Simulating Polaritonic Ground States on Noisy Quantum Devices.

The recent advent of quantum algorithms for noisy quantum devices offers a new route toward simulating strong light-matter interactions of molecules in optical cavities for polaritonic chemistry. In this work, we introduce a general framework for simulating electron-photon-coupled systems on small, noisy quantum devices. This method is based on the variational quantum eigensolver (VQE) with the polaritonic unitary coupled cluster (PUCC) ansatz. To achieve chemical accuracy, we exploit various symmetries in qubit reduction methods, such as electron-photon parity, and use recently developed error mitigation schemes, such as the reference zero-noise extrapolation method. We explore the robustness of the VQE-PUCC approach across a diverse set of regimes for the bond length, cavity frequency, and coupling strength of the H2 molecule in an optical cavity. To quantify the performance, we measure two properties: ground-state energy, fundamentally relevant to chemical reactivity, and photon number, an experimentally accessible general indicator of electron-photon correlation.

Emerging ESG reporting of higher education institutions in China.

This paper investigates the ESG reporting practices of Chinese higher education institutions (HEIs). Based on Global Reporting Initiative's common reporting standards and the education sector-specific indicators proposed by earlier studies, we construct a disclosure framework of 112 indicators classified into environmental, social, governance, and educational dimensions. We manually collect all ESG-related information disclosed by 147 elite Chinese HEIs from various channels, including 8 standalone sustainability reports, around 600 annual reports, 139 charters, official websites, and official social media accounts, for the period 2020-2023. The results demonstrate how Chinese HEIs disclose different types of ESG information via different channels, with most of the information disclosed through channels other than standalone sustainability reports. Most Chinese HEIs do not adopt any specific disclosure standards but loosely follow the Sustainable Development Goals (SDGs) in reporting. We further assess the quality of the disclosed information for each indicator and observe that, quality-wise, governance > educational > social > environmental, highlighting the necessity for Chinese HEIs to enhance environmental reporting. Next, we investigate the determinants of reporting quality and find that an HEI's number of faculty members is a more significant factor associated with its ESG reporting quality than other factors (i.e., number of students, funding, expenditure). Chinese HEIs are advised to report in a more balanced manner across the four dimensions in a standalone report using an education-oriented indicator-based framework instead of the current SDGs-based framework, to improve the completeness, materiality, and comparability of information.

Dissociation dynamics of a diatomic molecule in an optical cavity.

We study the dissociation dynamics of a diatomic molecule, modeled as a Morse oscillator, coupled to an optical cavity. A marked suppression of the dissociation probability, both classical and quantum, is observed for cavity frequencies significantly below the fundamental transition frequency of the molecule. We show that the suppression in the probability is due to the nonlinearity of the dipole function. The effect can be rationalized entirely in terms of the structures in the classical phase space of the model system.

Chemical reactivity under collective vibrational strong coupling.

Recent experiments of chemical reactions in optical cavities have shown great promise to alter and steer chemical reactions, but still remain poorly understood theoretically. In particular, the origin of resonant effects between the cavity and certain vibrational modes in the collective limit is still subject to active research. In this paper, we study the unimolecular dissociation reactions of many molecules, collectively interacting with an infrared cavity mode, through their vibrational dipole moment. We find that the reaction rate can slow down by increasing the number of aligned molecules, if the cavity mode is resonant with a vibrational mode of the molecules. We also discover a simple scaling relation that scales with the collective Rabi splitting, to estimate the onset of reaction rate modification by collective vibrational strong coupling and numerically demonstrate these effects for up to 104 molecules.

Single nuclei transcriptomics of muscle reveals intra-muscular cell dynamics linked to dystrophin loss and rescue.

