Recombinant ferritin-based nanoparticles as neoantigen carriers significantly inhibit tumor growth and metastasis.

BACKGROUND: Tumor neoantigen peptide-based vaccines, systemic immunotherapies that enhance antitumor immunity by activating and expanding antigen-specific T cells, have achieved remarkable results in the treatment of a variety of solid tumors. However, how to effectively deliver neoantigens to induce robust antitumor immune responses remains a major obstacle. RESULTS: Here, we developed a safe and effective neoantigen peptide delivery system (neoantigen-ferritin nanoparticles, neoantigen-FNs) that successfully achieved effective lymph node targeting and induced robust antitumor immune responses. The genetically engineered self-assembled particles neoantigen-FNs with a size of 12 nm were obtained by fusing a neoantigen with optimized ferritin, which rapidly drainage to and continuously accumulate in lymph nodes. The neoantigen-FNs vaccine induced a greater quantity and quality of antigen-specific CD8+ T cells and resulted in significant growth control of multiple tumors, dramatic inhibition of melanoma metastasis and regression of established tumors. In addition, no obvious toxic side effects were detected in the various models, indicating the high safety of optimized ferritin as a vaccine carrier. CONCLUSIONS: Homogeneous and safe neoantigen-FNs could be a very promising system for neoantigen peptide delivery because of their ability to efficiently drainage to lymph nodes and induce efficient antitumor immune responses.

Integrated cytological and transcriptomic analyses provide new insights into restoration of pollen viability in synthetic allotetraploid Brassica carinata.

KEY MESSAGE: Upregulation of genes involved in DNA damage repair and sperm cell differentiation leads to restoration of pollen viability in synthetic allotetraploid B. carinata after chromosome doubling. Apart from the well-known contribution of polyploidy to crop improvement, polyploids can also be induced for other purposes, such as to restore the viability of sterile hybrids. The mechanism related to viability transition between the sterile allodiploid and the fertile allotetraploid after chromosome doubling are not well understood. Here, we synthesised allodiploid B. carinata (2n = 2x = 17) and allotetraploid B. carinata (2n = 4x = 34) as models to investigate the cytological and transcriptomic differences during pollen development. The results showed that after chromosome doubling, the recovery of pollen viability in allotetraploid was mainly reflected in the stabilisation of microtubule spindle morphology, normal meiotic chromosome behaviour, and normal microspore development. Interestingly, the deposition and degradation of synthetic anther tapetum were not affected by polyploidy. Transcription analysis showed that the expression of genes related to DNA repair (DMC1, RAD51, RAD17, SPO11-2), cell cycle differentiation (CYCA1;2, CYCA2;3) and ubiquitination proteasome pathway (UBC4, PIRH2, CDC53) were positively up-regulated during pollen development of synthetic allotetraploid B. carinata. In summary, these results provide some refreshing updates about the ploidy-related restoration of pollen viability in newly synthesised allotetraploid B. carinata.

Polyploidization: A Biological Force That Enhances Stress Resistance.

Organisms with three or more complete sets of chromosomes are designated as polyploids. Polyploidy serves as a crucial pathway in biological evolution and enriches species diversity, which is demonstrated to have significant advantages in coping with both biotic stressors (such as diseases and pests) and abiotic stressors (like extreme temperatures, drought, and salinity), particularly in the context of ongoing global climate deterioration, increased agrochemical use, and industrialization. Polyploid cultivars have been developed to achieve higher yields and improved product quality. Numerous studies have shown that polyploids exhibit substantial enhancements in cell size and structure, physiological and biochemical traits, gene expression, and epigenetic modifications compared to their diploid counterparts. However, some research also suggested that increased stress tolerance might not always be associated with polyploidy. Therefore, a more comprehensive and detailed investigation is essential to complete the underlying stress tolerance mechanisms of polyploids. Thus, this review summarizes the mechanism of polyploid formation, the polyploid biochemical tolerance mechanism of abiotic and biotic stressors, and molecular regulatory networks that confer polyploidy stress tolerance, which can shed light on the theoretical foundation for future research.

lncRNA GAS5 suppresses rheumatoid arthritis by inhibiting miR-361-5p and increasing PDK4.

Rheumatoid arthritis (RA) is an inflammatory disease that causes hyperplasia of synovial tissue and cartilage destruction. This research was to investigate the effects of lncRNA GAS5/miR-361-5p/PDK4 on rheumatoid arthritis. By qRT-PCR, GAS5 and PDK4 were found to be overexpressed in synovial tissue, fibroblast-like synoviocytes of RA patients and LPS-induced chondrocytes, while the miR-361-5p expression was significantly reduced. GAS5 overexpression resulted in a decrease in the proliferation and Bcl-2 protein expression, and an increase in the Bax protein level. On the contrary, miR-361-5p sponged by GAS5 could accelerate chondrocyte proliferation, inhibit apoptosis. PDK4 targeted by miR-361-5p could inhibit RA, and partially eliminated the effect of miR-361-5p on RA. Our study suggested that GAS5 suppressed RA by competitively adsorbing miR-361-5p to modulate PDK4 expression.

