Abstract
Doping has been widely used to control the charge carrier concentration in organic semiconductors. However, in conjugated polymers, n-doping is often limited by the tradeoff between doping ...efficiency and charge carrier mobilities, since dopants often randomly distribute within polymers, leading to significant structural and energetic disorder. Here, we screen a large number of polymer building block combinations and explore the possibility of designing n-type conjugated polymers with good tolerance to dopant-induced disorder. We show that a carefully designed conjugated polymer with a single dominant planar backbone conformation, high torsional barrier at each dihedral angle, and zigzag backbone curvature is highly dopable and can tolerate dopant-induced disorder. With these features, the designed diketopyrrolopyrrole (DPP)-based polymer can be efficiently n-doped and exhibit high n-type electrical conductivities over 120 S cm
−1
, much higher than the reference polymers with similar chemical structures. This work provides a polymer design concept for highly dopable and highly conductive polymeric semiconductors.
Ketone body β-hydroxybutyrate (BHB) has received more and more attentions, because it possesses a lot of beneficial, life-preserving effects in the fields of clinical science and medicine. However, ...the role of BHB in intestinal inflammation has not yet been investigated.
Colonic mucosa of inflammatory bowel disease (IBD) patients and healthy controls were collected for evaluation of BHB level. Besides, the therapeutic effect of exogenous BHB in a murine model of acute dextran sulfate sodium (DSS)-induced colitis were assessed by body weight change, colon length, disease activity index, and histopathological sections. The regulatory effectors of BHB were analyzed by RT-qPCR, immunofluorescence, and microbe analysis in vivo. Moreover, the molecular mechanism of BHB was further verified in bone marrow-derived macrophages (BMDMs).
In this study, significantly reduced BHB levels were found in the colonic mucosa from IBD patients and correlated with IBD activity index. In addition, we demonstrated that the administration of exogenous BHB alleviated the severity of acute experimental colitis, which was characterized by less weight loss, disease activity index, colon shortening, and histology scores, as well as decreased crypt loss and epithelium damage. Furthermore, BHB resulted in significantly increased colonic expression of M2 macrophage-associated genes, including IL-4Ra, IL-10, arginase 1 (Arg-1), and chitinase-like protein 3, following DSS exposure, suggesting an increased M2 macrophage skewing in vivo. Moreover, an in vitro experiment revealed that the addition of BHB directly promoted STAT6 phosphorylation and M2 macrophage-specific gene expression in IL-4-stimulated macrophages. Besides, we found that BHB obviously increased M2 macrophage-induced mucosal repair through promoting intestinal epithelial proliferation. However, the enhancement effect of BHB on M2 macrophage-induced mucosal repair and anti-inflammation was completely inhibited by the STAT6 inhibitor AS1517499.
In summary, we show that BHB promotes M2 macrophage polarization through the STAT6-dependent signaling pathway, which contributes to the resolution of intestinal inflammation and the repair of damaged intestinal tissues. Our finding suggests that exogenous BHB supplement may be a useful therapeutic approach for IBD treatment.
ObjectiveThis meta-analysis was performed to investigate the correlation between von Willebrand factor (vWF) antigen and hepatic venous pressure gradient (HVPG) and to evaluate the diagnostic ...performance of vWF to detect clinically significant portal hypertension (CSPH) and severe portal hypertension (SPH).DesignSystematic review and meta-analysis.MethodsMEDLINE, EMBASE, Web of Science and the Cochrane Library were screened up to 5 April 2018. Studies related to the diagnostic performance of vWF to detect CSPH and/or SPH with HVPG as the reference standard were included. Study quality was assessed by using the Quality Assessment of Diagnostic Accuracy Studies scale. Two authors independently used a standardised form to extract data.OutcomesThe primary outcome was the correlation coefficient between vWF and HVPG. The secondary outcome was the diagnostic performance of vWF to detect CSPH or SPH.ResultsA total of six articles involving 994 patients were included in this study. Five of the included articles were used to stratify the results for the correlation coefficient, three for the diagnostic performance of CSPH and two for SPH. The pooled correlation coefficient based on the random effects model was 0.54 (95% CI 0.35 to 0.69), thus suggesting a moderate correlation between vWF and HVPG. The pooled sensitivity, specificity and area under the curve of vWF for CSPH detection were 82% (95% CI 78 to 86), 76% (95% CI 68 to 83) and 0.87 (95% CI 0.80 to 0.94), respectively. Regarding the ability of vWF to detect SPH, the pooled sensitivity and specificity were 86% (95% CI 80 to 90) and 75% (95% CI 66 to 83), respectively. These results supported the satisfactory diagnostic performance of vWF for CSPH and SPH detection.ConclusionsvWF, as a novel biomarker, has a moderate correlation with HVPG and shows a satisfactory performance for the diagnosis of CSPH and SPH in patients with cirrhosis.