In Duchenne muscular dystrophy, dystrophin loss leads to chronic muscle damage, dysregulation of repair, fibro-fatty replacement, and weakness. We develop methodology to efficiently isolate individual nuclei from minute quantities of frozen skeletal muscle, allowing single nuclei sequencing of irreplaceable archival samples and from very small samples. We apply this method to identify cell and gene expression dynamics within human DMD and mdx mouse muscle, characterizing effects of dystrophin rescue by exon skipping therapy at single nuclei resolution. DMD exon 23 skipping events are directly observed and increased in myonuclei from treated mice. We describe partial rescue of type IIa and IIx myofibers, expansion of an MDSC-like myeloid population, recovery of repair/remodeling M2-macrophage, and repression of inflammatory POSTN1 + fibroblasts in response to exon skipping and partial dystrophin restoration. Use of this method enables exploration of cellular and transcriptomic mechanisms of dystrophin loss and repair within an intact muscle environment. Our initial findings will scaffold our future work to more directly examine muscular dystrophies and putative recovery pathways.

Exploring the Relationship Between ESG Performance and Green Bond Issuance.

As an important part of green financial instruments, green bonds have become increasingly popular in recent years. This study employs green bond issuance as a proxy to measure investors' recognition of a firm's sustainable activities by linking literature on ESG and financial performance and those on green bond issuance. This study innovatively creates the datasets by combining the ESG performance of Chinese listed companies with their green bond issuance from 2016 to 2020 based on the Wind and CSMAR databases and examines the relationship between the performance of ESG dimensions and green bond issuance from the perspective of listed firms in the emerging market. The results indicate that decent ESG practices not only increase the propensity in green bond issuance by listed firms but also help them issue more green bonds. More specifically, we found evidence to support this finding from every dimension of these sustainable practices. However, this study identified the negative effect of financial performance in issuing green bonds when combining the effect of ESG performance.

Entangled photons from composite cascade emitters.

One of the most versatile sources for entangled photons are emitters that interact via more than one tunable mechanism. Here, we demonstrate how hybridization and dipole-dipole interactions-potentially simultaneously available in colloidal quantum dots and molecular aggregates-leveraged in conjunction can couple simple, well understood emitters into composite emitters with flexible control over the level structure. We show that cascade decay through carefully designed level structures can result in emission of frequency-entangled photons with Bell states and three-photon GHZ states as example cases. These results pave the way toward rational design of quantum optical emitters of entangled photons.

Cavity-Modified Unimolecular Dissociation Reactions via Intramolecular Vibrational Energy Redistribution.

While the emerging field of vibrational polariton chemistry has the potential to overcome traditional limitations of synthetic chemistry, the underlying mechanism is not yet well understood. Here, we explore how the dynamics of unimolecular dissociation reactions that are rate-limited by intramolecular vibrational energy redistribution (IVR) can be modified inside an infrared optical cavity. We study a classical model of a bent triatomic molecule, where the two outer atoms are bound by anharmonic Morse potentials to the center atom coupled to a harmonic bending mode. We show that an optical cavity resonantly coupled to particular anharmonic vibrational modes can interfere with IVR and alter unimolecular dissociation reaction rates when the cavity mode acts as a reservoir for vibrational energy. These results lay the foundation for further theoretical work toward understanding the intriguing experimental results of vibrational polaritonic chemistry within the context of IVR.

Defect Polaritons from First Principles.

Control over the optical properties of defects in solid-state materials is necessary for their application in quantum technologies. In this study, we demonstrate, from first principles, how to tune these properties via the formation of defect polaritons in an optical cavity. We show that the polaritonic splitting that shifts the absorption energy of the lower polariton is much higher than can be expected from a Jaynes-Cummings interaction. We also find that the absorption intensity of the lower polariton increases by several orders of magnitude, suggesting a possible route toward overcoming phonon-limited single-photon emission from defect centers. These findings are a result of an effective continuum of electronic transitions near the lowest-lying electronic transition that dramatically enhances the strength of the light-matter interaction. We expect our findings to spur experimental investigations of strong light-matter coupling between defect centers and cavity photons for applications in quantum technologies.

The evolution of safety-adjusted transportation efficiency for the road system in China.

