Herpesviruses assimilate kinesin to produce motorized viral particles.

Neurotropic alphaherpesviruses initiate infection in exposed mucosal tissues and, unlike most viruses, spread rapidly to sensory and autonomic nerves where life-long latency is established1. Recurrent infections arise sporadically from the peripheral nervous system throughout the life of the host, and invasion of the central nervous system may occur, with severe outcomes2. These viruses directly recruit cellular motors for transport along microtubules in nerve axons, but how the motors are manipulated to deliver the virus to neuronal nuclei is not understood. Here, using herpes simplex virus type I and pseudorabies virus as model alphaherpesviruses, we show that a cellular kinesin motor is captured by virions in epithelial cells, carried between cells, and subsequently used in neurons to traffic to nuclei. Viruses assembled in the absence of kinesin are not neuroinvasive. The findings explain a critical component of the alphaherpesvirus neuroinvasive mechanism and demonstrate that these viruses assimilate a cellular protein as an essential proviral structural component. This principle of viral assimilation may prove relevant to other virus families and offers new strategies to combat infection.

The HSV-1 pUL37 protein promotes cell invasion by regulating the kinesin-1 motor.

Neurotropic alphaherpesviruses, including herpes simplex virus type 1 (HSV-1), recruit microtubule motor proteins to invade cells. The incoming viral particle traffics to nuclei in a two-step process. First, the particle uses the dynein-dynactin motor to sustain transport to the centrosome. In neurons, this step is responsible for long-distance retrograde axonal transport and is an important component of the neuroinvasive property shared by these viruses. Second, a kinesin-dependent mechanism redirects the particle from the centrosome to the nucleus. We have reported that the kinesin motor used during the second step of invasion is assimilated into nascent virions during the previous round of infection. Here, we report that the HSV-1 pUL37 tegument protein suppresses the assimilated kinesin-1 motor during retrograde axonal transport. Region 2 (R2) of pUL37 was required for suppression and functioned independently of the autoinhibitory mechanism native to kinesin-1. Furthermore, the motor domain and proximal coiled coil of kinesin-1 were sufficient for HSV-1 assimilation, pUL37 suppression, and nuclear trafficking. pUL37 localized to the centrosome, the site of assimilated kinesin-1 activation during infection, when expressed in cells in the absence of other viral proteins; however, pUL37 did not suppress kinesin-1 in this context. These results indicate that the pUL37 tegument protein spatially and temporally regulates kinesin-1 via the amino-terminal motor region in the context of the incoming viral particle.

Highly efficient and stable InP/ZnSe/ZnS quantum dot light-emitting diodes.

Quantum dot (QD) light-emitting diodes (LEDs) are ideal for large-panel displays because of their excellent efficiency, colour purity, reliability and cost-effective fabrication1-4. Intensive efforts have produced red-, green- and blue-emitting QD-LEDs with efficiencies of 20.5 per cent4, 21.0 per cent5 and 19.8 per cent6, respectively, but it is still desirable to improve the operating stability of the devices and to replace their toxic cadmium composition with a more environmentally benign alternative. The performance of indium phosphide (InP)-based materials and devices has remained far behind those of their Cd-containing counterparts. Here we present a synthetic method of preparing a uniform InP core and a highly symmetrical core/shell QD with a quantum yield of approximately 100 per cent. In particular, we add hydrofluoric acid to etch out the oxidative InP core surface during the growth of the initial ZnSe shell and then we enable high-temperature ZnSe growth at 340 degrees Celsius. The engineered shell thickness suppresses energy transfer and Auger recombination in order to maintain high luminescence efficiency, and the initial surface ligand is replaced with a shorter one for better charge injection. The optimized InP/ZnSe/ZnS QD-LEDs showed a theoretical maximum external quantum efficiency of 21.4 per cent, a maximum brightness of 100,000 candelas per square metre and an extremely long lifetime of a million hours at 100 candelas per square metre, representing a performance comparable to that of state-of-the-art Cd-containing QD-LEDs. These as-prepared InP-based QD-LEDs could soon be usable in commercial displays.

Elucidating Singlet-Fission-Born Multiexciton Dynamics via Molecular Engineering: A Dilution Principle Extended to Quintet Triplet Pair.

