Wavelength scaling of high harmonic yields and cutoff energies in solids driven by mid-infrared pulses.

The effect of driving wavelengths on high harmonic generation (HHG) have long been a fundamental research topic. However, despite of abundant efforts, the investigation of wavelength scaling of HHG in solids is still confined within the scope of theoretical predictions. In this work, we for the first time to the best of our knowledge, experimentally reveal wavelength scaling of HHG yields and cutoff energy in three typical solid media (namely pristine crystals GaSe, CdTe and polycrystalline ZnSe), driven in a broad mid-infrared (MIR) range from 4.0 to 8.7 µm. It is revealed that when the driving wavelength is shorter than 6.5-7.0 µm, HHG yields decrease monotonously with the MIR driving wavelengths, while they rise abruptly by 1-3 orders of magnitude driven at longer wavelength and exhibit a crest at 7.5 µm. In addition, the cutoff energies are found independent on driving wavelengths across the broad MIR pump spectral range. We propose that the interband mechanism dominates the HHG process when the driving wavelength is shorter than 6.5-7.0 µm, and as the driving wavelength increases, intraband contribution leads to an abrupt rise of the HHG yields, which is verified by the HHG polarization measurement driven at 3.0 and 7.0 µm. This work not only experimentally demonstrate the wavelength scaling of HHG in solids, but more importantly blazes the trail for optimizing the HHG performance by choosing a driving wavelength and provides experimental method to distinguish the interband and intraband dynamics.

Micropatterned Hydrogels with Highly Ordered Cellulose Nanocrystals for Visually Monitoring Cardiomyocytes.

Cardiac microphysiological systems are accurate in vitro platforms that reveal the biological mechanisms underlying cardiopathy, accelerating pharmaceutical research in this field. Current cardiac microphysiological devices and organs-on-chips consist of several layers prepared with complex, multi-step processes. Incorporating inorganic photonic crystals may cause long-term biocompatibility issues. Herein, micropatterned hydrogels with anisotropic structural colors are prepared by locking shear-oriented tunicate cellulose nanocrystals (TCNCs) in hydrogel networks through in situ polymerization, allowing the visualization and monitoring of cardiomyocytes. The anisotropic hydrogels are composed of highly ordered TCNCs with bright interference color and micro-grooved methacrylated gelatin with excellent biocompatibility. The microgroove patterns induce cardiomyocyte alignment and the autonomous beating of cardiomyocytes causes the hydrogels to deform, dynamically shifting the interference color. These micropatterned hydrogels could noninvasively monitor real-time changes of cardiomyocytes under pharmaceutical treatment and electrical stimulation through wavelength shifts in the transmittance spectra. This system provides a new way to detect the beat rate of cardiac tissue and it may contribute to high throughput develop.

Ultrabroad (3.7-17†µm) tunable femtosecond optical parametric amplifier based on BaGa4Se7 crystal.

We demonstrate the first (to the best of our knowledge) tunable femtosecond (fs) mid-infrared (MIR) optical parametric amplifier (OPA) based on BaGa4Se7 (BGSe) crystal with an ultra-broadband spectral range. Benefiting from the broad transparency range, high nonlinearity, and relatively large bandgap of BGSe, the MIR OPA pumped at 1030 nm with a repetition of 50 kHz has an output spectrum that is tunable across an extremely wide spectral range spanning from 3.7 to 17 µm. The maximum output power of the MIR laser source is measured as 10 mW at a center wavelength of 16 µm, corresponding to a quantum conversion efficiency of 5%. Power scaling is straightforwardly achieved by using a stronger pump in BGSe with an available large aperture size. A pulse width of 290 fs centered at 16 µm is supported by the BGSe OPA. Our experimental result indicates that BGSe crystal could serve as a promising nonlinear crystal for fs MIR generation with an ultra-broadband tuning spectral range via parametric downconversion for applications such as MIR ultrafast spectroscopy.

Investigating and Resolving Cardiotoxicity Induced by COVID-19 Treatments using Human Pluripotent Stem Cell-Derived Cardiomyocytes and Engineered Heart Tissues.