Traffic accident is a grievous problem that costs more than one million lives worldwide every year, but remains understudied in transportation efficiency literature. This paper develops safety-adjusted transportation efficiency to account for the negative outcomes in transportation including accidents, fatalities, injuries and property loss. We model the transportation efficiency under the data envelopment analysis (DEA) framework by treating the accident-related negative outcomes as undesirable outputs. Two DEA models, based on radial and non-radial structures respectively, are proposed for panel data. We apply the methods to 31 provinces in China over a 20-year horizon 1998-2017. We find that the evolution of China's overall safety-adjusted transportation efficiency follows a U-shaped path: It deteriorated between 1998 and 2002, steadily improved from 2002 to 2012, and stabilized during 2012-2017. The majority of the provinces improved their safety-adjusted transportation efficiency from 1998 to 2017, except for one province that maintained the status quo and three provinces that experienced a decline in performance. Improvement analysis is carried out to identify gaps in accident-related factors that each province should close to attain best-practice. Further, we find strong evidence of unconditional ß-convergence and σ-convergence in safety-adjusted transportation efficiency, indicating that the provinces with low initial efficiency generally grew more rapidly and the dispersion of provincial efficiency levels diminished. The main findings are substantially different from the regular transportation efficiency analysis that does not consider the accident-related undesirable factors. The safety-adjusted transportation efficiency can convey important information that the regular transportation efficiency fails to capture.

Quantum Interfaces to the Nanoscale.

Scalable quantum information systems would store, manipulate, and transmit quantum information locally and across a quantum network, but no single qubit technology is currently robust enough to perform all necessary tasks. Defect centers in solid-state materials have emerged as potential intermediaries between other physical manifestations of qubits, such as superconducting qubits and photonic qubits, to leverage their complementary advantages. It remains an open question, however, how to design and to control quantum interfaces to defect centers. Such interfaces would enable quantum information to be moved seamlessly between different physical systems. Understanding and constructing the required interfaces would, therefore, unlock the next big steps in quantum computing, sensing, and communications. In this Perspective, we highlight promising coupling mechanisms, including dipole-, phonon-, and magnon-mediated interactions, and discuss how contributions from nanotechnologists will be paramount in realizing quantum information processors in the near-term.

Fibroblast growth factor 23 (FGF23) induces ventricular arrhythmias and prolongs QTc interval in mice in an FGF receptor 4-dependent manner.

Fibroblast growth factor 23 (FGF23) is a phosphate regulating protein hormone released by osteocytes. FGF23 becomes markedly elevated in chronic kidney disease (CKD), for which the leading cause of death is cardiovascular disease, particularly sudden cardiac death. Previously, we found that FGF23 increases intracellular Ca2+ in cardiomyocytes and alters contractility in mouse ventricles ex vivo via FGF receptor 4 (FGFR4). In the present study, we demonstrate that FGF23 induces cardiac arrhythmias and prolongs QTc interval in mice, and we tested whether these effects are mediated through FGFR4. In isolated Langendorff perfused hearts, FGF23 perfusion increased mechanical arrhythmias in the form of premature ventricular beats (PVBs), and induced runs of ventricular tachycardia in 6 of 11 animals, which were attenuated with pretreatment of an anti-FGFR4 blocking antibody. Ex vivo ECG analysis of isolated intact hearts showed increased ventricular arrhythmias and QTc prolongation after FGF23 infusion compared with vehicle. In vivo, injection of FGF23 into the jugular vein led to the emergence of premature ventricular contractions (PVCs) in 5 out of 11 experiments. FGF23 also produced a significant lengthening effect upon QTc interval in vivo. In vivo FGFR4 blockade ameliorated the arrhythmogenic and QTc prolonging effects of FGF23. Finally, FGF23 increased cardiomyocyte Ca2+ levels in intact left ventricular muscle which was inhibited by FGR4 blockade. We conclude that FGF23/FGFR4 signaling in the heart may contribute to ventricular arrhythmogenesis and repolarization disturbances commonly observed in patients with CKD via Ca2+ overload and may be an important therapeutic target to reduce cardiac mortality in CKD.NEW & NOTEWORTHY Here we provide direct evidence that fibroblast growth factor 23 (FGF23), a phosphaturic hormone elevated in chronic kidney disease, is proarrhythmic. FGF23 acutely triggered ventricular arrhythmias and prolonged corrected QT interval (QTc) in isolated mouse hearts and in vivo. FGF23 also increased Ca2+ levels in ventricular muscle tissue. Blockade of the FGF receptor 4 signaling pathway using a monoclonal antibody ameliorated ventricular arrhythmias, QTc prolongation, and elevated ventricular Ca2+ induced by FGF23, and may represent a potential therapeutic target in chronic kidney disease.

