Extremely efficient terahertz high-harmonic generation in graphene by hot Dirac fermions.

Multiple optical harmonic generation-the multiplication of photon energy as a result of nonlinear interaction between light and matter-is a key technology in modern electronics and optoelectronics, because it allows the conversion of optical or electronic signals into signals with much higher frequency, and the generation of frequency combs. Owing to the unique electronic band structure of graphene, which features massless Dirac fermions1-3, it has been repeatedly predicted that optical harmonic generation in graphene should be particularly efficient at the technologically important terahertz frequencies4-6. However, these predictions have yet to be confirmed experimentally under technologically relevant operation conditions. Here we report the generation of terahertz harmonics up to the seventh order in single-layer graphene at room temperature and under ambient conditions, driven by terahertz fields of only tens of kilovolts per centimetre, and with field conversion efficiencies in excess of 10-3, 10-4 and 10-5 for the third, fifth and seventh terahertz harmonics, respectively. These conversion efficiencies are remarkably high, given that the electromagnetic interaction occurs in a single atomic layer. The key to such extremely efficient generation of terahertz high harmonics in graphene is the collective thermal response of its background Dirac electrons to the driving terahertz fields. The terahertz harmonics, generated via hot Dirac fermion dynamics, were observed directly in the time domain as electromagnetic field oscillations at these newly synthesized higher frequencies. The effective nonlinear optical coefficients of graphene for the third, fifth and seventh harmonics exceed the respective nonlinear coefficients of typical solids by 7-18 orders of magnitude7-9. Our results provide a direct pathway to highly efficient terahertz frequency synthesis using the present generation of graphene electronics, which operate at much lower fundamental frequencies of only a few hundreds of gigahertz.

Ultrafast Tunable Terahertz-to-Visible Light Conversion through Thermal Radiation from Graphene Metamaterials.

Several technologies, including photodetection, imaging, and data communication, could greatly benefit from the availability of fast and controllable conversion of terahertz (THz) light to visible light. Here, we demonstrate that the exceptional properties and dynamics of electronic heat in graphene allow for a THz-to-visible conversion, which is switchable at a sub-nanosecond time scale. We show a tunable on/off ratio of more than 30 for the emitted visible light, achieved through electrical gating using a gate voltage on the order of 1 V. We also demonstrate that a grating-graphene metamaterial leads to an increase in THz-induced emitted power in the visible range by 2 orders of magnitude. The experimental results are in agreement with a thermodynamic model that describes blackbody radiation from the electron system heated through intraband Drude absorption of THz light. These results provide a promising route toward novel functionalities of optoelectronic technologies in the THz regime.

Out of Asia? Expansion of Eurasian Lyme borreliosis causing genospecies display unique evolutionary trajectories.

Vector-borne pathogens exist in obligate transmission cycles between vector and reservoir host species. Host and vector shifts can lead to geographic expansion of infectious agents and the emergence of new diseases in susceptible individuals. Three bacterial genospecies (Borrelia afzelii, Borrelia bavariensis, and Borrelia garinii) predominantly utilize two distinct tick species as vectors in Asia (Ixodes persulcatus) and Europe (Ixodes ricinus). Through these vectors, the bacteria can infect various vertebrate groups (e.g., rodents, birds) including humans where they cause Lyme borreliosis, the most common vector-borne disease in the Northern hemisphere. Yet, how and in which order the three Borrelia genospecies colonized each continent remains unclear including the evolutionary consequences of this geographic expansion. Here, by reconstructing the evolutionary history of 142 Eurasian isolates, we found evidence that the ancestors of each of the three genospecies probably have an Asian origin. Even so, each genospecies studied displayed a unique substructuring and evolutionary response to the colonization of Europe. The pattern of allele sharing between continents is consistent with the dispersal rate of the respective vertebrate hosts, supporting the concept that adaptation of Borrelia genospecies to the host is important for pathogen dispersal. Our results highlight that Eurasian Lyme borreliosis agents are all capable of geographic expansion with host association influencing their dispersal; further displaying the importance of host and vector association to the geographic expansion of vector-borne pathogens and potentially conditioning their capacity as emergent pathogens.

