Excellent capacitive storage performance of N-doped porous carbon derived from the orientation-guidance coupled with in-situ activation methodology.

The orientation-guidance coupled with in-situ activation methodology is developed to synthesize the N-doped porous carbon (NPC) with well-developed porosity and high specific surface area, using coal pitch as a carbon precursor. The orientation-guidance and activation are dedicated to generating microporous and mesoporous channels, respectively. The in-situ N incorporation into the carbon skeleton is realized along with the formation of porous carbon (PC), ensuring the uniformity of N doping. As an electrode material of supercapacitor, benefiting from the robust hexagon-like building block decorated with micro-mesoporous channels and N doping, NPC electrode affords a significant improvement in capacitive energy-storage performance, achieving a specific capacitance of up to 333F g-1 at 1 A/g, which far exceeds those of PC and activated carbon. Notably, even under high mass loading of 10 mg cm-2, the NPC maintains a satisfactory capacitance of 258F g-1 at 1 A/g. When employed as the anode in Li-ion capacitor (LIC), apart from exhibiting enhanced anode behavior compared to graphite anode, NPC also delivers exceptional cyclability. Furthermore, density functional theory calculations have validated the enhanced electrical conductivity and Li storage ability contributed by N doping, providing a theoretical foundation for the observed improvements in electrochemical performance. A full LIC configured with NPC anode delivers extraordinary Ragone performance and outstanding cyclability. This work also proposes a feasible way to realize the oriented conversion of coal pitch into high-performance electrode materials for electrochemical energy-storage devices.

Effectiveness and safety of segmentectomy vs. wedge resection for the treatment of patients with operable non­small cell lung cancer: A meta­analysis and systematic review.

The present study compared the differences in effectiveness and safety between segmentectomy (ST) and wedge resection (WR) in patients with operable non-small cell lung cancer (NSCLC). The PubMed, EMBASE, Cochrane Library and Web of Science databases were searched for papers published from inception until July 2023. The inclusion criteria were based on the population, intervention, comparator, outcomes and study designs. ROBINS-I was selected to assess the risk of bias and quality of evidence in the included non-randomised studies. Appropriate effect sizes were selected, and subgroup analyses, heterogeneity tests, sensitivity analyses and publication bias were applied. A total of 18 retrospective studies were included, involving 19,381 patients with operable NSCLC. The 5-year overall survival rate [hazard ratio (HR), 0.19; 95% confidence interval (CI), 0.04, 0.34; P=0.014; I2=76.3%], lung cancer-specific survival rate (HR, 0.3; 95% CI, 0.21, 0.38; P<0.01; I2=13.8%) and metastasis rate [odds ratio (OR), 1.56; 95% CI, 1.03, 2.38; P=0.037] in patients with operable NSCLC treated with WR were worse than those in patients treated with ST. The incidence of postoperative complications (OR, 0.44; 95% CI, 0.23, 0.82) in the WR group was lower than in the ST treatment group. There was no difference in postoperative recurrence (OR, 2.15; 95% CI, 0.97, 4.74; P=0.058) and mortality (risk difference, 0.04; 95% CI, -0.03, 0.11; P=0.287) between groups. Based on current evidence, patients with NSCLC treated with ST surgery have better postoperative survival but more complications than those patients treated with WT, while the effect of WR and ST on the recurrence rate and distant metastasis rate remains controversial.

Intrinsically Safe Lithium Metal Batteries Enabled by Thermo-electrochemical Compatible in-situ Polymerized Solid-state Electrolytes.

In-situ polymerized solid-state electrolytes have attracted much attention due to high Li-ion conductivity, conformal interface contact, and low interface resistance, but are plagued by lithium dendrite, interface degradation, and inferior thermal stability, which thereby leads to limited lifespan and severe safety hazards for high-energy lithium metal batteries (LMBs). Herein, we propose an in-situ polymerized electrolyte by copolymerization of 1,3-dioxolane with 1,3,5-tri glycidyl isocyanurate (TGIC) as a cross-linking agent, which realizes a synergy of battery thermal safety and interface compatibility with Li anode. Functional TGIC enhances the electrolyte polymeric level. The unique carbon-formation mechanism facilitates flame retardancy and eliminates the battery fire risk. In the meantime, TGIC-derived inorganic-rich interphase inhibits interface side reactions and promotes uniform Li plating. Intrinsically safe LMBs with nonflammability and outstanding electrochemical performances under extremely temperatures (130 °C) are achieved. This functional polymer design shows a promising prospect for the development of safe LMBs. This article is protected by copyright. All rights reserved.

