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1.
Nat Commun ; 15(1): 3815, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719823

ABSTRACT

Running speed degradation of insect-scale (less than 5 cm) legged microrobots after carrying payloads has become a bottleneck for microrobots to achieve high untethered locomotion performance. In this work, we present a 2-cm legged microrobot (BHMbot, BeiHang Microrobot) with ultrafast untethered running speeds, which is facilitated by the complementary combination of bouncing length and bouncing frequency in the microrobot's running gait. The untethered BHMbot (2-cm-long, 1760 mg) can achieve a running speed of 17.5 BL s-1 and a turning centripetal acceleration of 65.4 BL s-2 at a Cost of Transport of 303.7 and a power consumption of 1.77 W. By controlling its two front legs independently, the BHMbot demonstrates various locomotion trajectories including circles, rectangles, letters and irregular paths across obstacles through a wireless control module. Such advancements enable the BHMbot to carry out application attempts including sound signal detection, locomotion inside a turbofan engine and transportation via a quadrotor.

2.
Int J Mol Sci ; 25(10)2024 May 16.
Article in English | MEDLINE | ID: mdl-38791459

ABSTRACT

Extracellular vesicles (EVs) are nano-sized particles involved in intercellular communications that intrinsically possess many attributes as a modern drug delivery platform. Haematococcus pluvialis-derived EVs (HpEVs) can be potentially exploited as a high-value-added bioproduct during astaxanthin production. The encapsulation of HpEV cargo is a crucial key for the determination of their biological functions and therapeutic potentials. However, little is known about the composition of HpEVs, limiting insights into their biological properties and application characteristics. This study examined the protein composition of HpEVs from three growth phases of H. pluvialis grown under high light (350 µmol·m-2·s-1) and sodium acetate (45 mM) stresses. A total of 2038 proteins were identified, the majority of which were associated with biological processes including signal transduction, cell proliferation, cell metabolism, and the cell response to stress. Comparative analysis indicated that H. pluvialis cells sort variant proteins into HpEVs at different physiological states. It was revealed that HpEVs from the early growth stage of H. pluvialis contain more proteins associated with cellular functions involved in primary metabolite, cell division, and cellular energy metabolism, while HpEVs from the late growth stage of H. pluvialis were enriched in proteins involved in cell wall synthesis and secondary metabolism. This is the first study to report and compare the protein composition of HpEVs from different growth stages of H. pluvialis, providing important information on the development and production of functional microalgal-derived EVs.


Subject(s)
Extracellular Vesicles , Proteome , Sodium Acetate , Extracellular Vesicles/metabolism , Proteome/metabolism , Sodium Acetate/metabolism , Sodium Acetate/pharmacology , Light , Proteomics/methods , Stress, Physiological , Chlorophyceae/metabolism , Chlorophyceae/growth & development , Chlorophyta/metabolism , Chlorophyta/growth & development
3.
FEBS Lett ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38782868

ABSTRACT

Tumor cells can express the immune checkpoint protein programmed death-1 (PD-1), but how cancer cell-intrinsic PD-1 is regulated in response to cellular stresses remains largely unknown. Here, we uncover a unique mechanism by which the chemotherapy drug doxorubicin (Dox) regulates cancer cell-intrinsic PD-1. Dox upregulates PD-1 mRNA while reducing PD-1 protein levels in tumor cells. Although Dox shortens the PD-1 half-life, it fails to directly induce PD-1 degradation. Instead, we observe that Dox promotes the interaction between peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase (NGLY1) and PD-1, facilitating NGLY1-mediated PD-1 deglycosylation and destabilization. The maintenance of PD-1 sensitizes tumor cells to Dox-mediated antiproliferative effects. Our study unveils a regulatory mechanism of PD-1 in response to Dox and highlights a potential role of cancer cell-intrinsic PD-1 in Dox-mediated antitumor effects.

