Uncoordinated chemistry enables highly conductive and stable electrolyte/filler interfaces for solid-state lithium-sulfur batteries.

Composite-polymer-electrolytes (CPEs) embedded with advanced filler materials offer great promise for fast and preferential Li+ conduction. The filler surface chemistry determines the interaction with electrolyte molecules and thus critically regulates the Li+ behaviors at the interfaces. Herein, we probe into the role of electrolyte/filler interfaces (EFI) in CPEs and promote Li+ conduction by introducing an unsaturated coordination Prussian blue analog (UCPBA) filler. Combining scanning transmission X-ray microscope stack imaging studies and first-principle calculations, fast Li+ conduction is revealed only achievable at a chemically stable EFI, which can be established by the unsaturated Co-O coordination in UCPBA to circumvent the side reactions. Moreover, the as-exposed Lewis-acid metal centers in UCPBA efficiently attract the Lewis-base anions of Li salts, which facilitates the Li+ disassociation and enhances its transference number (tLi+). Attributed to these superiorities, the obtained CPEs realize high room-temperature ionic conductivity up to 0.36 mS cm-1 and tLi+ of 0.6, enabling an excellent cyclability of lithium metal electrodes over 4,000 h as well as remarkable capacity retention of 97.6% over 180 cycles at 0.5 C for solid-state lithium-sulfur batteries. This work highlights the crucial role of EFI chemistry in developing highly conductive CPEs and high-performance solid-state batteries.

SIKs Regulate HDAC7 Stabilization and Cytokine Recall in Late-Stage T Cell Effector Differentiation.

Understanding the mechanisms underlying the acquisition and maintenance of effector function during T cell differentiation is important to unraveling how these processes can be dysregulated in the context of disease and manipulated for therapeutic intervention. In this study, we report the identification of a previously unappreciated regulator of murine T cell differentiation through the evaluation of a previously unreported activity of the kinase inhibitor, BioE-1197. Specifically, we demonstrate that liver kinase B1 (LKB1)-mediated activation of salt-inducible kinases epigenetically regulates cytokine recall potential in effector CD8+ and Th1 cells. Evaluation of this phenotype revealed that salt-inducible kinase-mediated phosphorylation-dependent stabilization of histone deacetylase 7 (HDAC7) occurred during late-stage effector differentiation. HDAC7 stabilization increased nuclear HDAC7 levels, which correlated with total and cytokine loci-specific reductions in the activating transcription mark histone 3 lysine 27 acetylation (H3K27Ac). Accordingly, HDAC7 stabilization diminished transcriptional induction of cytokine genes upon restimulation. Inhibition of this pathway during differentiation produced effector T cells epigenetically poised for enhanced cytokine recall. This work identifies a previously unrecognized target for enhancing effector T cell functionality.

Helix-Induced Asymmetric Self-Assembly of π-Conjugated Block Copolymers: From Controlled Syntheses to Distinct Properties.