Abstract
Background
The goal of this paper was to assess the quality of primary healthcare services at community health centres (CHCs) from the demand (patient) and supplier (healthcare service ...institution) angles.
Methods
This study was conducted at six CHCs in the Greater Bay Area of China. Between August and October 2019, 1,568 patients were recruited (55.8% women and 44.2% men). We evaluated the service quality of CHCs using the National Committee for Quality Assurance Patient-Centred Medical Home (NCQA-PCMH) recognition questionnaire. We assessed patients’ experiences with medical and health services using the Primary Care Assessment Tools (PCAT).
Results
PCAT total and sub-domains scores were significantly difference at the six CHCs (
P
< 0.001). Among the six CHCs, Shayuan CHC had the highest PCAT total and sub-domain scores and the highest NCQA-PCMH total and sub-domain scores, as well. Older (> 60 years), female, lower education, and employee medical-insured individuals had better patient experiences.
Conclusions
Our results indicate that CHCs could improve their service quality by improving both institutional health service quality based on NCQA-PCMH assessment and patient experiences based on PCAT scales. These findings can help inform patient-centred primary healthcare policy and management.
Portal vein velocity (PVV) has shown a reasonable correlation with the presence of portal hypertension in patients with cirrhosis. This study aims to evaluate the value of PVV for diagnosing ...clinically significant portal hypertension (CSPH) and predicting the risk of variceal hemorrhage (VH) in patients with hepatitis B virus (HBV)-related cirrhosis.
A cohort of 166 consecutive adult patients with HBV-related cirrhosis was recruited in this retrospective study from two high-volume liver centers in China between April 2015 and April 2017. The performance of PVV and other non-invasive parameters for diagnosing CSPH and predicting the risk of VH was studied.
PVV demonstrated the best performance for diagnosing CSPH (defined as an HVPG ≥10 mmHg) in patients with HBV-related cirrhosis among the included non-invasive predictors with the area under the receiver operating characteristic curve (AUC), specificity, and sensitivity of 0.745, 50%, and 93.5%, respectively. Other non-invasive markers, including APRI, AAR, LS, FIB-4, and diameter of the portal vein, did not show sufficient performance with the AUCs of 0.565, 0.560, 0.544, 0.529, and 0.474, respectively. With regard to predicting the risk of VH (defined as an HVPG ≥12 mmHg), PPV also exhibited a moderate performance with an AUC of 0.762, which was superior to that of the aforementioned markers. By using two cutoff values of PVV to rule-out (11.65 cm/s) and rule-in (20.20 cm/s) CSPH, 30 (33.7%) patients showed definite results categories, with 23 (76.7%) patients were well classified and 7 (23.3%) were misclassified. Fifty-nine (66.3%) patients were with indeterminate results. By using PVV values of 13.10 cm/s and 21.40 cm/s to rule-out and rule-in HVPG ≥ 12mmHg, 34 (38.2%) patients has definite results, among whom 26 (76.5%) were well classified and 8 (23.5%) were misclassified. And 55 (61.8%) patients required further evaluation.
PPV is insufficient to serve as a non-invasive parameter for identifying CSPH and predicting the risk of VH in patients with HBV-related cirrhosis.
n-Doped conjugated polymers usually show low electrical conductivities and low thermoelectric power factors, limiting their applications in n-type organic thermoelectrics. Here, we report the ...synthesis of a new diketopyrrolopyrrole (DPP) derivative, pyrazine-flanked DPP (PzDPP), with the deepest LUMO level in all the reported DPP derivatives. Based on PzDPP, a donor–acceptor copolymer, P(PzDPP-CT2), is synthesized. The polymer displays a deep LUMO energy level and strong interchain interaction with a short π–π stacking distance of 3.38 Å. When doped with n-dopant N-DMBI, P(PzDPP-CT2) exhibits high n-type electrical conductivities of up to 8.4 S cm–1 and power factors of up to 57.3 μW m–1 K–2. These values are much higher than previously reported n-doped DPP polymers, and the power factor also ranks the highest in solution-processable n-doped conjugated polymers. These results suggest that PzDPP is a promising high-performance building block for n-type organic thermoelectrics and also highlight that, without sacrificing polymer interchain interactions, efficient n-doping can be realized in conjugated polymers with careful molecular engineering.