4.
Int J Biol Macromol ; 268(Pt 1): 131863, 2024 May.
Article in English | MEDLINE | ID: mdl-38670188

ABSTRACT

The complement system is pivotal in innate immune defense, with Complement 1qb (C1qb) playing a key role in recognizing immune complexes and initiating the classical pathway. In this research, we cloned the full-length cDNA of silver pomfret (Pampus argenteus) c1qb and demonstrated its role in mediating defense responses against Nocardia seriolae (N. seriolae) infection, which notably causes significant economic losses in the aquaculture industry. Our investigation revealed that N. seriolae infection led to tissue damage in fish bodies, as observed in tissue sections. Subsequent analysis of differential genes (DEGs) in the transcriptome highlighted genes linked to apoptosis and inflammation. Through experiments involving overexpression and interference of c1qb in vitro, we confirmed that c1qb could suppress N. seriolae-induced apoptosis and inflammation. Moreover, overexpression of c1qb hindered N. seriolae invasion, and the purified and replicated C1qb protein displayed antimicrobial properties. Additionally, our study unveiled that overexpression of c1qb might stimulate the expression of membrane attack complexes (MAC), potentially enhancing opsonization and antibacterial effects. In conclusion, our findings offer valuable insights into the immune antibacterial mechanisms of c1qb and contribute to the development of strategies for controlling N. seriolae.


Subject(s)
Apoptosis , Complement C1q , Complement Membrane Attack Complex , Inflammation , Nocardia , Complement C1q/metabolism , Complement C1q/genetics , Apoptosis/genetics , Animals , Complement Membrane Attack Complex/metabolism , Inflammation/genetics , Inflammation/metabolism , Fish Diseases/immunology , Fish Diseases/microbiology , Nocardia Infections/immunology , Nocardia Infections/microbiology , Nocardia Infections/metabolism , Nocardia Infections/genetics
5.
iScience ; 27(5): 109643, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38650987

ABSTRACT

Redox regulation is a fundamental physiological phenomenon related to oxygen-dependent metabolism, and skeletal muscle is mainly regarded as a primary site for oxidative phosphorylation. Several studies have revealed the importance of reactive oxygen and nitrogen species (RONS) in the signaling process relating to muscle adaptation during exercise. To date, improving knowledge of redox signaling in modulating exercise adaptation has been the subject of comprehensive work and scientific inquiry. The primary aim of this review is to elucidate the molecular and biochemical pathways aligned to RONS as activators of skeletal muscle adaptation and to further identify the interconnecting mechanisms controlling redox balance. We also discuss the RONS-mediated pathways during the muscle adaptive process, including mitochondrial biogenesis, muscle remodeling, vascular angiogenesis, neuron regeneration, and the role of exogenous antioxidants.

6.
Fish Shellfish Immunol ; 149: 109589, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38685444

ABSTRACT

Members of the Signal Transducer and Activator of Transcription (STAT) family function pivotally as transcriptional activators integral to the modulation of inflammatory responses. The aquaculture of silver pomfret is frequently compromised by the imposition of exogenous stressors, which include thermal fluctuations, notably low-temperatures, diminished oxygen levels, and the onslaught of bacterial pathogens. Notwithstanding the critical impact of these stressors, the scientific literature presents a notable gap in our understanding of the STAT pathway's role in the silver pomfret's adaptive response mechanisms. To address this lacuna, we identified stat genes in the silver pomfret-denominated as Pastat1, Pastat2, Pastat3, Pastat4, and Pastat5-through a thorough and systematic bioinformatics analysis. Further scrutiny of the gene configurations and constituent motifs has elucidated that STAT proteins possess analogous structural frameworks and exhibit significant evolutionary preservation. Subsequently, the expression patterns of five stat genes were verified by RT-qPCR in twelve different tissues and four growth periods in healthy fish, showing that the expression of Pastat genes was temporally and spatially specific, with most of the stat genes expressed at higher levels in the spleen, following muscle, gill, and liver. Transcriptomic analysis of exposure to exogenous stressors, specifically formaldehyde and low-temperature conditions, elucidated that Pastat1 and Pastat2 genes exhibited a heightened sensitivity to these environmental challenges. RT-qPCR assays demonstrated a marked alteration in the expression profiles of jak1 and Pastat gene suites in PaS upon prolonged bacterial infection subsequent to these exogenous insults. Moreover, the gene expression of the downstream effectors involved in innate immunity and apoptosis displayed marked deviations. This study additionally elucidated the Pastat gene family's role in modulating the innate immune response and apoptotic regulation within the silver pomfret during exogenous stressors and subsequent pathogenic incursions.


