Visible-light-excited robust room-temperature phosphorescence of dimeric single-component luminophores in the amorphous state.

Organic room temperature phosphorescence (RTP) has significant potential in various applications of information storage, anti-counterfeiting, and bio-imaging. However, achieving robust organic RTP emission of the single-component system is challenging to overcome the restriction of the crystalline state or other rigid environments with cautious treatment. Herein, we report a single-component system with robust persistent RTP emission in various aggregated forms, such as crystal, fine powder, and even amorphous states. Our experimental data reveal that the vigorous RTP emissions rely on their tight dimers based on strong and large-overlap π-π interactions between polycyclic aromatic hydrocarbon (PAH) groups. The dimer structure can offer not only excitons in low energy levels for visible-light excited red long-lived RTP but also suppression of the nonradiative decays even in an amorphous state for good resistance of RTP to heat (up to 70 °C) or water. Furthermore, we demonstrate the water-dispersible nanoparticle with persistent RTP over 600 nm and a lifetime of 0.22 s for visible-light excited cellular and in-vivo imaging, prepared through the common microemulsion approach without overcaution for nanocrystal formation.

Evaluating the Demand for Nucleic Acid Testing in Different Scenarios of COVID-19 Transmission: A Simulation Study.

INTRODUCTION: The 2019 novel coronavirus (COVID-19) has been recognized as the most severe human infectious disease pandemic in the past century. To enhance our ability to control potential infectious diseases in the future, this study simulated the influence of nucleic acid testing on the transmission of COVID-19 across varied scenarios. Additionally, it assessed the demand for nucleic acid testing under different circumstances, aiming to furnish a decision-making foundation for the implementation of nucleic acid screening measures, the provision of emergency materials, and the allocation of human resources. METHODS: Considering the transmission dynamics of COVID-19 and the preventive measures implemented by countries, we explored three distinct levels of epidemic intensity: community transmission, outbreak, and sporadic cases. Integrating the theory of scenario analysis, we formulated six hypothetical epidemic scenarios, each corresponding to possible occurrences during different phases of the pandemic. We developed an improved SEIR model, validated its accuracy using real-world data, and conducted a comprehensive analysis and prediction of COVID-19 infections under these six scenarios. Simultaneously, we assessed the testing resource requirements associated with each scenario. RESULTS: We compared the predicted number of infections simulated by the modified SEIR model with the actual reported cases in Israel to validate the model. The root mean square error (RMSE) was 350.09, and the R-squared (R2) was 0.99, indicating a well-fitted model. Scenario 4 demonstrated the most effective prevention and control outcomes. Strengthening non-pharmaceutical interventions and increasing nucleic acid testing frequency, even under low testing capacity, resulted in a delayed epidemic peak by 78 days. The proportion of undetected cases decreased from 77.83% to 31.21%, and the overall testing demand significantly decreased, meeting maximum demand even with low testing capacity. The initiation of testing influenced case detection probability. Under high testing capacity, increasing testing frequency elevated the detection rate from 36.40% to 77.83%. Nucleic acid screening proved effective in reducing the demand for testing resources under diverse epidemic prevention and control strategies. While effective interventions and nucleic acid screening measures substantially diminished the demand for testing-related resources, varying degrees of insufficient testing capacity may still persist. CONCLUSIONS: The nucleic acid detection strategy proves effective in promptly identifying and isolating infected individuals, thereby mitigating the infection peak and extending the time to peak. In situations with constrained testing capacity, implementing more stringent measures can notably decrease the number of infections and alleviate resource demands. The improved SEIR model demonstrates proficiency in predicting both reported and unreported cases, offering valuable insights for future infection risk assessments. Rapid evaluations of testing requirements across diverse scenarios can aptly address resource limitations in specific regions, offering substantial evidence for the formulation of future infectious disease testing strategies.

Understanding the mental health impacts of biological disasters: Lessons from Taiwan's experience with COVID-19.

