relationships with the traits measured. These findings provide further understanding of the molecular mechanisms influencing muscle and fat accretion in cull beef cows. Full article

Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase (RTK) that is involved in cell survival, proliferation, and differentiation of haematopoietic progenitors of lymphoid and myeloid lineages. Oncogenic mutations in the FLT3 gene, resulting in constitutively active FLT3 variants, are frequently found in patients with acute myeloid leukaemia (AML). In particular, patients expressing FLT3 ITD (internal tandem duplications of the juxtamembrane domain of FLT3) correlate with poor patient survival. Targeting FLT3-mutated leukaemic stem cells is therefore a key to the efficient treatment of patients with relapsed/refractory AML. The efficacy of approved tyrosine kinase inhibitors is regularly compromised by various resistance pathways or secondary mutations. Based on the current molecular understanding of aberrant signal transduction pathways and cell transformation, novel alternative treatment approaches can be exploited for therapeutic purposes. In particular, new insights into the regulation of the activity of counteracting protein tyrosine phosphatases (PTPs), the aberrant biogenesis and activation of mutant FLT3 proteins, as well as common factors controlling cell transformation are attractive avenues. This review summarises the current knowledge about the regulation of the oncogenic activities of mutant FLT3 proteins and discusses possible options for alternative treatments. Full article