Ribosome dysfunction underlies the pathogenesis of many cancers and heritable ribosomopathies. Here, we investigate how mutations in either ribosomal protein large (RPL) or ribosomal protein small (RPS) subunit genes selectively affect erythroid progenitor development and clinical phenotypes in Diamond-Blackfan anemia (DBA), a rare ribosomopathy with limited therapeutic options. Using single-cell assays of patient-derived bone marrow, we delineated two distinct cellular trajectories segregating with ribosomal protein genotypes. Almost complete loss of erythroid specification was observed in RPS-DBA. In contrast, we observed relative preservation of qualitatively abnormal erythroid progenitors and precursors in RPL-DBA. Although both DBA genotypes exhibited a proinflammatory bone marrow milieu, RPS-DBA was characterized by erythroid differentiation arrest, whereas RPL-DBA was characterized by preserved GATA1 expression and activity. Compensatory stress erythropoiesis in RPL-DBA exhibited disordered differentiation underpinned by an altered glucocorticoid molecular signature, including reduced ZFP36L2 expression, leading to milder anemia and improved corticosteroid response. This integrative analysis approach identified distinct pathways of erythroid failure and defined genotype-phenotype correlations in DBA. These findings may help facilitate therapeutic target discovery.

the low-cost 'tHz torch' technology, which exploits the thermal infrared spectrum (ca. 10 to 100 THz), was recently introduced to provide secure low data rate communications links across short distances. in this paper, a thermodynamics-based approach is proposed for greatly enhancing the sensitivity of detection with non-stationary thermal radiation, generated by thermal emitters that have been modulated well beyond their thermal time constants. Here, cognitive demodulation is employed and, unlike all previous demonstrators, allows truly asynchronous operation by dynamically predicting the thermal transients for the next bit to be received. The result is a five-fold increase in the reported operational figure of merit (Range × Bit Rate) for 'THz Torch' wireless communications links. A single-channel (2 m × 125 bps) prototype and an 8-channel frequency-division multiplexed (0.5 m × 1,000 bps) prototype are demonstrated as proof-of-principle exemplars for the enhanced method of demodulation. Measurements show superior bit error rate performance with an increase in range and bit rate, when compared with conventional threshold detection. this work represents a paradigm shift in thermal-based modulation-demodulation of digital data, and offers a practical solution for the implementation of future ubiquitous secure 'THz Torch' wireless communications links; as well as other applications.Wireless links represent the fastest growing area within the digital communications industry. The history of transmitting data wirelessly can be traced back to ancient China, using smoke signaling for long-distance communication. Other early examples of wireless communications include optical telegraphy (Heliography) from the 19th century and photophone in the early 20th century 1 . Today, wireless communications systems play a crucial role in every aspects of human life.In general, wireless communications systems can be found in most parts of the electromagnetic (EM) spectrum; at radio frequencies that extend upwards into the far-infrared (i.e., covering the (sub-)microwave 2 , millimeter-wave 3 and (sub)-terahertz bands 4,5 ) and at optical wavelengths that extend downwards (i.e., across the visible light spectrum 6 into the near-infrared 7 ). However, little research and development has been reported on thermal infrared (i.e., around the near-infrared, having atmospheric transmission windows from 20-40 THz and 60-100 THz) wireless communications links. Until recently, the thermal infrared spectrum has been generally confined to applications that include motion sensing, target acquisition 8 and thermography 9 (e.g., digital thermometers and thermal cameras); having relatively low-cost components that work with incoherent radiation, when compared to extremely expensive components used in coherent systems 10 operating at radio frequencies and optical wavelengths.In 2011, the first thermal infrared wireless communications system 11 was reported, which exploited the use of extremely low-cost thermal emitters (miniature incandescent light ...

Lactoferrin (LF) has demonstrated stimulation of osteogenic differentiation of mesenchymal stem cells (MSCs). Long non-coding RNAs (lncRNAs) participate in regulating the osteogenic differentiation processes. However, the impact of LF on lncRNA expression in MSC osteogenic differentiation is poorly understood. Our aim was to investigate the effects of LF on lncRNAs expression profiles, during osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), by RNA sequencing. A total number of 1331 putative lncRNAs were identified in rBMSCs during osteogenic differentiation in the study. LF influenced the expression of 120 lncRNAs (differentially expressed lncRNAs [DELs], Fold change > 1.5 or < −1.5; p < 0.05) in rBMSCs on day 14 of osteogenic differentiation, consisted of 60 upregulated and 60 down-regulated. Furthermore, the potential functions of DELs were of prediction by searching their target cis- and trans-regulated protein-coding genes. The bioinformatic analysis of DELs target gene revealed that LF led to the disfunction of transforming growth factor beta stimulus (TGF-β) and positive regulation of I-κappa B kinase/NF-κappa B signaling pathway, which may relate to osteogenic differentiation of rBMSCs. Our work is the first profiling of lncRNA in osteogenic differentiation of rBMSCs induced by LF, and provides valuable insights into the potential mechanisms for LF promoting osteogenic activity.

Lactoferrin (LF) exerts a promoting bone health function. The effects of LF on bone formation at the metabolic level have been less explored. Urinary metabolic profiling of growing Sprague-Dawley (SD) rats LF-supplemented (1000 mg/kg bw) for four weeks were explored by Liquid chromatography–tandem mass spectrometry (LC-MS/MS). The serum markers of bone formation and bone resorption, the bone mass, and the osteogenesis markers of femur were measured by an enzyme-linked immunosorbent assay, micro-computerized tomography, and immunohistochemistry, respectively. Compared with the control, LF supplementation improved bone formation (p < 0.05), reduced bone resorption (p < 0.05), enhanced femoral bone mineral density and microarchitecture (p < 0.05), and upregulated osteocalcin, osterix, and Runx-2 expression (p < 0.05) of femur. LF upregulated 69 urinary metabolites. KEGG and pathway enrichment analyses of those urinary metabolites, and the Person’s correlation analyses among those urinary metabolites and bone status revealed that LF impacted on bone formation via regulatory comprehensive pathways including taurine and hypotaurine metabolism, arginine and proline metabolism, cyanoamino acid metabolism, nitrogen metabolism, nicotinate and nicotinamide metabolism, and fatty acid biosynthesis. The present study indicated the metabolomics is a useful and practical tool to elucidate the mechanisms by which LF augments bone mass formation in growing animals.

The immunomodulatory activity of a few Lactobacillus exopolysaccharides (EPS) has been reported. However, whether Lactobacillus EPS can promote the differentiation of CD4 T lymphocytes (CD4+T) cells into T-helper 17 cells (Th17 cells) in the Peyer’s Patches (PPs) of mice has not been addressed. In this study, we found the molecular weight (M w) of the purified EPS from L. casei ranged from 2.7 × 106 Da to 1.7 × 107 Da, and the average M w was approximately 8.4 × 106 Da. In healthy BALB/c mice, EPS elevated the numbers of Th17 cells and levels of Th17-related cytokines. In vitro, EPS induced BMDCs to stimulate the differentiation of CD4+T cells of PPs into Th17 cells and the related cytokine secretions. Results suggest that L. casei EPS can effectively induce and promote the differentiation of CD4+T cells of PPs into Th17 cells in healthy mice and has the potential ability to improve intestinal mucosa immunity.