MiR-106a targets ATG7 to inhibit autophagy and angiogenesis after myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is an acute condition in which the heart muscle dies due to the lack of blood supply. Previous research has suggested that autophagy and angiogenesis play vital roles in the prevention of heart failure after MI, and miR-106a is considered to be an important regulatory factor in MI. But the specific mechanism remains unknown. In this study, using cultured venous endothelial cells and a rat model of MI, we aimed to identify the potential target genes of miR-106a and discover the mechanisms of inhibiting autophagy and angiogenesis. METHODS: We first explored the biological functions of miR-106a on autophagy and angiogenesis on endothelial cells. Then we identified ATG7, which was the downstream target gene of miR-106a. The expression of miR-106a and ATG7 was investigated in the rat model of MI. RESULTS: We found that miR-106a inhibits the proliferation, cell cycle, autophagy and angiogenesis, but promoted the apoptosis of vein endothelial cells. Moreover, ATG7 was identified as the target of miR-106a, and ATG7 rescued the inhibition of autophagy and angiogenesis by miR-106a. The expression of miR-106a in the rat model of MI was decreased but the expression of ATG7 was increased in the infarction areas. CONCLUSION: Our results indicate that miR-106a may inhibit autophagy and angiogenesis by targeting ATG7. This mechanism may be a potential therapeutic treatment for MI.

Characterization of PANoptosis-related genes and the immune landscape in moyamoya disease.

Moyamoya disease (MMD) is a cerebrovascular narrowing and occlusive condition characterized by progressive stenosis of the terminal portion of the internal carotid artery and the formation of an abnormal network of dilated, fragile perforators at the base of the brain. However, the role of PANoptosis, an apoptotic mechanism associated with vascular disease, has not been elucidated in MMD. In our study, a total of 40 patients' genetic data were included, and a total of 815 MMD-related differential genes were screened, including 215 upregulated genes and 600 downregulated genes. Among them, DNAJA3, ESR1, H19, KRT18 and STK3 were five key genes. These five key genes were associated with a variety of immune cells and immune factors. Moreover, GSEA (gene set enrichment analysis) and GSVA (gene set variation analysis) showed that the different expression levels of the five key genes affected multiple signaling pathways associated with MMD. In addition, they were associated with the expression of MMD-related genes. Then, based on the five key genes, a transcription factor regulatory network was constructed. In addition, targeted therapeutic drugs against MMD-related genes were obtained by the Cmap drug prediction method: MST-312, bisacodyl, indirubin, and tropanyl-3,5-dimethylbenzoate. These results suggest that the PANoptosis-related genes may contribute to the pathogenesis of MMD through multiple mechanisms.

An O/N/S-rich porous Fe-based metal-organic framework (MOF) for gold recovery from the aqueous phase with excellent performance.

