Liver steatosis is becoming increasingly common in patients with chronic hepatitis B (CHB), and its effect on liver stiffness measurement (LSM), as assessed by transient elastography, remains ...controversial. Seven hundred and fifty‐five patients with CHB and normal serum alanine aminotransferase levels, who underwent vibration‐controlled transient elastography and liver biopsy, were included in the study. We examined whether the histological degree of liver steatosis affects the accuracy of transient elastography‐assessed LSM in these patients. Among the 755 CHB patients included in the study, 286 (37.9%) had liver steatosis, of whom 156 had grade S1, 74 had grade S2, and 56 had grade S3 on histology. Presence of liver steatosis was independently associated with greater body mass index (BMI, adjusted‐odds ratio OR = 5.786, 95% CI: 3.998–8.373, p = 0.018), and higher serum total cholesterol (adjusted‐OR = 7.944, 95% CI: 4.731–13.339, p < 0.001) and triglyceride levels (adjusted‐OR = 2.777, 95% CI: 2.050–3.761, p < 0.001). There was no significant association between liver steatosis and fibrosis stage (OR = 1.016, 95% CI: 0.905–1.140, p = 0.790). Age (B‐coefficient = 0.020, 95% CI: 0.001–0.040, p = 0.044), BMI (B‐coefficient = 0.060, 95% CI: 0.011–0.127, p = 0.019), serum gamma‐glutamyl‐transpeptidase (GGT, B‐coefficient = 0.015, 95% CI: 0.001–0.029, p = 0.032), positivity for HBeAg (B‐coefficient = −0.816, 95% CI: −1.568 to −0.064, p = 0.034), as well as liver fibrosis stage (B‐coefficient = 2.796, 95% CI: 2.501–3.090, p < 0.001), and inflammation activity grade (B‐coefficient = 0.648, 95% CI: 0.162–1.135, p = 0.009) were all independently associated with higher LSM, while no significant association was found between degree of liver steatosis and LSM. Among patients with the same histological fibrosis stage, LSM values did not show any significant difference among patients with absent, mild, moderate or severe steatosis. We conclude that liver steatosis has no significant effect on transient elastography‐measured LSM in CHB patients with normal serum alanine aminotransferase levels.
A series of heteroleptic cyclometalated Ir(III) complexes for OLEDs application have been investigated theoretically to explore their electronic structures and spectroscopic properties. The ...geometries, electronic structures, lowest‐lying singlet absorptions, and triplet emissions of (pdbi)2Ir(acac), (F‐pdbi)2Ir(acac), (pdbi)2Ir(dpis), (F‐pdbi)2Ir(dpis), (pdbi)2Ir(tpip), and (F‐pdbi)2Ir(tpip) were investigated with density function theory (DFT) and time‐dependent density functional theory (TD‐DFT), where pdbi denotes 1‐(4‐fluorophenyl)‐5‐methyl‐3‐phenyl‐2,3‐dihydro‐1H‐1,3‐benzodiazole, acac denotes acetylacetonate, dpis denotes diphenylimidodisilicate, and tpip denotes tetraphenylimido‐diphosphinate. In addition, we analyzed the spin‐orbit coupling constant of these six complexes, and the results showed that the six complexes have a high ability of interlinear scampering. We hope this research can serve as a reference for practical experimental synthesis aspects.
Throughout modern society, electronic devices have become indispensable tools for people to use, and display technology is ubiquitous in daily life, such as small OLED panels used in cell phone folding screens. Here, we study a series of organic light‐emitting molecules with low efficiency roll‐off to explore their relationship with ISC, hoping that our research can bring more light to the field of OLED light‐emitting like a “butterfly.”
Highlights
The zeolitic imidazolate framework functionalized modified layered double hydroxide (ZIF-8@MLDH) composite membranes with superior structural stability and Li
+
permeability are prepared ...by selectively growing ZIF-8 nanoparticles in the framework defects of the MLDH membrane.