Light-matter interaction of a molecule in a dissipative cavity from first principles.

Cavity-mediated light-matter coupling can dramatically alter opto-electronic and physico-chemical properties of a molecule. Ab initio theoretical predictions of these systems need to combine non-perturbative, many-body electronic structure theory-based methods with cavity quantum electrodynamics and theories of open-quantum systems. Here, we generalize quantum-electrodynamical density functional theory to account for dissipative dynamics of the cavity and describe coupled cavity-single molecule interactions in the weak-to-strong-coupling regimes. Specifically, to establish this generalized technique, we study excited-state dynamics and spectral responses of benzene and toluene under weak-to-strong light-matter coupling. By tuning the coupling, we achieve cavity-mediated energy transfer between electronically excited states. This generalized ab initio quantum-electrodynamical density functional theory treatment can be naturally extended to describe cavity-mediated interactions in arbitrary electromagnetic environments, accessing correlated light-matter observables and thereby closing the gap between electronic structure theory, quantum optics, and nanophotonics.

Hybridized Defects in Solid-State Materials as Artificial Molecules.

Two-dimensional materials can be crafted with structural precision approaching the atomic scale, enabling quantum defects-by-design. These defects are frequently described as "artificial atoms" and are emerging optically addressable spin qubits. However, interactions and coupling of such artificial atoms with each other, in the presence of the lattice, warrants further investigation. Here we present the formation of "artificial molecules" in solids, introducing a chemical degree of freedom in control of quantum optoelectronic materials. Specifically, in monolayer hexagonal boron nitride as our model system, we observe configuration- and distance-dependent dissociation curves and hybridization of defect orbitals within the bandgap into bonding and antibonding orbitals, with splitting energies ranging from ∼10 meV to nearly 1 eV. We calculate the energetics of cis and trans out-of-plane defect pairs CHB-CHB against an in-plane defect pair CB-CB and find that in-plane defect pair interacts more strongly than out-of-plane pairs. We demonstrate an application of this chemical degree of freedom by varying the distance between CB and VN of CBVN and observe changes in the predicted peak absorption wavelength from the visible to the near-infrared spectral band. We envision leveraging this chemical degree of freedom of defect complexes to precisely control and tune defect properties toward engineering robust quantum memories and quantum emitters for quantum information science.

Elevated postischemic tissue injury and leukocyte-endothelial adhesive interactions in mice with global deficiency in caveolin-2: role of PAI-1.

Ischemia/reperfusion (I/R)-induced rapid inflammation involving activation of leukocyte-endothelial adhesive interactions and leukocyte infiltration into tissues is a major contributor to postischemic tissue injury. However, the molecular mediators involved in this pathological process are not fully known. We have previously reported that caveolin-2 (Cav-2), a protein component of plasma membrane caveolae, regulated leukocyte infiltration in mouse lung carcinoma tumors. The goal of the current study was to examine if Cav-2 plays a role in I/R injury and associated acute leukocyte-mediated inflammation. Using a mouse small intestinal I/R model, we demonstrated that I/R downregulates Cav-2 protein levels in the small bowel. Further study using Cav-2-deficient mice revealed aggravated postischemic tissue injury determined by scoring of villi length in H&E-stained tissue sections, which correlated with increased numbers of MPO-positive tissue-infiltrating leukocytes determined by IHC staining. Intravital microscopic analysis of upstream events relative to leukocyte transmigration and tissue infiltration revealed that leukocyte-endothelial cell adhesive interactions in postcapillary venules, namely leukocyte rolling and adhesion were also enhanced in Cav-2-deficient mice. Mechanistically, Cav-2 deficiency increased plasminogen activator inhibitor-1 (PAI-1) protein levels in the intestinal tissue and a pharmacological inhibition of PAI-1 had overall greater inhibitory effect on both aggravated I/R tissue injury and enhanced leukocyte-endothelial interactions in postcapillary venules in Cav-2-deficient mice. In conclusion, our data suggest that Cav-2 protein alleviates tissue injury in response to I/R by dampening PAI-1 protein levels and thereby reducing leukocyte-endothelial adhesive interactions.NEW & NOTEWORTHY The role of caveolin-2 in regulating ischemia/reperfusion (I/R) tissue injury and the mechanisms underlying its effects are unknown. This study uses caveolin-2-deficient mouse and small intestinal I/R injury models to examine the role of caveolin-2 in the leukocyte-dependent reperfusion injury. We demonstrate for the first time that caveolin-2 plays a protective role from the I/R-induced leukocyte-dependent reperfusion injury by reducing PAI-1 protein levels in intestinal tissue and leukocyte-endothelial adhesive interactions in postcapillary venules.

