Publisher Correction: K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8+ T cell activation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8(+) T cell activation.

The key molecular mechanisms that control signaling via T cell antigen receptors (TCRs) remain to be fully elucidated. Here we found that Nrdp1, a ring finger-type E3 ligase, mediated Lys33 (K33)-linked polyubiquitination of the signaling kinase Zap70 and promoted the dephosphorylation of Zap70 by the acidic phosphatase-like proteins Sts1 and Sts2 and thereby terminated early TCR signaling in CD8(+) T cells. Nrdp1 deficiency significantly promoted the activation of naive CD8(+) T cells but not that of naive CD4(+) T cells after engagement of the TCR. Nrdp1 interacted with Zap70 and with Sts1 and Sts2 and connected K33 linkage of Zap70 to Sts1- and Sts2-mediated dephosphorylation. Our study suggests that Nrdp1 terminates early TCR signaling by inactivating Zap70 and provides new mechanistic insights into the non-proteolytic regulation of TCR signaling by E3 ligases.

Integrated multi-omics analysis and machine learning developed diagnostic markers and prognostic model based on Efferocytosis-associated signatures for septic cardiomyopathy.

Septic cardiomyopathy (SCM) is characterized by an abnormal inflammatory response and increased mortality. The role of efferocytosis in SCM is not well understood. We used integrated multi-omics analysis to explore the clinical and genetic roles of efferocytosis in SCM. We identified six module genes (ATP11C, CD36, CEBPB, MAPK3, MAPKAPK2, PECAM1) strongly associated with SCM, leading to an accurate predictive model. Subgroups defined by EFFscore exhibited distinct clinical features and immune infiltration levels. Survival analysis showed that the C1 subtype with a lower EFFscore had better survival outcomes. scRNA-seq analysis of peripheral blood mononuclear cells (PBMCs) from sepsis patients identified four genes (CEBPB, CD36, PECAM1, MAPKAPK2) associated with high EFFscores, highlighting their role in SCM. Molecular docking confirmed interactions between diagnostic genes and tamibarotene. Experimental validation supported our computational results. In conclusion, our study identifies a novel efferocytosis-related SCM subtype and diagnostic biomarkers, offering new insights for clinical diagnosis and therapy.

FOXL2 regulates RhoA expression to change actin cytoskeleton rearrangement in granulosa cells of chicken pre-ovulatory follicles.

Forkhead box L2 (FOXL2) is an indispensable key regulator of female follicular development, and it plays important roles in the morphogenesis, proliferation, and differentiation of follicle granulosa cells (GCs), such as establishing normal estradiol signaling and regulating steroid hormone synthesis. Nevertheless, the effects of FOXL2 on GC morphology and the underlying mechanism remain unknown. Using FOXL2 ChIP-seq analysis, we found that FOXL2 target genes significantly enriched in the actin cytoskeleton-related pathways. We confirmed that FOXL2 inhibited the expression of RhoA, a key gene for actin cytoskeleton rearrangement, by binding to TCATCCATCTCT in RhoA promoter region. In addition, the overexpression of FOXL2 in GCs induced the depolymerization of F-actin and the disordered of the actin filaments, resulting in a slowdown in the expansion of GCs, while silencing FOXL2 inhibited F-actin depolymerization and stabilized the actin filaments, thereby accelerating GC expansion. RhoA/ROCK pathway inhibitor Y-27632 exhibited similar effects to FOXL2 overexpression, even reversed the actin polymerization in FOXL2 silencing GCs. This study revealed for the first time that FOXL2 regulated GC actin cytoskeleton by RhoA/ROCK pathway, thus affecting GC expansion. Our findings provide new insights for constructing the regulatory network of FOXL2 and propose a potential mechanism for facilitating rapid follicle expansion, thereby laying a foundation for further understanding follicular development.

Ultrathin and Self-Supporting MOF/COF-Based Composite Membranes for Hydrogen Separation and Purification from Coke Oven Gas.