The tailor-made ZIF-8@MLDH membrane has a large Li
+
permeability of up to 1.73 mol m
-2
h
-1
and a high Li
+
/Mg
2+
selectivity of 31.9, which exceed most of the current 2D lamellar membranes.
Two-dimensional (2D) membrane-based ion separation technology has been increasingly explored to address the problem of lithium resource shortage, yet it remains a sound challenge to design 2D membranes of high selectivity and permeability for ion separation applications. Zeolitic imidazolate framework functionalized modified layered double hydroxide (ZIF-8@MLDH) composite membranes with high lithium-ion (Li
+
) permeability and excellent operational stability were obtained in this work by in situ depositing functional ZIF-8 nanoparticles into the nanopores acting as framework defects in MLDH membranes. The defect-rich framework amplified the permeability of Li
+
, and the site-selective growth of ZIF-8 in the framework defects bettered its selectivity. Specifically speaking, the ZIF-8@MLDH membranes featured a high permeation rate of Li
+
up to 1.73 mol m
−2
h
−1
and a desirable selectivity of Li
+
/Mg
2+
up to 31.9. Simulations supported that the simultaneously enhanced selectivity and permeability of Li
+
are attributed to changes in the type of mass transfer channels and the difference in the dehydration capacity of hydrated metal cations when they pass through nanochannels of ZIF-8. This study will inspire the ongoing research of high-performance 2D membranes through the engineering of defects.
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•4-octyl itaconate ameliorates acute respiratory distress syndrome via inhibiting LPS-mediated alveolar macrophage pyroptosis and inflammation.•4-octyl itaconate rescues LPS-induced ...mitochondrial dysfunction and cytosolic escape of mitochondrial DNA.•4-octyl itaconate suppresses the cGAS-STING-IRF3 pathway.•4-octyl itaconate exerts an anti-pyroptosis effect in a STING/IRF3-dependent manner.
Acute respiratory distress syndrome (ARDS) is a high-mortality pulmonary disorder characterized by an intense inflammatory response and a cytokine storm. As of yet, there is no proven effective therapy for ARDS. Itaconate, an immunomodulatory derivative accumulated during inflammatory macrophage activation, has attracted widespread attention for its potent anti-inflammatory and anti-oxidative properties. This study pointed to explore the protective impacts of 4-octyl itaconate (4-OI) on ARDS. The results showed that lung injury was attenuated markedly after 4-OI pre-treatment, as represented by decreased pulmonary edema, inflammatory cell infiltration, and production of inflammatory factors. LPS stimulation induced NLRP3-mediated pyroptosis in vitro and in vivo, as represented by the cleavage of gasdermin D (GSDMD), IL-18 and IL-1β release, and these changes could be prevented by 4-OI pretreatment. Mechanistically, 4-OI eliminated mitochondrial reactive oxygen species (mtROS) and mtDNA escaping to the cytosol through the opening mitochondrial permeability transition pore (mPTP) in alveolar macrophages (AMs) under oxidative stress. In addition, 4-OI pretreatment markedly downregulated cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING) expression, and interferon regulatory factor 3 (IRF3) phosphorylation in vitro and in vivo. Meanwhile, inhibition of STING/IRF3 pathway alleviated NLRP3-mediated pyroptosis induced by LPS in vitro. Taken together, this study indicated that 4-OI ameliorated ARDS by rescuing mitochondrial dysfunction and inhibiting NLRP3-mediated macrophage pyroptosis in a STING/IRF3-dependent manner, which further revealed the potential mechanism of itaconate in preventing inflammatory diseases.
