Circularly polarized organic light‐emitting diodes (CP‐OLEDs) that enable circularly polarized luminescence (CPL) are promising for 3D display and photonic applications. However, the device ...efficiency and CPL character of CP‐OLEDs still lag behind the practical requirements. Here, two pairs of axially chiral emitting enantiomers, flexible (R/S)‐ODQPXZ and rigid (R/S)‐ODPPXZ, are reported by fusing (R/S)‐octahydro‐binaphthol chiral source, diphenyl quinoxaline (DQ)/dibenzoa,cphenazine (DP) acceptors and phenoxazine (PXZ) donors. The symmetrical chiral‐acceptor‐donor configuration endows them thermally activated delayed fluorescence (TADF) properties with small singlet–triplet energy gaps of 0.16 and 0.07 eV, high photoluminescence quantum yields of 92% and 89% in doped films, and obvious mirror‐image CPL characteristics, respectively. The CP‐OLEDs based on these TADF enantiomers not only show a maximum external quantum efficiency of 28.3% with yellow emission for (R/S)‐ODQPXZ and 20.3% with orange‐red emission for (R/S)‐ODPPXZ, but also display the CPL with dissymmetry factors (gEL) of 6.0 × 10−4 and 2.4 × 10−3, respectively. The high efficiency and obvious CPL of (R)‐ODPPXZ arise from a synergetic interplay of the TADF skeleton and the rigid coplanar acceptor for efficient chiral induction and suppressed intramolecular rotational quenching.
Chiral thermally activated delayed fluorescence enantiomers are designed by combining chiral fragment and symmetrical rigid acceptor, leading to high‐efficiency circularly polarized organic light‐emitting diodes with excellent efficiency over 20% and considerable circularly polarized luminescence in orange‐red region.
Impaired macroautophagy/autophagy and high levels of glycolysis are prevalent in liver cancer. However, it remains unknown whether there is a regulatory relationship between autophagy and glycolytic ...metabolism. In this study, by utilizing cancer cells with basal or impaired autophagic flux, we demonstrated that glycolytic activity is negatively correlated with autophagy level. The autophagic degradation of HK2 (hexokinase 2), a crucial glycolytic enzyme catalyzing the conversion of glucose to glucose-6-phosphate, was found to be involved in the regulation of glycolysis by autophagy. The Lys63-linked ubiquitination of HK2 catalyzed by the E3 ligase TRAF6 was critical for the subsequent recognition of HK2 by the autophagy receptor protein SQSTM1/p62 for the process of selective autophagic degradation. In a tissue microarray of human liver cancer, the combination of high HK2 expression and high SQSTM1 expression was shown to have biological and prognostic significance. Furthermore, 3-BrPA, a pyruvate analog targeting HK2, significantly decreased the growth of autophagy-impaired tumors in vitro and in vivo (p < 0.05). By demonstrating the regulation of glycolysis by autophagy through the TRAF6- and SQSTM1-mediated ubiquitination system, our study may open an avenue for developing a glycolysis-targeting therapeutic intervention for treatment of autophagy-impaired liver cancer.
One of the major challenges in using electrical energy is the efficiency in its storage. Current methods, such as chemical batteries, hydraulic pumping, and water splitting, suffer from low energy ...density or incompatibility with current transportation infrastructure. Here, we report a method to store electrical energy as chemical energy in higher alcohols, which can be used as liquid transportation fuels. We genetically engineered a lithoautotrophic microorganism, Ralstonia eutropha H16, to produce isobutanol and 3-methyl-1-butanol in an electro-bioreactor using CO(2) as the sole carbon source and electricity as the sole energy input. The process integrates electrochemical formate production and biological CO(2) fixation and higher alcohol synthesis, opening the possibility of electricity-driven bioconversion of CO(2) to commercial chemicals.
Acute kidney injury (AKI) is commonly present in critically ill patients with sepsis. Early prediction of short-term reversibility of AKI is beneficial to risk stratification and clinical treatment ...decision. The study sought to use machine learning methods to discriminate between transient and persistent sepsis-associated AKI. Septic patients who developed AKI within the first 48 h after ICU admission were identified from the Medical Information Mart for Intensive Care III database. AKI was classified as transient or persistent according to the Acute Disease Quality Initiative workgroup consensus. Five prediction models using logistic regression, random forest, support vector machine, artificial neural network and extreme gradient boosting were constructed, and their performance was evaluated by out-of-sample testing. A simplified risk prediction model was also derived based on logistic regression and features selected by machine learning algorithms. A total of 5984 septic patients with AKI were included, 3805 (63.6%) of whom developed persistent AKI. The artificial neural network and logistic regression models achieved the highest area under the receiver operating characteristic curve (AUC) among the five machine learning models (0.76, 95% confidence interval CI 0.74-0.78). The simplified 14-variable model showed adequate discrimination, with the AUC being 0.76 (95% CI 0.73-0.78). At the optimal cutoff of 0.63, the sensitivity and specificity of the simplified model were 63% and 76% respectively. In conclusion, a machine learning-based simplified prediction model including routine clinical variables could be used to differentiate between transient and persistent AKI in critically ill septic patients. An easy-to-use risk calculator can promote its widespread application in daily clinical practice.
Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients' lives, well-being, and socialization abilities. However, CPSP has been poorly ...studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities.
Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow.
Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage.
This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.
The microphase separation of polyurethane is the result of thermodynamic incompatibility between the hard and soft segments, which plays a significant role in its micro structure and performance. In ...recent years, many researches about the microphase separation of polyurethane have been reported. However, there is a gap in summarizing the recent advances in the characterization methods and applications about it. To fill in this gap, this paper carefully compared and analyzed the characterization methods of the microphase separation such as Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), Dynamic thermomechanical analyzer (DMA), Atomic force microscopy (AFM), Transmission electron microscopy (TEM), and Small-angle X-ray scattering (SAXS). Moreover, applicaitions of the microphase separated polyurethane in shape memory, water resistance, and gas separation are also discussed in detail.
•The paper systematically compared and analyzed the characterization methods of the polyurethane microphase separation.•Influences of the microphase separation on the physical properties are discussed in detail.•The relationship betwwen the microphase separation and hydrogen bond is summarized.
Abstract
Context
Chronic low-grade inflammation may play a crucial role in the pathogenesis of gestational diabetes mellitus (GDM). However, prospective studies on the relations of inflammatory blood ...cell parameters during pregnancy with GDM are lacking.
Objective
To prospectively investigate the associations of inflammatory blood cell parameters in both early and middle pregnancy, and their change patterns from early to middle pregnancy, with GDM risk.
Methods
We used data from the Tongji-Shuangliu Birth Cohort. Inflammatory blood cell parameters (white blood cells WBC, neutrophils, lymphocytes, monocytes, neutrophil to lymphocyte ratio NLR, and platelets) were assayed before 15 weeks and between 16 and 28 weeks of gestational age. Logistic regression was used to evaluate the associations between inflammatory blood cell parameters and GDM.
Results
Of the 6354 pregnant women, 445 were diagnosed with GDM. After adjustment for potential confounders, WBC, neutrophils, lymphocytes, monocytes, and NLR in early pregnancy were positively associated with GDM risk (odds ratios 95% CI for extreme-quartile comparison were 2.38 1.76-3.20, 2.47 1.82-3.36, 1.40 1.06-1.85, 1.69 1.27-2.24, and 1.51 1.12-2.02, respectively, all P for trend ≤ .010). Similarly, higher levels of WBC, neutrophils, monocytes, and NLR in middle pregnancy were associated with increased risk of GDM (all P for trend ≤ .014). Stable high levels (≥ median in both early and middle pregnancy) of WBC, neutrophils, monocytes, and NLR were positively associated with GDM risk (all P ≤ .001).
Conclusion
Increased WBC, neutrophils, monocytes, and NLR in both early and middle pregnancy and their stable high levels from early to middle pregnancy were associated with higher GDM risk, highlighting that they might be clinically relevant for identifying individuals at high risk for GDM.
Autophagy is a degradative pathway that delivers cellular components to the lysosome for degradation. The role of autophagy in cell differentiation is poorly understood. Here we show that CaMKII can ...directly phosphorylate Beclin 1 at Ser90 to promote K63-linked ubiquitination of Beclin 1 and activation of autophagy. Meanwhile, CaMKII can also promote K63-linked ubiquitination of inhibitor of differentiation 1/2 (Id-1/2) by catalyzing phosphorylation of Id proteins and recruiting TRAF-6. Ubiquitinated Id-1/Id-2 can then bind to p62 and be transported to autolysosomes for degradation. Id degradation promotes the differentiation of neuroblastoma cells and reduces the proportion of stem-like cells. Our study proposes a mechanism by which autophagic degradation of Id proteins can regulate cell differentiation. This suggests that targeting of CaMKII and the regulation of autophagic degradation of Id may be an effective therapeutic strategy to induce cell differentiation in neuroblastoma.
Chitosan (CS) with good hydrophilicity and charged property was used to modify graphene oxide (GO), the obtained GO‐CS was used as a novel modifier to fabricate thin film composite forward osmosis ...(FO) membranes. The results revealed that the amino groups on CS reacted with carboxyl groups on GO, and the lamellar structure of the GO nanosheets was peeled off by CS, resulting in the reducing of their thicknesses. The GO‐CS improved the hydrophilicity of polyethersulfone (PES) substrate, and their contact angles decreased to 64° with the addition of GO‐CS in the substrate. GO‐CS also increased the porosity of the substrate and surface roughness of FO membrane, thereby optimizing the water flux and reverse salt flux of FO membrane. The average water flux of the FO membrane reached the optimal flux of 21.34 L/(m2 h) when GO‐CS addition was 0.5 wt%, and further addition of GO‐CS to the substrate would decrease the water flux of FO membrane, and the reverse salt flux also decreased to the lowest value of 2.26 g/(m2 h). However, the salt rejection of the membrane increased from 91.4% to 95.1% when GO‐CS addition increased from 0.5 to 1.0 wt% under FO mode using 1 mol/L sodium chloride (NaCl) solution as draw solution (DS). In addition, high osmotic pressure favored water permeation, and at the same concentration of DS, magnesium chloride (MgCl2) exhibited better properties than NaCl. These results all suggested that GO‐CS was a good modifier to fabricate FO membrane, and MgCl2 was a good DS candidate.