Coke oven gas (COG) is considered to be one of the most likely raw materials for large-scale H2 production in the near or medium term, with membrane separation technologies standing out from traditional technologies due to their less energy-intensive structures as well as simple operation and occupation. Based on the "MOF-in/on-COF" pore modification strategy, the COF membrane (named the PBD membrane) and ZIF-67 were used as assembly elements to design advanced molecular sieving membranes for hydrogen separation. The composition and microstructure of membranes before and after ZIF-67 loading as well as ZIF-67-in-PBD membranes under different preparation conditions (metal ion concentration, metal-ligand ratio, and reaction time) were investigated by various characterizations to reveal the synthesis regularity and microstructure regulation. Furthermore, H2/CH4 separation performances and separation mechanisms were also analyzed and compared. Finally, a dense, continuous, ultrathin, and self-supporting ZIF-67-in-PBD membrane with a Co2+ concentration of 0.02 mol/L, a metal-ligand ratio of 1:4, and a reaction time of 6 h exhibited the largest specific surface area, micropore proportion, and the best H2/CH4 separation selectivity (α = 33.48), which was significantly higher than the Robeson upper limit and was in a leading position among reported MOF membranes. The separation mechanism was mainly size screening, and adsorption selectivity also contributed a little.

A High-Quality Data Set of Protein-Ligand Binding Interactions Via Comparative Complex Structure Modeling.

High-quality protein-ligand complex structures provide the basis for understanding the nature of noncovalent binding interactions at the atomic level and enable structure-based drug design. However, experimentally determined complex structures are scarce compared with the vast chemical space. In this study, we addressed this issue by constructing the BindingNet data set via comparative complex structure modeling, which contains 69,816 modeled high-quality protein-ligand complex structures with experimental binding affinity data. BindingNet provides valuable insights into investigating protein-ligand interactions, allowing visual inspection and interpretation of structural analogues' structure-activity relationships. It can also be used for evaluating machine-learning-based scoring functions. Our results indicate that machine learning models trained on BindingNet could reduce the bias caused by buried solvent-accessible surface area, as we previously found for models trained on the PDBbind data set. We also discussed strategies to improve BindingNet and its potential utilization for benchmarking the molecular docking methods and ligand binding free energy calculation approaches. The BindingNet complements PDBbind in constructing a sufficient and unbiased protein-ligand binding data set and is freely available at http://bindingnet.huanglab.org.cn.

Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

A systems-biology approach identifies co-expression modules in response to low phosphate supply in maize lines of different breeding history.

Plants cope with low phosphorus availability by adjusting growth and metabolism through transcriptomic and proteomic adaptations. We hypothesize that selected genotypes with distinct phosphorous (P) use efficiency covering the breeding history of European Flint heterotic pool provide a tool to reveal general and genotype-specific molecular responses to P limitation. We reconstructed protein and gene co-expression networks by weighted correlation network analysis and related these to phosphate deficiency-induced traits. In roots, low phosphate supply resulted in a decreasing abundance of proteins in the oxidative pentose phosphate pathway and a negative correlation with root and shoot phosphate content. We observed an increase in abundance and positive correlation with root and shoot phosphate content for proteins in sucrose biosynthesis, lipid metabolism, respiration and RNA processing. Purple acid phosphatases, superoxide dismutase and phenylalanine ammonia lyase were identified as being upregulated under low phosphate in all genotypes. Overall, correlations between protein and mRNA abundance changes were limited, with ribosomal proteins and the ubiquitin protein degradation pathway exclusively responding with protein abundance changes. Carbohydrate, phospho- and sulfo-lipid metabolism showed abundance changes at the protein and mRNA levels. These partially non-overlapping proteomic and transcriptomic adjustments to low phosphate suggest sugar and lipid metabolism as metabolic processes associated with improved P use efficiency specifically in Founder Flint lines. We identified a mitogen-activated protein kinase-kinase as a potential genotype-specific regulator of sucrose metabolism at low phosphate in Founder Flint line EP1. We conclude that, during breedingt of Elite Flint lines, regulation of primary metabolism has changed to result in a distinct low phosphate response in Founder lines.