Nanog expression is heterogeneous and dynamic in embryonic stem cells (ESCs). However, the mechanism for stabilizing pluripotency during the transitions between Nanog(high) and Nanog(low) states is ...not well understood. Here we report that Dax1 acts in parallel with Nanog to regulate mouse ESC (mESCs) identity. Dax1 stable knockdown mESCs are predisposed towards differentiation but do not lose pluripotency, whereas Dax1 overexpression supports LIF-independent self-renewal. Although partially complementary, Dax1 and Nanog function independently and cannot replace one another. They are both required for full reprogramming to induce pluripotency. Importantly, Dax1 is indispensable for self-renewal of Nanog(low) mESCs. Moreover, we report that Dax1 prevents extra-embryonic endoderm (ExEn) commitment by directly repressing Gata6 transcription. Dax1 may also mediate inhibition of trophectoderm differentiation independent or as a downstream effector of Oct4. These findings establish a basal role of Dax1 in maintaining pluripotency during the state transition of mESCs and somatic cell reprogramming.
This study aimed to develop and validate a nomogram based on immune checkpoint genes (ICGs) for predicting prognosis and immune checkpoint blockade (ICB) efficacy in lung adenocarcinoma (LUAD) ...patients. A total of 385 LUAD patients from the TCGA database and 269 LUAD patients in the combined dataset (GSE41272 + GSE50081) were divided into training and validation cohorts, respectively. Three different machine learning algorithms including random forest (RF), least absolute shrinkage and selection operator (LASSO) logistic regression analysis, and support vector machine (SVM) were employed to select the predictive markers from 82 ICGs to construct the prognostic nomogram. The X-tile software was used to stratify patients into high- and low-risk subgroups based on the nomogram-derived risk scores. Differences in functional enrichment and immune infiltration between the two subgroups were assessed using gene set variation analysis (GSVA) and various algorithms. Additionally, three lung cancer cohorts receiving ICB therapy were utilized to evaluate the ability of the model to predict ICB efficacy in the real world. Five ICGs were identified as predictive markers across all three machine learning algorithms, leading to the construction of a nomogram with strong potential for prognosis prediction in both the training and validation cohorts (all AUC values close to 0.800). The patients were divided into high- (risk score ≥ 185.0) and low-risk subgroups (risk score < 185.0). Compared to the high-risk subgroup, the low-risk subgroup exhibited enrichment in immune activation pathways and increased infiltration of activated immune cells, such as CD8 + T cells and M1 macrophages (P < 0.05). Furthermore, the low-risk subgroup had a greater likelihood of benefiting from ICB therapy and longer progression-free survival (PFS) than did the high-risk subgroup (P < 0.05) in the two cohorts receiving ICB therapy. A nomogram based on ICGs was constructed and validated to aid in predicting prognosis and ICB treatment efficacy in LUAD patients.
Polyelectrolyte complexes with sulfonate ionic cross-linking and free sulfate groups were fabricated from chitosan (CS) and poly (sodium vinylsulfonate) (PVS) via the “complexation-sulfation” method. ...Homogenous membranes (S-PVS/CS PECMs) were prepared exhibiting both high flux and water selectivity in dehydrating various alcohols and the separation performance was proportional to the content of free sulfate groups. For example, in dehydrating 10wt% water/ethanol mixture at 70°C, the flux and water content in permeate for the S-PVS/CS-3 PECM was 1980g/m2h and 99.55wt%, respectively. Moreover, the separation performance was stable versus an operation time of 120h and could dehydrate an azeotropic water/ethanol mixture to fuel grade ethanol. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and ζ potential were employed to characterize chemical structures, compositions, and charge properties of S-PVS/CS PECs. Scanning electron microscopy and contact angle measurement were exploited to investigate the morphology and hydrophilicity of S-PVS/CS PECMs. In addition, swelling and sorption behavior of S-PVS/CS PECMs were determined to interpret separation performances.
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•PECs with sulfonate ionic cross-linking and free sulfate groups were fabricated.•PV dehydration performances were enhanced by introducing strong acid groups.•The flux was proportional to the amount of free sulfate groups.•PECMs could dehydrate an azeotropic water/ethanol mixture to fuel grade ethanol.