Coronavirus disease 2019 continues to spread worldwide. Given the urgent need for effective treatments, many clinical trials are ongoing through repurposing approved drugs. However, clinical data regarding the cardiotoxicity of these drugs are limited. Human pluripotent stem cell-derived cardiomyocytes (hCMs) represent a powerful tool for assessing drug-induced cardiotoxicity. Here, by using hCMs, it is demonstrated that four antiviral drugs, namely, apilimod, remdesivir, ritonavir, and lopinavir, exhibit cardiotoxicity in terms of inducing cell death, sarcomere disarray, and dysregulation of calcium handling and contraction, at clinically relevant concentrations. Human engineered heart tissue (hEHT) model is used to further evaluate the cardiotoxic effects of these drugs and it is found that they weaken hEHT contractile function. RNA-seq analysis reveals that the expression of genes that regulate cardiomyocyte function, such as sarcomere organization (TNNT2, MYH6) and ion homeostasis (ATP2A2, HCN4), is significantly altered after drug treatments. Using high-throughput screening of approved drugs, it is found that ceftiofur hydrochloride, astaxanthin, and quetiapine fumarate can ameliorate the cardiotoxicity of remdesivir, with astaxanthin being the most prominent one. These results warrant caution and careful monitoring when prescribing these therapies in patients and provide drug candidates to limit remdesivir-induced cardiotoxicity.

Spike-based adenovirus vectored COVID-19 vaccine does not aggravate heart damage after ischemic injury in mice.

An unprecedented number of COVID-19 vaccination campaign are under way worldwide. The spike protein of SARS-CoV-2, which majorly binds to the host receptor angiotensin converting enzyme 2 (ACE2) for cell entry, is used by most of the vaccine as antigen. ACE2 is highly expressed in the heart and has been reported to be protective in multiple organs. Interaction of spike with ACE2 is known to reduce ACE2 expression and affect ACE2-mediated signal transduction. However, whether a spike-encoding vaccine will aggravate myocardial damage after a heart attack via affecting ACE2 remains unclear. Here, we demonstrate that cardiac ACE2 is up-regulated and protective after myocardial ischemia/reperfusion (I/R). Infecting human cardiac cells or engineered heart tissues with a spike-based adenovirus type-5 vectored COVID-19 vaccine (AdSpike) does not affect their survival and function, whether subjected to hypoxia-reoxygenation injury or not. Furthermore, AdSpike vaccination does not aggravate heart damage in wild-type or humanized ACE2 mice after I/R injury, even at a dose that is ten-fold higher as used in human. This study represents the first systematic evaluation of the safety of a leading COVID-19 vaccine under a disease context and may provide important information to ensure maximal protection from COVID-19 in patients with or at risk of heart diseases.

Glycyrrhizin Protects Mice Against Experimental Autoimmune Encephalomyelitis by Inhibiting High-Mobility Group Box 1 (HMGB1) Expression and Neuronal HMGB1 Release.

The inflammatory mediator high-mobility group box 1 (HMGB1) plays a critical role in the pathogenesis of human multiple sclerosis (MS) and mouse experimental autoimmune encephalomyelitis (EAE). Glycyrrhizin (GL), a glycoconjugated triterpene extracted from licorice root, has the ability to inhibit the functions of HMGB1; however, GL's function against EAE has not been thoroughly characterized to date. To determine the benefit of GL as a modulator of neuroinflammation, we used an in vivo study to examine GL's effect on EAE along with primary cultured cortical neurons to study the GL effect on HMGB1 release. Treatment of EAE mice with GL from onset to the peak stage of disease resulted in marked attenuation of EAE severity, reduced inflammatory cell infiltration and demyelination, decreased tumor necrosis factor-alpha (TNF-α), IFN-γ, IL-17A, IL-6, and transforming growth factor-beta 1, and increased IL-4 both in serum and spinal cord homogenate. Moreover, HMGB1 levels in different body fluids were reduced, accompanied by a decrease in neuronal damage, activated astrocytes and microglia, as well as HMGB1-positive astrocytes and microglia. GL significantly reversed HMGB1 release into the medium induced by TNF-α stimulation in primary cultured cortical neurons. Taken together, the results indicate that GL has a strong neuroprotective effect on EAE mice by reducing HMGB1 expression and release and thus can be used to treat central nervous system inflammatory diseases, such as MS.