Biological disasters pose a growing challenge in the 21st century, significantly impacting global society. Taiwan has experienced such disasters, resulting in long-term consequences like loss of life, trauma, economic decline, and societal disruptions. Post-disaster, mental health issues such as fear, anxiety, depression, post-traumatic stress disorder (PTSD), and stress surge, accompanied by increased suicide rates. The Coronavirus disease 2019 (COVID-19) (also called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) pandemic, recognized as a biological disaster, triggered lockdowns and quarantines in Taiwan, causing lifestyle changes, economic recession, and so on. These shifts may elevate uncertainty about the future, intensifying mental stress and leading to a rise in various mental illnesses. This article reviews mental health studies conducted in Taiwan during the pandemic, emphasizing the need to integrate this research for future preparedness and interventions regarding the mental health impacts of biological disasters, including COVID-19. Further research is essential to explore long-term effects, interventions, and generalizability.

Post-stroke Chinese pure alexia: linguistic features and neuropsychological profiles.

PURPOSE: Very few cases of Chinese pure alexia have been reported to date. We aim to summarize the linguistic features and neuropsychological profiles of Chinese pure alexia through a case series study. METHODS: 11 consecutive patients with post-stroke Chinese pure alexia and 11 healthy controls were included. The Aphasia Battery of Chinese (ABC) and 68-Chinese character oral reading test (68-character test) were used to evaluate the reading and writing ability. Reading errors were classified based on the performance of 68-character test. Neuropsychological profiles were evaluated with corresponding scales. The possible correlation between the reading ability and the writing ability or neuropsychological performance was analyzed. RESULTS: The patients had a correct rate of 43.7 ± 23.2% in the 68-character test, significantly lower (P < 0.001) than that of controls. Shape-similar error was the most common type of reading error (101/209, 48.3%). The ABC total writing score rate of the patients ranged from 68.9% to 98.7% (median, 90.5%), significantly lower (P < 0.001) than that of the controls. The patients also showed worse performance in MMSE, auditory verbal learning test, Boston naming test, intersecting pentagons copying and clock-drawing test (all P < 0.05). In the patient group, the correct rate of 68-character test was significantly correlated with the ABC total writing score rate (P = 0.008), the score rate of Boston naming test (P = 0.017), and the clock-drawing test score (P = 0.010). CONCLUSION: Shape-similar errors may be a characteristic of Chinese pure alexia. The correlation between visuospatial dysfunction and pure alexia might explain the frequent occurrence of shape-similar errors in Chinese pure alexia.

Optimal resource allocation model for COVID-19: a systematic review and meta-analysis.

BACKGROUND: A lack of health resources is a common problem after the outbreak of infectious diseases, and resource optimization is an important means to solve the lack of prevention and control capacity caused by resource constraints. This study systematically evaluated the similarities and differences in the application of coronavirus disease (COVID-19) resource allocation models and analyzed the effects of different optimal resource allocations on epidemic control. METHODS: A systematic literature search was conducted of CNKI, WanFang, VIP, CBD, PubMed, Web of Science, Scopus and Embase for articles published from January 1, 2019, through November 23, 2023. Two reviewers independently evaluated the quality of the included studies, extracted and cross-checked the data. Moreover, publication bias and sensitivity analysis were evaluated. RESULTS: A total of 22 articles were included for systematic review; in the application of optimal allocation models, 59.09% of the studies used propagation dynamics models to simulate the allocation of various resources, and some scholars also used mathematical optimization functions (36.36%) and machine learning algorithms (31.82%) to solve the problem of resource allocation; the results of the systematic review show that differential equation modeling was more considered when testing resources optimization, the optimization function or machine learning algorithm were mostly used to optimize the bed resources; the meta-analysis results showed that the epidemic trend was obviously effectively controlled through the optimal allocation of resources, and the average control efficiency was 0.38(95%CI 0.25-0.51); Subgroup analysis revealed that the average control efficiency from high to low was health specialists 0.48(95%CI 0.37-0.59), vaccines 0.47(95%CI 0.11-0.82), testing 0.38(95%CI 0.19-0.57), personal protective equipment (PPE) 0.38(95%CI 0.06-0.70), beds 0.34(95%CI 0.14-0.53), medicines and equipment for treatment 0.32(95%CI 0.12-0.51); Funnel plots and Egger's test showed no publication bias, and sensitivity analysis suggested robust results. CONCLUSION: When the data are insufficient and the simulation time is short, the researchers mostly use the constructor for research; When the data are relatively sufficient and the simulation time is long, researchers choose differential equations or machine learning algorithms for research. In addition, our study showed that control efficiency is an important indicator to evaluate the effectiveness of epidemic prevention and control. Through the optimization of medical staff and vaccine allocation, greater prevention and control effects can be achieved.