Optical rectification and electro-optic sampling in quartz.

We report the electro-optic sampling (EOS) response and the terahertz (THz) optical rectification (OR) of the z-cut α-quartz. Due to its small effective second-order nonlinearity, large transparency window and hardness, freestanding thin quartz plates can faithfully measure the waveform of intense THz pulses with MV/cm electric-field strength. We show that both its OR and EOS responses are broad with extension up to ∼8 THz. Strikingly, the latter responses are independent of the crystal thickness, a plausible indication of dominant surface contribution to the total second-order nonlinear susceptibility of quartz at THz frequencies. Our study introduces the crystalline quartz as a reliable THz electro-optic medium for high field THz detection, and characterize its emission as a common substrate.

Omsk hemorrhagic fever virus is a tick-borne encephalitis virus adapted to muskrat through host-jumping.

Omsk hemorrhagic fever was first described in the early 1940s and is a natural focal infection, spread exclusively in four regions of Western Siberia, and associated with muskrat (Ondatra zibethicus). The etiological agent of this disease is the Omsk hemorrhagic fever virus (OHFV) which is closely related to the tick-borne encephalitis virus (TBEV), and its range entirely lies within the TBEV area. OHFV belongs to the mammalian tick-borne flaviviruses and the ecological group of arboviruses. The problem concerning the origin of OHFV remains unresolved to date. This study analyzed all nucleotide sequences of the OHFV genome obtained in the present study and available in GenBank, including the E gene fragment and the amino acid sequences of the surface glycoprotein encoded by it. The conclusions, based on the clusteron approach, suggest that OHFV originated directly from the TBEV of the Far Eastern subtype due to the host-jump phenomenon, that is, through a rapid change from an arthropod host, Ixodes persulcatus, to a rodent, O. zibethicus. The muskrat was introduced to Western Siberia in the second half of the 1930s. The peculiarities of the biology and ecology of the muskrat in the new habitat became the reason for the TBEV cross-species transmission. Calculations show that host-jumping occurred between 1931 and 1947 and accompanied a cascade of adaptive amino acid substitutions in protein E. As a result, the virus changed its transmission to contact, alimentary, and airborne routes. Based on the data obtained, OHFV would be more correctly attributed to zoonotic viruses transmitted by rodents and, accordingly, to the ecological group of roboviruses.

Associations of prepubertal urinary phthalate metabolite concentrations with pubertal onset among a longitudinal cohort of boys.

BACKGROUND: Although phthalate exposures have been associated with adverse effects on male reproductive health, few studies have explored longitudinal associations with male pubertal development. OBJECTIVES: We examined the association of prepubertal urinary concentrations of phthalate metabolites with age at pubertal onset in a prospective cohort of Russian boys. METHODS: At enrollment at ages 8-9 years, medical history, dietary, and demographic information was collected. At entry and annually, physical examinations and pubertal staging [Genitalia (G), Pubarche (P), and testicular volume (TV, in ml)] were conducted and spot urines were collected. Prepubertal urine samples (defined as either TV = 1, 2 and G = 1, 2 or TV = 3 and G = 1) were pooled for each boy and phthalate metabolite concentrations were quantified using isotope dilution LC-MS/MS at Moscow State University. We measured 15 metabolites including those from anti-androgenic parent phthalates (AAPs) such as di (2-ethylhexyl) (DEHP) and di-isononyl (DiNP) phthalates as well as monobenzyl (MBzP), mono-n-butyl (MnBP), and mono-isobutyl (MiBP) metabolites. We calculated the molar sums of DEHP (∑DEHP), DiNP (∑DiNP), and AAP (∑AAP) metabolites. Separate interval-censored models were used to assess associations of quartiles of prepubertal phthalate metabolites with each pubertal onset indicator, G2+, P2+ and TV > 3 mL, adjusted for covariates and urine specific gravity. RESULTS: 304 boys had 752 prepubertal urine samples (median 2, range: 1-6) for pooling. In adjusted models, higher urinary AAPs were consistently associated with later pubertal onset (P2) with mean shifts ranging from 8.4 to 14.2 months for the highest versus lowest quartiles. Significantly later onset for G2 and TV > 3 mL was observed for higher versus lower quartiles of MiBP, MBzP, ∑DEHP and ∑DiNP. CONCLUSIONS: On average, boys with higher concentrations of prepubertal urinary AAPs had later pubertal onset by six months to over a year. The impact of AAPs on timing of male puberty may be attributable to disruption of androgen-dependent biological pathways.