Conspectusπ-Conjugated polymers have gained significant interest because of their potential applications in optoelectronics, bioelectronics, and other domains. The controlled synthesis of π-conjugated block polymers optimizes their performance and enables novel properties and functions. However, precise control of the self-assembled architectures of π-conjugated polymers remains a formidable challenge. Inspired by the precise helical architectures of biomacromolecules, the helical polymers and the supramolecular helical assemblies have gained significant attention. Helical polymers with an excess of one-handed helicity can be optically active with a strong tendency toward self-assembly. Incorporating a helical polymer into a π-conjugated polymer can induce asymmetric helical assemblies, leading to novel chiral materials with unique functionalities.To control the self-assembly of architectures, π-conjugated polymers are usually synthesized into block copolymers by incorporating a polymer with self-assembling characteristics. Although various π-conjugated block copolymers have been produced, precise and asymmetric self-assembly is still challenging and has rarely been addressed. Incorporating helical polymers into the π-conjugated polymers can induce a precise and asymmetric self-assembly, which transfers the chirality of the helical polymer block to the π-conjugated polymer, resulting in chiral supramolecular architectures with unique chiroptical properties and functionalities. However, synthesizing hybrid block copolymers containing two distinct polymer blocks is complicated. Some general strategies such as connecting the chain ends of two preformed homopolymers and extending the chain of a prefabricated π-conjugated polymer with a second monomer are time-consuming and require complex synthetic protocols. Therefore, developing novel strategies for the facile synthesis of π-conjugated block copolymers with a predictable molar mass, low dispersity, and tunable composition is of practical importance.Recently, we investigated a controlled synthesis of helical polyisocyanides, helical polyallenes, and helical polycarbenes by developing advanced Pd(II) and Ni(II) catalysts. These helical polymers were successfully incorporated into π-conjugated polymers, including polythiophene, polyfluorene, and poly(phenyleneethynylene), via a one-pot sequential living block polymerization of the two distinct monomers using Pd(II)- or Ni(II)-complexes as catalysts. As a result, a variety of well-defined π-conjugated block copolymers containing helical polymeric blocks were readily synthesized. Although the copolymerized monomers possess different structures and polymerization mechanisms, the one-pot block copolymerization followed a living polymerization mechanism and provided the desired π-conjugated block copolymers in high yields with controlled molar mass, narrow size distribution, and tunable composition.Remarkably, the helical polymeric block induces the π-conjugated block copolymer asymmetric self-assembly into a supramolecular, one-handed helical architecture resulting in distinct optical properties. More interestingly, by utilizing the crystallization of conjugated blocks and one-handed helical blocks, the crystallization-driven and helix-induced precise asymmetric living self-assembly yielded a family of uniform and single-handed helical architectures with controlled dimensions, narrow distribution, and well-defined helicity. The transfer of helical chirality to the supramolecular architectures rendered the achiral π-conjugated blocks with unique chiroptical properties such as the emission of white light over a broad optical spectrum and the circularly polarized luminescence.

Helical Polyallenes: From Controlled Synthesis to Distinct Properties.

Polyallenes with appropriate pendants can form stable helices and exhibit significant optical activity. These helical polyallenes contain reactive double bonds that allow for further functionalization, making them a class of chiral functional materials with broad application prospects. This review article delves into the intricacies of synthesizing well-defined helical polyallenes through controlled synthetic methodologies, including helix-sense selective living polymerization, regioselective and asymmetric living polymerization, and one-pot block copolymerization of allenes with aryl monomers. The systemically outlined characteristics of the resulting helical polyallenes and related copolymers are summarized include their unique chiroptical properties, stimuli-responsiveness, helix-induced chiral self-assembly, and circularly polarized luminescence (CPL). Additionally, current challenges and future perspectives in the research of controlled synthesis, functionalities, and applications of helical polyallenes are discussed in detail.

Hybrid Soft-Rigid Active Prosthetics Laboratory Exercise for Hands-On Biomechanical and Biomedical Engineering Education.

This paper introduces a hands-on laboratory exercise focused on assembling and testing a hybrid soft-rigid active finger prosthetic for biomechanical and biomedical engineering (BME) education. This hands-on laboratory activity focuses on the design of a myoelectric finger prosthesis, integrating mechanical, electrical, sensor (i.e., inertial measurement units (IMUs), electromyography (EMG)), pneumatics, and embedded software concepts. We expose students to a hybrid soft-rigid robotic system, offering a flexible, modifiable lab activity that can be tailored to instructors' needs and curriculum requirements. All necessary files are made available in an open-access format for implementation. Off-the-shelf components are all purchasable through global vendors (e.g., DigiKey Electronics, McMaster-Carr, Amazon), costing approximately USD 100 per kit, largely with reusable elements. We piloted this lab with 40 undergraduate engineering students in a neural and rehabilitation engineering upper year elective course, receiving excellent positive feedback. Rooted in real-world applications, the lab is an engaging pedagogical platform, as students are eager to learn about systems with tangible impacts. Extensions to the lab, such as follow-up clinical (e.g., prosthetist) and/or technical (e.g., user-device interface design) discussion, are a natural means to deepen and promote interdisciplinary hands-on learning experiences. In conclusion, the lab session provides an engaging journey through the lifecycle of the prosthetic finger research and design process, spanning conceptualization and creation to the final assembly and testing phases.

Supramolecular Polymer Frameworks with Controlled and Uniform Pore Apertures.