Development and validation of a 23-gene expression signature for molecular subtyping of medulloblastoma in a long-term Chinese cohort.

PURPOSE: Medulloblastoma is the most common childhood malignant brain tumor and is a leading cause of cancer-related death in children. Recent transcriptional studies have shown that medulloblastomas comprise at least four molecular subgroups, each with distinct demographics, genetics, and clinical outcomes. Medulloblastoma subtyping has become critical for subgroup-specific therapies. The use of gene expression assays to determine the molecular subgroup of clinical specimens is a long-awaited application of molecular biology for this pediatric cancer. METHODS: In the current study, we established a medulloblastoma transcriptome database of 460 samples retrieved from three published datasets (GSE21140, GSE37382, and GSE37418). With this database, we identified a 23-gene signature that is significantly associated with the medulloblastoma subgroups and achieved a classification accuracy of 95.2%. RESULTS: The 23-gene signature was further validated in a long-term cohort of 142 Chinese medulloblastoma patients. The 23-gene signature classified 21 patients as WNT (15%), 41 as SHH (29%), 16 as Group 3 (11%), and 64 as Group 4 (45%). For patients of WNT, SHH, Group 3, and Group 4, 5-year overall-survival rate reached 80%, 62%, 27%, and 47%, respectively (p < 0.0001), meanwhile 5-year progression-free survival reached 80%, 52%, 27%, and 45%, respectively (p < 0.0001). Besides, SHH/TP53-mutant tumors were associated with worse prognosis compared with SHH/TP53 wild-type tumors and other subgroups. We demonstrated that subgroup assignments by the 23-gene signature and Northcott's NanoString assay were highly comparable with a concordance rate of 96.4%. CONCLUSIONS: In conclusion, we present a novel gene signature that is capable of accurately and reliably assigning FFPE medulloblastoma samples to their molecular subgroup, which may serve as an auxiliary tool for medulloblastoma subtyping in the clinic. Future incorporation of this gene signature into prospective clinical trials is warranted to further evaluate its clinical.

A network meta-analysis of risk factors of infection among close contacts of COVID-19.

Objective: We aimed to use network meta-analysis to compare the impact of infection risk factors of close contacts with COVID-19, identify the most influential factors and rank their subgroups. It can provide a theoretical basis for the rapid and accurate tracking and management of close contacts. Methods: We searched nine databases from December 1, 2019 to August 2, 2023, which only took Chinese and English studies into consideration. Odd ratios (ORs) were calculated from traditional meta-estimated secondary attack rates (SARs) for different risk factors, and risk ranking of these risk factors was calculated by the surface under the cumulative ranking curve (SUCRA). Results: 25 studies with 152647 participants identified. Among all risk factors, the SUCRA of type of contact was 69.6 % and ranked first. Among six types of contact, compared with transportation contact, medical contact, social contact and other, daily contact increased risk of infection by 12.11 (OR: 12.11, 95 % confidence interval (CI): 6.51-22.55), 7.76 (OR: 7.76, 95 % CI: 4.09-14.73), 4.65 (OR: 4.65, 95 % CI: 2.66-8.51) and 8.23 OR: 8.23, 95 % CI: 4.23-16.01) times, respectively. Overall, SUCRA ranks from highest to lowest as daily contact (94.7 %), contact with pollution subjects (78.4 %), social contact (60.8 %), medical contact (31.8 %), other (27.9 %), transportation contact (6.4 %). Conclusion: The type of contact had the greatest impact on COVID-19 close contacts infection among the risk factors we included. Daily contact carried the greatest risk of infection among six types of contact, followed by contact with pollution subjects, social contact, other, medical contact and transportation contact. The results can provide scientific basis for rapid assess the risk of infection among close contacts based on fewer risk factors and pay attention to high-risk close contacts during management, thereby reducing tracking and management costs.