Subject(s)
Fish Diseases , Fish Proteins , Immunity, Innate , Perciformes , STAT Transcription Factors , Stress, Physiological , Animals , Fish Proteins/genetics , Fish Proteins/immunology , Fish Proteins/chemistry , Fish Diseases/immunology , Perciformes/immunology , Perciformes/genetics , Immunity, Innate/genetics , STAT Transcription Factors/genetics , STAT Transcription Factors/metabolism , Gene Expression Regulation/immunology , Gene Expression Regulation/drug effects , Gene Expression Profiling/veterinary , Phylogeny , Sequence Alignment/veterinary , Vibrio Infections/immunology , Vibrio Infections/veterinary , Amino Acid Sequence
7.
Fish Shellfish Immunol ; 149: 109546, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38614412

ABSTRACT

Histones and their N-terminal or C-terminal derived peptides have been studied in vertebrates and presented as potential antimicrobial agents playing important roles in the innate immune defenses. Although histones and their derived peptides had been reported as components of innate immunity in invertebrates, the knowledge about the histone derived antimicrobial peptides (HDAPs) in invertebrates are still limited. Using a peptidomic technique, a set of peptide fragments derived from the histones was identified in this study from the serum of microbes challenged Mytilus coruscus. Among the 85 identified histone-derived-peptides with high confidence, 5 HDAPs were chemically synthesized and the antimicrobial activities were verified, showing strong growth inhibition against Gram-positive bacteria, Gram-negative bacteria, and fungus. The gene expression level of the precursor histones matched by representative HDAPs were further tested using q-PCR, and the results showed a significant upregulation of the histone gene expression levels in hemocytes, gill, and mantle of the mussel after immune stress. In addition, three identified HDAPs were selected for preparation of specific antibodies, and the corresponding histones and their derived C-terminal fragments were detected by Western blotting in the blood cell and serum of immune challenged mussel, respectively, indicating the existence of HDAPs in M. coruscus. Our findings revealed the immune function of histones in Mytilus, and confirmed the existence of HDAPs in the mussel. The identified Mytilus HDAPs represent a new source of immune effector with antimicrobial function in the innate immune system, and thus provide promising candidates for the treatment of microbial infections in aquaculture and medicine.


Subject(s)
Antimicrobial Peptides , Histones , Immunity, Innate , Mytilus , Animals , Mytilus/immunology , Mytilus/genetics , Histones/immunology , Histones/genetics , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/genetics , Antimicrobial Peptides/chemistry , Immunity, Innate/genetics , Gram-Negative Bacteria/physiology , Gram-Negative Bacteria/drug effects
8.
J Am Chem Soc ; 146(15): 10432-10442, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38498436

