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The 3 rd -Gen OLED materials employing thermally-activated delayed fluorescence (TADF) combine advantages of first two for high-efficiency and low-cost devices. Though urgently needed, blue TADF emitters have not met stability requirement for applications. It is essential to elucidate the degradation mechanism and identify the tailored descriptor for material stability and device lifetime. Here, via in-material chemistry, we demonstrate chemical degradation of TADF materials involves critical role of bond cleavage at triplet state rather than singlet, and disclose the difference between bond dissociation energy of fragile bonds and first triplet state energy (BDE- E T1 ) is linearly correlated with logarithm of reported device lifetime for various blue TADF emitters. This significant quantitative correlation strongly reveals the degradation mechanism of TADF materials have general characteristic in essence and BDE- E T1 could be the shared “longevity gene”. Our findings provide a critical molecular descriptor for high-throughput-virtual-screening and rational design to unlock the full potential of TADF materials and devices. High throughput virtual screening of robust blue thermally activated delayed fluorescent emitters has yet been implemented. Here, authors reveal a linear relationship of the difference between bond dissociate energy and first triplet state energy with the logarithm of device operational lifetime.

Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.

Background Circular RNAs (circRNAs) are a new type of stable noncoding RNA and have been proven to play a crucial role in osteoporosis. This study explored the role and mechanism of hsa_circ_0001485 in osteogenic differentiation. Methods Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Ontology (GO) enrichment analysis were performed according to the previous sequencing data in human bone marrow mesenchymal stem cells (BMSC) before and after the induction of osteogenic differentiation on the differentially expressed circRNAs, to screen out signaling pathways associated with osteogenic differentiation. The hFOB 1.19 cells were used to verify the function and mechanism of specific circRNAs in osteogenic differentiation. Additionally, small interfering fragments and overexpression plasmids were used to determine the role of specific circRNAs during osteogenic differentiation. Furthermore, pull-down experiments and mass spectrometry were performed to determine the proteins that bind to specific circRNAs. Results The KEGG and GO enrichment analyses showed that the TGFβ-BMP signaling pathway was related to the osteogenic differentiation process, and four circRNAs were associated with the pathway. The quantitative polymerase chain reaction analysis revealed that hsa_circ_0001485 expression was increased during the osteogenic differentiation process of BMSCs. Knockdown of hsa_circ_0001485 suppressed the activity of the alkaline phosphatase enzyme and the expression of RUNX2, osteopontin, and osteocalcin in the osteogenic hFOB 1.19 cells, whereas overexpression of hsa_circ_0001485 promoted their expression. Additionally, we found that hsa_circ_0001485 and BMPR2 targeted binding to activate the TGFβ-BMP signaling pathway and promoted osteogenic differentiation through mass spectrometry analysis. Conclusion This study demonstrates that hsa_circ_0001485 is highly expressed in the osteogenic hFOB 1.19 cells, which activate the TGFβ-BMP pathway through targeted binding of BMPR2, and plays a positive role in regulating osteogenic differentiation.

Background Pulmonary hemorrhage (PH) in respiratory distress syndrome (RDS) in extremely preterm infants exhibits a high mortality rate and poor long-term outcomes. The aim of the present study was to develop a machine learning (ML) predictive model for RDS with PH in extremely preterm infants. Methods We performed a retrospective analysis of extremely preterm infants with RDS at the Children’s Hospital of Soochow University between January 2015 and January 2021. We applied three ML algorithms—logistic regression (LR), random forest (RF), and extreme gradient boosting (XGBoost)—to evaluate the performance of each model using the area under the curve (AUC), and developed a predictive model based on the optimal model. We calculated SHapley Additive exPlanations (SHAP) values to determine variables importance and show visualization results, and constructed a nomogram for individualized prediction. Results A total of 309 patients with RDS were enrolled, including 48 (15.5%) with PH. A total of 29 variables were collected, including demographic and clinical characteristics, laboratory data, and image classification. According to the AUC values, the RF model performed best (AUC = 0.868). Based on the SHAP values, the top five important variables in the RF model were gestational age, PaO 2 /FiO 2 , birth weight, mean platelet volume, and Apgar score at 5 min. Conclusions Our study showed that the RF model could be used to predict the risk of PH in RDS in extremely preterm infants. The nomogram provides clinicians with an effective tool for early warning and timely management.