Porous frameworks with controlled pore structure and tunable aperture are greatly demanded. However, precise synthesis of this kind of materials is a formidable challenge. Herein, we report the fabrication of two-dimensional (2D) supramolecular polymer frameworks using a precisely synthesized rod-like helical polyisocyanide as link. Four three-arm star-shaped polyisocyanides with the degree of the polymerization of 10, 20, 30 and 40, and having 2-ureido-4[1H]-pyrimidinone (UPy) terminals were synthesized. 2D-Crystalline polymer frameworks with apertures of 5.3, 10.1, 13.9, and 19.1 nm were respectively obtained through intermolecular hydrogen bonding interaction between the terminal Upy units. The pore aperture is dependent on the length of polyisocyanide backbone. Thus, well-defined supramolecular polymer frameworks with controlled and uniform hexagonal pores were obtained, as proved by small-angle X-ray scattering (synchrotron radiation facility), atomic force microscopy, and Brunauer-Emmett-Teller analyses. The frameworks with uniform large pore aperture were used to purify nanomaterials and immobilize biomacromolecules. For instance, the membranes of the polymer frameworks could size-fractionation of silver nanoparticles into uniform nanoparticles with very low dispersity. The frameworks with large aperture facilitated the inclusion of myoglobin and enhanced the stability and catalytic activity.

Cyclic Polymers: Controlled Synthesis, Properties and Perspectives.

Recently, cyclic polymers have attracted increasing interest due to their unique topologies, properties, and functions compared to the linear analogues. This mini-review focuses on the recent advances in the synthesis and applications of cyclic polymers. First, the main synthetic methods for cyclic polymers, namely ring closure and ring expansion methods, are presented and discussed, followed by a review on the exploration of the properties and applications of synthetic cyclic polymers. Finally, a critical assessment of the preliminary studies exploring the efficient synthesis and potential applications of cyclic polymers are presented, and the remaining challenges in the field as well as ideas for solving these challenges will be discussed.

Turfgrass-dependent mycotrophic change enhances soil deterioration in dry, cold and high-alkali environments.

AIMS: Soil quality is undergoing severe degradation under anthropogenic effects. Different methods of land management have been implemented for soil reclamation, such as turfing. Although widely accepted to improve soil quality, turfing in specific environments may also culminate in soil deterioration. We aim to know how turfing impacts soils by changing mycobiomes. METHODS AND RESULTS: The soil physicochemical properties and ITS metabarcoding were used to investigate mycobiome diversity and eco-function differences between the eudicot Dianthus plumarius and the monocot Poa pratensis in dry, cold, and high-alkali soil. The effects of plantation and the rhizosphere (e.g. root exudates) were tested. We showed that the change in soil mycobiomes in different planted bulk soils and rhizospheres could mainly be attributed to species turnover, with minor nestedness. Unexpectedly, the soil deteriorates more following turfing. The increasing saprotrophs in planted bulk soil were more marked in the monocot than in the eudicot, even the rhizosphere effect alleviated saprotrophic risks in the rhizosphere. CONCLUSIONS: Turfing deteriorates the health of high-alkali soil by reducing nitrification, and upshift the soil saprotrophs in a dry and cold environment.

Genome-wide characterization of LBD transcription factors in switchgrass (Panicum virgatum L.) and the involvement of PvLBD12 in salt tolerance.

KEY MESSAGE: PvLBD12 enhanced the salt tolerance by increasing proline accumulation, improving K+ accumulation, and decreasing reactive oxygen species level in switchgrass. Abiotic stresses are the serious factors which limit plant development and productivity and restrict the agricultural economy. It is important, therefore, to understand the mechanism of abiotic tolerance in plants. Lateral organ boundaries domain (LBD) proteins as plant-specific transcription factors play important function in plant lateral organ development, plant regeneration, and abiotic stress. In our study, we identify 69 LBD members from switchgrass genome-wide sequences and classify them based on their homology with LBD proteins in Arabidopsis. RT-qPCR showed that PvLBD genes had different expression patterns under abiotic stress conditions, indicating that they play important roles in various stress. PvLBD12 was selected as a candidate gene for further functional analysis because it had the highest expression level under salt stress. Overexpression of PvLBD12 enhanced salt tolerance by altering a wide range of physiological responses (like increased proline accumulation, reduced malondialdehyde production, improved K+ accumulation, and reduced Na+ absorption) in switchgrass. Some stress response genes such as proline biosynthesis gene PvP5CS1, vacuolar Na+(K+)/H+ antiporter gene PvNHX1, two key ROS-scavenging enzyme genes PvCAT and PvSOD were all upregulated in PvLBD12 overexpression lines. Taken together, PvLBD12 plays a pivotal role in response to salt stress by increasing proline accumulation, improving K+ accumulation, reducing Na+ absorption, and decreasing reactive oxygen species level. It will be better to understand the potential biological functions of LBD genes in other plants.

