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.

Motor imagery therapy improved upper limb motor function in stroke patients with hemiplegia by increasing functional connectivity of sensorimotor and cognitive networks.

Background: Motor imagery therapy (MIT) showed positive effects on upper limbs motor function. However, the mechanism by which MIT improves upper limb motor function is not fully understood. Therefore, our purpose was to investigate the changes in functional connectivity (FC) within and outside the sensorimotor network (SMN) induced by MIT associated with improvement in upper limb motor function in stroke patients. Methods: A total of 26 hemiplegic stroke patients were randomly divided into MIT (n = 13) and control (n = 13) groups. Fugl-Meyer Assessment Upper Extremity Scale (FMA-UL), Modified Barthel Index (MBI) and resting-state functional magnetic resonance imaging (rs-fMRI) were evaluated in the two groups before treatment and 4 weeks after treatment. The efficacy of MIT on motor function improvement in stroke patients with hemiplegia was evaluated by comparing the FMA-UL and MBI scores before and after treatment in the two groups. Furthermore, the FC within the SMN and between the SMN and the whole brain was measured and compared before and after different treatment methods in stroke patients. The correlation analysis between the improvement of upper limbs motor function and changes in FC within the SMN and between the SMN and the whole brain was examined. Results: The FCs between ipsilesional primary motor cortex (M1.I) and contralateral supplementary motor area (SMA.C), M1.I and ipsilesional SMA (SMA.I), and SMA.C and contralateral dorsolateral premotor cortex (DLPM.C) significantly increased in the control group but decreased in the MIT group; while the FC between SMA.C and contralateral primary somatosensory cortex (S1.C) significantly increased in the control group but showed no significant difference in the MIT group. The FCs between M1.I and the ipsilesional hippocampal gyrus and ipsilesional middle frontal gyrus significantly decreased in the control group but increased in the MIT group; while the FC in the contralateral anterior cingulate cortex significantly increased in the MIT group but there was no significant difference in the control group. The results of the correlation analysis showed that the differences in abnormal intra-FCs within the SMN negatively correlated with the differences in FMA and MBI, and the difference in abnormal inter-FCs of the SMN positively correlated with the differences in FMA and MBI. Conclusions: MIT can improve upper limb motor function and daily activities of stroke patients, and the improvement effect of conventional rehabilitation therapy (CRT) combined with MIT is significantly higher than that of CRT alone. CRT may improve the upper limb motor function of stroke patients with hemiplegia mainly through the functional reorganization between SMN, while MIT may mainly increase the interaction between SMN and other brain networks.

One-pot asymmetric living copolymerization-induced chiral self-assemblies and circularly polarized luminescence.

Controlled synthesis of conjugated block polymers enables the optimization of their self-assembly and may lead to distinct optical properties and functionalities. Herein, we report a direct chain extension of one-handed helical poly(acyl methane) with 1-ethynyl-4-iodo-2,5-bis(octyloxy)benzene, affording well-defined π-conjugated poly(acyl methane)-b-poly(phenylene ethynylene) copolymers. Although the distinct monomers are polymerized via different mechanisms, the one-pot copolymerization follows a living polymerization manner, giving the desired optically active block copolymers with controllable molar mass and low distribution. The block copolymerization induced chiral self-assembly simultaneously due to the one-handed helicity of the poly(acyl methane) block, giving spherical nanoparticles, one-handed helices, and chiral micelles with controlled dimensions regarding the composition of the generated copolymers. Interestingly, the chiral assemblies exhibit clear circularly polarized luminescence with tunable handedness and a high dissymmetric factor.

Baseline high-sensitivity C-reactive protein and glycosylated hemoglobinA1c predict adverse outcomes in patients with chronic coronary syndromes undergoing percutaneous coronary intervention.

