Use of Inflammatory Biomarkers and Real-Time Cardiac Catheterisation to Evaluate the Left Ventricular Diastolic Function in Patients With Diastolic Heart Failure.

BACKGROUND: Interleukin (IL)-17 and its related cytokines have been shown to be involved in myocardial fibrosis and irreversible ventricular remodelling, which have predictive values in the development of left ventricular diastolic dysfunction (LVDD). This study aimed to assess the correlation between IL-17 and LVDD, and investigate the prognostic value of IL-17 among patients with normal left ventricular ejection fraction (LVEF). METHODS: A total of 120 patients with normal LVEF underwent left ventricular (LV) catheterisation for LV end-diastolic pressure (LVEDP) measurement and routine echocardiography. The follow-up period was 30 (18, 35) months. RESULTS: The levels of IL-17 and IL-6 from the systemic blood were significantly increased in non-heart failure (HF) patients with LVDD (p<0.001). Receiver operating characteristic (ROC) revealed that the combination of IL-17 and IL-6 showed the highest diagnostic accuracy in predicting LVDD (AUC, 0.890; 95% CI, 0.835-0.945; p<0.001), and the cut-off value was 41.5 pg/mL. On logistic regression analysis, the increment of the combination of IL-17 and IL-6 was an independent predictor for the prognosis of LVDD (odds ratio, 1.25; 95% CI, 1.01-1.12; p<0.05). According to the cut-off value of the combination of IL-17 and IL-6, the patients with lower levels of IL-17 and IL-6 (<41.5 pg/mL group) had a better prognosis. The increased levels of IL17 and IL-6 were significantly correlated with the levels of fibrotic parameters. CONCLUSIONS: Assessment of LVDD by measuring the combination of IL-17 and IL-6 might provide valuable prognostic significance for non-HF patients with LVDD.

Origin of Energy Dissipation in the Oligomeric Fucoxanthin-Chlorophyll a/c Binding Proteins.

Fucoxanthin-chlorophyll proteins (FCPs) are a family of photosynthetic light-harvesting complex (LHC) proteins found in diatoms. They efficiently capture photons and regulate their functions, ensuring diatom survival in highly fluctuating light. FCPs are present in different oligomeric states in vivo, but functional differences among these FCP oligomers are not yet fully understood. Here we characterized two types of antenna complexes (FCP-B/C dimers and FCP-A tetramers) that coexist in the marine centric diatom Chaetoceros gracilis using both time-resolved fluorescence and transient absorption spectroscopy. We found that the FCP-B/C complex did not show fluorescence quenching, whereas FCP-A was severely quenched, via an ultrafast excitation energy transfer (EET) pathway from Chl a Qy to the fucoxanthin S1/ICT state. These results highlight the functional differences between FCP dimers and tetramers and indicate that the EET pathway from Chl a to carotenoids is an energy dissipation mechanism conserved in a variety of photosynthetic organisms.

Structural and functional properties of different types of siphonous LHCII trimers from an intertidal green alga Bryopsis corticulans.

Light-harvesting complexes of photosystem II (LHCIIs) in green algae and plants are vital antenna apparatus for light harvesting, energy transfer, and photoprotection. Here we determined the structure of a siphonous-type LHCII trimer from the intertidal green alga Bryopsis corticulans by X-ray crystallography and cryo-electron microscopy (cryo-EM), and analyzed its functional properties by spectral analysis. The Bryopsis LHCII (Bry-LHCII) structures in both homotrimeric and heterotrimeric form show that green light-absorbing siphonaxanthin and siphonein occupied the sites of lutein and violaxanthin in plant LHCII, and two extra chlorophylls (Chls) b replaced Chls a. Binding of these pigments expands the blue-green light absorption of B. corticulans in the tidal zone. We observed differences between the Bry-LHCII homotrimer crystal and cryo-EM structures, and also between Bry-LHCII homotrimer and heterotrimer cryo-EM structures. These conformational changes may reflect the flexibility of Bry-LHCII, which may be required to adapt to light fluctuations from tidal rhythms.

Photoinduced chlorophyll charge transfer state identified in the light-harvesting complex II from a marine green alga Bryopsis corticulans.