Clinical performance of nucleotide MALDI-TOF-MS in the rapid diagnosis of pulmonary tuberculosis and drug resistance.

OBJECTIVE: To evaluate the application value of nucleotide matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) technology in the rapid diagnosis of pulmonary tuberculosis (PTB) and its drug resistance. METHODS: From February 2021 to January 2022, respiratory specimens from 214 suspected PTB patients at the First Hospital of Quanzhou were collected. Nucleotide MALDI-TOF-MS and BACTEC MGIT 960 culture methods were used for the detection of Mycobacterium tuberculosis (MTB) and drug resistance to anti-tuberculosis drugs. RESULTS: Compared with culture method, nucleotide MALDI-TOF-MS technology had a sensitivity, specificity, and accuracy of 92.2%, 74.1%, and 82.7%, respectively, for the detection of MTB in respiratory specimens. With clinical diagnosis as the reference standard, the sensitivity and accuracy of nucleotide MALDI-TOF-MS were 82.5% and 86.0%, respectively, which were higher than those of the culture method (69.2% and 78.0%, respectively). The specificity of nucleotide MALDI-TOF-MS was 93.0%, which was slightly lower than that of culture method (95.8%). As for drug resistance, the results of nucleotide MALDI-TOF-MS exhibited good consistence with culture methods for rifampin, isoniazid, ethambutol, and streptomycin. CONCLUSION: Nucleotide MALDI-TOF-MS detection has a good clinical performance for rapid detection of MTB and drug sensitivity to rifampin, isoniazid, ethambutol, and streptomycin directly on respiratory specimens.

Ferroptosis: a new strategy for cardiovascular disease.

Cardiovascular disease (CVD) is currently one of the prevalent causes of human death. Iron is one of the essential trace elements in the human body and a vital component of living tissues. All organ systems require iron for various metabolic processes, including myocardial and skeletal muscle metabolism, erythropoiesis, mitochondrial function, and oxygen transport. Its deficiency or excess in the human body remains one of the nutritional problems worldwide. The total amount of iron in a normal human body is about 3-5 g. Iron deficiency may cause symptoms such as general fatigue, pica, and nerve deafness, while excessive iron plays a crucial role in the pathophysiological processes of the heart through ferroptosis triggered by the Fenton reaction. It differs from other cell death modes based on its dependence on the accumulation of lipid peroxides and REDOX imbalance, opening a new pathway underlying the pathogenesis and mechanism of CVDs. In this review, we describe the latest research progress on the mechanism of ferroptosis and report its crucial role and association with miRNA in various CVDs. Finally, we summarise the potential therapeutic value of ferroptosis-related drugs or ferroptosis inhibitors in CVDs.

Striatonigral distribution of a fluorescent reporter following intracerebral delivery of genome editors.

Introduction: Targeted gene editing is proposed as a therapeutic approach for numerous disorders, including neurological diseases. As the brain is organized into neural networks, it is critical to understand how anatomically connected structures are affected by genome editing. For example, neurons in the substantia nigra pars compacta (SNpc) project to the striatum, and the striatum contains neurons that project to the substantia nigra pars reticulata (SNpr). Methods: Here, we report the effect of injecting genome editors into the striatum of Ai14 reporter mice, which have a LoxP-flanked stop cassette that prevents expression of the red fluorescent protein tdTomato. Two weeks following intracerebral delivery of either synthetic nanocapsules (NCs) containing CRISPR ribonucleoprotein targeting the tdTomato stop cassette or adeno-associated virus (AAV) vectors expressing Cre recombinase, the brains were collected, and the presence of tdTomato was assessed in both the striatum and SN. Results: TdTomato expression was observed at the injection site in both the NC- and AAV-treated groups and typically colocalized with the neuronal marker NeuN. In the SN, tdTomato-positive fibers were present in the pars reticulata, and SNpr area expressing tdTomato correlated with the size of the striatal genome edited area. Conclusion: These results demonstrate in vivo anterograde axonal transport of reporter gene protein products to the SNpr following neuronal genome editing in the striatum.