Visible Helicity Induction and Memory in Polyallene toward Circularly Polarized Luminescence, Helicity Discrimination, and Enantiomer Separation.

Inspired by biological helices (e.g., DNA), artificial helical polymers have attracted intense attention. However, precise synthesis of one-handed helices from achiral materials remains a formidable challenge. Herein, a series of achiral poly(biphenyl allene)s with controlled molar mass and low dispersity were prepared and induced into one-handed helices using chiral amines and alcohols. The induced one-handed helix was simultaneously memorized, even after the chiral inducer was removed. The switchable induction processes were visible to naked eye; the achiral polymers exhibited blue emission (irradiated at 365 nm), whereas the induced one-handed helices exhibited cyan emission with clear circularly polarized luminescence. The induced helices formed stable gels in various solvents with helicity discrimination ability: the same-handed helix gels were self-healing, whereas the gels of opposite-handed helicity were self-sorted. Moreover, the induced helices could separate enantiomers via enantioselective crystallization with high efficiency and switchable enantioselectivity.

Precise Synthesis of Optically Active and Thermo-degradable Poly(trifluoromethyl methylene) with Circularly Polarized Luminescence.

Developing high performance and environment-friendly fluoropolymers is greatly desired. In this work, we found that 2-diazo-1,1,1-trifluoroethane can be polymerized by air-stable alkyne-palladium(II) catalysts following a living polymerization mechanism, affording a fluoropolymer, poly(trifluoromethyl methylene) in high yield with controlled molar mass and low dispersity. This polymer bears trifluoromethyl on every main chain atom and thus has good resistance to chemical corrosion, high hydrophobicity, and excellent dielectric constant with low dielectric loss. Due to the steric hindrance between the trifluoromethyl pendants, the synthetic poly(trifluoromethyl methylene) can twist into a stable helix. The one-handed preferred helices synthesized using chiral PdII -catalysts exhibit high optical activity and circularly polarized luminescence. Remarkably, such polymer can be completely degraded to (E)-1,1,1,4,4,4-hexafluorobut-2-ene at high temperatures (>280 °C). Additionally, taking advantage of the living chain end, the polymer can be further modified.

Alloimperatorin activates apoptosis, ferroptosis, and oxeiptosis to inhibit the growth and invasion of breast cancer cells in vitro.

Breast cancer is the most common malignant tumour in women. Our research on alloimperatorin from Angelica dahurica showed that alloimperatorin inhibited breast cancer cell viability in a concentration- and time-dependent manner; it also showed that apoptosis and ferroptosis inhibitors significantly weakened the antisurvival effect of alloimperatorin. Alloimperatorin clearly induced breast cancer cell apoptosis and increased the activities of caspase-3, caspase-8, caspase-9, and poly (ADP-ribose) polymerase; it also caused significant mitochondrial shrinkage, promoted the accumulation of Fe2+, reactive oxygen species, and malondialdehyde, and significantly reduced mRNA and protein expression levels of SLC7A11 and GPX4, indicating that alloimperatorin induces ferroptosis. In addition, alloimperatorin significantly promoted Kelch-like ECH-associated protein 1 (Keap1) expression; although it did not affect the expression of PGAM5 (mitochondrial serine/threonine protein phosphatase) and apoptosis-inducing factor mitochondria associated 1 (AIFM1), it significantly reduced the phosphorylation level of AIFM1. After downregulating the expression of Keap1, PGAM5, or AIFM1, the inhibitory effect of alloimperatorin on cell viability was significantly weakened, indicating that alloimperatorin regulates the Keap1/PGAM5/AIFM1 pathway to promote oxeiptosis. Alloimperatorin significantly inhibited the invasion of breast cancer cells, while Keap1 siRNA or GPX4 overexpression vectors significantly enhanced cell invasion and effectively reversed the anti-invasive effect of alloimperatorin. Therefore, alloimperatorin induces breast cancer cell apoptosis, ferroptosis, and oxeiptosis, thereby inhibiting cell growth and invasion.

Physicochemical and Biotic Changes and the Phylogenetic Evenness of Microbial Community in Soil Subjected to Phytoreclamation.