Recovering gold from wastewater has both economic and environmental benefits. However, how to effectively recover it is challenging. In this work, a novel Fe-based metal-organic framework (MOF) was synthesized and decorated with 2,5-thiophenedicarboxylic acid to have a well-developed porous architecture to effectively recover Au(III) from water. The maximum Au(III) sorption capacity by the finally-synthesized porous material MIL-101(Fe)-TDCA reached 2350 mg/g at pH = 6.00 ± 0.15, which is one of the highest among all literature-reported relevant materials including MOFs, and high sorption strength can be maintained within a wide pH range from 2.0 to 10.0. Besides, Au(III) sorption efficiency at low concentrations (i.e., 3.5 × 104 mg/mL) reached over 99%. Mechanically, outstanding Au(III) sorption by MIL-101(Fe)-TDCA resulted from the O/N/S-containing moieties on its surface, large surface area and porosity. The N- and S-containing functionalities (CS, CONH) served as electron donors to chelate Au(III). The O-containing (FeOFe, COFe, COOH, and coordinated H2O) and N-containing (CONH) moieties on MIL-101(Fe)-TDCA interacted with OH groups on the hydrolyzed species of Au(III) (AuCl3(OH)-, AuCl2(OH)2-, and AuCl(OH)3-) by hydrogen bond, which further increased Au(III) sorption. Furthermore, about 45.71% of Au(III) was reduced to gold nanoparticles by CS groups on the decorated 2,5-dithiophene dicarboxylic acid during sorption on MIL-101(Fe)-TDCA. Over 98.35% of Au(III) was selectively sorbed on MIL-101(Fe)-TDCA at pH 4.0, much higher than that of the coexisting heavy metal ions including Cu(II), Zn(II), Pb(II), and Ni(II) (< 5%), despite their same concentration at 0.01 mg/mL. Although sorption selectivity of a noble metal Pt(IV) by MIL-101(Fe)-TDCA is relatively poor (68.23%), it could be acceptable. Moreover, reusability of MIL-101(Fe)-TDCA is also excellent, since above 90.5% Au(III) still can be sorbed after two sorption-desorption cycles. Overall, excellent sorption performance and the roughly-calculated gold recycling benefits (26.30%) highlight that MIL-101(Fe)-TDCA is a promising porous material for gold recovery from the aqueous phase.

Study on analgesic effect of Shentong Zhuyu Decoction in neuropathic pain rats by network pharmacology and RNA-Seq.

ETHNOPHARMACOLOGICAL RELEVANCE: Shentong Zhuyu Decoction (STZYD) is a traditional prescription for promoting the flow of Qi and Blood which is often used in the treatment of low back and leg pain clinicall with unclear mechanism. Neuropathic pain (NP) is caused by disease or injury affecting the somatosensory system. LncRNAs may play a key role in NP by regulating the expression of pain-related genes through binding mRNAs or miRNAs sponge mechanisms. AIM OF THE STUDY: To investigate the effect and potential mechanism of STZYD on neuropathic pain. METHODS: Chronic constriction injury (CCI) rats, a commonly used animal model, were used in this study. The target of STZYD in NP was analyzed by network pharmacology, and the analgesic effect of STZYD in different doses (H-STZYD, M-STZYD, L-STZYD) on CCI rats was evaluated by Mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL). Meanwhile, RNA-seq assay was used to detect the changed mRNAs and lncRNAs in CCI rats after STZYD intervention. GO analysis, KEGG pathway analysis, and IPA analysis were used to find key target genes and pathways, verified by qPCR and Western Blot. The regulatory effect of lncRNAs on target genes was predicted by co-expression analysis and ceRNA network construction. RESULTS: We found that STZYD can improve hyperalgesia in CCI rats, and H-STZYD has the best analgesic effect. The results of network pharmacological analysis showed that STZYD could play an analgesic role in CCI rats through the MAPK/ERK/c-FOS pathway. By mRNA-seq and lncRNA-seq, we found that STZYD could regulate the expression of Cnr1, Cacng5, Gucy1a3, Kitlg, Npy2r, and Grm8, and inhibited the phosphorylation level of ERK in the spinal cord of CCI rats. A total of 27 lncRNAs were associated with the target genes and 30 lncRNAs, 83 miRNAs and 5 mRNAs participated in the ceRNA network. CONCLUSION: STZYD has the effect of improving hyperalgesia in CCI rats through the MAPK/ERK/c-FOS pathway, which is related to the regulation of lncRNAs to Cnr1 and other key targets.

Naringenin nanoparticles targeting cyclin B1 suppress the progression of rheumatoid arthritis-associated lung cancer by inhibiting fibroblast-to-myofibroblast transition.