Commercially available Ph3CB(C6F5)4 served as a highly efficient metal‐free and single‐component initiator not only for the carbocationic polymerization of polar and bulky aryl isocyanides with ...extremely high activity up to 1.2×107 g of polymer/(molcat. h), but also for the helical‐sense‐selective polymerization of chiral aryl isocyanides and copolymerization with achiral aryl isocyanides to afford high‐molecular‐weight functional poly(aryl isocyanide)s with good solubility as well as AIE characteristics and/or a single‐handed helical conformation.
Single and free: Commercially available Ph3CB(C6F5)4 served as a metal‐free, single‐component initiator for the carbocationic polymerization of polar and bulky aryl isocyanides with extremely high activity as well as the polymerization of chiral aryl isocyanides and their copolymerization with achiral aryl isocyanides to give polymers with single‐handed helicity (see scheme). The resulting polymers showed good solubility and aggregation‐induced emission.
Doping of polymeric semiconductors limits the miscibility between polymers and dopants. Although significant efforts have been devoted to enhancing miscibility through chemical modification, the ...electrical conductivities of n‐doped polymeric semiconductors are usually below 10 S cm−1. We report a different approach to overcome the miscibility issue by modulating the solution‐state aggregates of conjugated polymers. We found that the solution‐state aggregates of conjugated polymers not only changed with solvent and temperature but also changed with solution aging time. Modulating the solution‐state polymer aggregates can directly influence their solid‐state microstructures and miscibility with dopants. As a result, both high doping efficiency and high charge‐carrier mobility were simultaneously obtained. The n‐doped electrical conductivity of P(PzDPP‐CT2) can be tuned up to 32.1 S cm−1. This method can also be used to improve the doping efficiency of other polymer systems (e.g. N2200) with different aggregation tendencies and behaviors.
The dynamic behaviors of conjugated polymer aggregates in solution are correlated with the solid‐state doping efficiency of polymer films. The n‐type electrical conductivity of the polymer P(PzDPP‐CT2) can be significantly enhanced by controlling the dynamics of solution‐state aggregates. The method is general and can be used for other polymer systems with different aggregation tendencies and dynamic behaviors.
Background Ketone body beta-hydroxybutyrate (BHB) has received more and more attentions, because it possesses a lot of beneficial, life-preserving effects in the fields of clinical science and ...medicine. However, the role of BHB in intestinal inflammation has not yet been investigated. Methods Colonic mucosa of inflammatory bowel disease (IBD) patients and healthy controls were collected for evaluation of BHB level. Besides, the therapeutic effect of exogenous BHB in a murine model of acute dextran sulfate sodium (DSS)-induced colitis were assessed by body weight change, colon length, disease activity index, and histopathological sections. The regulatory effectors of BHB were analyzed by RT-qPCR, immunofluorescence, and microbe analysis in vivo. Moreover, the molecular mechanism of BHB was further verified in bone marrow-derived macrophages (BMDMs). Results In this study, significantly reduced BHB levels were found in the colonic mucosa from IBD patients and correlated with IBD activity index. In addition, we demonstrated that the administration of exogenous BHB alleviated the severity of acute experimental colitis, which was characterized by less weight loss, disease activity index, colon shortening, and histology scores, as well as decreased crypt loss and epithelium damage. Furthermore, BHB resulted in significantly increased colonic expression of M2 macrophage-associated genes, including IL-4Ra, IL-10, arginase 1 (Arg-1), and chitinase-like protein 3, following DSS exposure, suggesting an increased M2 macrophage skewing in vivo. Moreover, an in vitro experiment revealed that the addition of BHB directly promoted STAT6 phosphorylation and M2 macrophage-specific gene expression in IL-4-stimulated macrophages. Besides, we found that BHB obviously increased M2 macrophage-induced mucosal repair through promoting intestinal epithelial proliferation. However, the enhancement effect of BHB on M2 macrophage-induced mucosal repair and anti-inflammation was completely inhibited by the STAT6 inhibitor AS1517499. Conclusions In summary, we show that BHB promotes M2 macrophage polarization through the STAT6-dependent signaling pathway, which contributes to the resolution of intestinal inflammation and the repair of damaged intestinal tissues. Our finding suggests that exogenous BHB supplement may be a useful therapeutic approach for IBD treatment. Keywords: beta-Hydroxybutyrate, Inflammatory bowel disease, M2 macrophage, STAT6, Tissue repair
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![[Ph3C][B(C6F5)4]: A Highly ...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1433-7851/small "[Ph3C][B(C6F5)4]: A Highly Efficient Metal‐Free Single‐Component Initiator for the Helical‐Sense‐Selective Cationic Copolymerization of Chiral Aryl Isocyanides and Achiral Aryl Isocyanides")