Phytoreclamation is the intervention of plants to improve degraded soil quality, changing soil biotic and abiotic properties. Many studies have focused on microbial composition and bioactivity, but few explored the changes in phylogenetic assemblages of soil microbiota after phytoreclamation. This study compared microbiomes of bare land to those of planted soils and investigated how the rhizosphere environment affects microbial assemblages from monocot Poa pratensis and eudicot Dianthus plumarius plantings using 16S rRNA metabarcoding. The results showed that the biotic susceptibility of soil to the rhizosphere environment was higher than that of the abiotic. A noticeable change was in some soil physicochemical properties like Na, P, Zn, Cu, C, and sand-to-silt proportion before and after phytoreclamation, but not between the rhizosphere and bulk soil of plantings. Contrastingly, microbial composition and diversity were significantly affected by both turfing and rhizosphere effects and were more susceptible to differences in turfing or not than in planting species. In the turfgrass, the microbiome differences between plants were greater in the rhizosphere than in the surrounding bulk soil, indicating the proximal influence of root exudates. We also found that the main abiotic factors that influenced microbial composition were Na, Zn, NOx, N, and S; as for the phylogenetic assemblages, were by K levels and the increase of silt. Turfgrass decomposes soil aggregates and changes the physicochemical properties, thereby evens the phylogenetic clustering of the soil microbial community. We demonstrated that the deterministic process affects the microbial assemblage and acts as a selective agent of the soil microbiota in fundamental and realized niches. Phytoreclamation may lead to abiotic soil changes that reallocate resources to microbes. This could affect the phylogeny of the microbial assemblages and increase microbial richness.

A Versatile Method for the End-Functionalization of Polycarbenes.

End-functionalization is an effective strategy for constructing functional materials. A method for chain-end functionalization of helical polycarbenes is herein developed that relied on Sonogashira coupling reaction. In this work, a family of helical polycarbenes with controlled molecular mass (Mn ) and low polydispersity (Mw /Mn ) is readily prepared using Pd(II) and the Wei-Phos ligand as initiator. The Pd(II) complex is confirmed to remain at the chain end of polycarbene. Subsequently, a series of terminal alkyne derivatives with interesting functional groups, including the F atom, aldehyde, or anthracene groups, are synthesized. They could be installed at the chain end of polycarbene through Sonogashira coupling reaction catalyzed by the Pd(II) complex at the chain end. Moreover, a couple of hybrid block copolymers are easily obtained by installing terminal alkynes modified by another type of polymer. The structures of the isolated polymers are confirmed by 1 H nuclear magnetic resonance (1 H NMR), 19 F nuclear magnetic resonance (19 F NMR), 31 P nuclear magnetic resonance (31 P NMR), and Fourier transform infrared spectroscopy (FT-IR), respectively. The self-assembly properties of the hybrid block copolymers are also investigated by atomic force spectroscopy analysis. By the hereby developed method, various functional groups can be introduced at the chain end of helical polycarbenes for constructing functional polymer materials, moreover, the transition metal residues at the end of polymer chains can be easily removed.

Model studies towards prodrugs of the glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) containing a diazo precursor.

Two distinct diazo precursors, imidazotetrazine and nitrous amide, were explored as promoieties in designing prodrugs of 6-diazo-5-oxo-l-norleucine (DON), a glutamine antagonist. As a model for an imidazotetrazine-based prodrug, we synthesized (S)-2-acetamido-6-(8-carbamoyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)-5-oxohexanoic acid (4) containing the entire scaffold of temozolomide, a precursor of the DNA-methylating agent clinically approved for the treatment of glioblastoma multiforme. For a nitrous amide-based prodrug, we synthesized 2-acetamido-6-(((benzyloxy)carbonyl)(nitroso)amino)-5-oxohexanoic acid (5) containing a N-nitrosocarbamate group, which can be converted to a diazo moiety via a mechanism similar to that of streptozotocin, a clinically approved diazomethane-releasing drug containing an N-nitrosourea group. Preliminary characterization confirmed formation of N-acetyl DON (6), also known as duazomycin A, from compound 4 in a pH-dependent manner while compound 5 did not exhibit sufficient stability to allow further characterization. Taken together, our model studies suggest that further improvements are needed to translate this prodrug approach into glutamine antagonist-based therapy.

Benefit-risk profile of extended dual antiplatelet therapy beyond 1 year in patients with high risk of ischemic or bleeding events after PCI.