There is growing evidence of an elevated risk of lung cancer in patients with rheumatoid arthritis. The poor prognosis of rheumatoid arthritis-associated lung cancer and the lack of therapeutic options pose an even greater challenge to the clinical management of patients. This study aimed to identify potential molecular targets associated with the progression of rheumatoid arthritis-associated lung cancer and examine the efficacy of naringenin nanoparticles targeting cyclin B1. Mendelian randomizatio analysis revealed that rheumatoid arthritis has a positive correlation with the risk of lung cancer. Cyclin B1 was significantly upregulated in patients with rheumatoid arthritis-associated lung cancer and was significantly overexpressed in synovial tissue fibroblasts. Furthermore, the overexpression of cyclin B1 in rheumatoid arthritis fibroblast-like synoviocytes, which promotes their proliferation and fibroblast-to-myofibroblast transition, can significantly contribute to the growth and infiltration of lung cancer cells. Importantly, our prepared naringenin nanoparticles targeting cyclin B1 effectively attenuated proliferation and fibroblast-to-myofibroblast transition by blocking cells at the G2/M phase. In vivo experiments, naringenin nanoparticles targeting cyclin B1 significantly alleviated the development of collagen-induced arthritis and lung orthotopic tumors. Collectively, our results reveal that naringenin nanoparticles targeting cyclin B1 can suppress the progression of rheumatoid arthritis-associated lung cancer by inhibiting fibroblast-to-myofibroblast transition. These findings provide new insights into the treatment of rheumatoid arthritis-associated lung cancer therapy.

Evaluation of cerebrovascular reactivity in moyamoya disease using oxygen-dependent magnetic resonance imaging.

Moyamoya disease (MMD) is a rare cerebrovascular disorder marked by progressive stenosis of the internal carotid arteries. Assessing cerebral hemodynamics, specifically cerebrovascular reactivity (CVR), is vital for MMD management and prognosis. In this study, fMRI was performed in a prospective cohort of 47 patients with MMD and 32 healthy controls to investigate its utility in evaluating CVR and to explore the influence of cerebral posterior circulation compensation on CVR in MMD. The regions where the CVR values of participants with MMD were lower than those of healthy controls were primarily concentrated in the frontal, parietal, and temporal lobes (p < 0.05). In certain regions mainly supplied by posterior circulation, the CVR values of compensatory-normal subgroup tended to exceed those of compensatory-poor subgroup. fMRI can detect a significant decrease in CVR values in patients with MMD compared to healthy controls. Compensation for the posterior cerebral circulation may affect cerebrovascular reactivity.

GLUT1 regulates the release of VEGF-A in the alveolar epithelium of lipopolysaccharide-induced acute lung injury.

Acute lung injury (ALI) is a severe disease with high mortality and poor prognosis, characterized by excessive and uncontrolled inflammatory response. Vascular endothelial growth factor A (VEGF-A) contributes to the development and progression of ALI. The aim of this study was to evaluate the role of glucose transporter 1 (GLUT1) in alveolar epithelial VEGF-A production in lipopolysaccharide (LPS)-induced ALI. An ALI mouse model was induced by LPS oropharyngeal instillation. Mice were challenged with LPS and then treated with WZB117, a specific antagonist of GLUT1. For the vitro experiments, cultured A549 cells (airway epithelial cell line) were exposed to LPS, with or without the GLUT1 inhibitors WZB117 or BAY876. LPS significantly upregulated of GLUT1 and VEGF-A both in the lung from ALI mice and in cultured A549. In vivo, treatment with WZB117 not only markedly decreased LPS-induced pulmonary edema, injury, neutrophilia, as well as levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF), but also reduced VEGF-A production. Yet, the maximum tolerated concentration of WZB117 failed to suppress LPS-induced VEGF-A overexpression in vitro. While administration of BAY876 inhibited gene and protein expression as well as secretion of VEGF-A in response to LPS in A549. These results illustrated that GLUT1 upregulates VEGF-A production in alveolar epithelia from LPS-induced ALI, and inhibition of GLUT1 alleviates ALI.

Differential influences of forest floor-pyrolyzed biochar-derived and leached dissolved organic matter interaction with natural iron-bearing minerals in forest subsoil on the formation of mineral-associated soil organic matter.