Catalytic 1,3-Proton Transfer in Alkenes Enabled by Fe═NR Bond Cooperativity: A Strategy for pKa-Dictated Regioselective Transposition of C═C Double Bonds.

Transition metal catalyzed alkene double bond transposition usually involves metal hydride intermediates. Despite significant advances in the design of catalysts that dictate product selectivity, control over substrate selectivity is less advanced and transition metal catalysts that selectively transpose double bonds in substrates containing multiple 1-alkene functionalities are rare. Herein, we report that the three-coordinate high spin (S = 2) Fe(II) imido complex [Ph2B(tBuIm)2Fe═NDipp][K(18-C-6)THF2] (1-K(18-C-6)) catalyzes 1,3-proton transfer from 1-alkene substrates to afford 2-alkene transposition products. Mechanistic investigations involving kinetics, competition, and isotope labeling studies, supported by experimentally calibrated DFT computations, strongly support an unusual nonhydridic mechanism for alkene transposition that is enabled by the cooperative action of the iron center and basic imido ligand. As dictated by the pKa of the allylic protons, this catalyst enables the regioselective transposition of C═C double bonds in substrates containing multiple 1-alkenes. The high spin (S = 2) state of the complex allows a wide scope of functional groups to be tolerated, including those that are typical catalyst poisons, such as amines, N-heterocycles, and phosphines. These results demonstrate a new strategy for metal-catalyzed alkene transposition with predictable substrate regioselectivity.

1α,25-Dihydroxyvitamin D3 Improves Follicular Development and Steroid Hormone Biosynthesis by Regulating Vitamin D Receptor in the Layers Model.

1α,25-Dihydroxyvitamin D3 (VitD3) is the active form of vitamin D, and it regulates gene expression and protein synthesis in mammalian follicle development. However, the function of VitD3 in the follicular development of layers remains unclear. This study investigated, through in vivo and in vitro experiments, the effects of VitD3 on follicle development and steroid hormone biosynthesis in young layers. In vivo, ninety 18-week-old Hy-Line Brown laying hens were randomly divided into three groups for different treatments of VitD3 (0, 10, and 100 µg/kg). VitD3 supplementation promoted follicle development, increasing the number of small yellow follicles (SYFs) and large yellow follicles (LYFs) and the thickness of the granulosa layer (GL) of SYFs. Transcriptome analysis revealed that VitD3 supplementation altered gene expression in the ovarian steroidogenesis, cholesterol metabolism, and glycerolipid metabolism signaling pathways. Steroid hormone-targeted metabolomics profiling identified 20 steroid hormones altered by VitD3 treatment, with 5 being significantly different among the groups. In vitro, it was found that VitD3 increased cell proliferation, promoted cell-cycle progression, regulated the expression of cell-cycle-related genes, and inhibited the apoptosis of granulosa cells from pre-hierarchical follicles (phGCs) and theca cells from prehierarchical follicles (phTCs). In addition, the steroid hormone biosynthesis-related genes, estradiol (E2) and progesterone (P4) concentrations, and vitamin D receptor (VDR) expression level was significantly altered by VitD3. Our findings identified that VitD3 altered the gene expression related to steroid metabolism and the production of testosterone, estradiol, and progesterone in the pre-hierarchical follicles (PHFs), resulting in positive effects on poultry follicular development.

Integrated analysis of single-cell and bulk RNA sequencing identifies a signature based on macrophage marker genes involved in prostate cancer prognosis and treatment responsiveness.