ABSTRACT

As an efficient and clean energy carrier, hydrogen is expected to play a key role in future energy systems. However, hydrogen-storage technology must be safe with a high hydrogen-storage density, which is difficult to achieve. MgH2 is a promising solid-state hydrogen-storage material owing to its large hydrogen-storage capacity (7.6 wt %) and excellent reversibility, but its large-scale utilization is restricted by slow hydrogen-desorption kinetics. Although catalysts can improve the hydrogen-storage kinetics of MgH2, they reduce the hydrogen-storage capacity. Single-atom catalysts maximize the atom utilization ratio and the number of interfacial sites to boost the catalytic activity, while easy aggregation at high temperatures limits further application. Herein, we designed a single-atom Ni-loaded TiO2 catalyst with superior thermal stability and catalytic activity. The optimized 15wt%-Ni0.034@TiO2 catalyst reduced the onset dehydrogenation temperature of MgH2 to 200 °C. At 300 °C, the H2 released and absorbed 4.6 wt % within 5 min and 6.53 wt % within 10 s, respectively. The apparent activation energies of MgH2 dehydrogenation and hydrogenation were reduced to 64.35 and 35.17 kJ/mol of H2, respectively. Even after 100 cycles of hydrogenation and dehydrogenation, there was still a capacity retention rate of 97.26%. The superior catalytic effect is attributed to the highly synergistic catalytic activity of single-atom Ni, numerous oxygen vacancies, and multivalent Tix+ in the TiO2 support, in which the single-atom Ni plays the dominant role, accelerating electron transfer between Mg2+ and H- and weakening the Mg-H bonds. This work paves the way for superior hydrogen-storage materials for practical unitization and also extends the application of single-atom catalysis in high-temperature solid-state reactions.

9.
Bioresour Technol ; 399: 130597, 2024 May.
Article in English | MEDLINE | ID: mdl-38493940

ABSTRACT

The development of integrated co-production of multiple high-purity carotenoids from microalgal cells holds considerable significance for the valorization of microalgae. In this study, the economical microalga Nannochloropsis oceanica was identified as an accumulator of violaxanthin cycle carotenoids, including violaxanthin, antheraxanthin, and zeaxanthin. Notably, a novel and competent approach for the integrated co-production of violaxanthin cycle carotenoids was explored, encompassing four steps: microalgal cultivation, solvent extraction, octadecylsilyl open-column chromatography, and ethanol precipitation. Under optimal co-production conditions, the purities of the obtained violaxanthin, antheraxanthin, and zeaxanthin all exceeded 92%, with total recovery rates of approximately 51%, 40%, and 60%, respectively. Utilizing nuclear magnetic resonance techniques, the purified violaxanthin, antheraxanthin, and zeaxanthin were identified as all-trans-violaxanthin, all-trans-antheraxanthin, and all-trans-zeaxanthin, respectively. This method held significance for the multiproduct biorefinery of the microalga N. oceanica and carried potential future implications for the violaxanthin cycle carotenoids.


Subject(s)
Carotenoids , Xanthophylls , Zeaxanthins , Xanthophylls/chemistry
10.
Int J Biol Macromol ; 266(Pt 2): 131126, 2024 May.
Article in English | MEDLINE | ID: mdl-38527682

ABSTRACT

The objective of this study was to explore the potential of Antarctic krill-derived peptides as α-glucosidase inhibitors for the treatment of type 2 diabetes. The enzymolysis conditions of α-glucosidase inhibitory peptides were optimized by response surface methodology (RSM), a statistical method that efficiently determines optimal conditions with a limited number of experiments. Gel chromatography and LC-MS/MS techniques were utilized to determine the molecular weight (Mw) distribution and sequences of the hydrolysates. The identification and analysis of the mechanism behind α-glucosidase inhibitory peptides were conducted through conventional and computer-assisted techniques. The binding affinities between peptides and α-glucosidase were further validated using BLI (biolayer interferometry) assay. The results revealed that hydrolysates generated by neutrase exhibited the highest α-glucosidase inhibition rate. Optimal conditions for hydrolysis were determined to be an enzyme concentration of 6 × 103 U/g, hydrolysis time of 5.4 h, and hydrolysis temperature of 45 °C. Four peptides (LPFQR, PSFD, PSFDF, VPFPR) with strong binding affinities to the active site of α-glucosidase, primarily through hydrogen bonding and hydrophobic interactions. This study highlights the prospective utility of Antarctic krill-derived peptides in curtailing α-glucosidase activity, offering a theoretical foundation for the development of novel α-glucosidase inhibitors and related functional foods to enhance diabetes management.