Discovery of Bivalent GalNAc-Conjugated Betulin as a Potent ASGPR-Directed Agent against Hepatocellular Carcinoma.

Herein, we describe the design, synthesis, and biological evaluation of novel betulin and N-acetyl-d-galactosamine (GalNAc) glycoconjugates and suggest them as targeted agents against hepatocellular carcinoma. We prepared six conjugates derived via the C-3 and C-28 positions of betulin with one or two saccharide ligands. These molecules demonstrate high affinity to the asialoglycoprotein receptor (ASGPR) of hepatocytes assessed by in silico modeling and surface plasmon resonance tests. Cytotoxicity studies in vitro revealed a bivalent conjugate with moderate activity, selectivity of action, and cytostatic properties against hepatocellular carcinoma cells HepG2. An additional investigation confirmed the specific engagement with HepG2 cells by the enhanced generation of reactive oxygen species. Stability tests demonstrated its lability to acidic media and to intracellular enzymes. Therefore, the selected bivalent conjugate represents a new potential agent targeted against hepatocellular carcinoma. Further extensive studies of the cellular uptake in vitro and the real-time microdistribution in the murine liver in vivo for fluorescent dye-labeled analogue showed its selective internalization into hepatocytes due to the presence of GalNAc ligand in comparison with reference compounds. The betulin and GalNAc glycoconjugates can therefore be considered as a new strategy for developing therapeutic agents based on natural triterpenoids.

New Small-Molecule Glycoconjugates of Docetaxel and GalNAc for Targeted Delivery to Hepatocellular Carcinoma.

In this work, we have developed covalent and low molecular weight docetaxel delivery systems based on conjugation with N-acetyl-d-galactosamine and studied their properties related to hepatocellular carcinoma cells. The resulting glycoconjugates have an excellent affinity to the asialoglycoprotein receptor (ASGPR) in the nanomolar range of concentrations and a high cytotoxicity level comparable to docetaxel. Likewise, we observed the 21-75-fold increase in water solubility in comparison with parent docetaxel and prodrug lability to intracellular conditions with half-life values from 25.5 to 42 h. We also found that the trivalent conjugate possessed selective toxicity against hepatoma cells vs control cell lines (20-35 times). The absence of such selectivity in the case of monovalent conjugates indicates the effect of ligand valency. Specific ASGPR-mediated cellular uptake of conjugates was proved in vitro using fluorescent-labeled analogues. In addition, we showed an enhanced generation of reactive oxygen species in the HepG2 cells, which could be inhibited by the natural ligand of ASGPR. Overall, the obtained results highlight the potential of ASGPR-directed cytostatic taxane drugs for selective therapy of hepatocellular carcinoma.

Manual mass spectrometry de novo sequencing of the anionic host defense peptides of the Cuban Treefrog Osteopilus septentrionalis.

