Metal cations and anions are essential for versatile physiological processes. Dysregulation of specific ion levels in living organisms is known to have an adverse effect on normal biological events. ...Owing to the pathophysiological significance of ions, sensitive and selective methods to detect these species in biological systems are in high demand. Because they can be used in methods for precise and quantitative analysis of ions, organic dye-based ratiometric fluorescent probes have been extensively explored in recent years. In this review, recent advances (2015-2019) made in the development and biological applications of synthetic ratiometric fluorescent probes are described. Particular emphasis is given to organic dye-based ratiometric fluorescent probes that are designed to detect biologically important and relevant ions in cells and living organisms. Also, the fundamental principles associated with the design of ratiometric fluorescent probes and perspectives about how to expand their biological applications are discussed.
Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are suggested to be responsible for drug resistance and cancer relapse due in part to their ability to self-renew themselves and ...differentiate into heterogeneous lineages of cancer cells. Thus, it is important to understand the characteristics and mechanisms by which CSCs display resistance to therapeutic agents. In this review, we highlight the key features and mechanisms that regulate CSC function in drug resistance as well as recent breakthroughs of therapeutic approaches for targeting CSCs. This promises new insights of CSCs in drug resistance and provides better therapeutic rationales to accompany novel anticancer therapeutics.
Optimal antiplatelet monotherapy during the chronic maintenance period in patients who undergo coronary stenting is unknown. We aimed to compare head to head the efficacy and safety of aspirin and ...clopidogrel monotherapy in this population.
We did an investigator-initiated, prospective, randomised, open-label, multicentre trial at 37 study sites in South Korea. We enrolled patients aged at least 20 years who maintained dual antiplatelet therapy without clinical events for 6–18 months after percutaneous coronary intervention with drug-eluting stents (DES). We excluded patients with any ischaemic and major bleeding complications. Patients were randomly assigned (1:1) to receive a monotherapy agent of clopidogrel 75 mg once daily or aspirin 100 mg once daily for 24 months. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater, in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02044250.
Between March 26, 2014, and May 29, 2018, we enrolled 5530 patients. 5438 (98·3%) patients were randomly assigned to either the clopidogrel group (2710 49·8%) or to the aspirin group (2728 50·2%). Ascertainment of the primary endpoint was completed in 5338 (98·2%) patients. During 24-month follow-up, the primary outcome occurred in 152 (5·7%) patients in the clopidogrel group and 207 (7·7%) in the aspirin group (hazard ratio 0·73 95% CI 0·59–0·90; p=0·0035).
Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention with DES significantly reduced the risk of the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and BARC bleeding type 3 or greater. In patients requiring indefinite antiplatelet monotherapy after percutaneous coronary intervention, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future adverse clinical events.
ChongKunDang, SamJin, HanMi, DaeWoong, and the South Korea Ministry of Health and Welfare.
Semiconductors are the basis of many vital technologies such as electronics, computing, communications, optoelectronics, and sensing. Modern semiconductor technology can trace its origins to the ...invention of the point contact transistor in 1947. This demonstration paved the way for the development of discrete and integrated semiconductor devices and circuits that has helped to build a modern society where semiconductors are ubiquitous components of everyday life. A key property that determines the semiconductor electrical and optical properties is the bandgap. Beyond graphene, recently discovered two-dimensional (2D) materials possess semiconducting bandgaps ranging from the terahertz and mid-infrared in bilayer graphene and black phosphorus, visible in transition metal dichalcogenides, to the ultraviolet in hexagonal boron nitride. In particular, these 2D materials were demonstrated to exhibit highly tunable bandgaps, achieved via the control of layers number, heterostructuring, strain engineering, chemical doping, alloying, intercalation, substrate engineering, as well as an external electric field. We provide a review of the basic physical principles of these various techniques on the engineering of quasi-particle and optical bandgaps, their bandgap tunability, potentials and limitations in practical realization in future 2D device technologies.
Obesity and metabolic syndrome (MetS) are associated with high risk of cardiac dysfunction and heart failure. We assessed the effect of obesity and metabolic health status on left ventricular (LV) ...structure and function in subjects without overt heart disease.
In 789 subjects (58.8±13.0 years, 50.7% males) without overt heart disease, LV morphology and function were compared among 6 groups stratified by body mass index (BMI) (normal weight, overweight and obese) and metabolic health status (meeting ≤1 criterion of MetS excluding waist circumference defined as metabolically healthy; otherwise, metabolically unhealthy).
