Browse Articles
Discover research articles across all indexed journals
YAP Overcomes Mechanical Barriers to Induce Mitotic Rounding and Adult Cardiomyocyte Division
BACKGROUND: Many specialized cells in adult organs acquire a state of cell cycle arrest and quiescence through unknown mechanisms. Our limited understanding of mammalian cell cycle arrest is derived primarily from cell culture models. Adult mammalian cardiomyocytes, a classic example of cell cycle arrested cells, exit the cell cycle postnatally and remain in an arrested state for the life of the organism. Cardiomyocytes can be induced to re-enter the cell cycle by YAP5SA, an active form of the Hippo signaling pathway effector YAP. METHODS: We performed clonal analyses to determine the cell cycle kinetics of YAP5SA cardiomyocytes. We also performed single-cell RNA sequencing, marker gene analysis, and functional studies to examine how YAP5SA cardiomyocytes progress through the cell cycle. RESULTS: We discovered that YAP5SA-expressing cardiomyocytes divided efficiently, with >20% of YAP5SA cardiomyocyte clones containing ≥2 cardiomyocytes. YAP5SA cardiomyocytes re-entered cell cycle at the G1/S transition and had an S phase lasting ≈48 hours. Sarcomere disassembly is required for cardiomyocyte progression from S to G2 phase and the induction of mitotic rounding. Although oscillatory Cdk expression was induced in YAP5SA cardiomyocytes, these cells inefficiently progressed through G2 phase. This is improved by inhibiting P21 function, implicating checkpoint activity as an additional barrier to YAP5SA-induced cardiomyocyte division. CONCLUSIONS: Our data reveal that YAP5SA overcomes the mechanically constrained myocardial microenvironment to induce mitotic rounding with cardiomyocyte division, thus providing new insights into the in vivo mechanisms that maintain cell cycle quiescence in adult mammals.
Hydrogen-terminated single crystal diamond MOSFET with the dielectric of Ga2O3
In this work, the first fabrication and investigation of normally-off single crystal hydrogen-sterminated diamond MOSFETs with Ga2O3 dielectric has been successfully carried out. 50-nm-thick Ga2O3 was deposited by electron-beam evaporation technique at room temperature. The maximum drain current was −36 mA/mm, which was 164 times larger than previous work. Based on the transfer characteristic curve, the threshold voltage, on/off ratio and extrinsic transconductance were −0.37 V, 2.3 × 107, and 9.8 mS/mm, respectively. The effective mobility of the MOSFET was calculated to be 264.1 cm2/V ⋅s at VGS = − 1 V. This work may significantly promote the application of H-diamond FETs.
Evaluating the effectiveness of different intervention measures for an outbreak of mycoplasma pneumoniae in hangzhou based on a dynamic model
Efficacy and Safety of Finerenone Across the Ejection Fraction Spectrum in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Prespecified Analysis of the FINEARTS-HF Trial
BACKGROUND: The effects of treatments for heart failure (HF) may vary among patients according to left ventricular ejection fraction (LVEF). In FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure), the nonsteroidal mineralocorticoid receptor antagonist finerenone reduced the risk of cardiovascular death and total worsening HF events in patients with HF with mildly reduced or preserved ejection fraction. We examined the effect of finerenone according to LVEF in FINEARTS-HF. METHODS: FINEARTS-HF was a randomized, placebo-controlled trial examining the efficacy and safety of finerenone in patients with HF and LVEF ≥40%. The treatment effect of finerenone was examined in prespecified analyses according to LVEF categories (<50%, ≥50% to <60%, and ≥60%) and with LVEF as a continuous variable. The primary outcome was a composite