RATIONALE: Host defense peptides accumulated in the skin glands of the animals constitute the basis of the adaptive and immune system of amphibians. The peptidome of the Cuban frog Osteopilus septentrionalis was established using tandem mass spectrometry as the best analytical tool to elucidate the sequence of these peptides. METHODS: Manual interpretation of complementary collision-induced dissociation (CID), higher energy collision-induced dissociation (HCD), and electron transfer dissociation (ETD) tandem mass spectra recorded with an Orbitrap Elite mass spectrometer in liquid chromatography/mass spectrometry (LC/MS) mode was used to sequence the peptide components of the frog skin secretion, obtained by mild electrostimulation. RESULTS: Although the vast majority of amphibian peptides discovered so far are cationic, surprisingly only anionic peptides were identified in the skin secretion of the Cuban frog Osteopilus septentrionalis. Mass spectrometry allowed the sequences to be established of 16 representatives of new peptide families: septenins 1 and septenins 2. The highest sequence coverage when dealing with these anionic peptides was obtained with CID normalized collision energy 35 and HCD normalized collision energy 28. CONCLUSIONS: Mirror-symmetrical peptides are sequenced using N-terminal acetylation. Acetylated Ser is reliably distinguished from isomeric Glu by the loss of ketene from b-ions containing the corresponding residue. Calculations of the physicochemical and structural properties of the discovered anionic septenins 1 and 2 allowed the mechanism of their interaction with microbe cells to be postulated.

High conservation combined with high plasticity: genomics and evolution of Borrelia bavariensis.

BACKGROUND: Borrelia bavariensis is one of the agents of Lyme Borreliosis (or Lyme disease) in Eurasia. The genome of the Borrelia burgdorferi sensu lato species complex, that includes B. bavariensis, is known to be very complex and fragmented making the assembly of whole genomes with next-generation sequencing data a challenge. RESULTS: We present a genome reconstruction for 33 B. bavariensis isolates from Eurasia based on long-read (Pacific Bioscience, for three isolates) and short-read (Illumina) data. We show that the combination of both sequencing techniques allows proper genome reconstruction of all plasmids in most cases but use of a very close reference is necessary when only short-read sequencing data is available. B. bavariensis genomes combine a high degree of genetic conservation with high plasticity: all isolates share the main chromosome and five plasmids, but the repertoire of other plasmids is highly variable. In addition to plasmid losses and gains through horizontal transfer, we also observe several fusions between plasmids. Although European isolates of B. bavariensis have little diversity in genome content, there is some geographic structure to this variation. In contrast, each Asian isolate has a unique plasmid repertoire and we observe no geographically based differences between Japanese and Russian isolates. Comparing the genomes of Asian and European populations of B. bavariensis suggests that some genes which are markedly different between the two populations may be good candidates for adaptation to the tick vector, (Ixodes ricinus in Europe and I. persulcatus in Asia). CONCLUSIONS: We present the characterization of genomes of a large sample of B. bavariensis isolates and show that their plasmid content is highly variable. This study opens the way for genomic studies seeking to understand host and vector adaptation as well as human pathogenicity in Eurasian Lyme Borreliosis agents.

Synthesis and Evaluation of New Trivalent Ligands for Hepatocyte Targeting via the Asialoglycoprotein Receptor.

Since the asialoglycoprotein receptor (also known as the "Ashwell-Morell receptor" or ASGPR) was discovered as the first cellular mammalian lectin, numerous drug delivery systems have been developed and several gene delivery systems associated with multivalent ligands for liver disease targeting are undergoing clinical trials. The success of these systems has facilitated the further study of new ligands with comparable or higher affinity and less synthetic complexity. Herein, we designed two novel trivalent ligands based on the esterification of tris(hydroxymethyl) aminomethane (TRIS) followed by the azide-alkyne Huisgen cycloaddition with azido N-acetyl-d-galactosamine. The presented triazolyl glycoconjugates exhibited good binding to ASGPR, which was predicted using in silico molecular docking and assessed by a surface plasmon resonance (SPR) technique. Moreover, we demonstrated the low level of in vitro cytotoxicity, as well as the optimal spatial geometry and the required amphiphilic balance, for new, easily accessible ligands. The conjugate of a new ligand with Cy5 dye exhibited selective penetration into HepG2 cells in contrast to the ASGPR-negative PC3 cell line.