Inflammation resolution is an active process, the failure of which causes uncontrolled inflammation which underlies many chronic diseases. Therefore, endogenous pathways that regulate inflammation resolution are fundamental and of wide interest. Here, we demonstrate that phagocyte respiratory burst-induced hypoxia activates macrophage erythropoietin signalling to promote acute inflammation resolution. This signalling is activated following acute but not chronic inflammation. Pharmacological or genetical inhibition of the respiratory burst suppresses hypoxia and macrophage erythropoietin signalling. Macrophage-specific erythropoietin receptor-deficient mice and chronic granulomatous disease (CGD) mice, which lack the capacity for respiratory burst, display impaired inflammation resolution, and exogenous erythropoietin enhances this resolution in WT and CGD mice. Mechanistically, erythropoietin increases macrophage engulfment of apoptotic neutrophils via PPARγ, promotes macrophage removal of debris and enhances macrophage migration to draining lymph nodes. Together, our results provide evidences of an endogenous pathway that regulates inflammation resolution, with important implications for treating inflammatory conditions. Hypoxia induced during inflammation promotes the resolution phase. Here the authors show that the hypoxia results from the respiratory burst in myeloid cells, and induces local EPO production and signaling, which enhances macrophage phagocytosis of debris and migration to draining lymph nodes to promote resolution.

Charged species can be effectively stacked on paper-based analytical device (PAD) taking advantage of ion concentration polarization (ICP) effect. Protein, as ampholyte species, could also be stacked using this effect to improve its detection sensitivity. In this work, a protein detection method was proposed based on online ICP stacking and successfully used for the detection of total protein from urine samples. We showed that proteins from physiological samples can be directly and repeatedly loaded onto the depletion region of the ICP interface established by a piece of cation exchange membrane on a paper fluidic channel, and the protein content can be cumulatively stacked as a narrow band as visually observed by smartphone camera. Colorimetric detection of model protein (phyco) showed that at least 60-fold preconcentration could be achieved with this method. With post-staining of the stacked albumin from artificial urine, a linear response in the diagnostic meaningful range of 50–350 mg/L (R2 = 0.994) was achieved. Total protein from clinical urine samples was detected, and the recovery rate was found in the range of 93–108%, and the RSD was less than 11%. Comparative assays showed no significant difference between the results of this and that of the clinical method. This paper demonstrated the feasibility of online stacking and sensitive detection of proteins from physiological samples using PAD-ICP platform.

Acute myocardial infarction (AMI) is one of the main causes of death in the world, and the incidence of AMI is increasing in the young population. Drug-coated balloon (DCB) has become an effective concept for the treatment of in-stent restenosis, small vessel disease, bifurcation lesions, high blood risk conditions, and even de novo large vessel disease. To ensure whether DCB can play an alternative role in AMI, we conducted a comprehensive meta‐analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of DCB in the treatment of AMI. Electronic databases were searched for RCTs that compared DCB with stent for AMI. The primary outcome was major adverse cardiac events (MACEs), the secondary outcome was late lumen loss (LLL). RevMan 5.3 software and RStudio software were used for data analysis. Five RCTs involving 528 patients with 6–12 months of follow-up were included. There was no significant difference in the incidence of MACEs between DCB group and stent group (RR, 0.85; 95% CI 0.42 to 1.74; P  = 0.66). Lower LLL was shown in DCB group (WMD, − 0.29; 95% CI − 0.46 to − 0.12; P  < 0.001). This meta-analysis of RCT showed that DCB might provide a promising way on AMI compared with stents. Rigorous patients’ selection and adequate predilation of culprit lesions are necessary to optimize results and prevent bailout stent implantation. PROSPERO registration number : CRD42020214333.

Background This study aims to assess the recovery patterns and factors influencing outcomes in patients with common peroneal nerve (CPN) injury. Methods This retrospective study included 45 patients with CPN injuries treated between 2009 and 2019 in Jing’an District Central Hospital. The surgical interventions were categorized into three groups: neurolysis (group A; n  = 34 patients), nerve repair (group B; n  = 5 patients) and tendon transfer (group C; n  = 6 patients). Preoperative and postoperative sensorimotor functions were evaluated using the British Medical Research Council grading system. The outcome of measures included the numeric rating scale, walking ability, numbness and satisfaction. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal time interval between injury and surgery for predicting postoperative foot dorsiflexion function, toe dorsiflexion function, and sensory function. Results Surgical interventions led to improvements in foot dorsiflexion strength in all patient groups, enabling most to regain independent walking ability. Group A (underwent neurolysis) had significant sensory function restoration ( P  < 0.001), and three patients in Group B (underwent nerve repair) had sensory improvements. ROC analysis revealed that the optimal time interval for achieving M3 foot dorsiflexion recovery was 9.5 months, with an area under the curve (AUC) of 0.871 (95% CI = 0.661–1.000, P  = 0.040). For M4 foot dorsiflexion recovery, the optimal cut-off was 5.5 months, with an AUC of 0.785 (95% CI = 0.575–0.995, P  = 0.020). When using M3 toe dorsiflexion recovery or S4 sensory function recovery as the gold standard, the optimal cut-off remained at 5.5 months, with AUCs of 0.768 (95% CI = 0.582–0.953, P  = 0.025) and 0.853 (95% CI = 0.693–1.000, P  = 0.001), respectively. Conclusions Our study highlights the importance of early surgical intervention in CPN injury recovery, with optimal outcomes achieved when surgery is performed within 5.5 to 9.5 months post-injury. These findings provide guidance for clinicians in tailoring treatment plans to the specific characteristics and requirements of CPN injury patients.