Endothelial deficiency of insulin-like growth factor-1 receptor reduces endothelial barrier function and promotes atherosclerosis in Apoe-deficient mice.

Insulin-like growth factor-1 (IGF-1) decreases atherosclerosis in apolipoprotein E (Apoe)-deficient mice when administered systemically. However, mechanisms for its atheroprotective effect are not fully understood. We generated endothelium-specific IGF-1 receptor (IGF1R)-deficient mice on an Apoe-deficient background to assess effects of IGF-1 on the endothelium in the context of hyperlipidemia-induced atherosclerosis. Endothelial deficiency of IGF1R promoted atherosclerotic burden, when animals were fed on a high-fat diet for 12 wk or normal chow for 12 mo. Under the normal chow feeding condition, the vascular relaxation response to acetylcholine was increased in the endothelial IGF1R-deficient aorta; however, feeding of a high-fat diet substantially attenuated the relaxation response, and there was no difference between endothelial IGF1R-deficient and control mice. The endothelium and its intercellular junctions provide a barrier function to the vasculature. In human aortic endothelial cells, IGF-1 upregulated occludin, claudin 5, VE-cadherin, JAM-A, and CD31 expression levels, and vice versa, specific IGF1R inhibitor, picropodophyllin, an IGF1R-neutralizing antibody (αIR3), or siRNA to IGF1R abolished the IGF-1 effects on junction and adherens proteins, suggesting that IGF-1 promoted endothelial barrier function. Moreover, endothelial transwell permeability assays indicated that inhibition of IGF-1 signaling elevated solute permeability through the monolayer of human aortic endothelial cells. In summary, endothelial IGF1R deficiency increases atherosclerosis, and IGF-1 positively regulates tight junction protein and adherens junction protein levels and endothelial barrier function. Our findings suggest that the elevation of the endothelial junction protein level is, at least in part, the mechanism for antiatherogenic effects of IGF-1.NEW & NOTEWORTHY Endothelial insulin-like growth factor-1 (IGF-1) receptor deficiency significantly elevated atherosclerotic burden in apolipoprotein E-deficient mice, mediated at least in part by downregulation of intercellular junction proteins and, thus, elevated endothelial permeability. This study revealed a novel role for IGF-1 in supporting endothelial barrier function. These findings suggest that IGF-1's ability to promote endothelial barrier function may offer a novel therapeutic strategy for vascular diseases such as atherosclerosis.

Myeloperoxidase instigates proinflammatory responses in a cecal ligation and puncture rat model of sepsis.