Nano-Ni/Co-PBA as high-performance cathode material for aqueous sodium-ion batteries.

Prussian blue analogues (PBAs) are reliable and promising cathode materials for aqueous sodium-ion batteries (ASIBs) owing to their open three-dimensional frameworks, outstanding stability, and low production costs. However, PBAs containing only a single type of transition-metal ion often have limited charge-storage capacities in aqueous systems. This study reports the first example of K0.11Ni0.39Co0.79[Fe(CN)6]·2.04H2O nanoparticles (Ni/Co-PBA) being used as a high-capacity cathode material for ASIBs. Owing to multi-electron redox reactions involving Co and Fe ions, Ni/Co-PBA has an initial capacity of 65 mAh g-1and a capacity retention rate of 80% after 1000 cycles at 1.0 A g-1, indicating its outstanding cycle performance and capacity retention. Ex-situ x-ray diffraction spectroscopy, Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy, cyclic voltammetry, electrochemical impedance spectroscopy, and the galvanostatic intermittent titration technique were used to analyze the redox mechanisms and kinetics of Ni/Co-PBA. Ni/Co-PBA-based ASIBs are among the most promising energy-storage technologies for large-scale fixed energy-storage systems because of their outstanding electrochemical performance, low costs, and high efficiency.

Nonviral base editing of KCNJ13 mutation preserves vision in a model of inherited retinal channelopathy.

Clinical genome editing is emerging for rare disease treatment, but one of the major limitations is the targeting of CRISPR editors' delivery. We delivered base editors to the retinal pigmented epithelium (RPE) in the mouse eye using silica nanocapsules (SNCs) as a treatment for retinal degeneration. Leber congenital amaurosis type 16 (LCA16) is a rare pediatric blindness caused by point mutations in the KCNJ13 gene, a loss of function inwardly rectifying potassium channel (Kir7.1) in the RPE. SNCs carrying adenine base editor 8e (ABE8e) mRNA and sgRNA precisely and efficiently corrected the KCNJ13W53X/W53X mutation. Editing in both patient fibroblasts (47%) and human induced pluripotent stem cell-derived RPE (LCA16-iPSC-RPE) (17%) showed minimal off-target editing. We detected functional Kir7.1 channels in the edited LCA16-iPSC-RPE. In the LCA16 mouse model (Kcnj13W53X/+ΔR), RPE cells targeted SNC delivery of ABE8e mRNA preserved normal vision, measured by full-field electroretinogram (ERG). Moreover, multifocal ERG confirmed the topographic measure of electrical activity primarily originating from the edited retinal area at the injection site. Preserved retina structure after treatment was established by optical coherence tomography (OCT). This preclinical validation of targeted ion channel functional rescue, a challenge for pharmacological and genomic interventions, reinforced the effectiveness of nonviral genome-editing therapy for rare inherited disorders.

Non-viral approaches for gene therapy and therapeutic genome editing across the blood-brain barrier.

The success of brain-targeted gene therapy and therapeutic genome editing hinges on the efficient delivery of biologics bypassing the blood-brain barrier (BBB), which presents a significant challenge in the development of treatments for central nervous system disorders. This is particularly the case for nucleic acids and genome editors that are naturally excluded by the BBB and have poor chemical stability in the bloodstream and poor cellular uptake capability, thereby requiring judiciously designed nanovectors administered systemically for intracellular delivery to brain cells such as neurons. To overcome this obstacle, various strategies for bypassing the BBB have been developed in recent years to deliver biologics to the brain via intravenous administration using non-viral vectors. This review summarizes various brain targeting strategies and recent representative reports on brain-targeted non-viral delivery systems that allow gene therapy and therapeutic genome editing via intravenous administration, and highlights ongoing challenges and future perspectives for systemic delivery of biologics to the brain via non-viral vectors.

Neointima abating and endothelium preserving - An adventitia-localized nanoformulation to inhibit the epigenetic writer DOT1L.