Subject(s)
Euphausiacea , Glycoside Hydrolase Inhibitors , Peptides , alpha-Glucosidases , Euphausiacea/chemistry , Animals , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Peptides/chemistry , Peptides/pharmacology , Peptides/isolation & purification , alpha-Glucosidases/metabolism , alpha-Glucosidases/chemistry , Hydrolysis , Protein Hydrolysates/chemistry , Protein Hydrolysates/pharmacology , Powders , Antarctic Regions , Amino Acid Sequence , Molecular Weight
11.
Int J Mol Sci ; 25(3)2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38339176

ABSTRACT

Growth is a fundamental aspect of aquaculture breeding programs, pivotal for successful cultivation. Understanding the mechanisms that govern growth and development differences across various stages can significantly boost seedling production of economically valuable species, thereby enhancing aquaculture efficiency and advancing the aquaculture industry. Mytilus coruscus, a commercially vital marine bivalve, underscores this importance. To decipher the intricate molecular mechanisms dictating growth and developmental disparities in marine shellfish, we conducted transcriptome sequencing and meticulously analyzed gene expression variations and molecular pathways linked to growth traits in M. coruscus. This study delved into the molecular and gene expression variations across five larval development stages, with a specific focus on scrutinizing the differential expression patterns of growth-associated genes using RNA sequencing and quantitative real-time PCR analysis. A substantial number of genes-36,044 differentially expressed genes (DEGs)-exhibited significant differential expression between consecutive developmental stages. These DEGs were then categorized into multiple pathways (Q value < 0.05), including crucial pathways such as the spliceosome, vascular smooth muscle contraction, DNA replication, and apoptosis, among others. In addition, we identified two pivotal signaling pathways-the Hedgehog (Hh) signaling pathway and the TGF-beta (TGF-ß) signaling pathway-associated with the growth and development of M. coruscus larvae. Ten key growth-related genes were pinpointed, each playing crucial roles in molecular function and the regulation of growth traits in M. coruscus. These genes and pathways associated with growth provide deep insights into the molecular basis of physiological adaptation, metabolic processes, and growth variability in marine bivalves.


Subject(s)
Hedgehog Proteins , Mytilus , Animals , Hedgehog Proteins/genetics , Mytilus/genetics , Larva/genetics , Plant Breeding , Gene Expression Profiling , Transforming Growth Factor beta/genetics
12.
Stress Biol ; 4(1): 12, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38319560

ABSTRACT

Phyllosphere endophytes play a critical role in a myriad of biological functions, such as maintaining plant health and overall fitness. They play a determinative role in crop yield and quality by regulating vital processes, such as leaf functionality and longevity, seed mass, apical growth, flowering, and fruit development. This study conducted a comprehensive bibliometric analysis aiming to review the prevailing research trajectories in phyllosphere endophytes and harness both primary areas of interest and emerging challenges. A total of 156 research articles on phyllosphere endophytes, published between 2002 and 2022, were retrieved from the Web of Science Core Collection (WoSCC). A systematic analysis was conducted using CiteSpace to visualize the evolution of publication frequency, the collaboration network, the co-citation network, and keywords co-occurrence. The findings indicated that initially, there were few publications on the topic of phyllosphere endophytes. However, from 2011 onwards, there was a notable increase in the number of publications on phyllosphere endophytes, gaining worldwide attention. Among authors, Arnold, A Elizabeth is widely recognized as a leading author in this research area. In terms of countries, the USA and China hold the highest rankings. As for institutional ranking, the University of Arizona is the most prevalent and leading institute in this particular subject. Collaborative efforts among the authors and institutions tend to be confined to small groups, and a large-scale collaborative network needs to be established. This study identified the influential journals, literature, and hot research topics. These findings also highlight the interconnected nature of key themes, e.g., phyllosphere endophyte research revolves around the four pillars: diversity, fungal endophytes, growth, and endophytic fungi. This study provides an in-depth perspective on phyllosphere endophytes studies, revealing the identification of biodiversity and microbial interaction of phyllosphere endophytes as the principal research frontiers. These analytical findings not only elucidate the recent trajectory of phyllosphere endophyte research but also provide invaluable insights for similar studies and their potential applications on a global scale.