Myeloperoxidase (MPO)-derived hypochlorous (HOCl) reacts with membrane plasmalogens to yield α-chlorofatty aldehydes such as 2-chlorofatty aldehyde (2-ClFALD) and its metabolite 2-chlorofatty acid (2-ClFA). Recent studies showed that 2-ClFALD and 2-ClFA serve as mediators of the inflammatory responses to sepsis by as yet unknown mechanisms. Since no scavenger for chlorinated lipids is available and on the basis of the well-established role of the MPO/HOCl/chlorinated lipid axis in inflammatory responses, we hypothesized that treatment with MPO inhibitors (N-acetyl lysyltyrosylcysteine amide or 4-aminobenzoic acid hydrazide) would inhibit inflammation and proinflammatory mediator expression induced by cecal ligation and puncture (CLP). We used intravital microscopy to quantify in vivo inflammatory responses in Sham and CLP rats with or without MPO inhibition. Small intestines, mesenteries, and lungs were collected to assess changes in MPO-positive staining and lung injury, respectively, as well as free 2-ClFA and proinflammatory mediators levels. CLP caused neutrophil infiltration, 2-ClFA generation, acute lung injury, leukocyte-/platelet-endothelium interactions, mast cell activation (MCA), plasminogen activator inhibitor-1 (PAI-1) production, and the expression of several cytokines, chemokines, and vascular endothelial growth factor, changes that were reduced by MPO inhibition. Pretreatment with a PAI-1 inhibitor or MC stabilizer prevented CLP-induced leukocyte-endothelium interactions and MCA, and abrogated exogenous 2-ClFALD-induced inflammatory responses. Thus, we provide evidence that MPO instigates these inflammatory changes in CLP and that chlorinated lipids may serve as a mechanistic link between the enzymatic activity of MPO and PAI-1- and mast cell-dependent adhesive interactions, providing a rationale for new therapeutic interventions in sepsis.NEW & NOTEWORTHY Using two distinct myeloperoxidase (MPO) inhibitors, we show for the first time that MPO plays an important role in producing increases in free 2-chlorofatty aldehyde (2-ClFALD)-a powerful proinflammatory chlorinated lipid in plasma and intestine-a number of cytokines and other inflammatory mediators, leukocyte and platelet rolling and adhesion in postcapillary venules, and lung injury in a cecal ligation and puncture model of sepsis. In addition, the use of a plasminogen activator inhibitor-1 (PAI-1) inhibitor or a mast cell stabilizer prevented inflammatory responses in CLP-induced sepsis. PAI-1 inhibition also prevented the proinflammatory responses to exogenous 2-ClFALD superfusion. Thus, our study provides some of the first evidence that MPO-derived free 2-ClFA plays an important role in CLP-induced sepsis by a PAI-1- and mast cell-dependent mechanism.

Impact of multidisciplinary engagement in a quality improvement blood conservation protocol for craniosynostosis.

OBJECTIVE: Patients undergoing open cranial vault remodeling for craniosynostosis frequently experience substantial blood loss requiring blood transfusion. Multiple reports in the literature have evaluated the impact of individual blood conservation techniques on blood transfusion rates during craniosynostosis surgery. The authors engaged a multidisciplinary team and assessed the impact of input from multiple stakeholders on the evolution of a comprehensive quality improvement protocol aimed at reducing or eliminating blood transfusion in patients undergoing open surgery for craniosynostosis. METHODS: Over a 4-year period from 2012 to 2016, 39 nonsyndromic patients were operated on by a single craniofacial plastic surgeon. Initially, no clear blood conservation protocol existed, and specific interventions were individually driven. In 2014, a new pediatric neurosurgeon joined the craniofacial team, and additional stakeholders in anesthesiology, transfusion medicine, critical care, and hematology were brought together to evaluate opportunities for developing a comprehensive blood conservation protocol. The initial version of the protocol involved the standardized administration of intraoperative aminocaproic acid (ACA) and the use of a cell saver. In the second version of the protocol, the team implemented the preoperative use of erythropoietin (EPO). In addition, intraoperative and postoperative resuscitation and transfusion guidelines were more clearly defined. The primary outcomes of estimated blood loss (EBL), transfusion rate, and intraoperative transfusion volume were analyzed. The secondary impact of multidisciplinary stakeholder input was inferred by trends in the data obtained with the implementation of the partial and full protocols. RESULTS: Implementing the full quality improvement protocol resulted in a 66% transfusion-free rate at the time of discharge compared to 0% without any conservation protocol and 27% with the intermediate protocol. The administration of EPO significantly increased starting hemoglobin/hematocrit (11.1 g/dl/31.8% to 14.7 g/dl/45.6%, p < 0.05). The group of patients receiving ACA had lower intraoperative EBL than those not receiving ACA, and trends in the final-protocol cohort, which had received both preoperative EPO and intraoperative ACA, demonstrated decreasing transfusion volumes, though the decrease did not reach statistical significance. CONCLUSIONS: Patients undergoing open calvarial vault remodeling procedures benefit from the input of a multidisciplinary stakeholder group in blood conservation protocols. Further research into comprehensive protocols for blood conservation may benefit from input from the full surgical team (plastic surgery, neurosurgery, anesthesiology) as well as additional pediatric subspecialty stakeholders including transfusion medicine, critical care, and hematology.