Open vascular reconstructions such as bypass are common treatments for cardiovascular disease. Unfortunately, neointimal hyperplasia (IH) follows, leading to treatment failure for which there is no approved therapy. Here we combined the strengths of tailoring nanoplatforms for open vascular reconstructions and targeting new epigenetic mechanisms. We produced adhesive nanoparticles (ahNP) that could be pen-brushed and immobilized on the adventitia to sustainably release pinometostat, an inhibitor drug selective to the epigenetic writer DOT1L that catalyzes histone-3 lysine-79 dimethylation (H3K79me2). This treatment not only reduced IH by 76.8% in injured arteries mimicking open reconstructions in obese Zucker rats with human-like diseases but also avoided the shortcoming of endothelial impairment in IH management. In mechanistic studies, chromatin immunoprecipitation (ChIP) sequencing revealed co-enrichment of the histone mark H3K27ac(acetyl) and its reader BRD4 at the gene of aurora kinase B (AURKB), where H3K79me2 was also enriched as indicated by ChIP-qPCR. Accordingly, DOT1L co-immunoprecipitated with H3K27ac. Furthermore, the known IH driver BRD4 governed the expression of DOT1L which controlled AURKB's protein level, revealing a BRD4- > DOT1L- > AURKB axis. Consistently, AURKB-selective inhibition reduced IH. Thus, this study presents a prototype nanoformulation suited for open vascular reconstructions, and the new insights into chromatin modulators may aid future translational advances.

Mirror therapy combined with contralaterally controlled functional electrical stimulation for the upper limb motor function after stroke: a randomized controlled trial.

PURPOSE: In this study, we investigated the effects of mirror therapy (MT) combined with contralaterally controlled functional electrical stimulation (CCFES) on upper limb motor function, activities of daily life, and corticospinal excitability in post-stroke patients. METHODS: Sixty post-stroke patients were randomly divided into four groups: CCFES, MT, MT combined with CCFES, and control. All the patients underwent routine rehabilitation. Those in the MT, CCFES, MT combined with CCFES, and control groups received MT, CCFES, MT combined with CCFES, and routine rehabilitation alone, respectively. Upper limb motor function, activities of daily living, and corticospinal excitability were evaluated before and after a 3-week intervention period. RESULTS: MT combined with CCFES demonstrated a significantly greater therapeutic effect on motor function of the paretic wrist than CCFES, MT, or routine rehabilitation alone. However, there was no significant difference in the overall motor function of the affected upper limb, activities of daily life, or corticospinal excitability between the MT combined with CCFES group and the other three groups. CONCLUSION: MT combined with CCFES may be a potential adjuvant therapy to promote motor function in paretic wrist after stroke.

The combined therapy of mirror therapy (MT) and contralaterally controlled functional electrical stimulation (CCFES) may be a potential adjuvant therapy to promote motor function in paretic wrists after stroke.MT combined with CCFES could be incorporated into rehabilitation programs for post-stroke patients with impaired upper limb motor function.Exploring the potential benefits of combining different rehabilitation therapies could inform the development of more effective interventions.

Targeted PERK inhibition with biomimetic nanoclusters confers preventative and interventional benefits to elastase-induced abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is a progressive aortic dilatation, causing ∼80% mortality upon rupture. Currently, there is no approved drug therapy for AAA. Surgical repairs are invasive and risky and thus not recommended to patients with small AAAs which, however, account for ∼90% of the newly diagnosed cases. It is therefore a compelling unmet clinical need to discover effective non-invasive strategies to prevent or slow down AAA progression. We contend that the first AAA drug therapy will only arise through discoveries of both effective drug targets and innovative delivery methods. There is substantial evidence that degenerative smooth muscle cells (SMCs) orchestrate AAA pathogenesis and progression. In this study, we made an exciting finding that PERK, the endoplasmic reticulum (ER) stress Protein Kinase R-like ER Kinase, is a potent driver of SMC degeneration and hence a potential therapeutic target. Indeed, local knockdown of PERK in elastase-challenged aorta significantly attenuated AAA lesions in vivo. In parallel, we also conceived a biomimetic nanocluster (NC) design uniquely tailored to AAA-targeting drug delivery. This NC demonstrated excellent AAA homing via a platelet-derived biomembrane coating; and when loaded with a selective PERK inhibitor (PERKi, GSK2656157), the NC therapy conferred remarkable benefits in both preventing aneurysm development and halting the progression of pre-existing aneurysmal lesions in two distinct rodent models of AAA. In summary, our current study not only establishes a new intervention target for mitigating SMC degeneration and aneurysmal pathogenesis, but also provides a powerful tool to facilitate the development of effective drug therapy of AAA.