In the tumor microenvironment, tumor-associated macrophages (TAMs) interact with cancer cells and contribute to the progression of solid tumors. Nonetheless, the clinical significance of TAM-related biomarkers in prostate cancer (PCa) is largely unexplored. The present study aimed to construct a macrophage-related signature (MRS) for predicting PCa patient prognosis based on macrophage marker genes. Six cohorts comprising 1056 PCa patients with RNA-Seq and follow-up data were enrolled. Based on macrophage marker genes identified by single-cell RNA-sequencing (scRNA-seq) analysis, univariate analysis, least absolute shrinkage and selection operator (Lasso)-Cox regression, and machine learning procedures were performed to derive a consensus MRS. Receiver operating characteristic curve (ROC), concordance index, and decision curve analyses were used to confirm the predictive capacity of the MRS. The predictive performance of the MRS for recurrence-free survival (RFS) was stable and robust, and the MRS outperformed traditional clinical variables. Furthermore, high-MRS-score patients presented abundant macrophage infiltration and high-expression levels of immune checkpoints (CTLA4, HAVCR2, and CD86). The frequency of mutations was relatively high in the high-MRS-score subgroup. However, the low-MRS-score patients had a better response to immune checkpoint blockade (ICB) and leuprolide-based adjuvant chemotherapy. Notably, abnormal ATF3 expression may be associated with docetaxel and cabazitaxel resistance in PCa cells, T stage, and the Gleason score. In this study, a novel MRS was first developed and validated to accurately predict patient survival outcomes, evaluate immune characteristics, infer therapeutic benefits, and provide an auxiliary tool for personalized therapy.

Impact of Submucosal Saline Injection During Cold Snare Polypectomy for Colorectal Polyps Sized 3-9 mm: A Multicenter Randomized Controlled Trial.

INTRODUCTION: The role of submucosal injection during cold snare polypectomy (CSP) remains uncertain. In this study, we investigated the impact of submucosal saline injection during CSP for colorectal polyps sized 3-9 mm. METHODS: This was a multicenter randomized controlled trial conducted in 6 Chinese centers between July and September 2020 (ChiCTR2000034423). Patients with nonpedunculated colorectal polyps sized 3-9 mm were randomized in a 1:1 ratio to either CSP with submucosal injection (SI-CSP) or conventional CSP (C-CSP). The primary outcome was the incomplete resection rate (IRR). Secondary outcomes included procedure time, intraprocedural bleeding, delayed bleeding, and perforation. RESULTS: One hundred fifty patients with 234 polyps in the SI-CSP group and 150 patients with 216 polyps in the C-CSP group were included in the analysis. The IRR was not decreased in the SI-CSP group compared with that in the C-CSP group (1.7% vs 1.4%, P = 1.000). The median procedure time in the SI-CSP group was significantly longer than that in the C-CSP group (108 seconds vs 48 seconds, P < 0.001). The incidences of intraprocedural bleeding and delayed bleeding were not significantly different between the 2 groups ( P = 0.531 and P = 0.250, respectively). There was no perforation in either group. DISCUSSION: Submucosal saline injection during CSP for colorectal polyps sized 3-9 mm did not decrease the IRR or reduce adverse events but prolonged the procedure time.

Metal-Stabilized Thiyl Radicals Design Inspired by Elemental Periodic Extension Notion for Ligand-Based Alkene Addition.

Inspired by alkene addition to the Ru and Re tris(thiolate) complexes via carbon-sulfur bond formation/cleavage reactions along with a periodic extension catalysis notion, a comparative study of the electronic structures, mechanisms, and reactivities for ethylene addition to the Os and Tc tris(thiolate) complexes was performed by DFT and high-level ab initio quantum calculations. The oxidized Os and Tc complexes were revealed to exhibit sufficient radical characters on the ligands to support their reaction with ethylene, whereas neutral Tc tris(thiolate) complex featuring little thiyl radical character renders no reactivity toward ethylene. Differential reactivities of these tris(thiolate) complexes was deemed to derive from the synergy of the thiyl radical character, the electronegativity, the row, and the charge. Extending from Ru and Re tris(thiolate) complexes to their Os and Tc counterparts can help us to get insightful rationales that would promote further research on alkene addition to metal-stabilized thiyl radicals.