Introduction: This study explored the ability of high-sensitivity C-reactive protein (hs-CRP) and glycosylated hemoglobin A1c (HbA1c) to predict adverse cardiac and cerebrovascular outcomes in patients with chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). Methods: In total, 4083 consecutive patients with CCS undergoing PCI were investigated throughout 2013 at a single center. The primary endpoint was all-cause death at the 5-year follow-up. Hs-CRP and HbA1c data were collected on admission. Results: The highest quartile of hs-CRP had a significantly increased the risk of all-cause death, with an adjusted HR of 1.747 (95 % CI 1.066-2.863), while, there was no difference in all-cause death among the groups of HbA1c after adjustment, with an adjusted HR of 1.383 (95 % CI 0.716-2.674). The highest quartiles for hs-CRP and HbA1c in the study population had a significantly increased risk of major adverse cardiac and cerebrovascular events (MACCE), with an adjusted hazard ratios (HR) of 1.263 (95 % confidence intervals [CI] 1.032-1.545) for hs-CRP and an adjusted HR of 1.417 (95 % CI 1.091-1.840) for HbA1c. Remarkably, the incidence of all-cause death and that of MACCE were significantly increased when both hs-CRP and HbA1c were elevated (HR 1.971, 95 % CI 1.079-3.601, P = 0.027 and HR 1.560, 95 % CI 1.191-2.042), P = 0.001, respectively). Addition of hs-CRP and HbA1c to conventional risk factors significantly improved prediction of the risk of all cause death (net reclassification index 0.492, P < 0.001; integrated discrimination improvement 0.007, P = 0.011) and MACCE (net reclassification index 0.160, P < 0.001; integrated discrimination improvement 0.006, P < 0.001). Conclusions: Hs-CRP and HbA1c can serve as independent predictors of MACCE in patients with CCS undergoing PCI. Furthermore, a combination of hs-CRP and HbA1c could predict all cause death and MACCE better than each component individually.

Transcriptomic analysis of ncRNAs and mRNAs interactions during drought stress in switchgrass.

Switchgrass (Panicum virgatum L.) plays a pivotal role as a bioenergy feedstock in the production of cellulosic ethanol and contributes significantly to enhancing ecological grasslands and soil quality. The utilization of non-coding RNAs (ncRNAs) has gained momentum in deciphering the intricate genetic responses to abiotic stress in various plant species. Nevertheless, the current research landscape lacks a comprehensive exploration of the responses of diverse ncRNAs, including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs), to drought stress in switchgrass. In this study, we employed whole transcriptome sequencing to comprehensively characterize the expression profiles of both mRNA and ncRNAs during episodes of drought stress in switchgrass. Our analysis identified a total of 12,511 mRNAs, 59 miRNAs, 38 circRNAs, and 368 lncRNAs that exhibited significant differential expression between normal and drought-treated switchgrass leaves. Notably, the majority of up-regulated mRNAs displayed pronounced enrichment within the starch and sucrose metabolism pathway, as validated through KEGG analysis. Co-expression analysis illuminated that differentially expressed (DE) lncRNAs conceivably regulated 1308 protein-coding genes in trans and 7110 protein-coding genes in cis. Furthermore, both cis- and trans-target mRNAs of DE lncRNAs exhibited enrichment in four common KEGG pathways. The intricate interplay between lncRNAs and circRNAs with miRNAs via miRNA response elements was explored within the competitive endogenous RNA (ceRNA) network framework. As a result, we constructed elaborate regulatory networks, including lncRNA-novel_miRNA480-mRNA, lncRNA-novel_miRNA304-mRNA, lncRNA/circRNA-novel_miRNA122-PvSS4, and lncRNA/circRNA-novel_miRNA14-PvSS4, and subsequently validated the functionality of the target gene, starch synthase 4 (PvSS4). Furthermore, through the overexpression of PvSS4, we ascertained its capacity to enhance drought tolerance in yeast. However, it is noteworthy that PvSS4 did not exhibit any discernible impact under salt stress conditions. These findings, as presented herein, not only contribute substantively to our understanding of ceRNA networks but also offer a basis for further investigations into their potential functions in response to drought stress in switchgrass.

Thermo-responsive chiral micelles as recyclable organocatalyst for asymmetric Rauhut-Currier reaction in water.