Background Osteoporosis, resulting from an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation, affects millions globally. Recent studies have identified type H vessels (CD31 hi EMCN hi ) as a specialized subset of bone blood vessels that positively regulate bone formation. This study aims to investigate the effects of metformin on bone mass, strength, and angiogenesis in osteoporotic mice, and to elucidate the underlying molecular mechanisms, particularly focusing on the YAP1/TAZ-HIF1α axis. Methods Osteoporotic mice were administered metformin, and bone mass and strength were measured. In vivo and in vitro angiogenesis assays were performed under hypoxic conditions. Expression levels of YAP1/TAZ and HIF1α were assessed in femoral metaphysis and hypoxia-cultured human microvascular endothelial cells (HMECs). Small interfering RNA was used to interfere with HIF1α or YAP1/TAZ expression in hypoxia-cultured HMECs. Additionally, we employed AAV-mediated overexpression of YAP1/TAZ in vivo to determine whether elevated YAP1/TAZ levels alter metformin’s effects on bone mass and angiogenesis. Results Metformin significantly enhanced bone mass and strength in osteoporotic mice. It also promoted angiogenesis under hypoxia conditions both in vivo and in vitro. Metformin reduced YAP1/TAZ expression while increasing HIF1α expression in both the femoral metaphysis of osteoporotic mice and hypoxia-cultured HMECs. Interference with HIF1α or YAP1/TAZ confirmed that metformin enhances HIF1α and its target genes primarily by inhibiting YAP1/TAZ. Furthermore, overexpression of YAP1/TAZ partially reversed the bone-protective effect of metformin, leading to reduced HIF1α levels and diminished type H vessel formation. Conclusion Our findings suggest that metformin holds promise as a therapeutic agent for osteoporosis by enhancing type H vessel formation through the inhibition of the YAP1/TAZ-HIF1α axis. Graphical abstract

Plastic phenotype convention between glioma stem cells (GSCs) and non-stem tumor cells (NSTCs) significantly fuels glioblastoma heterogeneity that causes therapeutic failure. Recent progressions indicate that glucose metabolic reprogramming could drive cell fates. However, the metabolic pattern of GSCs and NSTCs and its association with tumor cell phenotypes remain largely unknown. Here we found that GSCs were more glycolytic than NSTCs, and voltage-dependent anion channel 2 (VDAC2), a mitochondrial membrane protein, was critical for metabolic switching between GSCs and NSTCs to affect their phenotypes. VDAC2 was highly expressed in NSTCs relative to GSCs and coupled a glycolytic rate-limiting enzyme platelet-type of phosphofructokinase (PFKP) on mitochondrion to inhibit PFKP-mediated glycolysis required for GSC maintenance. Disruption of VDAC2 induced dedifferentiation of NSTCs to acquire GSC features, including the enhanced self-renewal, preferential expression of GSC markers, and increased tumorigenicity. Inversely, enforced expression ofVDAC2 impaired the self-renewal and highly tumorigenic properties of GSCs. PFK inhibitor clotrimazole compromised the effect of VDAC2 disruption on glycolytic reprogramming and GSC phenotypic transition. Clinically, VDAC2 expression inversely correlated with glioma grades (Immunohistochemical staining scores of VDAC2 were 4.7 ± 2.8, 3.2 ± 1.9, and 1.9 ± 1.9 for grade II, grade III, and IV, respectively, p  < 0.05 for all) and the patients with high expression of VDAC2 had longer overall survival than those with low expression of VDAC2 ( p  = 0.0008). In conclusion, we demonstrate that VDAC2 is a new glycolytic regulator controlling the phenotype transition between glioma stem cells and non-stem cells and may serves as a new prognostic indicator and a potential therapeutic target for glioma patients.