Photon diagnostics at the FLASH THz beamline.

The THz beamline at FLASH, DESY, provides both tunable (1-300 THz) narrow-bandwidth (∼10%) and broad-bandwidth intense (up to 150 uJ) THz pulses delivered in 1 MHz bursts and naturally synchronized with free-electron laser X-ray pulses. Combination of these pulses, along with the auxiliary NIR and VIS ultrashort lasers, supports a plethora of dynamic investigations in physics, material science and biology. The unique features of the FLASH THz pulses and the accelerator source, however, bring along a set of challenges in the diagnostics of their key parameters: pulse energy, spectral, temporal and spatial profiles. Here, these challenges are discussed and the pulse diagnostic tools developed at FLASH are presented. In particular, a radiometric power measurement is presented that enables the derivation of the average pulse energy within a pulse burst across the spectral range, jitter-corrected electro-optical sampling for the full spectro-temporal pulse characterization, spatial beam profiling along the beam transport line and at the sample, and a lamellar grating based Fourier transform infrared spectrometer for the on-line assessment of the average THz pulse spectra. Corresponding measurement results provide a comprehensive insight into the THz beamline capabilities.

Thiourea Modified Doxorubicin: A Perspective pH-Sensitive Prodrug.

A novel approach to the synthesis of pH-sensitive prodrugs has been proposed: thiourea drug modification. Resulting prodrugs can release the cytotoxic agent and the biologically active 2-thiohydantoin in the acidic environment of tumor cells. The concept of acid-catalyzed cyclization of thioureas to 2-thiohydantoins has been proven using a FRET model. Dual prodrugs of model azidothymidine, cytotoxic doxorubicin, and 2-thiohydantoin albutoin were obtained, which release the corresponding drugs in the acidic environment. The resulting doxorubicin prodrug was tested on prostate cancer cells and showed that the thiourea-modified prodrug is less cytotoxic (average IC50 ranging from 0.5584 to 0.9885 µM) than doxorubicin (IC50 ranging from 0.01258 to 0.02559 µM) in neutral pH 7.6 and has similar toxicity (average IC50 ranging from 0.4970 to 0.7994 µM) to doxorubicin (IC50 ranging from 0.2303 to 0.8110 µM) under mildly acidic conditions of cancer cells. Cellular and nuclear accumulation in PC3 tumor cells of Dox prodrug is much higher than accumulation of free doxorubicin.

Synthesis and biological evaluation of novel doxorubicin-containing ASGP-R-targeted drug-conjugates.

Asialoglycoprotein receptor (ASGP-R) belongs to a wide family of C-type lectins and it is currently regarded as an attractive protein in the field of targeted drug delivery (TDD). It is abundantly expressed in hepatocytes and can be found predominantly on the sinusoidal surface especially of HepG2 cells. Therefore, ASGP-R can be used for the TDD of anticancer therapeutics against HCC and molecular diagnostic tools. To date, a variety of mono- and multivalent selective ASGP-R ligands have been discovered. Although many of these compounds have demonstrated a relatively high binding affinity towards the target, the reported synthetic schemes are not handled, complicated and include many non-trivial steps. In the current study, we describe a convenient and versatile synthetic approach to novel monovalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose fragment as an ASGP-R-recognition "core-head" and well-known nonselective cytostatic - Doxorubicin (Dox). This is the first example of the direct conjugation of a drug molecule to the ASGP-targeted warhead by a really convenient manner via a simple linker sequence. The performed MTS-based biological evaluation in HepG2 cells revealed the novel conjugates as having anticancer activity. Confocal microscopy showed that the molecules readily penetrated HepG2 membrane and were mainly localized within the cytoplasm instead of the nucleus. Per contra, Dox under the same conditions demonstrated good anticancer activity and was predominantly concentrated in the nucleus. Therefore, we speculate that the amide "trigger" that we have used in this study for linker attachment is a sufficiently stable inside the cells to be enzymatically or spontaneously degraded. As a consequence, we did not observe the release of the drug. Ligands containing triggers that are more liable towards endogenous hydrolysis within the tissue of targeting are strongly required.