Multiexciton in singlet exciton fission represents a critical quantum state with significant implications for both solar cell applications and quantum information science. Two distinct fields of interest explore contrasting phenomena associated with the geminate triplet pair: one focusing on the persistence of long-lived correlation and the other emphasizing efficient decorrelation. Despite the pivotal nature of multiexciton processes, a comprehensive understanding of their dependence on the structural and spin properties of materials is currently lacking in experimental realizations. To address this gap in knowledge, molecular engineering was employed to modify the TIPS-tetracene structures, enabling an investigation of the structure-property relationships in spin-related multiexciton processes. In lieu of the time-resolved electron paramagnetic resonance technique, two time-resolved magneto-optical spectroscopies were implemented for quantitative analysis of spin-dependent multiexciton dynamics. The utilization of absorption and fluorescence signals as complementary optical readouts, in the presence of a magnetic field, provided crucial insights into geminate triplet pair dynamics. These insights encompassed the duration of multiexciton correlation and the involvement of the spin state in multiexciton decorrelation. Furthermore, simulations based on our kinetic models suggested a role for quintet dilution in multiexciton dynamics, surpassing the singlet dilution principle established by the Merrifield model. The integration of intricate model structures and time-resolved magneto-optical spectroscopies served to explicitly elucidate the interplay between structural and spin properties in multiexciton processes. This comprehensive approach not only contributes to the fundamental understanding of these processes but also aligns with and reinforces previous experimental studies of solid states and theoretical assessments.

Nanographene-Fused Expanded Carbaporphyrin Tweezers.

A nanographene-fused expanded carbaporphyrin (5) and its BF2 complex (6) were synthesized. Single-crystal X-ray structures revealed that 5 and 6 are connected by two hexa-peri-hexabenzocoronene (HBC) units and two dipyrromethene or BODIPY units, respectively. As prepared, 5 and 6 both show nonaromatic character with figure-of-eight carbaoctaphyrin (1.1.1.0.1.1.1.0) cores and adopt tweezers-like conformations characterized by a partially confined space between the two constituent HBC units. The distance between the HBC centers is >10 Å, while the dihedral angles between the two HBC planes are 30.5 and 35.2° for 5 and 6, respectively. The interactions between 5 and 6 and fullerene C60 were studied both in organic media and in the solid state. Proton NMR spectral titrations of 5 and 6 with C60 revealed a 1:1 binding mode for both macrocycles. In toluene-d8, the corresponding binding constants were determined to be 1141 ± 17 and 994 ± 10 M-1 for 5 and 6, respectively. Single-crystal X-ray diffraction structural analyses confirmed the formation of 1:1 fullerene inclusion complexes in the solid state. The C60 guests in both complexes are found within triangular pockets composed of two HBC units from the tweezers-like receptor most closely associated with the bound fullerene, as well as an HBC unit from an adjacent host. Femtosecond transient absorption measurements revealed subpicosecond ultrafast charge separation between 5 (and 6) and C60 in the complexes. To the best of our knowledge, the present report provides the first example wherein a nanographene building block is incorporated into the core of a porphyrinic framework.

Acesulfame potassium upregulates PD-L1 in HCC cells by attenuating autophagic degradation.

Artificial sweeteners, which contain no or few calories, have been widely used in various foods and beverages, and are regarded as safe alternatives to sugar by the Food and Drug Administration. While several studies suggest that artificial sweeteners are not related to cancer development, some research has reported their potential association with the risk of cancers, including hepatocellular carcinoma (HCC). Here, we investigated whether acesulfame potassium (Ace K), a commonly used artificial sweetener, induces immune evasion of HCC cells by upregulating programmed death ligand-1 (PD-L1). Ace K elevated the protein levels of PD-L1 in HCC cells without increasing its mRNA levels. The upregulation of PD-L1 protein levels in HCC cells by Ace K was induced by attenuated autophagic degradation of PD-L1, which was mediated by the Ace K-stimulated ERK1/2-mTORC1 signaling pathway. Ace K-induced upregulation of PD-L1 attenuated T cell-mediated death of HCC cells, thereby promoting immune evasion of HCC cells. In summary, the present study suggests that Ace K promotes HCC progression by upregulating the PD-L1 protein level.

One-Stop Plasmonic Nanocube-Excited SERS Immunoassay Platform of Multiple Cardiac Biomarkers for Rapid Screening and Progressive Tracing of Acute Myocardial Infarction.