of total (first and recurrent) worsening HF events and cardiovascular death. RESULTS: Baseline LVEF data were available for 5993 of the 6001 participants in FINEARTS-HF. Mean and median LVEF were 53±8% and 53% (interquartile range, 46%–58%), respectively. LVEF was <50% in 2172 (36%), between 50% and <60% in 2674 (45%), and ≥60% in 1147 (19%). Patients with higher LVEF were older, were more commonly female, were less likely to have a history of coronary artery disease, and more frequently had a history of hypertension and chronic kidney disease compared with those with a lower LVEF. Finerenone reduced the risk of cardiovascular death and total HF events consistently across LVEF categories (LVEF <50% rate ratio, 0.84 [95% CI, 0.68–1.03]; LVEF ≥50% to <60% rate ratio, 0.80 [0.66–0.97]; and LVEF ≥60% rate ratio, 0.94 [0.70–1.25]; P interaction =0.70). There was no modification of the benefit of finerenone across the range of LVEF when analyzed as a continuous variable ( P interaction =0.28). There was a similar consistent effect of finerenone on reducing the total number of worsening HF events (continuous P interaction =0.26). CONCLUSIONS: In patients with HF with mildly reduced or preserved ejection fraction, finerenone reduced the risk of cardiovascular death and worsening HF events, irrespective of LVEF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04435626. URL: https://eudract.ema.europa.eu ; Unique identifier: 2020-000306-29.
Charge-mediated electric control of the perpendicular magnetic anisotropy in Fe–Ga/PMN-PT composite multiferroic
We present an experimental study of the magnetoelectric coupling in the Fe-Ga/Pb[(Mg1/3Nb2/3)O3]0.68-[PbTiO3]0.31 thin-film multiferroic composite using x-ray magnetic circular dichroism and ferromagnetic resonance (FMR). Our measurements show evidence for a charge-mediated coupling mechanism, suggested by the asymmetric magnetic remanence (Mrem) behavior under opposite electric fields (±E) and the asymmetric resonance field (Hr) in the FMR measurements. Also, the FMR measurements reveal a perpendicular magnetic anisotropy that can be related to an interface charge effect and it is tunable by the E field. Ab initio calculations support the existence of a charge-mediated coupling at the Fe–Ga/PMN-PT interface.
Novel insights into insect mediated polystyrene biodegradation through bacterial genome analyses
Abstract Plastic pollution is a significant environmental challenge of contemporary age. Polystyrene (PS), among the most commonly used plastic polymers worldwide, is highly durable and difficult to degrade. Despite various disposal strategies, PS continues to impact biodiversity, human health, and ecosystems. Recently, the scientific community has focused on the potential role of microorganisms for plastic biodegradation, particularly those from the gut of plastivorous insects. In a previous study, three bacterial strains, each representing a distinct taxonomic group (Klebsiella, Pseudomonas, and Stenotrophomonas), were isolated from Alphitobius diaperinus larvae after rearing on a PS diet and enriched in a medium with PS as the sole carbon source. The Stenotrophomonas sp. strain, here identified as S. indicatrix, showed the greatest potential for PS degradation. The present study investigates the genetic profile of the newly isolated S. indicatrix strain DAI2m/c through genome sequencing, to identify enzyme-encoding genes involved in the intracellular metabolic pathways responsible for the biodegradation of the styrene monomer. Our findings indicate that the genome of S. indicatrix strain DAI2m/c encodes all enzymes required for one of the two recognized styrene degradation pathways, suggesting its ability to convert styrene into byproducts that are then utilized for cellular energy production.
Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach
There is a new awareness of the widespread nature of metabolic dysfunction–associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular–liver–metabolic health. Metabolic dysfunction and associated insulin resistance, together with the predilection for ectopic fat deposition in the liver and surrounding tissues, are associated with elevated risk of endothelial dysfunction, systemic inflammatory response, and ectopic fat deposition in the epicardium. This complex pathophysiology can accelerate atherogenic dyslipidemia, atherogenesis, diastolic dysfunction, valvular calcification, and cardiac arrhythmias. Despite the mounting evidence of mechanistic pathways underpinning MASLD and CVD, current recommendations have not clearly focused upon MASLD as a risk factor or target for intervention in CVD. We have brought together a diverse range of international experts committed to promoting cardiovascular–liver–metabolic health and related outcomes across the globe. The overarching goal of this document is to offer a construct for clinicians in the cardiovascular field with regards to (1) diagnosis and screening of MASLD through the use of noninvasive serum and imaging tests; (2) screening for CVD in all individuals with MASLD regardless of established atherosclerotic risk factors; and (3) the approach to management of MASLD with respect to prevention of CVD through lifestyle, as well as pharmacologic and surgical strategies. To achieve this, the modified Delphi method was applied and a series of evidence-based quality standard recommendations have been identified.
Generation of non-diffracting vortex beams by an Archimedean spiral plate
The non-diffraction beams are featured with maintained phase and intensity profiles, which have been utilized in various fields. Previous approaches for producing non-diffraction beams focused on designed cubic optical elements, resulting in limitations for integrated applications. Here, we design a mask with a binary Archimedean spiral structure for generating a high-order non-diffraction vortex beam. The produced plate imparts a conical phase to the incident beam, enabling the modulated beam to possess the characteristics of a Bessel wave, i.e., the spiral phase, non-diffraction, and self-healing. This mask may find promising applications, e.g., optical communication and imaging.
Improving the resilience of urban transportation to natural disasters: the case of Changchun, China
What Is the Mechanism of Atrial Fibrillation Initiation?
Modeling and dynamic analysis of split torsion transmission system considering backlash and center distance errors
Sickle Trait and Alpha Thalassemia Increase NOS-Dependent Vasodilation of Human Arteries Through Disruption of Endothelial Hemoglobin-eNOS Interactions
BACKGROUND: Severe malaria is associated with impaired nitric oxide (NO) synthase (NOS)–dependent vasodilation, and reversal of this deficit improves survival in murine models. Malaria might have selected for genetic polymorphisms that increase endothelial NO signaling and now contribute to heterogeneity in vascular function among humans. One protein potentially selected for is alpha globin, which, in mouse models, interacts with endothelial NOS (eNOS) to negatively regulate NO signaling. We sought to evaluate the impact of alpha globin gene deletions on NO signaling and unexpectedly found human arteries use not only alpha but also beta globin to regulate eNOS. METHODS: The eNOS-hemoglobin complex was characterized by multiphoton imaging, gene expression analysis, and coimmunoprecipitation studies of human resistance arteries. Novel contacts between eNOS and hemoglobin were mapped using molecular modeling and simulation. Pharmacological or genetic disruption of the eNOS-hemoglobin complex was evaluated using pressure myography. The association between alpha globin gene deletion and blood pressure was assessed in a population study. RESULTS: Alpha and beta globin transcripts were detected in the endothelial layer of the artery wall. Imaging colocalized alpha and beta globin proteins with eNOS at myoendothelial junctions. Immunoprecipitation demonstrated that alpha globin and beta globin form a complex with eNOS and cytochrome b5 reductase. Modeling predicted negatively charged glutamic acids at positions 6 and 7 of beta globin to interact with positively charged arginines at positions 97 and 98 of eNOS. Arteries from donors with a glutamic acid–to–valine substitution at beta globin position 6 (sickle trait) exhibited increased NOS-dependent vasodilation. Alpha globin gene deletions were associated with decreased arterial alpha globin expression, increased NOS-dependent vasodilation, and lower blood pressure. Mimetic peptides that targeted the interactions between hemoglobin and eNOS recapitulated the effects of these genetic variants on human arterial vasoreactivity. CONCLUSIONS: Alpha and beta globin subunits of hemoglobin interact with eNOS to restrict NO signaling in human resistance arteries. Malaria-protective genetic variants that alter the expression of alpha globin or the structure of beta globin are associated with increased NOS-dependent vasodilation. Targeting the hemoglobin-eNOS interface could potentially improve NO signaling in diseases of endothelial dysfunction such as severe malaria or chronic cardiovascular conditions.