Trimethylamine-N-oxide acutely increases cardiac muscle contractility.

Cardiovascular disease is a major cause of morbidity and mortality among patients with chronic kidney disease (CKD). Trimethylamine-N-oxide (TMAO), a uremic metabolite that is elevated in the setting of CKD, has been implicated as a nontraditional risk factor for cardiovascular disease. While association studies have linked elevated plasma levels of TMAO to adverse cardiovascular outcomes, its direct effect on cardiac and smooth muscle function remains to be fully elucidated. We hypothesized that pathological concentrations of TMAO would acutely increase cardiac and smooth muscle contractility. These effects may ultimately contribute to cardiac dysfunction during CKD. High levels of TMAO significantly increased paced, ex vivo human cardiac muscle biopsy contractility (P < 0.05). Similarly, TMAO augmented contractility in isolated mouse hearts (P < 0.05). Reverse perfusion of TMAO through the coronary arteries via a Langendorff apparatus also enhanced cardiac contractility (P < 0.05). In contrast, the precursor molecule, trimethylamine (TMA), did not alter contractility (P > 0.05). Multiphoton microscopy, used to capture changes in intracellular calcium in paced, adult mouse hearts ex vivo, showed that TMAO significantly increased intracellular calcium fluorescence (P < 0.05). Interestingly, acute administration of TMAO did not have a statistically significant influence on isolated aortic ring contractility (P > 0.05). We conclude that TMAO directly increases the force of cardiac contractility, which corresponds with TMAO-induced increases in intracellular calcium but does not acutely affect vascular smooth muscle or endothelial function of the aorta. It remains to be determined if this acute inotropic action on cardiac muscle is ultimately beneficial or harmful in the setting of CKD.NEW & NOTEWORTHY We demonstrate for the first time that elevated concentrations of TMAO acutely augment myocardial contractile force ex vivo in both murine and human cardiac tissue. To gain mechanistic insight into the processes that led to this potentiation in cardiac contraction, we used two-photon microscopy to evaluate intracellular calcium in ex vivo whole hearts loaded with the calcium indicator dye Fluo-4. Acute treatment with TMAO resulted in increased Fluo-4 fluorescence, indicating that augmented cytosolic calcium plays a role in the effects of TMAO on force production. Lastly, TMAO did not show an effect on aortic smooth muscle contraction or relaxation properties. Our results demonstrate novel, acute, and direct actions of TMAO on cardiac function and help lay the groundwork for future translational studies investigating the complex multiorgan interplay involved in cardiovascular pathogenesis during CKD.

Nanomagnonic Cavities for Strong Spin-Magnon Coupling and Magnon-Mediated Spin-Spin Interactions.

We present a theoretical approach to use ferromagnetic or ferrimagnetic nanoparticles as microwave nanomagnonic cavities to concentrate microwave magnetic fields into deeply subwavelength volumes ∼10^{-13} mm^{3}. We show that the field in such nanocavities can efficiently couple to isolated spin emitters (spin qubits) positioned close to the nanoparticle surface reaching the single magnon-spin strong-coupling regime and mediate efficient long-range quantum state transfers between isolated spin emitters. Nanomagnonic cavities thus pave the way toward magnon-based quantum networks and magnon-mediated quantum gates.