Rapid and precise acute myocardial infarction (AMI) diagnosis is essential for preventing patient death. In addition, the complementary roles of creatine kinase muscle brain (CK-MB) and cardiac troponin I (cTnI) cardiac biomarkers in the early and late stages of AMI demand their simultaneous detection, which is difficult to implement using conventional fluorescence and electrochemical technologies. Here, a nanotechnology-based one-stop immuno-surface-enhanced Raman scattering (SERS) detection platform is reported for multiple cardiac indicators for the rapid screening and progressive tracing of AMI events. Optimal SERS is achieved using optical property-based, excitation wavelength-optimized, and high-yield anisotropic plasmonic gold nanocubes. Optimal immunoassay reaction efficiencies are achieved by increasing immobilized antibodies. Multiple simultaneous detection strategies are implemented by incorporating two different Raman reports with narrow wavenumbers corresponding to two indicators and by establishing a computational SERS mapping process to accurately detect their concentrations, irrespective of multiple enzymes in the human serum. The SERS platform precisely estimated AMI onset and progressive timing in human serum and made rapid AMI identification feasible using a portable Raman spectrometer. This integrated platform is hypothesized to significantly contribute to emergency medicine and forensic science by providing timely treatment and observation.

Cyclic Azobenzene-BODIPY Hybrids.

Cyclic azobenzene-BODIPY hybrids were synthesized via cyclization by 1) acid-catalysed condensation of azobenzene-bridged dipyrroles with 3,5-di-tert-butylbenzaldehyde, 2) oxidation with DDQ, and 3) metalation with BF3 ⋅ Et2 O. The structures of many cyclic hybrids have been confirmed by single crystal X-ray analysis. The absorption spectra of the hybrids reveal the effective cyclic conjugation. The ultrafast measurements reveal that the photoexcited decays of these cyclic hybrids depend upon the ring size and connectivity.

Bisphenol A regulates bladder cells responses via control of G2/M-phase cell cycle, apoptotic signaling, MAPK pathway, and transcription factor-associated MMP modulation.

Bisphenol A (BPA), an exogenous endocrine-disrupting chemical, is widely used to produce polycarbonate plastics. The widely used BPA has been detected in human urine samples, raising public anxiety about the detrimental effects of BPA on the bladder. In this study, we explored regulatory mechanisms for the adverse effects of BPA in human bladder BdFC and T24 cells. BPA induced extrinsic and intrinsic apoptosis and G2/M cell cycle arrest caused by the ATM-CHK1/CHK2-CDC25c-CDC2 signaling, which ultimately inhibited the growth of human bladder cells. We also found that BPA decreased the binding activity of AP-1 and NF-κB transcription factors in human bladder cells, which inhibited migration and invasion through matrix metallopeptidase-2 and -9 inactivation. Phosphorylation of MAPKs was implicated with BPA-mediated detrimental effects in human bladder cells. Collectively, our results provide a novel explanation for the underlying molecular mechanisms that BPA induces cytotoxicity in human bladder cells.

Cyclic Carbaporphyrin Arrays.

Two cyclic carbaporphyrin arrays (trimer 6 and tetramer 7) were synthesized from a dibrominated carbaporphyrin precursor (5) via a one-pot Yamamoto-type coupling. Single-crystal X-ray diffraction analyses revealed that 6 and 7 contain three and four covalently linked carbaporphyrin (formally dicarbacorrole) units, respectively. Trimer 6 adopts a roughly planar conformation and tetramer 7 adopts an up-and-down zig-zag conformation. Both 6 and 7 contain a [n]cyclo-meta-phenylene ([n]CMP) core, namely, [6]- and [8]CMP for 6 and 7, respectively. Transient absorption (TA) anisotropy and pump-power-dependent excited-state decay studies provided evidence for excitation energy transfer (EET) within both trimer 6 and tetramer 7. The exciton energy hopping (EEH) times were estimated to be 18 and 35 ps for 6 and 7, respectively, as inferred from pump-power-dependent TA measurements. Since the center-to-center distances between adjacent carbaporphyrin units are similar in 6 and 7, the different EEH times are attributed to differences in the orientation of the transition dipoles in these two congeneric arrays. The orientation factor κ2, the key parameter defining the Förster resonance energy transfer efficiency, was calculated to be 2.15 and 1.03 for 6 and 7, respectively, a finding that supports the shorter excitation energy hopping time seen in the case of trimer 6. To our knowledge, this is the first time that covalently linked cyclic carbaporphyrin arrays were synthesized using a single carbaporphyrin as the starting point and that EET between carbaporphyrin subunits constrained within a well-defined polycyclic framework has been correlated with structural differences.