The vertical sequestration of dissolved organic matter (DOM) by iron minerals along the soil profile is assumed to be central to the long-term storage of the soil organic matter (SOM) pool. However, there is limited information available about how the interaction between DOM and natural iron-bearing minerals shape mineral SOM associations quantitatively and qualitatively in forest subsoils. Here, we systematically investigated the influences of forest organic layer-pyrolyzed biochar-derived DOM (BDOM) and leached DOM (LDOM) on quantity, molecular composition, and diversity of deposition layer-derived iron minerals-associated OM by using Fourier transform ion cyclotron resonance mass spectrometry and other complementary spectroscopy. Results indicated natural iron minerals (FeOx1 and FeOx2) had a greater capacity for sorbing LDOM with higher aromaticity and molecular weight than those of BDOM, and the higher proportion of goethite and short-order-range phase in natural iron minerals was closely related to the increased OM adsorption capacity. We also observed the preferential sorption of oxygen/nitrogen-rich polycyclic aromatic compounds and carboxylic-containing compounds in LDOM and concurrent the potential release of lignin-like/aromatics compounds and carboxyl/nitrogen-less aliphatic compounds from native OM coprecipitates into the solution. However, unsaturated and oxidized phenolic compounds in BDOM had a stronger affinity for FeOx through hydrophobic partitioning and specific polar interactions, and concomitantly the partial release of nitrogen-free aliphatic and other carboxyl-rich compounds. More nitrogen structures in aromatic-containing compounds can improve the saturation level and polarity of BDOM. Compared with BDOM, LDOM exerted a stronger control over the exchange of native OM from subsoil natural iron-bearing minerals and substantially enhanced the molecular diversity of the reconstituted mineral-associated OM during the adsorptive fractionation. Overall, these findings suggest the compositional evolution of DOM profoundly shapes SOM formation and persistence in forest subsoils, which is the key to understanding DOM cycling and contaminant fate during its passage through the soil.

A Dynamically Stable Mixed Conducting Interphase for All-Solid-State Lithium Metal Batteries.

All-solid-state lithium (Li) metal batteries (ASSLMBs) employing sulfide solid electrolytes have attracted increasing attention owing to superior safety and high energy density. However, the instability of sulfide electrolytes against Li metal induces the formation of two types of incompetent interphases, solid electrolyte interphase (SEI) and mixed conducting interphase (MCI), which significantly blocks rapid Li-ion transport and induces uneven Li deposition and continuous interface degradation. In this contribution, a dynamically stable mixed conducting interphase (S-MCI) is proposed by in situ stress self-limiting reaction to achieve the compatibility of Li metal with composite sulfide electrolytes (Li6 PS5 Cl (LPSCl) and Li10 GeP2 S12 (LGPS)). The rational design of composite electrolytes utilizes the expansion stress induced by the electrolyte decomposition to in turn constrain the further decomposition of LGPS. Consequently, the S-MCI inherits the high dynamical stability of LPSCl-derived SEI and the lithiophilic affinity of Li-Ge alloy in LGPS-derived MCI. The Li||Li symmetric cells with the protection of S-MCI can operate stably for 1500 h at 0.5 mA cm-2 and 0.5 mAh cm-2 . The Li||NCM622 full cells present stable cycling for 100 cycles at 0.1 C with a high-capacity retention of 93.7%. This work sheds fresh insight into constructing electrochemically stable interphase for high-performance ASSLMBs.

Regulation of SiO2 Nanoparticles on the Adsorptive Fractionation of Dissolved Organic Matter by Goethite.