The light-harvesting complex II of Bryopsis corticulans (B-LHCII), a green alga, differs from that of spinach (S-LHCII) in chlorophyll (Chl) and carotenoid (Car) compositions. We investigated ultrafast excitation dynamics of B-LHCII with visible-to-near infrared time-resolved absorption spectroscopy. Absolute fluorescence quantum yield (Φ FL) of LHCII and spectroelectrochemical (SEC) spectra of Chl a and b were measured to assist the spectral analysis. Red-light excitation at Chl Qy-band, but not Car-band, induced transient features resembling the characteristic SEC spectra of Chl a ⋅+ and Chl b ⋅-, indicating ultrafast photogeneration of Chl-Chl charge transfer (CT) species; Φ FL and 3Car∗ declined whereas CT species increased upon prolonging excitation wavelength, showing positive correlation of 1Chl∗ deactivation with Chl-Chl CT formation. Moreover, ultrafast Chl b-to-Chl a and Car-to-Chl singlet excitation transfer were illustrated. The red-light induction of Chl-Chl CT species, as also observed for S-LHCII, is considered a general occurrence for LHCIIs in light-harvesting form.

Structural insights into photosystem II supercomplex and trimeric FCP antennae of a centric diatom Cyclotella meneghiniana.

Diatoms are dominant marine algae and contribute around a quarter of global primary productivity, the success of which is largely attributed to their photosynthetic capacity aided by specific fucoxanthin chlorophyll-binding proteins (FCPs) to enhance the blue-green light absorption under water. We purified a photosystem II (PSII)-FCPII supercomplex and a trimeric FCP from Cyclotella meneghiniana (Cm) and solved their structures by cryo-electron microscopy (cryo-EM). The structures reveal detailed organizations of monomeric, dimeric and trimeric FCP antennae, as well as distinct assemblies of Lhcx6_1 and dimeric FCPII-H in PSII core. Each Cm-PSII-FCPII monomer contains an Lhcx6_1, an FCP heterodimer and other three FCP monomers, which form an efficient pigment network for harvesting energy. More diadinoxanthins and diatoxanthins are found in FCPs, which may function to quench excess energy. The trimeric FCP contains more chlorophylls c and fucoxanthins. These diversified FCPs and PSII-FCPII provide a structural basis for efficient light energy harvesting, transfer, and dissipation in C. meneghiniana.

Structure of a diatom photosystem II supercomplex containing a member of Lhcx family and dimeric FCPII.

Diatoms rely on fucoxanthin chlorophyll a/c-binding proteins (FCPs) for their great success in oceans, which have a great diversity in their pigment, protein compositions, and subunit organizations. We report a unique structure of photosystem II (PSII)-FCPII supercomplex from Thalassiosira pseudonana at 2.68-Å resolution by cryo-electron microscopy. FCPIIs within this PSII-FCPII supercomplex exist in dimers and monomers, and a homodimer and a heterodimer were found to bind to a PSII core. The FCPII homodimer is formed by Lhcf7 and associates with PSII through an Lhcx family antenna Lhcx6_1, whereas the heterodimer is formed by Lhcf6 and Lhcf11 and connects to the core together with an Lhcf5 monomer through Lhca2 monomer. An extended pigment network consisting of diatoxanthins, diadinoxanthins, fucoxanthins, and chlorophylls a/c is revealed, which functions in efficient light harvesting, energy transfer, and dissipation. These results provide a structural basis for revealing the energy transfer and dissipation mechanisms and also for the structural diversity of FCP antennas in diatoms.

Epigenetic modifications in the accumulation and function of myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSCs) are key players under various pathologic conditions, such as cancer. Epigenetic modifications such as DNA methylation, RNA-mediated processes, and histone modification can alter gene transcription, and thus regulating pathological process. Studies have shown that epigenetic modification contributes to the accumulation and function of MDSCs. This review summarizes the crosstalk between the epigenetic alterations and MDSCs functions, and briefly introduces how the accumulation and function of MDSCs caused by epigenetic modification impact on the disease development, which represents as a promising therapeutic strategy for the related disorders.