Antioxidant vitamins supplementation reduce endometriosis related pelvic pain in humans: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain. METHODS: A systematic search of PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNK) databases was conducted to identify relevant studies published in English and Chinese up to 16 March 2023. The search terms used were "endometriosis" OR "endometrioma" OR "endometrium" AND "antioxidant" OR "Vitamin C" OR "Vitamin E" OR "Vitamin D" OR "25-OHD" OR "25(OH)D" OR "25-hydroxyvitamin D". Eligible studies were randomized controlled trials (RCTs) that assessed pain scores using the Visual Analogue Scale (VAS). Mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the effect of antioxidant vitamins supplementation on endometriosis. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: A total of 13 RCTs involving 589 patients were included in this meta-analysis. We identified 11 studies that evaluated the effect of antioxidant vitamins supplementation on endometriosis-related pain. The results indicated that the supplementation of antioxidant vitamins can effectively alleviate endometriosis-related pain. Subgroup analysis showed that the supplementation of vitamin E (with or without vitamin C) had a positive effect on improving clinical pelvic pain in patients with chronic pelvic pain. Conversely, supplementation of vitamin D was associated with a reduction in pelvic pain in endometriosis patients, but the difference was not statistically significant compared to the placebo. Additionally, we observed changes in oxidative stress markers following vitamin supplementation. Plasma malondialdehyde (MDA) concentration decreased in patients with endometriosis after antioxidant vitamin supplementation, and the plasma MDA level was inversely correlated with the time and dose of vitamin E and C supplementation. Furthermore, the inflammatory markers in peritoneal fluid, including RANTES, interleukin-6, and monocyte chemoattractant protein-1, significantly decreased after antioxidant therapy. These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation. CONCLUSIONS: The included studies support the potential role of antioxidant vitamins in the management of endometriosis. Supplementation with antioxidant vitamins effectively reduced the severity of dysmenorrhea, improved dyspareunia and pelvic pain, and enhanced quality of life in these patients. Therefore, antioxidant vitamin therapy could be considered as an alternative treatment method, either alone or in combination with other approaches, for endometriosis-related pain. TRIAL REGISTRATION: PROSPERO registration number: CRD42023415198.

A pilot study of cord blood-derived natural killer cells as maintenance therapy after autologous hematopoietic stem cell transplantation.

Natural killer (NK) cell based immunotherapy is an emerging strategy in hematologic malignancies because allogeneic NK cells can provide potent antitumor immunity without inducing graft-versus-host disease. Thus, we expanded cord blood-derived NK (CB-NK) cells ex vivo from random (MHC mismatched and KIR mismatched) donors, and investigate the feasibility and efficacy of repeated infusions CB-NK cells as maintenance therapy after autologous hematopoietic stem cell transplantation (ASCT). Thirty-one patients with acute myeloid leukemia and high-risk lymphoma received ASCT and the adoptive CB-NK cell multiple infusions for maintenance therapy. Patients received a median dose of 5.98 × 107/kg (range, 1.87-17.69 × 107/kg) CB-NK cells and 23 patients completed four infusions, 8 patients received three infusions. Only mild infusion reactions occurred in 15.5% of 116 infusions. Compared to a contemporaneous cohort of 90 patients who did not receive NK cell therapy, the adoptive transfer of CB-NK cells as maintenance treatment showed a tendency of difference in decreasing the relapse rate between CB-NK group and control group (9.7% vs 24.4%). The patients who receiving NK cell infusions had a better PFS and OS than controls (4 year PFS, 84.4 ± 8.3% vs 73.5 ± 5.4%; and 4 year OS, 100% vs 78.1 ± 5.4%) . These findings demonstrate safety and validity of maintenance therapy using CB-NK cells multiple infusions after ASCT, and it is worthy of further clinical trial verification.