LV ejection fraction (LVEF) was not different among the 6 groups (P>0.05). However, high BMI and poor metabolic health were associated with poorer global longitudinal strain (GLS), higher LV mass index (LVMI) and higher E/e' (P<0.001). Poor metabolic health status was associated with greater adverse changes in LV structure and function than obesity, and among MetS components, high systolic blood pressure (SBP) showed the greatest impact. Higher SBP, BMI and triglycerides were independently associated with worse GLS, and higher SBP was also associated with worse LVMI and E/e´. GLS, LVMI and E/e´ worsened in proportion to the number of MetS criteria or continuous MetS scores. Adverse myocardial changes associated with obesity were significant in the metabolically healthy group, but not in the metabolically unhealthy group.
Obesity and poor metabolic health status were associated with subclinical decrement in LV systolic and diastolic function, and higher LV mass, but not with LVEF, in subjects without overt heart disease.
Abstract
Polaritons in two-dimensional materials provide extreme light confinement that is difficult to achieve with metal plasmonics. However, such tight confinement inevitably increases optical ...losses through various damping channels. Here we demonstrate that hyperbolic phonon polaritons in hexagonal boron nitride can overcome this fundamental trade-off. Among two observed polariton modes, featuring a symmetric and antisymmetric charge distribution, the latter exhibits lower optical losses and tighter polariton confinement. Far-field excitation and detection of this high-momenta mode become possible with our resonator design that can boost the coupling efficiency via virtual polariton modes with image charges that we dub ‘image polaritons’. Using these image polaritons, we experimentally observe a record-high effective index of up to 132 and quality factors as high as 501. Further, our phenomenological theory suggests an important role of hyperbolic surface scattering in the damping process of hyperbolic phonon polaritons.
Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, binds Toll-like receptor 4 (TLR4)-MD2 complex and activates innate immune responses. LPS transfer to ...TLR4-MD2 is catalyzed by both LPS binding protein (LBP) and CD14. To define the sequential molecular interactions underlying this transfer, we reconstituted in vitro the entire LPS transfer process from LPS micelles to TLR4-MD2. Using electron microscopy and single-molecule approaches, we characterized the dynamic intermediate complexes for LPS transfer: LBP-LPS micelles, CD14-LBP-LPS micelle, and CD14-LPS-TLR4-MD2 complex. A single LBP molecule bound longitudinally to LPS micelles catalyzed multi-rounds of LPS transfer to CD14s that rapidly dissociated from LPB-LPS complex upon LPS transfer via electrostatic interactions. Subsequently, the single LPS molecule bound to CD14 was transferred to TLR4-MD2 in a TLR4-dependent manner. The definition of the structural determinants of the LPS transfer cascade to TLR4 may enable the development of targeted therapeutics for intervention in LPS-induced sepsis.
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•Observation of dynamic intermediated formed during LPS transfer by TEM•Reconstitution of the entire LPS transfer cascade to TLR4-MD2 on TIRF microscopy•Identification of key charged residues in LBP and CD14 for dynamic LPS transfer•CD14-LPS complex interact with TLR4 LRR13-LRR15 domain for LPS transfer to MD2
Lipopolysaccharide (LPS) of Gram-negative bacteria activates host innate immune responses. Ryu et al. investigates dynamic intermediates in the LBP-CD14-mediated LPS transfer to TLR4-MD2 down to the single-molecule resolution with negative-stain TEM and TIRF analysis, thus identifying the key molecular determinants in LBP, CD14, and TLR4 for efficient LPS transfer.
Various biochars (BCs) have been developed to remove heavy metals contained in road runoff; however, there is insufficient information regarding the competitive adsorption efficiency of modified BC ...with regard to heavy metals due to a lack of comparative evaluation based on BC properties and modification methods. In this study, three different types of BC (RBC: rice husk, WBC: wood chip, MBC: mixture) were modified following five different methods: acidic, alkaline, oxidic, and manganese oxide (MnOx) and iron oxide (FeOx) impregnation. The changes in the physicochemical and morphological properties of the modified BC were investigated, and the adsorption characteristics of three heavy metals (Cd, Pb, and Zn) under single and mixed conditions were compared and evaluated. The improvements in the BC properties varied for different BC types and modification methods; in particular, alkaline and manganese modification caused substantial the changes in the surface area and functional groups (such as aromatic ring, –OH, and Mn–O groups). The BC prepared by manganese oxide impregnation absorbed a high amount of heavy metals (>9.15 mg/g) even under mixed conditions through cation exchange and surface complexation. The distribution coefficient (Kd) of heavy metals was high in the order of Pb > Cd > Zn; thus, the adsorption of Pb replaced that of Zn in competitive adsorption due to the difference in their affinity to BC. Therefore, the results suggest that BC prepared by manganese oxide impregnation is suitable for removing heavy metals from road runoff, as it maintained high heavy metals adsorption regardless of the BC material, even under competitive conditions.