13.
Int J Mol Med ; 53(4)2024 Apr.
Article in English | MEDLINE | ID: mdl-38334226

ABSTRACT

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation assay data shown in Figs. 4C and 6D and the Transwell migration and invasion assay data shown in Figs. 4D, 6E and 6F were strikingly similar to data appearing in different form in other research articles written by different authors at different research institutes that had either already been published, or were submitted for publication at around the same time. Owing to the fact that contentious data in the above article had already been published elsewhere prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 47: 54, 2021; DOI: 10.3892/ijmm.2021.4887].

14.
Nat Commun ; 15(1): 1362, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38355937

ABSTRACT

Metastasis is the major cause of lung cancer-related death, but the mechanisms governing lung tumor metastasis remain incompletely elucidated. SE translocation (SET) is overexpressed in lung tumors and correlates with unfavorable prognosis. Here we uncover SET-associated transcription factor, zinc finger and BTB domain-containing protein 11 (ZBTB11), as a prometastatic regulator in lung tumors. SET interacts and collaborates with ZBTB11 to promote lung cancer cell migration and invasion, primarily through SET-ZBTB11 complex-mediated transcriptional activation of matrix metalloproteinase-9 (MMP9). Additionally, by transcriptional repression of proline-rich Gla protein 2 (PRRG2), ZBTB11 links Yes-associated protein 1 (YAP1) activation to drive lung tumor metastasis independently of SET-ZBTB11 complex. Loss of ZBTB11 suppresses distal metastasis in a lung tumor mouse model. Overexpression of ZBTB11 is recapitulated in human metastatic lung tumors and correlates with diminished survival. Our study demonstrates ZBTB11 as a key metastatic regulator and reveals diverse mechanisms by which ZBTB11 modulates lung tumor metastasis.


Subject(s)
Lung Neoplasms , Animals , Humans , Mice , Cell Line, Tumor , Cell Movement/genetics , Gene Expression Regulation , Lung/pathology , Lung Neoplasms/pathology , Neoplasm Invasiveness/pathology , Neoplasm Metastasis/pathology , Oncogene Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
15.
Mar Drugs ; 22(2)2024 Jan 27.
Article in English | MEDLINE | ID: mdl-38393036

ABSTRACT

Microalgae are considered to be natural producers of bioactive pigments, with the production of pigments from microalgae being a sustainable and economical strategy that promises to alleviate growing demand. Chlorophyll, as the main pigment of photosynthesis, has been widely studied, but its medicinal applications as an antioxidant, antibacterial, and antitumor reagent are still poorly understood. Chlorophyll is the most important pigment in plants and algae, which not only provides food for organisms throughout the biosphere, but also plays an important role in a variety of human and man-made applications. The biological activity of chlorophyll is closely related to its chemical structure; its specific structure offers the possibility for its medicinal applications. This paper reviews the structural and functional roles of microalgal chlorophylls, commonly used extraction methods, and recent advances in medicine, to provide a theoretical basis for the standardization and commercial production and application of chlorophylls.


Subject(s)
Microalgae , Humans , Chlorophyll/chemistry , Photosynthesis , Antioxidants/pharmacology , Antioxidants/chemistry , Plants
16.
Soft Robot ; 11(2): 361-370, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38190294