Theoretical Understanding of Reactions of Rhenium and Ruthenium Tris(thiolate) Complexes with Unsaturated Hydrocarbons: Noninnocent Nature of the Ligand, Mechanism, and Origin of Differential Reactivity.

In retrospect to the complexity induced by the noninnocent ligands in identifying the transition metal's oxidation state and correlating the ligand's noninnocence with reactivity, the reactions of alkene/alkyne addition to rhenium/ruthenium tris(thiolate) complexes are particularly good cases for shedding light on the chemistry of the dppbt ligand, including its noninnocent nature, ligand-centered mechanism, and origin of differential reactivity. Density functional theory (DFT) combined with the high-level ab initio calculations performed herein demonstrates that, upon alkene/alkyne addition, the orbital symmetry properly regulates the reaction to form ligand-centered cis-interligand dithioethers as the most favorable pathway. The neutral and cationic Re and Ru dithioethers are revealed via DFT calculations to be in a low-spin ground state; on the contrary, high-level ab initio methods confirm that the dicationic Re-dithioethers exhibit obvious multireference character with antiferromagnetic coupling between Re-dyz and S1-py. The metal-stabilized thiyl radicals play a pivotal role in delivering the reactivity of [RuL3]+ and [ReL3]+/2+ toward alkene/alkyne rather than [ReL3], where [RuL3]+ and [ReL3]+/2+ present significant radical characters on ligand S2, yet neutral [ReL3] has little such feature, from which differential reactivity arises. Faster styrene addition to Ru tris(thiolate) in contrast to Re tris(thiolate) has been properly interpreted using DFT calculations with major products assigned. The deeper understanding gained in this work would illuminate further experimental exploration in adding alkene/alkyne to other metal-stabilized thiyl radicals.

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy.

Cyclometalated iridium(III) complexes are of significant importance in the field of antitumor photodynamic therapy (PDT), whether they exist as single molecules or are incorporated into nanomaterials. Nevertheless, a comprehensive examination of the relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors of two-photon excited PDT can be anticipated to be further multiplied, particularly in relation to intricate nonlinear optical properties. At present, a comprehensive body of research on this topic is lacking, and few discernible patterns have been identified. In this study, through systematic structure regulation, the nitro-substituted styryl group and 1-phenylisoquinoline ligand containing YQ2 was found to be the most potent infrared two-photon excitable photosensitizer in a 4 × 3 combination library of cyclometalated Ir(III) complexes. YQ2 could enter cells via an energy-dependent and caveolae-mediated pathway, bind specifically to mitochondria, produce 1O2 in response to 808 nm LPL irradiation, activate caspases, and induce apoptosis. In vitro, YQ2 displayed a remarkable phototherapy index for both malignant melanoma (>885) and non-small-cell lung cancer (>1234) based on these functions and was minimally deleterious to human normal liver and kidney cells. In in vivo antitumor phototherapy, YQ2 inhibited tumor growth by an impressive 85% and could be eliminated from the bodies of mice with a half-life as short as 43 h. This study has the potential to contribute significantly to the development of phototherapeutic drugs that are extremely effective in treating large, profoundly located solid tumors as well as the understanding of the structure-activity relationship of Ir(III)-based PSs in PDT.

A two-dimensional borophene monolayer with ideal Dirac nodal-line fermions.

As a relatively new member of two-dimensional materials, borophene has gained huge interest over the past years, especially in the field of discovering new topological materials, such as Dirac nodal line semimetals. Here, based on first-principles calculations, for the first time, we find a completely flat borophene monolayer (named χ2/9) with ideal Dirac nodal line states around the Fermi level. A tight-binding model using the Slater-Koster approach is proposed to demonstrate that the unique electronic feature of χ2/9 that mainly originated from the first-nearest neighbor interactions of the pz orbitals of boron. According to our symmetry analysis, the Dirac nodal line in χ2/9 is guaranteed by the out-of-plane mirror or C2 rotational symmetry and the negligible pz orbital coupling. The chemical bonding analysis reveals the rare electronic properties of this material, which can be attributed to the multicentered π bonds.