Karyotypic stability of Fragaria (strawberry) species revealed by cross-species chromosome painting.

Chromosome karyotyping analysis is particularly useful in determining species relationships and the origin of polyploid species. Identification of individual chromosomes is the foundation for karyotype development. For Fragaria (strawberry) species, definitive identification of the individual chromosomes is extremely difficult because of their small size and similar shape. Here, we identified all chromosomes for 11 representative Fragaria species with different ploidy using a set of oligonucleotide-based probes developed in Fragaria vesca. Comprehensive molecular cytogenetic karyotypes were established based on the individually identified chromosomes. In addition, we used oligo probes to assign the 5S and 45S rDNA loci to specific chromosomes in 16 Fragaria species. We found that these Fragaria species maintained a remarkably conserved karyotype. No inter-chromosomal structural rearrangements at the cytological level were observed in any of the chromosomes among these species. Despite karyotypic stability and similarity, variations in the signal intensity of oligo probes were observed among the homologous chromosomes in several polyploid species. Moreover, most Fragaria species also showed differences in the distribution patterns of 45S and 5S rDNA. These data provide new insights into the origins of several polyploid Fragaria species.

Enrichment and purification of red pigments from defective mulberry fruits using biotransformation in a liquid-liquid-solid three-phase system.

A large number of defective mulberries are discarded each year because mulberries are easy to break. The red pigments from defective mulberries are recognized as the sustainable sources of anthocyanins extracted from nature. Cyanidin-3-O-rutinoside and cyanidin-3-O-glucoside are the main components of mulberry red pigments, accounting for 50% and 40% of the total, respectively. Cyanidin-3-O-glucoside exhibits anticancer, hypoglycemic, and liver and visceral protection properties. Cyanidin-3-O-glucoside can be prepared by enzymatically hydrolyzing the rhamnosidase bond of cyanidin-3-O-rutinoside. To obtain mulberry red pigment with a high purity of cyanidin-3-O-glucoside, immobilized α-L-rhamnosidase was added to the aqueous two-phase system to construct a liquid-liquid-solid three-phase enzyme catalytic system. After optimization, the three-phase system was composed of 27.12% (w/w) ethanol, 18.10% (w/w) ammonium sulfate, 15% (w/w) mulberry juice, 4.24% (w/w) immobilized α-L-rhamnosidase, and 35.54% (w/w) pure water. The three-phase system was employed to enrich and purify cyanidin-3-O-glucoside at pH 5 and 45 °C for 1 h. The purity of cyanidin-3-O-glucoside was increased from 40 to 82.42% with cyanidin-3-O-rutinoside conversion of 60.68%. The immobilized α-L-rhamnosidase could be reused seven times, maintaining a relative activity of over 50%. Overall, the developed system provided an efficient and simple approach for high purity mulberry red pigment production and recycling in the field of sustainable agriculture. Graphical abstract.

MIR4435-2HG regulates cancer cell behaviors in oral squamous cell carcinoma cell growth by upregulating TGF-ß1.

MIR4435-2HG has been characterized as an oncogenic lncRNA in several types of cancer, while its role in oral squamous cell carcinoma (OSCC, a major subtype of oral cancer) has not been characterized. We explored the functionality of MIR4435-2HG in OSCC and investigated its interactions with TGF-ß1. Blood samples were extracted from OSCC patients (n = 44) and healthy volunteers (n = 38), RT-qPCR, CCK-8, Transwell assays and western blot were performed in this study. The results showed that levels of MIR4435-2HG and TGF-ß1 in plasma were upregulated in OSCC. Across OSCC plasma samples, TGF-ß1 and MIR4435-2HG were significantly and positively correlated. Overexpression of MIR4435-2HG resulted in upregulated TGF-ß1 expression, while exogenous TGF-ß1 treatment had no effect on the expression of MIR4435-2HG. Overexpression of MIR4435-2HG and exogenous TGF-ß1 treatment led to promoted, while TGF-ß inhibitor led to inhibited migration, proliferation and invasion of cancer cells. Moreover, TGF-ß inhibitor led to reduced effects of overexpressing MIR4435-2HG. Therefore, MIR4435-2HG regulates the behaviors of OSCC cells by promoting the expression of TGF-ß1.