Isomeric thermally activated delayed fluorescence emitters for highly efficient organic light-emitting diodes.

The isomeric strategy is an important design concept in molecular design that has a non-negligible influence on molecular properties. Herein, two isomeric thermally activated delayed fluorescence (TADF) emitters (NTPZ and TNPZ) are constructed with the same skeleton consisting of an electron donor and electron acceptor but different connection sites. Systematic investigations show that NTPZ exhibits a small energy gap, large up-conversion efficiency, low non-radiative decay, and high photoluminescence quantum yield. Further theoretical simulations reveal that the excited molecular vibrations play a key role in regulating the non-radiative decays of the isomers. Therefore, an NTPZ based OLED achieves better electroluminescence performances, such as a higher external quantum efficiency of 27.5% compared to a TNPZ based OLED (18.3%). This isomeric strategy not only provides an opportunity to deeply understand the relationship between substituent locations and molecular properties, but also affords a simple and effective strategy to enrich TADF materials.

Guanidinium-Rich Lipopeptide-Based Nanoparticle Enables Efficient Gene Editing in Skeletal Muscles.

Genome editing mediated by the CRISPR-Cas system holds great promise for the treatment of genetic diseases. However, safe and efficient in vivo delivery of CRISPR genome editing machinery remains a challenge. Here, we report a lipopeptide-based nanoparticle (LNP) that can efficiently deliver the CRISPR Cas9/sgRNA ribonucleoprotein (RNP) and enable efficient genome editing both in vitro and in vivo. An artificial lipopeptide, GD-LP, was constructed by linking a hydrophilic guanidinium-rich head to an oleic acid-based hydrophobic tail via a disulfide bond. LNP formed by the self-assembly of GD-LP can easily form a complex with RNP with a loading content of up to 20 wt %. The resulting RNP-LNP nanocomplex led to 72.6% gene editing efficiency in GFP-HEK cells with negligible cytotoxicity. The LNP also showed significantly higher transfection efficiencies than Lipofectamine 2000 for the delivery of mRNA in NIH 3T3 and RAW 264.7 and the delivery of plasmid DNA in B78 cells. In vivo studies showed that intramuscular injection of the RNP-LNP nanocomplex in Ai14 mice induced efficient gene editing in muscular tissues. Moreover, the delivery of Cas9 RNP and donor DNA by LNP (i.e., RNP/ssODN-LNP nanocomplex) restored dystrophin expression, reduced skeletal muscle fibrosis, and significantly improved muscle strength in a Duchenne muscular dystrophy (DMD) mouse model.

Efficient in vivo neuronal genome editing in the mouse brain using nanocapsules containing CRISPR-Cas9 ribonucleoproteins.

Genome editing of somatic cells via clustered regularly interspaced short palindromic repeats (CRISPR) offers promise for new therapeutics to treat a variety of genetic disorders, including neurological diseases. However, the dense and complex parenchyma of the brain and the post-mitotic state of neurons make efficient genome editing challenging. In vivo delivery systems for CRISPR-Cas proteins and single guide RNA (sgRNA) include both viral vectors and non-viral strategies, each presenting different advantages and disadvantages for clinical application. We developed non-viral and biodegradable PEGylated nanocapsules (NCs) that deliver preassembled Cas9-sgRNA ribonucleoproteins (RNPs). Here, we show that the RNP NCs led to robust genome editing in neurons following intracerebral injection into the healthy mouse striatum. Genome editing was predominantly observed in medium spiny neurons (>80%), with occasional editing in cholinergic, calretinin, and parvalbumin interneurons. Glial activation was minimal and was localized along the needle tract. Our results demonstrate that the RNP NCs are capable of safe and efficient neuronal genome editing in vivo.