Environmental friendly metal halides have become emerging candidates as energy downconverting emitters for lighting and X-ray imaging applications. Herein, luminescent single crystals of tetramethylammonium manganese chloride (C 4 H 12 NMnCl 3 ) and tetraethylammonium bromide ((C 8 H 20 N) 2 MnBr 4 ) are synthesized via a facile room-temperature evaporation method. C 4 H 12 NMnCl 3 and (C 8 H 20 N) 2 MnBr 4 with octahedrally and tetrahedrally coordinated Mn 2+ have correspondingly exhibited red and green emission peaking at 635 and 515 nm both originating from 4 T 1 -6 A 1 transition of Mn 2+ with high photoluminescence quantum yield (PLQY) of 91.8% and 85.1% benefiting from their specific crystal structures. Thanks to their strong photoexcitation under blue light, high PLQY, tunable emission spectra, good environmental stability, the white light-emitting diode based on blending of C 4 H 12 NMnCl 3 and (C 8 H 20 N) 2 MnBr 4 delivers an outstanding luminous efficacy of 96 lm W −1 , approaching commercial level, and shows no obvious photoluminescence intensity degradation after 3000 h under operation. In addition, manganese halides also demonstrate interesting characteristics under X-ray excitation, C 4 H 12 NMnCl 3 and (C 8 H 20 N) 2 MnBr 4 exhibit steady-state X-ray light yields of 50 500 and 24 400 photons MeV −1 , low detectable limits of 36.9 and 24.2 nGy air s −1 , good radiation hardness, and X-ray imaging demonstration with high-resolution of 5 lp mm −1 . This work presents a new avenue for luminescent Mn-based metal halides toward multifunctional light-emitting applications.
Cotton, with cellulose-enriched mature fibers, is the largest source of natural textiles. Through a map-based cloning strategy, we isolated an industrially important lint fiber development gene (Li ) that encodes an MYB-MIXTA-like transcription factor (MML) on chromosome D12 (GhMML4_D12). Virus-induced gene silencing or decreasing the expression of the GhMML4_D12 gene in n NSM plants resulted in a significant reduction in epidermal cell prominence and lint fiber production. GhMML4_D12 is arranged in tandem with GhMML3, another MIXTA gene responsible for fuzz fiber development. These two very closely related MIXTA genes direct fiber initiation production in two specialized cell forms: lint and fuzz fibers. They may control the same metabolic pathways in different cell types. The MIXTAs expanded in Malvaceae during their evolution and produced a Malvaceae-specific family that regulates epidermal cell differentiation, different from the gene family that regulates leaf hair trichome development. Cotton has developed a unique transcriptional regulatory network for fiber development. Characterization of target genes regulating fiber production has provided insights into the molecular mechanisms underlying cotton fiber development and has allowed the use of genetic engineering to increase lint yield by inducing more epidermal cells to develop into lint rather than fuzz fibers.
Recently, chimeric antigen receptor (CAR)-T cell therapy has shown great promise in treating haematological malignancies1–7. However, CAR-T cell therapy currently has several limitations8–12. Here we successfully developed a two-in-one approach to generate non-viral, gene-specific targeted CAR-T cells through CRISPR–Cas9. Using the optimized protocol, we demonstrated feasibility in a preclinical study by inserting an anti-CD19 CAR cassette into the AAVS1 safe-harbour locus. Furthermore, an innovative type of anti-CD19 CAR-T cell with PD1 integration was developed and showed superior ability to eradicate tumour cells in xenograft models. In adoptive therapy for relapsed/refractory aggressive B cell non-Hodgkin lymphoma (ClinicalTrials.gov, NCT04213469), we observed a high rate (87.5%) of complete remission and durable responses without serious adverse events in eight patients. Notably, these enhanced CAR-T cells were effective even at a low infusion dose and with a low percentage of CAR+ cells. Single-cell analysis showed that the electroporation method resulted in a high percentage of memory T cells in infusion products, and PD1 interference enhanced anti-tumour immune functions, further validating the advantages of non-viral, PD1-integrated CAR-T cells. Collectively, our results demonstrate the high safety and efficacy of non-viral, gene-specific integrated CAR-T cells, thus providing an innovative technology for CAR-T cell therapy.
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