The benefits and harms of dual antiplatelet therapy (DAPT) continuation with aspirin and clopidogrel beyond 1 year after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation for high ischemic or bleeding risk patients remain unclear. All consecutive patients undergoing PCI were prospectively included in the Fuwai PCI Registry from January 2013 to December 2013. We evaluated 7521 patients who were at high risk for thrombotic or hemorrhagic complications and were events free at 1 year after the index procedure. "TWILIGHT-like" patients with high risk of bleeding or ischemic events were defined by clinical and angiographic criteria. The primary ischemic outcome was major adverse cardiac and cerebrovascular events [MACCE] (a composite of all-cause death, myocardial infarction, or stroke). Median follow-up duration was 2.4 years. The risk of MACCE was significantly lower in DAPT>1-year group (n = 5252) than DAPT≤1-year group (n = 2269) (1.5% vs. 3.8%; hazard ratio [HR]: 0.37; 95% confidence interval [CI]: 0.27-0.50; P < .001). This difference was largely driven by a lower risk of all-cause death. In contrast, the risk of Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding was statistically similar between the two groups (1.0% vs. 1.1%; HR: 0.80; 95% CI: 0.50-1.28; P = .346). Results were consistent after multivariable regression and propensity-score matching. Prolonged DAPT beyond 1 year after DES implantation resulted in a significantly lower rate of atherothrombotic events, including a mortality benefit, with no higher risk of clinically relevant bleeding in "TWILIGHT-like" patients who were at high-risk for ischemic or bleeding events.

Association of lipoprotein(a) with platelet aggregation and thrombogenicity in patients undergoing percutaneous coronary intervention.

This study aimed to evaluate the association of lipoprotein(a) levels with platelet aggregation and thrombogenicity in patients undergoing percutaneous coronary intervention (PCI), and to investigate the ischemic outcome on this population. Lipoprotein(a) and modified thrombelastography were measured in 6601 consecutive patients underwent PCI on dual antiplatelet therapy. Cox proportional regression analysis was applied to illustrate the ischemic events in a 2-year follow up. The mean levels of lipoprotein(a) were 29.0 mg/dl. Patients with higher lipoprotein(a) levels had significantly accelerated fibrin generation (lower K time and bigger α angle) and greater clot strength (higher maximum amplitude (MA)) than patients with lower lipoprotein(a) levels (P < .001). Moreover, the higher lipoprotein(a) group also exhibited significantly higher adenosine diphosphate (ADP) induced platelet aggregation (MAADP) by thrombelastography platelet mapping assay than lower lipoprotein(a) group. Cox regression analyzes revealed that patients with higher lipoprotein(a) levels had a 16% higher risk of major adverse cardiovascular and cerebrovascular events (HR 1.159, 95%CI: 1.005-1.337, P = .042) compared with patients with lower lipoprotein(a) levels. This association persisted after adjustment for a broad spectrum of risk factors (HR 1.174, 95%CI: 1.017-1.355, P = .028). High plasma lipoprotein(a) levels were associated with increased platelet aggregation and ischemic events in patients underwent PCI. Lipoprotein(a) might indicate the need for prolonged antiplatelet therapy.

Mesenchymal stem cells derived-exosomes as a new therapeutic strategy for acute soft tissue injury.

The study aimed to investigate the role of exosomes derived from rat bone marrow mesenchymal stem cells (rBMSCs) in acute soft tissue injury and its related mechanisms. Exosomes were isolated from rBMSCs and characterized by Nanosight NS300 particle size analyser (NTA), transmission electron microscopy (TEM), and western blot. Twenty four rats were randomly divided into four groups (n = 6): control group, strike group, rBMSCs group, and rBMSCs-exo group. Haematoxylin-eosin (HE) staining was used to observe the morphology. Real-time quantification PCR (RT-qPCR) and western blot were used to analyse the expression of IL-1A, IL-12A, COL11A1, COL4A4, and Wnt4. NTA, TEM and western blot results showed that exosomes isolated from rBMSCs were cup-shaped morphology with a size of about 100 nm. HE staining showed that there was severe soft tissue inflammation in strike group, and the symptoms were alleviated after rBMSCs and rBMSCs-exo treatment. RT-qPCR and western blot indicated that in the strike group, the expression levels of IL-1A and IL-12A were significantly increased, and their expressions were decreased markedly by exosomes treatment. In addition, after treatment, the expression levels of COL11A1 and Wnt4 were up-regulated, while the expression of COL4A4 was down-regulated. Exosomes isolated from rBMSCs could improve acute soft tissue injury, and may be used as a new therapeutic strategy acute soft tissue injury. SIGNIFICANCE OF THE STUDY: Acute soft tissue injury is a common clinical exercise injury, which has a significant impact on people's health and work ability. Exosomes have been attracting increasing attention as a media of cell-to-cell communication. This study showed that exosomes isolated from rBMSCs could improve acute soft tissue injury by inhibiting inflammatory response, regulating the levels of COL11A1 and COL4A4, and up-regulating the expression of Wnt4. These will provide a new therapy strategy of acute soft tissue injury, and improve our understanding of the occurrence and development in acute soft tissue injury.