Synthesis and biological evaluation of novel mono- and bivalent ASGP-R-targeted drug-conjugates.

Asialoglycoprotein receptor (ASGP-R) is a promising biological target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-molecule conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose and anticancer drug - paclitaxel (PTX). Several molecules have demonstrated high affinity towards ASGP-R and good stability under physiological conditions, significant in vitro anticancer activity comparable to PTX, as well as good internalization via ASGP-R-mediated endocytosis. Therefore, the conjugates with the highest potency can be regarded as a promising therapeutic option against HCC.

Bacteria of the Family 'Candidatus Midichloriaceae' in Sympatric Zones of Ixodes Ticks: Genetic Evidence for Vertical Transmission.

Ixodes ticks transmit infectious agents and also harbor their own parasites and symbionts. The presumptive endosymbiont of Ixodes ricinus, 'Candidatus Midichloria mitochondrii', has a unique ability to invade mitochondria within tick ovarian cells and is transovarially transmitted with 100% efficiency. A closely related bacterium, provisionally named Montezuma (now 'Candidatus Lariskella arthropodarum'), was isolated from the Ixodes persulcatus ticks and human blood in 2004 as well as from Ixodes pavlovskyi in 2015. These microorganisms belong to the family 'Candidatus Midichloriaceae fam. nov.' and were detected not only in tick salivary glands, but also in animal blood. Nevertheless, the relative importance of vertical and horizontal routes for their transmission or maintenance in natural tick populations remains unclear. We analyzed the prevalence of L. arthropodarum and M. mitochondrii in two sympatric zones, where I. persulcatus/I. ricinus and I. persulcatus/I. pavlovskyi cohabit and produce interspecific hybrids. A specificity of the associations of L. arthropodarum with I. persulcatus (100%) and M. mitochondrii with I. ricinus (96.2%) was observed in the sympatric zone in Estonia, possibly showing poor contribution of the horizontal route to the overall prevalence of endosymbionts. L. arthropodarum was observed probably multiplying in I. pavlovskyi and also subjected to transovarial transmission, but much less efficiently compared to I. persulcatus. We revealed two new genetic variants of the rrl-rrf intergenic spacer of L. arthropodarum isolated from I. pavlovskyi ticks that possibly could indicate an ongoing process of adaptation of the microorganism to a new host species.

Clusterons as a tool for monitoring populations of tick-borne encephalitis virus.

Tick-borne encephalitis (TBE) is a natural focal viral neuroinfection that is widespread in the temperate zone of Eurasia. Knowledge of the genetic structure of tick-borne encephalitis virus (TBEV) populations is important for understanding, not only the origin and evolution of the virus, but also the formation and maintenance of natural foci. A new approach to the differentiation of TBEV strains within subtype, with clusterons as the basis of analysis, has recently been proposed. In the present study, the genetic structure of TBEV-Sib populations has been investigated based on 387 strains isolated in the Middle Urals (Sverdlovsk region). Fourteen of the 18 currently known TBEV-Sib clusterons were identified. They belong to the Asian and Eastern European (Baltic) groups. It was shown that each TBE foci could be characterized by a unique clusteron profile. Three clusterons that emerged within the last 50 years have been identified which implies an active evolutionary process in the TBEV-Sib populations. The greatest diversity of clusterons was observed in the south of the Middle Urals along the Trans-Siberian Way. Such a pattern could reflect the history of colonization of the area and is closely related to the roads passing from Siberia to the European part of Russia through the Urals. In this article, the principles of continuous monitoring in the regional and local TBE foci are proposed, based on the quantitative and qualitative analysis of TBEV-Sib clusteron profiles.