A Possible Mechanism for Aggregation-Induced Chlorophyll Fluorescence Quenching in Light-Harvesting Complex II from the Marine Green Alga Bryopsis corticulans.

The light-harvesting complex II of a green alga Bryopsis corticulans (B-LHCII) is peculiar in that it contains siphonein and siphonaxathin as carotenoid (Car). Since the S1 state of siphonein and siphonaxathin lies substantially higher than the Qy state of chlorophyll a (Chl a), the Chl a(Qy)-to-Car(S1) excitation energy transfer is unfeasible. To understand the photoprotective mechanism of algal photosynthesis, we investigated the influence of temperature on the excitation dynamics of B-LHCII in trimeric and aggregated forms. At room temperature, the aggregated form showed a 10-fold decrease in fluorescence intensity and lifetime than the trimeric form. Upon lowering the temperature, the characteristic 680 nm fluorescence (F-680) of B-LHCII in both forms exhibited systematic intensity enhancement and spectral narrowing; however, only the aggregated form showed a red emission extending over 690-780 nm (F-RE) with pronounced blueshift, lifetime prolongation, and intensity boost. The remarkable T-dependence of F-RE is ascribed to the Chl-Chl charge transfer (CT) species involved directly in the aggregation-induced Chl deactivation. The CT-quenching mechanism, which is considered to be crucial for B. corticulans photoprotection, draws strong support from the positive correlation of the Chl deactivation rate with the CT state population, as revealed by comparing the fluorescence dynamics of B-LHCII with that of the plant LHCII.

T helper 17 cell responses induce cardiac hypertrophy and remodeling in essential hypertension.

INTRODUCTION: An increasing body of evidence has shown that type 17 helper T (TH17) cell responses play an important role in the progression of cardiac remodeling stimulated by long­term pressure overload. OBJECTIVES: We aimed to investigate the relationship between TH17 responses and cardiac remodeling, and the prognostic value of TH17 responses in hypertensive patients. PATIENTS AND METHODS: A total of 187 adults with hypertension and 70 healthy controls were enrolled in the present study. TH17 cell frequencies, matrix metallopeptidase 9, procollagen type I, and procollagen type III were studied at baseline. All adults underwent routine echocardiography to assess left ventricular diastolic function (LVDF) at baseline and after 24 months of follow­up. RESULTS: The percentage of TH17 cells was increased in hypertensive patients, particularly in adults with left ventricular hypertrophy (LVH). Receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) of TH17 cells for predicting of LVH was 0.943 (95% CI, 0.914-0.971; P <0.001) and the cutoff value was 2.3%. On logistic regression analysis, the percentage of TH17 cells was an independent predictor of LVH (odds ratio, 1.47; 95% CI, 2.23-2.28; P = 0.005). The percentage of TH17 cells significantly correlated with the levels of fibrotic parameters. According to the cutoff value of TH17 cells, patients with a lower level of TH17 cell differentiation had a better prognosis. CONCLUSIONS: The differentiation of TH17 cells reflected the cardiac hypertrophy and remodeling response to hypertension­induced pressure overload, and it might be a potential inflammatory marker to predict the prognosis of hypertensive patients.

Genetic load, inbreeding depression and heterosis in an age-structured metapopulation.

In a metapopulation, the process of recurrent local extinction and recolonization gives rise to an age structure among demes. Recently established demes will tend to differ from older demes in terms of the levels of genetic diversity found within them and the way this diversity is distributed among demes in the same and different ages. The effects of population turnover on average levels of genetic diversity among demes in a metapopulation have been the focus of much attention, both for neutral and nonneutral loci, but much less is known about the distribution of nonneutral genetic diversity among demes of different ages. In this paper, we used computer simulations to study the distribution of genetic load, inbreeding depression and heterosis in an age-structured metapopulation. We found that, for mildly deleterious mutations, within-deme inbreeding depression increased, whereas heterosis and genetic load decreased with deme age following severe colonization bottlenecks. In contrast, recessive lethal alleles tended to be purged during colonization, with older populations showing higher genetic load and higher within-deme inbreeding depression. Heterosis caused by recessive lethal alleles and resulting from gene flow among different demes tended to be greatest for young demes, because the mutations responsible tended to be purged in the first few generations after colonization, but its effects increased again as populations grow older as a result of immigration. Our results point to a need for estimates of genetic diversity, genetic load, within-deme inbreeding depression and heterosis in demes of different age classes separately.