Prion diseases are infectious fatal neurodegenerative diseases including Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in cattle. The misfolding and conversion of cellular ...PrP in such mammals into pathogenic PrP is believed to be the key procedure. Rabbits are among the few mammalian species that exhibit resistance to prion diseases, but little is known about the molecular mechanism underlying such resistance. Here, we report that the crowding agents Ficoll 70 and dextran 70 have different effects on fibrillization of the recombinant full-length PrPs from different species: although these agents dramatically promote fibril formation of the proteins from human and cow, they significantly inhibit fibrillization of the rabbit protein by stabilizing its native state. We also find that fibrils formed by the rabbit protein contain less β-sheet structure and more α-helix structure than those formed by the proteins from human and cow. In addition, amyloid fibrils formed by the rabbit protein do not generate a proteinase K-resistant fragment of 15–16-kDa, but those formed by the proteins from human and cow generate such proteinase K-resistant fragments. Together, these results suggest that the strong inhibition of fibrillization of the rabbit PrP by the crowded physiological environment and the absence of such a protease-resistant fragment for the rabbit protein could be two of the reasons why rabbits are resistant to prion diseases.
Natural rubber (NR) is widely used in various fields including aerospace, military industry and transportation due to its superior elasticity and comprehensive mechanical properties. Nonetheless, the ...commercial NR prepared by different methods usually exhibits different mechanical properties, primarily due to variations in processing conditions during the conversion from latex to bulk rubber material. Consequently, this poses challenges in scientific research and industrial production of NR. In order to assess the properties of various commercially available NR and identify key structural and compositional components, this study systematically compares and analyzes four representative NR raw materials: air dried sheet (ADS), ribbed smoked sheets (RSS), constant viscidity NR (CV), and whole field latex rubber (WF). The investigation focuses on evaluating their static mechanical behavior, SIC behavior, wear resistance, and fatigue resistance. The findings indicate that protein and gel content exhibit a crucial influence on the NR properties. These constituents contribute to the formation of a high-crosslinking density region, generating a heterogeneous network structure within the rubber. This structure amplifies strains during deformation, leading to earlier and stronger strain-induced crystallization (SIC). Among the four commercial NR brands, RSS demonstrates superior overall mechanical and dynamic properties owing to its high protein and gel content. This study serves as a valuable reference for comprehending the differences in properties among various commercial NR, thereby offering guidance for the actual processing and selection of NR.
A series of heteroleptic cyclometalated Ir (III) complexes, which are used for OLED application, were investigated by DFT and TD-DFT method. The frontier molecular orbital character and charge ...transfer character shown that they have the advantages of low efficiency roll-off properties, which is a “stumbling block” in the process of OLED solid-lighting’s development. Namely, means the materials will play an important role in the journey development of OLED.
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•Cyclometalated iridium (III) complexes have received special attention as dopants for harvesting the otherwise nonemissive triplet states formed in OLEDs, but now, most of them cannot satisfy to be used for the applications, especially for Bright blue and Near-infrared, since that a fast reduction in efficiency known as roll-off, however, occurs when the drive current increases, this leads to a much lower luminance and more power consumption.•Thus in this paper, in order to find a kind of Bright blue and Near-infrared OLED materials with low efficiency roll-off properties, we theoretical design and investigate a series of Iridium complexes.•The geometries, electronic structures, the lowest-lying singlet absorptions, triplet emissions properties and the application value for organic light emitting devices were all analyzed by theory in this article.
A series metal iridium complexes were calculated using the method of DFT and TD-DFT under Gaussian 09 software. H atoms on the N counter in 2-(4-fluorophenyl)pyridine were replaced with methyl and nitro groups, respectively, to obtain two main ligands CFM(2-(4-fluorobrobenyl)-4-methylpyridine) and CFN(2-(4-fluorobrobenyl)-4-nitropyridine), then we obtained six complexes: (CFM)2Ir(acac), (CFM)2Ir(tpip), (CFM)3Ir, (CFN)2Ir(acac), (CFN)2Ir(tpip) and (CFN)3Ir, Where acac is represented as pentane-2, 4-dione, tpip as tetraphenylimido-diphosphinate. The electronic structure, the lowest singlet absorption, the triple excited states as well as the emission spectrum are also theoretically studied.
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