The First Record of Omsk Hemorrhagic Fever Virus and Tick-Borne Encephalitis Virus of Baltic Lineage from the Kemerovo Region of Russia.

Objectives: Tick-borne encephalitis virus Siberian subtype (TBEV-Sib) and Omsk hemorrhagic fever virus (OHFV) are causative agents of natural focal infections in Western Siberia, Russia. The distribution of TBEV phylogenetic lineages and OHFV in the Kemerovo Region of Western Siberia remains poorly investigated. Methods: The phylogenetic analyses of fragment genome sequences 26 flaviviruses identified in 2019 were performed, and the amino acid variation was determined to reveal to which clusteron they belong. The age of Baltic and Asian lineages of the TBEV-Sib was calculated for Kemerovo District and Region, respectively. Results: Twenty-five isolates were members of three TBEV-Sib phylogenetic lineages: Baltic (48%), Asian (36%), and East Siberian (16%). The Baltic lineage's eastern boundary is commonly thought to be in the Novosibirsk Region, but our data suggest that it may reach further east. Analysis of the Baltic lineage clusteron structure showed that the isolates found are unique (6) or belong to clusteron-founder 3D (1) and derived clusteron 3O (5). Based on the age of 3O clusteron, Baltic lineage could have appeared in the Kemerovo Region by the late 1970s. One of the isolated viruses turned out to be the OHFV of the first subtype and not to belong to any known clusteron. This finding is the first known detection of the virus outside the endemic area of Russia. Given the recent discovery of OHFV in Kazakhstan, it can be assumed that the area of this virus distribution is much wider than previously thought. Conclusions: This report provides insights into the population structure of TBEV and OHFV, which may be helpful for epidemiological investigation and surveillance of the viruses.

Tracing the dynamics of superconducting order via transient terahertz third-harmonic generation.

Ultrafast optical control of quantum systems is an emerging field of physics. In particular, the possibility of light-driven superconductivity has attracted much of attention. To identify nonequilibrium superconductivity, it is necessary to measure fingerprints of superconductivity on ultrafast timescales. Recently, nonlinear THz third-harmonic generation (THG) was shown to directly probe the collective degrees of freedoms of the superconducting condensate, including the Higgs mode. Here, we extend this idea to light-driven nonequilibrium states in superconducting La2-xSrxCuO4, establishing an optical pump-THz-THG drive protocol to access the transient superconducting order-parameter quench and recovering on few-picosecond timescales. We show in particular the ability of two-dimensional TH spectroscopy to disentangle the effects of optically excited quasiparticles from the pure order-parameter dynamics, which are unavoidably mixed in the pump-driven linear THz response. Benchmarking the gap dynamics to existing experiments shows the ability of driven THG spectroscopy to overcome these limitations in ordinary pump-probe protocols.

Magnon-phonon Fermi resonance in antiferromagnetic CoF2.

Understanding spin-lattice interactions in antiferromagnets is a critical element of the fields of antiferromagnetic spintronics and magnonics. Recently, coherent nonlinear phonon dynamics mediated by a magnon state were discovered in an antiferromagnet. Here, we suggest that a strongly coupled two-magnon-one phonon state in this prototypical system opens a novel pathway to coherently control magnon-phonon dynamics. Utilizing intense narrow-band terahertz (THz) pulses and tunable magnetic fields up to µ0Hext = 7 T, we experimentally realize the conditions of magnon-phonon Fermi resonance in antiferromagnetic CoF2. These conditions imply that both the spin and the lattice anharmonicities harvest energy from the transfer between the subsystems if the magnon eigenfrequency fm is half the frequency of the phonon 2fm = fph. Performing THz pump-infrared probe spectroscopy in conjunction with simulations, we explore the coupled magnon-phonon dynamics in the vicinity of the Fermi-resonance and reveal the corresponding fingerprints of nonlinear interaction facilitating energy exchange between these subsystems.