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•Biochar (BC) types were modified by different methods for heavy metal removal.•Physicochemical and morphological properties of the modified BC were examined.•Physical properties of RBC and chemical properties of BCs showed major changes.•Irrespective of BC type, manganese oxide-impregnated BC had the highest adsorption.•Competitive adsorption depended on the intrinsic properties of the heavy metals.
Muscle development and lipid accumulation in muscle critically affect meat quality of livestock. However, the genetic factors underlying myofiber-type specification and intramuscular fat (IMF) ...accumulation remain to be elucidated. Using two independent intercrosses between Western commercial breeds and Korean native pigs (KNPs) and a joint linkage-linkage disequilibrium analysis, we identified a 488.1-kb region on porcine chromosome 12 that affects both reddish meat color (a*) and IMF. In this critical region, only the MYH3 gene, encoding myosin heavy chain 3, was found to be preferentially overexpressed in the skeletal muscle of KNPs. Subsequently, MYH3-transgenic mice demonstrated that this gene controls both myofiber-type specification and adipogenesis in skeletal muscle. We discovered a structural variant in the promotor/regulatory region of MYH3 for which Q allele carriers exhibited significantly higher values of a* and IMF than q allele carriers. Furthermore, chromatin immunoprecipitation and cotransfection assays showed that the structural variant in the 5'-flanking region of MYH3 abrogated the binding of the myogenic regulatory factors (MYF5, MYOD, MYOG, and MRF4). The allele distribution of MYH3 among pig populations worldwide indicated that the MYH3 Q allele is of Asian origin and likely predates domestication. In conclusion, we identified a functional regulatory sequence variant in porcine MYH3 that provides novel insights into the genetic basis of the regulation of myofiber type ratios and associated changes in IMF in pigs. The MYH3 variant can play an important role in improving pork quality in current breeding programs.
: This pilot study aimed to evaluate the clinical effectiveness, cost-effectiveness, and safety of acupotomy combined with epidural steroid injection (ESI) in lumbosacral radiculopathy and examine ...its feasibility for the main study.
: This randomized, controlled, two-arm, parallel, assessor-blinded, pragmatic study included 50 patients with severe lumbosacral radiculopathy who had insufficient improvement after an ESI. Patients were randomized (1:1 ratio) into a combined treatment (acupotomy + ESI, experimental) and an ESI single treatment (control) group. Both groups underwent a total of two ESIs once every 2 weeks; the experimental group received eight additional acupotomy treatments twice a week for 4 weeks. Types of ESI included interlaminar, transforaminal, and caudal approaches. Drugs used in ESI comprised a 5-10 mL mixture of dexamethasone sodium phosphate (2.5 mg), mepivacaine (0.3%), and hyaluronidase (1500 IU). The primary outcome was the difference in changes from baseline in the Oswestry Disability Index (ODI) scores between the groups at weeks 4 and 8. The incremental cost-utility ratio (ICUR) was calculated to evaluate the cost-effectiveness between the groups. Adverse events (AEs) were assessed at all visits.
: Mean ODI scores for the experimental and control groups were -9.44 (95% confidence interval CI: -12.71, -6.17) and -2.16 (95% CI: -5.01, 0.69) at week 4, and -9.04 (95% CI: -12.09, -5.99) and -4.76 (95% CI: -7.68, -1.84) at week 8, respectively. The difference in ODI score changes was significant between the groups at week 4 (
= 0.0021). The ICUR of the experimental group versus the control group was as economical as 18,267,754 won/quality-adjusted life years. No serious AEs were observed.
: These results demonstrate the potential clinical effectiveness and cost-effectiveness of acupotomy combined with ESI for lumbosacral radiculopathy and its feasibility for a full-scale study. Larger, long-term follow-up clinical trials are needed to confirm these findings.
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