Leveraging Charge-Transfer Interactions in Through-Space-Coupled Pentacene Dendritic Oligomer for Singlet Exciton Fission.

Singlet exciton fission in organic chromophores has received much attention during the past decade. Inspired by numerous spectroscopic studies in the solid state, there have been vigorous efforts to study singlet exciton fission dynamics in covalently bonded oligomers, which aims to investigate underlying mechanisms of this intriguing process in simplified model systems. In terms of through-space orbital interactions, however, most of covalently bonded pentacene oligomers studied so far fall into weakly interacting systems since they manifest chain-like structures based on various (non)conjugated linkers. Therefore, it remains as a compelling question to answer how through-space interactions in the solid state intervene this photophysical process since it is hypersensitive to displacements and orientations between neighboring chromophores. Herein, as one of experimental studies to answer this question, we introduced a tight-packing dendritic structure whose mesityl-pentacene constituents are coupled via moderate through-space orbital interactions. Based on the comparison with a suitably controlled dendritic structure, which is in a weak coupling regime, important mechanistic viewpoints are tackled such as configurational mixings between singlet, charge-transfer, and triplet pair states and the role of chromophore multiplication. We underscore that our through-space-coupled dendritic oligomer in a quasi-intermediate coupling regime provides a hint on the interplay of multiconfigurational excited-states, which might have drawn complexity in singlet exciton fission kinetics throughout numerous solid-state morphologies.

Ultrafast Excited State Aromatization in Dihydroazulene.

Excited-state aromatization dynamics in the photochemical ring opening of dihydroazulene (DHA) is investigated by nonadiabatic molecular dynamics simulations in connection with the mixed-reference spin-flip (MRSF)-TDDFT method. It is found that, in the main reaction channel, the ring opening occurs in the excited state in a sequence of steps with increasing aromaticity. The first stage lasting ca. 200 fs produces an 8π semiaromatic S1 minimum (S1, min) through an ultrafast damped bond length alternation (BLA) movement synchronized with a partial planarization of the cycloheptatriene ring. An additional ca. 200 fs are required to gain the vibrational energy needed to overcome a ring-opening transition state characterized by an enhanced Baird aromaticity. Unlike other BLA motions of ππ* state, it was shown that their damping is a characteristic feature of aromatic bond-equalization process. In addition, some minor channels of the reaction have also been discovered, where noticeably higher barriers of the S1 non/antiaromatic transition structures must be surmounted. These anti-Baird channels led to reformation of DHA or other closed-ring products. The observed competition between the Baird and anti-Baird channels suggests that the quantum yield of photochemical products can be controllable by tipping their balance. Hence, here we suggest including the concept of anti-Baird, which would expand the applicability of Baird rule to much broader situations.

Realization of Stacked-Ring Aromaticity in a Water-Soluble Micellar Capsule.

Stacked-ring aromaticity arising from the close stacking of antiaromatic π-systems has recently received considerable attention. Here, we realize stacked-ring aromaticity via a rational supramolecular approach. A nanocapsule composed of bent polyaromatic amphiphiles was employed to encapsulate several antiaromatic norcorrole Ni(II) complexes (NCs) in water. The resulting micellar capsules display high stability toward heating and concentration change. The encapsulation resulted in the appearance of a broad absorption band in the near-infrared region, which is characteristic of norcorroles with close face-to-face stacking. Importantly, a meso-isopropyl NC, which does not exhibit π-stacking even in a concentrated solution or the crystalline phase, adopted π-stacking with stacked-ring aromaticity in the supramolecular micellar capsule.

V-Shaped Tröger Oligothiophenes Boost Triplet Formation by CT Mediation and Symmetry Breaking.

A new family of molecules obtained by coupling Tröger's base unit with dicyanovinylene-terminated oligothiophenes of different lengths has been synthesized and characterized by steady-state stationary and transient time-resolved spectroscopies. Quantum chemical calculations allow us to interpret and recognize the properties of the stationary excited states as well as the time-dependent mechanisms of singlet-to-triplet coupling. The presence of the diazocine unit in Tröger's base derivatives is key to efficiently producing singlet-to-triplet intersystem crossing mediated by the role of the nitrogen atoms and of the almost orthogonal disposition of the two thiophene arms. Spin-orbit coupling-mediated interstate intersystem crossing (ISC) is activated by a symmetry-breaking process in the first singlet excited state with partial charge transfer character. This mechanism is a characteristic of these molecular triads since the independent dicyanovinylene-oligothiophene branches do not display appreciable ISC. These results show how Tröger's base coupling of organic chromophores can be used to improve the ISC efficiency and tune their photophysics.