Developing eco-friendly chiral organocatalysts with the combined advantages of homogeneous catalysis and heterogeneous processes is greatly desired. In this work, a family of amphiphilic one-handed helical polyisocyanides bearing phosphine pendants is prepared, which self-assembles into well-defined chiral micelles in water and showed thermo-responsiveness with a cloud point of approximately 38.4 °C. The micelles with abundant phosphine moieties at the interior efficiently catalyze asymmetric cross Rauhut-Currier reaction in water. Various water-insoluble substrates are transferred to target products in high yield with excellent enantioselectivity. The yield and enantiomeric excess (ee) of the product generated in water are up to 90% and 96%, respectively. Meanwhile, the yields of the same R-C reaction catalyzed by the polymer itself in organic solvents is <16%, with an ee < 72%. The homogeneous reaction of the chiral micelles in water turns to heterogeneous at temperatures higher than the cloud point, and the catalyst precipitation facilitates product isolation and catalyst recovery. The polymer catalyst is recycled 10 times while maintaining activity and enantioselectivity.

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.

Soft robotics-inspired sensing system for detecting downward movement and pistoning in prosthetic sockets: A proof-of-concept study.

BACKGROUND: Vertical displacement of the residual limb within transtibial prosthetic socket, often known as "pistoning" or downward movement, may lead to skin breakdowns and ulcers. Downward movement is particularly difficult to self-manage for diabetic individuals living with amputation because of diminished sensation in the residual limb from peripheral neuropathy. Therefore, a customizable sensor at the distal end that can alert the users when high-risk downward movement and pistoning occurs is urgently needed. OBJECTIVES: Presented herein for the first time is a lightweight, inexpensive sensing system inspired by soft robotics that can detect the occurrence and severity of downward movement at the distal end. METHODS: The sensing system consists of a multilayered torus-shaped balloon, allowing easy integration with pin-lock socket systems. The design allows sensing of vertical displacement without imparting high reaction forces back onto the distal end. A benchtop compression tester was used to characterize system performance. Systematic and parametric benchtop tests were conducted to examine the sensor's physical characteristics. Long-term (24-h) stability of the sensor was also recorded. RESULTS: Compared with water, air was determined to be a better medium with a higher linear full-scale span (FSS) because of its compressible nature. Repeatable 0.5-mm vertical displacements yielded a linear (>0.99 R2) FSS of 4.5 mm and a sensitivity of 0.8 kPa/mm. The sensing system is highly precise, with as low as 1% FSS total error band and average hysteresis of 2.84% of FSS. Over 24 h, a 4% FSS drift was observed. CONCLUSION: Sensing system characteristics, coupled with low-cost, customizable fabrication, indicates promising performance for daily use to notify and alert transtibial prosthetic users of downward movement and/or pistoning.

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.

2023 China Guidelines for Lipid Management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

Controlled synthesis of cyclic helical polyisocyanides and bottlebrush polymers using a cyclic alkyne-Pd(II) catalyst.

Cyclic polymers have very unique structure and properties, and thus have drawn intense research attention. However, controlled synthesis of cyclic polymers with predictable molar mass and narrow distribution is still a challenging task. In this study, we developed a novel cyclic catalyst that initiates the ring-expansion polymerisation of isocyanides, producing a series of cyclic helical polymers with predictable molecular weight and low dispersity. Interestingly, the ring-expansion polymerization of the isocyanide macromonomers gives well-defined cyclic bottlebrush polymers. The cyclic topology was demonstrated using transmission electron microscopy.

Prolonging dual antiplatelet therapy improves the long-term prognosis in patients with diabetes mellitus undergoing complex percutaneous coronary intervention.

OBJECTIVE: To investigate the optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) requiring complex percutaneous coronary intervention (PCI). METHODS: A total of 2403 patients with DM who underwent complex PCI from January to December 2013 were consecutively enrolled in this observational cohort study and divided according to DAPT duration into a standard group (11-13 months, n = 689) and two prolonged groups (13-24 months, n = 1133; > 24 months, n = 581). RESULTS: Baseline characteristics, angiographic findings, and complexity of PCI were comparable regardless of DAPT duration. The incidence of major adverse cardiac and cerebrovascular event was lower when DAPT was 13-24 months than when it was 11-13 months or > 24 months (4.6% vs. 8.1% vs. 6.0%, P = 0.008), as was the incidence of all-cause death (1.9% vs. 4.6% vs. 2.2%, P = 0.002) and cardiac death (1.0% vs. 3.0% vs. 1.2%, P = 0.002). After adjustment for confounders, DAPT for 13-24 months was associated with a lower risk of major adverse cardiac and cerebrovascular event [hazard ratio (HR) = 0.544, 95% CI: 0.373-0.795] and all-cause death (HR = 0.605, 95% CI: 0.387-0.944). DAPT for > 24 months was associated with a lower risk of all-cause death (HR = 0.681, 95% CI: 0.493-0.942) and cardiac death (HR = 0.620, 95% CI: 0.403-0.952). The risk of major bleeding was not increased by prolonging DAPT to 13-24 months (HR = 1.356, 95% CI: 0.766-2.401) or > 24 months (HR = 0.967, 95% CI: 0.682-1.371). CONCLUSIONS: For patients with DM undergoing complex PCI, prolonging DAPT might improve the long-term prognosis by reducing the risk of adverse ischemic events without increasing the bleeding risk.