SiO2 nanoparticles (SiO2NPs) are most widely available and coexisting with DOM at the mineral-water interface; however, the role of SiO2NPs in DOM fractionation and the underlying mechanisms have not been fully understood. Using Fourier transform ion cyclotron resonance mass spectrometry, combined with Fourier transform infrared spectroscopy and X-ray adsorption fine structure spectroscopy, was employed to investigate the adsorptive fractionation of litter layer-derived DOM on goethite coexisting with SiO2NPs under different pH conditions. Results indicated that the inhibitory effect of the coexisting SiO2NPs on OM sorbed by goethite was waning as environmental pH increased due to the reduced steric interactions and the concurrent elevated hydrogen bonding/hydrophobic partitioning interactions on the goethite surface. We observed the coexisting SiO2NPs inhibited the adsorption of high carboxylic-containing condensed aromatic/aromatics compounds on goethite under different pH conditions while improving the adsorption of highly unsaturated aliphatic/phenolic and carbohydrate-like compounds in an alkaline and/or circumneutral environment. More nitrogen-containing structures may favor the adsorption of phenolic and nonaromatic compounds to goethite by counteracting the negative effect of SiO2NPs. These findings suggest that DOM sequestration may be significantly regulated by the coexisting SiO2NPs at the mineral-water interface, which may further influence the carbon-nitrogen cycling and contaminant fate in natural environments.

Flower color polymorphism of a wild Iris on the Qinghai-Tibet plateau.

BACKGROUND: Flower color plays a crucial role in attracting pollinators and facilitating environmental adaptation. Investigating the causes of flower color polymorphism and understanding their potential effects on both ecology and genetics can enhance our understanding of flower color polymorphism in wild plant. RESULTS: In this study, we examined the differences of potential male and female fitness between purple- and yellow- flower individuals in Iris potaninii on the Qinghai-Tibet Plateau, and screened key genes and positively selective genes involved in flower color change. Our results showed that yellow flower exhibited a higher pollen-to-ovule ratio. Yellow flowers were derived from purple flowers due to the loss of anthocyanins, and F3H could be an essential gene affecting flower color variation though expression regulation and sequence polymorphism in this species. Furthermore, our findings suggest that genes positively selected in yellow-flowered I. potaninii might be involved in nucleotide excision repair and plant-pathogen interactions. CONCLUSIONS: These results suggest that F3H induces the flower color variation of Iris potaninii, and the subsequent ecological and additive positive selection on yellow flowers may further enhance plant adaptations to alpine environments.

Diagnostic value of peripheral blood eosinophils for benign and malignant pulmonary nodule.

This retrospective study aims to assess the diagnostic utility of peripheral blood eosinophil counts in distinguishing between benign and malignant pulmonary nodules (PNs) prior to surgical intervention. We involved patients presenting with PNs measuring ≤30 mm as the primary CT imaging finding prior to surgical procedures at the General Hospital of Northern Theater Command in Shenyang, China, during the period spanning 2021 to 2022. Multivariable logistic regression analysis and receiver operator characteristic curve analysis, along with area under the curve (AUC) calculations, were used to determine the diagnostic value of eosinophil. A total of 361 patients with PN were included, consisting of 135 with benign PN and 226 with malignant PN. Multivariable logistic regression analysis showed that eosinophil percentage (OR = 1.909, 95% CI: 1.323-2.844, P < .001), absolute eosinophil value (OR = 0.001, 95% CI: 0.000-0.452, P = .033), tumor diameter (OR = 0.918, 95% CI: 0.877-0.959, P < .001), nodule type (OR = 0.227, 95% CI: 0.125-0.400, P < .001), sex (OR = 2.577, 95% CI: 1.554-4.329, P < .001), and age (OR = 0.967, 95% CI: 0.945-0.989, P = .004) were independently associated with malignant PN. The diagnostic value of regression model (AUC [95% CI]: 0.775 [0.725-0.825]; sensitivity: 74.3%; specificity: 71.1%) was superior to eosinophil percentage (AUC [95% CI]: 0.616 [0.556-0.677]; specificity: 66.8%; specificity: 51.1%) (Delong test: P < .001). Peripheral blood eosinophil percentage might be useful for early malignant PN diagnosis, and combining that with other characteristics might improve the diagnostic performance.

IRE1α/XBP-1 promotes ß-catenin signaling activation of airway epithelium in lipopolysaccharide-induced acute lung injury.