Percutaneous Coronary Intervention Complexity and Risk of Adverse Events in relation to High Bleeding Risk among Patients Receiving Drug-Eluting Stents: Insights from a Large Single-Center Cohort Study.

Background/Aim: The relation between complex percutaneous coronary intervention (PCI), high bleeding risk (HBR), and adverse events after coronary artery implantation of drug-eluting stents has been incompletely characterized. This study sought to investigate the ischemic and bleeding events after complex PCI including stratification according to HBR estimated by PARIS bleeding risk score. Methods: Between January 2013 and December 2013, 10,167 consecutive patients undergoing PCI were prospectively enrolled in Fuwai PCI Registry. Complex PCI was defined when having at least one of the following characteristics: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, treatment of chronic total occlusion, unprotected left main PCI, in-stent restenosis target lesion, and severely calcified lesion. The primary ischemic endpoint was major adverse cardiovascular events (MACE) (composite of cardiac death, myocardial infarction, definite/probable stent thrombosis, and target lesion revascularization), and primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Results: The median duration of follow-up was 29 months. In adjusted Cox regression analysis, patients having complex PCI procedures experienced higher risks of MACE (hazard ratio (HR): 1.63, 95% confidence interval (CI): 1.38-1.92; P < 0.001), compared with noncomplex PCI. In contrast, the risk of clinically relevant bleeding was statistically similar between the 2 groups (HR: 0.86 [0.66-1.11]; P = 0.238). There was no statistical interaction between HBR (PARIS bleeding score ≥8 or <8) and complex PCI in regard to MACE (adjusted P interaction = 0.388) and clinically relevant bleeding (adjusted P interaction = 0.279). Conclusions: Patients who had undergone complex PCI resulted in substantially more ischemic events, without an increase in clinically relevant bleeding risk, and these associations did not seem to be modified by HBR status. More intensified antiplatelet therapy may be beneficial for patients with complex percutaneous coronary revascularization procedures.

Two-Year Outcomes after Left Main Coronary Artery Percutaneous Coronary Intervention in Patients Presenting with Acute Coronary Syndrome.

OBJECTIVES: We aim to evaluate long-term outcomes after left main coronary artery (LMCA) percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS). BACKGROUND: PCI of the LMCA has been an acceptable revascularization strategy in stable coronary artery disease. However, limited studies on long-term clinical outcomes of LMCA PCI in ACS patients are available. METHODS: A total of 6429 consecutive patients with ACS undergoing PCI in Fuwai Hospital in 2013 were enrolled. Patients are divided into LMCA group and Non-LMCA group according to whether the target lesion was located in LMCA. Prognosis impact on 2-year major adverse cardiovascular and cerebrovascular events (MACCE) is analyzed. RESULTS: 155 (2.4%) patients had target lesion in LMCA, while 6274 (97.6%) patients belong to the non-LMCA group. Compared with non-LMCA patients, LMCA patients have generally more comorbidities and worse baseline conditions. Two-year follow-up reveals that LMCA patients have significantly higher rate of cardiac death (2.6% vs. 0.7%, p = 0.034), myocardial infarction (7.1% vs. 1.8%, p < 0.001), in-stent thrombosis (4.5% vs. 0.8%, p < 0.001), and stroke (7.1% vs. 6.4%, p = 0.025). After adjusting for confounding factors, LMCA remains independently associated with higher 2-year myocardial infarction rate (HR = 2.585, 95% CI = 1.243-5.347, p = 0.011). CONCLUSION: LMCA-targeted PCI is an independent risk factor for 2-year myocardial infarction in ACS patients.