Loss of α7nAChR enhances endothelial-to-mesenchymal transition after myocardial infarction via NF-κB activation.

The myocardial fibrosis in response to myocardial infarction (MI) is closely related to the dysbalance of endothelial-to-mesenchymal transition (EndMT). Although numerous reports indicate that α7 nicotinic acetylcholine receptor (α7nAChR) activates the cholinergic anti-inflammatory pathway (CAP) to regulate the magnitude of inflammatory responses, the role of α7nAChR in myocardial fibrosis, as well as the underlying mechanisms, have not been elucidated. In this study, we evaluated cardiac function, fibrosis, and EndMT signaling using a mouse model of MI and interleukin (IL)-1ß-induced human cardiac microvascular endothelial cells (HCMECs). In vivo, α7nAChR deletion increased cardiac dysfunction, exacerbated the cardiac inflammatory response, and NF-κB activation, and enhanced EndMT, as shown by higher expression levels of fibroblast markers (FSP-1, α-SMA, collagen I, Snail) and decreased levels of the FGFR1, glucocorticoid receptor (GR) and endothelial marker (CD31) compared to wild-type mice. In vitro, the pharmacological activation of α7nAChR with PNU282987 significantly inhibited IL-1ß-induced EndMT, as shown by a reduced transition to the fibroblast-like phenotype and the expression of fibrotic markers. Moreover, the IL-1ß-mediated activation of NF-κB pathway was suppressed by PNU282987. This anti-EndMT effect of α7nAChR was associated with regulation of Snail. Furthermore, Western blot analysis further revealed that the GR antagonist RU38486 could partially counteract the effect of PNU282987 on NF-κB expression. In conclusion, our results show that α7nAChR is involved in cardiac fibrosis by inhibiting EndMT, providing a novel approach to the treatment of MI.

Degradation of tetracycline by peroxymonosulfate activated with Mn0.85Fe2.15O4-CNTs: Key role of singlet oxygen.

Tetracycline (TC) is a kind of electron-rich organic, and singlet oxygen (1O2) oxidative pathway-based advanced oxidation processes (AOPs) have represented outstanding selective degradation to such pollutants. In this paper, an excellent prepared strategy for 1O2 dominated catalyst was adopted. A catalyst composed of non-stoichiometric doping Mn-Fe bimetallic oxide supported on CNTs (0.3-Mn0.85Fe2.15O4-CNTs) was synthesized and optimized by regulating the non-stoichiometric doping ratio of Mn & Fe and the loading amount of CNTs. Through optimization and control experiments, the optimized catalyst represented 94.9% of TC removal efficiency within 60 min in neutral condition under relatively low concentrations of Mn0.85Fe2.15O4-CNTs (0.4 g/L) and PMS (0.8 mM). Through SEM and XRD characterization, Mn0.85Fe2.15O4-CNTs was a hybrid of cubic Mn0.85Fe2.15O4 uniformly dispersing on CNTs. By the characterization of XPS and FT-IR, more CO bonds and low-valent Mn (II) & Fe (II) appeared in Mn0.85Fe2.15O4-CNTs. Reactive oxygen species (ROS) was determined by radical quenching experiments and electron spin resonance (EPR) spectroscopy, and 1O2 was verified to be the dominated ROS. The mechanism for PMS' activation was speculated, and more low-valent Mn (II) and Fe (II) contributed to the production of free-radical (•OH & SO4•-), while the reaction between PMS and the enhanced CO bond on Mn0.85Fe2.15O4-CNTs played a crucial part in the generation of 1O2. In addition, through the comparative degradation of four different organics with distinct charge densities, the excellent selectivity of 1O2-based oxidative pathway to electron-rich pollutants was found. This paper supplied a good strategy to prepare catalyst for PMS activation to form a 1O2-dominated oxidative pathway.