ABSTRACT

Insects and animals in nature generally have powerful muscles to guarantee their complex motion, such as crawling, running, and jumping. It is challenging for insect-sized robots to achieve controlled crawling and jumping within the scale of millimeters and milligrams. This article proposes a novelty bionic muscle actuator, where an electrical pulse is applied to generate joule heat to expand the actuator's chamber. Under the restoring force of the spring element, the chamber contracts back to the initial state to finish a complete cycle. The actuator can obtain high-frequency vibration under the high-frequency electrical signal. We propose a microrobot based on the novelty actuator to achieve controlled crawling and jumping over the obstacle of the millimeter-sized robot. The robot is fabricated with two actuators as a crawling module and one actuator as a jumping module, with a mass of 52 mg, length of 9.3 mm, width of 9.1 mm, and height of 4 mm. The microrobot has a maximum crawling turning velocity of 0.73 rad/s, a maximum jump height of 42 mm (10.5 times body height), and a maximum jump velocity of 0.91 m/s. This study extends the potential for applying the novelty bionic-muscle actuator to the microrobot.

17.
Biotechnol Biofuels Bioprod ; 17(1): 15, 2024 Jan 28.
Article in English | MEDLINE | ID: mdl-38282041

ABSTRACT

BACKGROUND: Microalgae-derived extracellular vesicles (EVs), which transfer their cargos to the extracellular environment to affect recipient cells, play important roles in microalgal growth and environmental adaptation. And, they are also considered as sustainable and renewable bioresources of delivery nanocarrier for bioactive molecules and/or artificial drug molecules. However, their molecular composition and functions remain poorly understood. RESULTS: In this study, isolation, characterization, and functional verification of Haematococcus pluvialis-derived EVs (HpEVs) were performed. The results indicated that HpEVs with typical EV morphology and size were secreted by H. pluvialis cells during the whole period of growth and accumulated in the culture medium. Cellular uptake of HpEVs by H. pluvialis was confirmed, and their roles in regulation of growth and various physiological processes of the recipient cells were also characterized. The short-term inhibition of HpEV secretion results in the accumulation of functional cellular components of HpEVs, thereby altering the biological response of these cells at the molecular level. Meanwhile, continuously inhibiting the secretion of HpEVs negatively influenced growth, and fatty acid and astaxanthin accumulation in H. pluvialis. Small RNA high-throughput sequencing was further performed to determine the miRNA cargoes and compelling details in HpEVs in depth. Comparative analysis revealed commonalities and differences in miRNA species and expression levels in three stages of HpEVs. A total of 163 mature miRNAs were identified with a few unique miRNAs reveal the highest expression levels, and miRNA expression profile of the HpEVs exhibited a clear stage-specific pattern. Moreover, a total of 12 differentially expressed miRNAs were identified and their target genes were classified to cell cycle control, lipid transport and metabolism, secondary metabolites biosynthesis and so on. CONCLUSION: It was therefore proposed that cargos of HpEVs, including miRNA constituents, were suggested potential roles in modulate cell physiological state of H. pluvialis. To summarize, this work uncovers the intercellular communication and metabolism regulation functions of HpEVs.

18.
Article in English | MEDLINE | ID: mdl-38181884

ABSTRACT

The razor clam Sinonovacula constricta is known for its richness in long-chain polyunsaturated fatty acids (LC-PUFA, C ≥ 20). Previously, we demonstrated that it possesses a complete LC-PUFA biosynthetic pathway. However, the mechanisms by which it senses the LC-PUFA pool to regulate their biosynthesis remain unclear. Here, we presented the LC-PUFA sensor UBXD8 as a critical molecule in this intriguing process. The S. constricta UBXD8 (ScUBXD8) shared all characteristic features of its mammalian counterpart and exhibited high mRNA levels in digestive tissues, suggesting its functional role in this bivalve species. By purification of ScUBXD8 protein in vitro, we discovered its ability to sense unsaturated fatty acids (UFA, C ≥ 14) but not saturated ones, as evidenced by polymerization detection. Furthermore, the intensity of ScUBXD8 polymerization increased progressively with longer acyl chain lengths, greater unsaturation degrees, and higher UFA concentrations. Exceptionally, for those located at the same node in LC-PUFA biosynthetic pathway, ScUBXD8 displayed a stronger sensitivity to n-6 UFA compared to n-3 UFA. These results suggested a critical role for ScUBXD8 in balancing fatty acids composition and ratio of n-6/n-3 UFA in S. constricta. Moreover, the UAS domain was confirmed essential for ScUBXD8 polymerization. Through knockdown of ScUbxd8 gene in vivo, there were significant shifts in expression patterns of genes related to LC-PUFA biosynthesis, concurrently influencing fatty acids compositions. These results suggested that ScUBXD8 likely plays a regulatory role in LC-PUFA biosynthesis, possibly through the INSIG-SREBP pathway. Collectively, this study proposed that S. constricta might maintain LC-PUFA homeostasis through UBXD8 to regulate their biosynthesis.