Development and validation of a score predicting mortality for older patients with mitral regurgitation.

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m2, NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m2, albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS: The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

2023 Chinese guideline for lipid management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of Chinese guideline for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "Chinese guideline for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with cardiovascular disease (CVD) risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

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.

First-in-human evaluation of a novel ultrathin sirolimus-eluting iron bioresorbable scaffold: 3-year outcomes of the IBS-FIM trial.

BACKGROUND: The first-generation polymeric bioresorbable scaffolds resulted in higher than acceptable 3-year rates of device-related adverse outcomes. AIMS: We aimed to assess the intermediate-term safety and performance of a novel ultrathin-strut sirolimus-eluting iron bioresorbable scaffold (IBS) in non-complex coronary lesions. METHODS: The prospective, single-arm, open-label IBS first-in-human study enrolled 45 patients, each with a single de novo lesion. Enrolled patients were randomly assigned to 2 follow-up cohorts. Angiographic and imaging follow-up with intravascular ultrasound and optical coherence tomography (OCT) were conducted at 6 and 24 months in cohort 1 (n=30) and at 12 and 36 months in cohort 2 (n=15). Clinical follow-up was conducted at 1, 6 and 12 months, and annually thereafter up to 5 years. The coprimary outcomes were target lesion failure (TLF) and angiographic late lumen loss (LLL) at 6 months. RESULTS: A total of 45 patients were enrolled between April 2018 and January 2019. The mean age was 53.2 years, 77.8% were male, and 26.7% had diabetes. The TLF rates were 2.2% at 6 months and 6.7% at 3 years, which in all cases were due to clinically indicated target lesion revascularisation. No deaths, myocardial infarctions or stent thromboses occurred during 3-year follow-up. In-scaffold LLL was 0.33±0.27 mm at 6 months and 0.37±0.57 mm at 3 years. By OCT, the proportion of covered struts was 99.8% at 6 months and 100% after 1 year. The 3-year strut absorption rate was 95.4%. CONCLUSIONS: In this first-in-human experience, an ultrathin IBS was safe and effective for the treatment of de novo non-complex coronary lesions up to 3-year follow-up.

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.

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.

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.

Synthesis and Pharmacological Characterization of a Difluorinated Analogue of Reduced Haloperidol as a Sigma-1 Receptor Ligand.

Reduced haloperidol (1) was previously reported to act as a potent sigma-1 receptor (S1R) ligand with substantially lower affinity to the dopamine D2 receptor (D2R) compared to haloperidol. It was also found to facilitate brain-derived neurotrophic factor (BDNF) secretion from astrocytic glial cell lines in a sigma-1 receptor (S1R)-dependent manner. Although an increase in BDNF secretion may have beneficial effects in some neurological conditions, the therapeutic utility of reduced haloperidol (1) is limited because it can be oxidized back to haloperidol in the body, a potent dopamine D2 receptor antagonist associated with well-documented adverse effects. A difluorinated analogue of reduced haloperidol, (±)-4-(4-chlorophenyl)-1-(3,3-difluoro-4-(4-fluorophenyl)-4-hydroxybutyl)piperidin-4-ol (2), was synthesized in an attempt to minimize the oxidation. Compound (±)-2 was found to exhibit high affinity to S1R and facilitate BDNF release from mouse brain astrocytes. It was also confirmed that compound 2 cannot be oxidized back to the corresponding haloperidol analogue in liver microsomes. Furthermore, compound 2 was distributed to the brain following intraperitoneal administration in mice and reversed the learning deficits in active avoidance tasks. These findings suggest that compound 2 could serve as a promising S1R ligand with therapeutic potential for the treatment of cognitive impairments.