South Devon Healthcare NHS Trust

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Heterologous Isomorphic Substitution Induces Optical Property Enhancement for Deep-UV Crystals: a Case in Rb[B₃O₃F₂(OH)₂]

Optical anisotropy is pivotal for optical crystals, and it can be characterized by the maximum algebraic difference in refractive indices. Improving the optical anisotropy, especially for deep-ultraviolet (UV) crystals, is still a challenge and of interest. Herein, a new hydroxyfluorooxoborate, Rb[B3O3F2(OH)2], was obtained by the heterologous isomorphic substitution strategy. Dual enhancement for the band gap and birefringence compared with the parent A[B3O3F2(OH)2] (A = [Ph4P]/[Ph3MeP]) compounds was achieved in Rb[B3O3F2(OH)2]. This considerable enhancement originates from the removal of organic components and the retention of a birefringence-active anionic framework. This enhancement pushes the application region from UV to deep-UV. This discovery not only expands the structural chemistry of borates but also demonstrates the viability of heterologous isomorphic substitution to design deep-UV crystals with enhanced optical property

LncRNA JPX contributes to Treg/Th17 imbalance in allergic rhinitis <i>via</i> targeting the miR-378g/CCL5 axis

Aim: T-regulatory (Treg)/T-helper (Th) 17 imbalance contributes to the pathogenesis of allergic rhinitis (AR). Long non-coding RNAs (lncRNAs) participate in the progression of AR. Herein, the effect of lncRNA JP X on Treg/Th17 balance in AR was explored. Methods: CD4+ T cells were isolated from patients with AR and healthy control. The percentage of Treg and Th17 cells were examined by flow cytometry. The levels of JP X, miR-378g, CCL5, T GF-β, and IL-17A were tested using qRT-P CR. The protein expression of Foxp3 and RORγt was measured by western blot. Results: The data showed that an imbalance of Treg/Th17 was associated with AR. Upregulation of JP X was found in AR, and knockdown of which improved the imbalance of Treg/Th17. Furthermore, JP X functioned as a sponge of miR-378g to upregulate CCL5. Inhibition of miR-378g reversed the effects on Treg/Th17 induced by silencing of JP X. Moreover, overexpression of CCL5 reversed miR-378g-induced effects. Conclusion: In conclusion, depletion of JP X promoted Treg/Th17 balance in AR via regulating the miR-378g/CCL5 axis. The findings provided a novel therapeutic insight for AR.</p

Table_1_Comparing the Effectiveness of Biodiversity Conservation Across Different Regions by Considering Human Efforts.DOCX

The effective allocation of funds is of significant importance for biodiversity conservation, but there is currently no scientific method for comparing the effectiveness of biodiversity conservation across different regions. Existing studies omit differences in the ecological background, such as the terrain, climate, hydrology, soil, and ecosystem, or do not differentiate between the impacts caused by humans and nature. To address these limitations, we take habitat quality as a proxy for biodiversity and quantify the human-induced habitat quality changes as a means of measuring the efforts of management departments, with the background differences eliminated using a reference condition index. The method is applied to the San Jiang Plain Wetlands and Northwest Tibet Qiang Tang Plateau Biodiversity National Key Ecological Function Region in China. The results show that the effects of human activities on habitat improvement or degradation are overestimated or underestimated if there is no differentiation between human and natural causes. Human-induced habitat quality changes broadly reflect the human efforts toward biodiversity conservation. By considering the human efforts and background differentiation, the proposed method allows the effectiveness of biodiversity conservation to be compared across different regions. This study provides a scientific reference for China’s transfer payment policy and for the biodiversity funds allocated in other countries. Furthermore, our results will guide the practice of improving habitat quality and biodiversity.</p

Additional file 1 of Pan-cancer transcriptional atlas of minimal residual disease links DUSP1 to chemotherapy persistence

Additional file 1: Table S1. Clinical information of the 1440 patients across 17 datasets

Additional file 2 of Forsythiaside A improves Influenza A virus infection through TLR7 signaling pathway in the lungs of mice

Additional file 2. Raw data RT-PCR

Additional file 1 of Forsythiaside A improves Influenza A virus infection through TLR7 signaling pathway in the lungs of mice