π-Extended Hexapyrrolylbenzenes: Exploring Charge-Transfer Phenomena in Donor-Acceptor Propellers.

A family of propeller-shaped donor-acceptor hexapyrrolylbenzenes (HPBs) were designed and synthesized by sequential nucleophilic substitution of hexafluorobenzene with π-extended pyrroles. In particular, four hybrids were obtained, containing various combinations of electron-rich and electron-poor acenaphthylene-fused pyrroles. Additionally, to probe the efficiency of ortho transfer interactions, a system was designed containing unique donor and acceptor subunits spatially separated with four unfunctionalized pyrroles. DFT calculations showed propeller-shaped geometries of all HPB molecules and separation of frontier molecular orbitals between donor and acceptor subunits. Steady-state and time-resolved photophysical measurements revealed charge-transfer (CT) character of the emission with strong positive dependence on solvent polarity. The principal CT pathway involves ortho-positioned pairs of donors and acceptors and requires bending of the acceptor in the excited state.

Xanthene-Separated 24 π-Electron Antiaromatic Rosarin Dimer.

Antiaromatic molecules have recently received attention because of their intrinsic properties, such as high reactivity and their narrow HOMO-LUMO gaps. Stacking of antiaromatic molecules has been predicted to induce three-dimensional aromaticity via frontier orbital interactions. Here, we report a covalently linked π-π stacked rosarin dimer that has been examined experimentally by steady-state absorption and transient absorption measurements and theoretically by quantum chemical calculations, including time-dependent density functional theory, anisotropy of induced current density, and nucleus-independent chemical shift calculations. Relative to the corresponding monomer, the dimer exhibits diminished antiaromaticity upon lowering the temperature to 77 K, a finding ascribed to intramolecular interactions between the macrocyclic rosarin subunits.

SGLT2 inhibitors prevent LPS-induced M1 macrophage polarization and alleviate inflammatory bowel disease by downregulating NHE1 expression.

BACKGROUND: Classically activated M1 macrophages, characterized by aberrant glycolysis and secretion of inflammatory cytokines, play pivotal roles in inflammatory diseases, including inflammatory bowel disease (IBD). Recently, sodium-glucose co-transporter 2 (SGLT2) inhibitors were shown to suppress Na+/H+ exchanger 1 (NHE1) and Na+/Ca2+ exchanger 1 (NCX1) activity, regulating downstream intracellular Ca2+ concentrations in cardiomyocytes. However, whether SGLT2 inhibitors regulate M1 macrophage polarization by downregulating NHE1 and NCX1 remains unknown. METHODS: We analyzed cellular responses to SGLT2 inhibitors using mouse bone marrow-derived macrophages and peritoneal macrophages treated with lipopolysaccharide (LPS). To induce IBD, we used a dextran sulfate sodium salt-induced colitis mouse model. RESULTS: We observed that NHE1 and NCX1 were overexpressed in LPS-treated macrophages, leading to M1 macrophage polarization. Mechanistically, NHE1 and NCX1-mediated Ca2+ accumulation in the macrophage resulted in enhanced glycolysis by promoting PI3K/AKT/mTORC1 signaling. SGLT2 inhibitors suppressed both the expression levels and activities of NHE1 and NCX1, and consequently downregulated PI3K/AKT/mTORC1 signaling and glycolysis in LPS-treated macrophages. We observed inhibition of LPS-stimulated M1 polarization and cytokine production by SGLT2 inhibitors in vitro, ex vivo, and in an IBD mouse model. CONCLUSIONS: NHE1 promotes M1 macrophage polarization and SGLT2 inhibitors are a novel strategy to treat M1 macrophage-mediated inflammatory diseases, including IBD.

Effect of Dynamic Taping versus Kinesiology Taping on Pain, Foot Function, Balance, and Foot Pressure in 3 Groups of Plantar Fasciitis Patients: A Randomized Clinical Study.