Experimental study on steady-state operation of organic Rankine cycle system under different operating conditions
Insights into the photocatalytic removal of malachite green organic pollutant by highly efficient hard responsive Ba1 − xCoxDyyFe12−yO19 catalysts
Full-dimensional accurate potential energy surface and dynamics for the unimolecular isomerization reaction CH3NC ⇌ CH3CN
The reaction CH3NC ⇌ CH3CN, a model reaction for the study of unimolecular isomerization, is important in astronomy and atmospheric chemistry and has long been studied by numerous experiments and theories. In this work, we report the first full-dimensional accurate potential energy surface (PES) of this reaction by the permutation invariant polynomial-neural network method based on 30 974 points, whose energies are calculated at the CCSD(T)-F12a/AVTZ level. Then, ring polymer molecular dynamics is used to derive the free energy barrier of the reaction at the experimental temperature range of 472.55–532.92 K. Reaction kinetics are studied at the high-pressure limit and in the fall-off region by standard transition state theory and the master equation, respectively. The calculated temperature- and pressure-dependent rate coefficients are in good agreement with previous experimental and theoretical results. Furthermore, quasi-classical trajectory simulations are performed on this PES to study the intramolecular energy transfer dynamics at initial vibrational energies of 4.336, 5.204, and 6.505 eV.
Efficacy of home based computerized adaptive cognitive training in patients with post stroke cognitive impairment: a randomized controlled trial
TIP 4 P 2005 Ice : Simulating water with two molecular states
Rigid, non-polarizable water models are very efficient from a computational point of view, and some of them have a great ability in predicting experimental properties. There is, however, little room for improvement in simulating water with this strategy, whose main shortcoming is that water molecules do not change their interaction parameters in response to the local molecular landscape. In this work, we propose a novel modeling strategy that involves using two rigid non-polarizable models as states that water molecules can adopt depending on their molecular environment. During the simulation, molecules dynamically transition from one state to another depending on a local order parameter that quantifies some local structural feature. In particular, molecules belonging to low- and high-tetrahedral order environments are represented with the TIP4P/2005 and TIP4P/Ice rigid models, respectively. In this way, the interaction between water molecules is strengthened when they acquire a tetrahedral coordination, which can be viewed as an effective way of introducing polarization effects. We call the resulting model TIP4P2005Ice and show that it outperforms either of the rigid models that build it. This multi-state strategy only slows down simulations by a factor of 1.5 compared to using a standard non-polarizable model and holds great promise for improving simulations of water and aqueous solutions.
Impact of thermal denaturation on renal volume reduction after partial nephrectomy using soft coagulation hemostasis
Polariton spectra under the collective coupling regime. I. Efficient simulation of linear spectra and quantum dynamics
We outline two general theoretical techniques to simulate polariton quantum dynamics and optical spectra under the collective coupling regimes described by a Holstein–Tavis–Cummings (HTC) model Hamiltonian. The first one takes advantage of sparsity of the HTC Hamiltonian, which allows one to reduce the cost of acting polariton Hamiltonian onto a state vector to the linear order of the number of states, instead of the quadratic order. The second one is applying the well-known Chebyshev series expansion approach for quantum dynamics propagation and to simulate the polariton dynamics in the HTC system; this approach allows us to use a much larger time step for propagation and only requires a few recursive operations of the polariton Hamiltonian acting on state vectors. These two theoretical approaches are general and can be applied to any trajectory-based non-adiabatic quantum dynamics methods. We apply these two techniques with our previously developed Lindblad-partially linearized density matrix approach to simulate the linear absorption spectra of the HTC model system, with both inhomogeneous site energy disorders and dipolar orientational disorders. Our numerical results agree well with the previous analytic and numerical work.