Echocardiographic evaluation of left ventricular end diastolic pressure in patients with diastolic heart failure: A comparative study with real-time catheterization.

To evaluate the left ventricular end diastolic pressure (LVEDP) in patients with diastolic heart failure by echocardiography and explore the clinical value of echocardiography.From July 2017 to January 2018, 120 patients were prospectively selected from the affiliated hospital of Jiangsu university diagnosed as diastolic heart failure (York Heart Association class ≥II, LVEF ≥50%). The patients were divided into group with LVEDP ≤15 mm hg (1 mm hg = 0.133 kpa) (43 cases) and the group with LVEDP >15 mm hg (77 cases) according to the real-time measurement of LVEDP. Receiver operator characteristic curves of each parameter of echocardiography in diagnosis of LVEDP were compared between the 2 groups.Common ultrasonic parameters such as left ventricular inflow tract blood flow propagation velocity, mitral valve diastole e peak velocity/mitral valve diastole a peak velocity, e peak deceleration time, a peak duration, and early diastole interventricular septum bicuspid annulus velocity e' (e'sep) were used to evaluate LVEDP elevation with low accuracy (AUC is only between 0.5 and 0.7). Other ultrasonic parameters such as left atrial volume index (LAVI), tricuspid regurgitation maximum flow rate (TRmax), early diastole left ventricular sidewall bicuspid annulus velocity e' (e'lat), average e', E/e'sep, E/e'lat, average E/e' were used to evaluate LVEDP elevation with a certain improvement in accuracy (AUC between 0.7 and 0.9). Propagation velocity, mitral valve diastole e peak velocity/mitral valve diastole a peak velocity, e peak deceleration time, a peak duration, e'sep, average e', E/e'sep have very low correlation with LVEDP (r = -0.283 to 0.281); LAVI, TRmax, e'lat, E/e'lat, average E/e' and LVEDP are not highly correlated (r = 0.330-0.478). Through real-time left ventricular manometry, multiple regression analysis showed that TRmax, average e', e'lat, LAVI were independently correlated with the actual measured LVEDP.Echocardiography can recognize the increase of LVEDP in patients with heart failure preserved by LVEF, and estimate the value of LVEDP roughly, which can reflect LVEDP to a certain extent, with high feasibility and accuracy.

Excitation dynamics and relaxation in the major antenna of a marine green alga Bryopsis corticulans.

The light-harvesting complexes II (LHCIIs) of spinach and Bryopsis corticulans as a green alga are similar in structure, but differ in carotenoid (Car) and chlorophyll (Chl) compositions. Carbonyl Cars siphonein (Spn) and siphonaxanthin (Spx) bind to B. corticulans LHCII likely in the sites as a pair of lutein (Lut) molecules bind to spinach LHCII in the central domain. To understand the light-harvesting and photoprotective properties of the algal LHCII, we compared its excitation dynamics and relaxation to those of spinach LHCII been well documented. It was found that B. corticulans LHCII exhibited a substantially longer chlorophyll (Chl) fluorescence lifetime (4.9 ns vs 4.1 ns) and a 60% increase of the fluorescence quantum yield. Photoexcitation populated 3Car* equally between Spn and Spx in B. corticulans LHCII, whereas predominantly at Lut620 in spinach LHCII. These results prove the functional differences of the LHCIIs with different Car pairs and Chl a/b ratios: B. corticulans LHCII shows the enhanced blue-green light absorption, the alleviated quenching of 1Chl*, and the dual sites of quenching 3Chl*, which may facilitate its light-harvesting and photoprotection functions. Moreover, for both types of LHCIIs, the triplet excitation profiles revealed the involvement of extra 3Car* formation mechanisms besides the conventional Chl-to-Car triplet transfer, which are discussed in relation to the ultrafast processes of 1Chl* quenching. Our experimental findings will be helpful in deepening the understanding of the light harvesting and photoprotection functions of B. corticulans living in the intertidal zone with dramatically changing light condition.