BACKGROUND: Acute lung injury (ALI), along with the more severe condition--acute respiratory distress syndrome (ARDS), is a major cause of respiratory failure in critically ill patients with high morbidity and mortality. Inositol-requiring protein 1α (IRE1α)/X box protein-1 (XBP1) pathway was proved to regulate lipopolysaccharide (LPS)-induced lung injury and inflammation. Yet, its role on epithelial ß-catenin in LPS-induced ALI remains to be elucidated. METHODS: LPS-induced models were generated in mice (5 mg/kg) and Beas-2B cells (200 µg/mL). Two selective antagonists of IRE1α (4µ8c and STF-083010) were respectively given to LPS-exposed mice and cultured cells. RESULTS: Up-regulated expression of endoplasmic reticulum (ER) stress markers immunoglobulin-binding protein (BIP) and spliced X box protein-1(XBP-1s) was detected after LPS exposure. Besides, LPS also led to a down-regulated total ß-catenin level in the lung and Beas-2B cells, with decreased membrane distribution as well as increased cytoplasmic and nuclear accumulation, paralleled by extensively up-regulated downstream targets of the Wnt/ß-catenin signaling. Treatment with either 4µ8c or STF-083010 not only significantly attenuated LPS-induced lung injury and inflammation, but also recovered ß-catenin expression in airway epithelia, preserving the adhesive function of ß-catenin while blunting its signaling activity. CONCLUSION: These results illustrated that IRE1α/XBP1 pathway promoted the activation of airway epithelial ß-catenin signaling in LPS-induced ALI.

Upregulated Cytoskeletal Proteins Promote Pathological Angiogenesis in Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) is a rare progressive vascular disease that leads to intracranial internal carotid artery stenosis and eventual occlusion. However, its pathogenesis remains unclear. The purpose of this study is to explore the role of abnormally expressed proteins in the pathogenesis of MMD. METHODS: Data-independent acquisition mass spectrometry identifies the differentially expressed proteins in MMD serum by detecting the serum from 60 patients with MMD and 20 health controls. The differentially expressed proteins were validated using enzyme linked immunosorbent assays. Immunofluorescence for superficial temporal artery and middle cerebral artery specimens was used to explore the morphological changes of vascular wall in MMD. In vitro experiments were used to explore the changes and mechanisms of differentially expressed proteins on endothelial cells. RESULTS: Proteomic analysis showed that a total of 14 726 peptides and 1555 proteins were quantified by mass spectrometry data. FLNA (filamin A) and ZYX (zyxin) proteins were significantly higher in MMD serum compared with those in health controls (Log2FC >2.9 and >2.8, respectively). Immunofluorescence revealed an intimal hyperplasia in superficial temporal artery and middle cerebral artery specimens of MMD. FLNA and ZYX proteins increased the proportion of endothelial cells in S phase and promoted their proliferation, angiogenesis, and cytoskeleton enlargement. Mechanistic studies revealed that AKT (serine/threonine kinase)/GSK-3ß (glycogen synthase kinase 3ß)/ß-catenin signaling pathway plays a major role in these FLNA- and ZYX-induced changes in endothelial cells. CONCLUSIONS: This study provides proteomic data on a large sample size of MMD. The differential expression of FLNA and ZYX in patient with MMD and following in vitro experiments suggest that these upregulated proteins are related to the pathology of cerebrovascular intimal hyperplasia in MMD and are involved in MMD pathogenesis, with diagnostic and therapeutic ramifications.

CPA-catalyzed asymmetric domino thia-Michael/aldol reactions for simultaneous chiral center and axial chirality formation.

A highly enantio- and diastereoselective domino thia-Michael/aldol reaction applying 5H-dibenzo[a,c][7]annulen-5-one as a Michael acceptor, catalyzed by a chiral phosphoric acid (CPA), has been developed. The bridged biaryl adduct contains multiple stereogenic centers in the bridging linkage as well as a thermodynamically controlled stereogenic axis. The energy difference between the two atropodiastereomers is about 9.1 kcal mol-1, which accounts for the observed excellent diastereoselectivity (>20 : 1).