Subject(s)
Bivalvia , Animals , Bivalvia/genetics , Bivalvia/metabolism , Fatty Acids, Unsaturated/metabolism , Mammals/metabolism
19.
Cancer Lett ; 584: 216614, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38246226

ABSTRACT

Liquid‒liquid phase separation (LLPS) is a general phenomenon recently recognized to be critically involved in the regulation of a variety of cellular biological processes, such as transcriptional regulation, heterochromatin formation and signal transduction, through the compartmentalization of proteins or nucleic acids into droplet-like condensates. These processes are directly or indirectly related to tumor initiation and treatment. Posttranslational modifications (PTMs), which represent a rapid and reversible mechanism involved in the functional regulation of proteins, have emerged as key events in modulating LLPS under physiological or pathophysiological conditions, including tumorigenesis and antitumor therapy. In this review, we introduce the biological functions participated in cancer-associated LLPS, discuss the potential roles of LLPS during tumor onset or therapy, and emphasize the mechanistic characteristics of LLPS regulated by PTMs and its effects on tumor progression. We then provide a perspective on further studies on LLPS and its regulation by PTMs in cancer research. This review aims to broaden the understanding of the functions of LLPS and its regulation by PTMs under normal or aberrant cellular conditions.


Subject(s)
Intrinsically Disordered Proteins , Neoplasms , Humans , Intrinsically Disordered Proteins/metabolism , Phase Separation , Protein Processing, Post-Translational , Neoplasms/genetics , Signal Transduction
20.
New Phytol ; 241(4): 1574-1591, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38062856

ABSTRACT

Fucoxanthin, a natural carotenoid that has substantial pharmaceutical value due to its anticancer, antioxidant, antiobesity, and antidiabetic properties, is biosynthesized from glyceraldehyde-3-phosphate (G3P) via a series of enzymatic reactions. However, our understanding of the transcriptional mechanisms involved in fucoxanthin biosynthesis remains limited. Using reverse genetics, the med8 mutant was identified based on its phenotype of reduced fucoxanthin content, and the biological functions of MED8 in fucoxanthin synthesis were characterized using approaches such as gene expression, protein subcellular localization, protein-protein interaction and chromatin immunoprecipitation assay. Gene-editing mutants of MED8 exhibited decreased fucoxanthin content as well as reduced expression levels of six key genes involved in fucoxanthin synthesis, namely DXS, PSY1, ZDS-like, CRTISO5, ZEP1, and ZEP3, when compared to the wild-type (WT) strain. Furthermore, we showed that MED8 interacts with HSF3, and genetic analysis revealed their shared involvement in the genetic pathway governing fucoxanthin synthesis. Additionally, HSF3 was required for MED8 association with the promoters of the six fucoxanthin synthesis genes. In conclusion, MED8 and HSF3 are involved in fucoxanthin synthesis by modulating the expression of the fucoxanthin synthesis genes. Our results increase the understanding of the molecular regulation mechanisms underlying fucoxanthin synthesis in the diatom P. tricornutum.


Subject(s)
Diatoms , Heat Shock Transcription Factors/metabolism , Diatoms/genetics , Diatoms/metabolism , Xanthophylls/metabolism , Carotenoids/metabolism
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