BACKGROUND Biomechanical dynamic tape supports muscles, joints, and ligaments and is used in ankle and foot injuries. Kinesiology tape (KT), also known as elastic tape, is widely used in sports medicine. Plantar fasciitis, due to inflammation of the plantar fascia, is a common cause of heel pain. This study aimed to compare the effects of dynamic taping and KT on pain, function, and balance in 3 groups of patients with plantar fasciitis. MATERIAL AND METHODS Sixty-nine patients with plantar fasciitis were randomly assigned to the dynamic taping with physical therapy (PT) group, the KT with PT group, and the control group (23 each). All groups received conservative physical therapy. Dynamic taping and KT were performed twice a week for 4 weeks, and the taping was removed after 12 h of application. Patients' pain, foot function, and balance were assessed using the visual analog scale (VAS), foot function index (FFI), and Y-balance test (YBT), respectively, before and immediately after the intervention. RESULTS In the FFI and YBT, the treatment provided to the dynamic taping with PT group with PT showed a greater effect than in the KT with PT group with PT (P<0.05), and the control group showed the lowest effect. Dynamic taping and KT with PT did not show significant differences in VAS and foot pressure, but both were more effective than the control group (P<0.05). CONCLUSIONS The results of this study suggest that dynamic taping with PT is the most effective method for FFI and YBT in patients with plantar fasciitis, and that dynamic taping and KT with PT are effective methods for treating pain and foot pressure.

Porphyrinoids, a unique platform for exploring excited-state aromaticity.

Recently, Baird (anti)aromaticity has been referred to as a description of excited-state (anti)aromaticity. With the term of Baird's rule, recent studies have intensively verified that the Hückel aromatic [4n + 2]π (or antiaromatic [4n]π) molecules in the ground state are reversed to give Baird aromatic [4n]π (or Baird antiaromatic [4n + 2]π) molecules in the excited states. Since the Hückel (anti)aromaticity has great influence on the molecular properties and reaction mechanisms, the Baird (anti)aromaticity has been expected to act as a dominant factor in governing excited-state properties and processes, which has attracted intensive scientific investigations for the verification of the concept of reversed aromaticity in the excited states. In this scientific endeavor, porphyrinoids have recently played leading roles in the demonstration of the aromaticity reversal in the excited states and its conceptual development. The distinct structural and electronic nature of porphyhrinoids depending on their (anti)aromaticity allow the direct observation of excited-state aromaticity reversal, Baird's rule. The explicit experimental demonstration with porphyrinoids has contributed greatly to its conceptual development and application in novel functional organic materials. Based on the significant role of porphyrinoids in the field of excited-state aromaticity, this review provides an overview of the experimental verification of the reversal concept of excited-state aromaticity by porphyrinoids and the recent progress on its conceptual application in novel functional molecules.

Peak systolic myocardial velocity in patients undergoing surgical aortic valve replacement for severe aortic stenosis: prognostic value and natural course.

Myocardial systolic longitudinal function has been known to decrease in patients with severe aortic stenosis (AS). Preoperative peak systolic myocardial velocity at the septal mitral valve annulus (S'), measured using Doppler tissue imaging, was used as an indicator for myocardial systolic longitudinal function. The prognostic value and natural course of S' after surgical aortic valve replacement for severe AS have not been elucidated. This retrospective observational study included patients from January 2006 to December 2018. The patients were divided to 2 groups (pre-S'HIGH vs. pre-S'LOW) with a cut-off 5.4 cm/s of preoperative S' (pre-S') that was identified by restricted cubic spline curve. The primary outcome was postoperative long-term all-cause mortality. Nine hundred and five patients were analyzed. All-cause mortality rate at the median follow-up period of 5.2 years was 12% in pre-S'LOW and 8% in pre-S'HIGH. Multivariate analysis showed that pre-S'LOW was associated with an increased all-cause mortality (hazard ratio, 1.60; 95% confidence interval, 1.04-2.48; P = 0.032). Significantly different trajectories of postoperative S' (post-S') were found between two groups (P < 0.001 for difference): In pre-S'LOW, post-S' increased within 6 months after surgery, and gradually decreased over time, whereas it slowly decreased up to 5 years after surgery and then reached a plateau in pre-S'HIGH. The difference in pre-S' level maintained over time, and remained consistent in the adjusted analysis. Pre-S' < 5.4 cm/s was found to be associated with an increased long-term all-cause mortality. In addition, the trajectories for post-S' were different according to pre-S', which remained after adjustment.