Additional file 1: Supplementary Figure 1. This figure represents the original picture of GAPDH in the WT mice of Fig. 5A in the manuscript. Supplementary Figure 2. This figure represents the original picture of TLR7 in the WT mice of Fig. 5A in the manuscript. Supplementary Figure 3. This figure represents the original picture of Myd88 in the WT mice of Fig. 5A in the manuscript. Supplementary Figure 4. This figure represents the original picture of NF-κB in the WT mice of Fig. 5A in the manuscript. Supplementary Figure 5. This figure represents the original picture of GAPDH in the TLR7−/− mice of Fig. 5A in the manuscript. Supplementary Figure 6. This figure represents the original picture of TLR7 in the TLR7−/− mice of Fig. 5A in the manuscript. Supplementary Figure 7. This figure represents the original picture of Myd88 in the TLR7−/− mice of Fig. 5A in the manuscript. Supplementary Figure 8. This figure represents the original picture of NF-κB in the TLR7−/− mice of Fig. 5A in the manuscript

A peptide derived from the N-terminus of charged multivesicular body protein 6 (CHMP6) promotes the secretion of gene editing proteins via small extracellular vesicle production

Extracellular vesicles (EVs) are a promising new therapeutic platform. However, the low cargo-loading efficiency limits their clinical translation. In this study, we developed a high-yield EV cargo-loading device and explored its ability to encapsulate gene editing proteins. A series of fusion protein-based systems were constructed and their cargo loading efficiencies were compared by a NanoGlo luciferase assay. A myristoylated (Myr) peptide tag cloned from the N-terminal region of charged multivesicular body protein 6 (CHMP6), termed Myr(CHMP6), outcompeted CD9, ARRDC1, and other short polypeptides as an active packaging device. As determined by nanoparticle tracking analysis and transmission electron microscopy, the overexpression of Myr(CHMP6) increased small EV (sEV) production in Lenti-X 293T  cells without altering sEV morphology. The high passive packaging efficiency of Myr(CHMP6) was also elucidated for unmodified cargo loading. Western blotting revealed that Myr(CHMP6) facilitated the loading of Cre and Cas9 into sEVs without the generation of packaging device-cargo fusion proteins. Furthermore, Myr(CHMP6)-modified sEVs loaded with Cre or Cas9 promoted gene-editing in recipient cells, as observed using a fluorescence reporter system. Subsequent investigation demonstrated a dose-dependent effect of Myr(CHMP6) tag-induced cargo-loading. Mechanistically, N-myristoylation alone was necessary but not sufficient for the effective packaging of proteins into EVs. Thus, our results indicated that Myr(CHMP6) induces sEV production and may be effective in loading gene editing proteins into sEVs for therapeutic purposes.</p

DataSheet_2_Development of a Novel Prognostic Model of Glioblastoma Based on m6A-Associated Immune Genes and Identification of a New Biomarker.pdf

BackgroundAccumulating evidence shows that m6A regulates oncogene and tumor suppressor gene expression, thus playing a dual role in cancer. Likewise, there is a close relationship between the immune system and tumor development and progression. However, for glioblastoma, m6A-associated immunological markers remain to be identified.MethodsWe obtained gene expression, mutation, and clinical data on glioblastoma from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Next, we performed univariate COX–least absolute shrinkage and selection operator (LASSO)–multivariate COX regression analyses to establish a prognostic gene signature and develop a corresponding dynamic nomogram application. We then carried out a clustering analysis twice to categorize all samples according to their m6A-regulating and m6A-associated immune gene expression levels (high, medium, and low) and calculated their m6A score. Finally, we performed quantitative reverse transcription-polymerase chain reaction, cell counting kit-8, cell stemness detection, cell migration, and apoptosis detection in vitro assays to determine the biological role of CD81 in glioblastoma cells.ResultsOur glioblastoma risk score model had extremely high prediction efficacy, with the area under the receiver operating characteristic curve reaching 0.9. The web version of the dynamic nomogram application allows rapid and accurate calculation of patients’ survival odds. Survival curves and Sankey diagrams indicated that the high-m6A score group corresponded to the groups expressing medium and low m6A-regulating gene levels and high m6A-associated prognostic immune gene levels. Moreover, these groups displayed lower survival rates and higher immune infiltration. Based on the gene set enrichment analysis, the pathophysiological mechanism may be related to the activation of the immunosuppressive function and related signaling pathways. Moreover, the risk score model allowed us to perform immunotherapy benefit assessment. Finally, silencing CD81 in vitro significantly suppressed proliferation, stemness, and migration and facilitated apoptosis in glioblastoma cells.ConclusionWe developed an accurate and efficient prognostic model. Furthermore, the correlation analysis of different stratification methods with tumor microenvironment provided a basis for further pathophysiological mechanism exploration. Finally, CD81 may serve as a diagnostic and prognostic biomarker in glioblastoma.</p