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Strong coupling between molecules and confined light modes of optical cavities to form polaritons can alter photochemistry, but the origin of this effect remains largely unknown. While theoretical models suggest a suppression of photochemistry due to the formation of new polaritonic potential energy surfaces, many of these models do not account for the energetic disorder among the molecules, which is unavoidable at ambient conditions. Here, we combine simulations and experiments to show that for an ultra-fast photochemical reaction such thermal disorder prevents the modification of the potential energy surface and that suppression is due to radiative decay of the lossy cavity modes. We also show that the excitation spectrum under strong coupling is a product of the excitation spectrum of the bare molecules and the absorption spectrum of the molecule-cavity system, suggesting that polaritons can act as gateways for channeling an excitation into a molecule, which then reacts normally. Our results therefore imply that strong coupling provides a means to tune the action spectrum of a molecule, rather than to change the reaction., (© 2024. The Author(s).)

High-spin molecules allow for bottom-up qubit design and are promising platforms for magnetic sensing and quantum information science. Optical addressability of molecular electron spins has also been proposed in first-row transition-metal complexes via optically detected magnetic resonance (ODMR) mechanisms analogous to the diamond-nitrogen-vacancy color center. However, significantly less progress has been made on the front of metal-free molecules, which can deliver lower costs and milder environmental impacts. At present, most luminescent open-shell organic molecules are π-diradicals, but such systems often suffer from poor ground-state open-shell characters necessary to realize a stable ground-state molecular qubit. In this work, we use alternancy symmetry to selectively minimize radical-radical interactions in the ground state, generating π-systems with high diradical characters. We call them m -dimers, referencing the need to covalently link two benzylic radicals at their meta carbon atoms for the desired symmetry. Through a detailed electronic structure analysis, we find that the excited states of alternant hydrocarbon m -diradicals contain important symmetries that can be used to construct ODMR mechanisms leading to ground-state spin polarization. The molecular parameters are set in the context of a tris(2,4,6-trichlorophenyl)methyl (TTM) radical dimer covalently tethered at the meta position, demonstrating the feasibility of alternant m -diradicals as molecular color centers.

The photoisomerization reaction of a fluorescent protein chromophore occurs on the ultrafast timescale. The structural dynamics that result from femtosecond optical excitation have contributions from vibrational and electronic processes and from reaction dynamics that involve the crossing through a conical intersection. The creation and progression of the ultrafast structural dynamics strongly depends on optical and molecular parameters. When using X-ray crystallography as a probe of ultrafast dynamics, the origin of the observed nuclear motions is not known. Now, high-resolution pump-probe X-ray crystallography reveals complex sub-ångström, ultrafast motions and hydrogen-bonding rearrangements in the active site of a fluorescent protein. However, we demonstrate that the measured motions are not part of the photoisomerization reaction but instead arise from impulsively driven coherent vibrational processes in the electronic ground state. A coherent-control experiment using a two-colour and two-pulse optical excitation strongly amplifies the X-ray crystallographic difference density, while it fully depletes the photoisomerization process. A coherent control mechanism was tested and confirmed the wave packets assignment., (© 2023. The Author(s).)

Exciton transport can be enhanced in the strong coupling regime where excitons hybridize with confined light modes to form polaritons. Because polaritons have group velocity, their propagation should be ballistic and long-ranged. However, experiments indicate that organic polaritons propagate in a diffusive manner and more slowly than their group velocity. Here, we resolve this controversy by means of molecular dynamics simulations of Rhodamine molecules in a Fabry-Pérot cavity. Our results suggest that polariton propagation is limited by the cavity lifetime and appears diffusive due to reversible population transfers between polaritonic states that propagate ballistically at their group velocity, and dark states that are stationary. Furthermore, because long-lived dark states transiently trap the excitation, propagation is observed on timescales beyond the intrinsic polariton lifetime. These insights not only help to better understand and interpret experimental observations, but also pave the way towards rational design of molecule-cavity systems for coherent exciton transport., (© 2023. Springer Nature Limited.)

Introduction: Ruminant production in the Black Sea basin (BSB) is critical for national economies and the subsistence of rural populations. Yet, zoonoses and transboundary animal diseases (TADs) are limiting and threatening the sector. To gain a more comprehensive understanding, this study characterizes key aspects of the ruminant sector in nine countries of the BSB, including Armenia, Azerbaijan, Belarus, Bulgaria, Georgia, Moldova, Romania, Türkiye, and Ukraine., Methods: We selected six priority ruminant diseases (anthrax, brucellosis, Crimean Congo haemorrhagic fever (CCHF), foot-and-mouth disease (FMD), lumpy skin disease (LSD), and peste des petits ruminants (PPR)) that are present or threaten to emerge in the region. Standardized questionnaires were completed by a network of focal points and supplemented with external sources. We examined country and ruminant-specific data such as demographics, economic importance, and value chains in each country. For disease-specific data, we analysed the sanitary status, management strategies, and temporal trends of the selected diseases., Results and Discussion: The shift from a centrally planned to a market economy, following the collapse of the Soviet Union, restructured the ruminant sector. This sector played a critical role in rural livelihoods within the BSB. Yet, it faced significant challenges such as the low sustainability of pastoralism, technological limitations, and unregistered farms. Additionally, ruminant health was hindered by informal animal trade as a result of economic factors, insufficient support for the development of formal trade, and socio-cultural drivers. In the Caucasus and Türkiye, where diseases were present, improvements to ruminant health were driven by access to trading opportunities. Conversely, European countries, mostly disease-free, prioritized preventing disease incursion to avoid a high economic burden. While international initiatives for disease management are underway in the BSB, there is still a need for more effective local resource allocation and international partnerships to strengthen veterinary health capacity, protect animal health and improve ruminant production., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Arede, Beltrán-Alcrudo, Aliyev, Chaligava, Keskin, Markosyan, Morozov, Oste, Pavlenko, Ponea, Starciuc, Zdravkova, Raizman, Casal and Allepuz.)

Multiscale molecular modeling is utilized to predict optical absorption and circular dichroism spectra of two single-point mutants of the Fenna-Matthews-Olson photosynthetic pigment-protein complex. The modeling approach combines classical molecular dynamics simulations with structural refinement of photosynthetic pigments and calculations of their excited states in a polarizable protein environment. The only experimental input to the modeling protocol is the X-ray structure of the wild-type protein. The first-principles modeling reproduces changes in the experimental optical spectra of the considered mutants, Y16F and Q198V. Interestingly, the Q198V mutation has a negligible effect on the electronic properties of the targeted bacteriochlorophyll a pigment. Instead, the electronic properties of several other pigments respond to this mutation. The molecular modeling demonstrates that a single-point mutation can induce long-range effects on the protein structure, while extensive structural changes near a pigment do not necessarily lead to significant changes in the electronic properties of that pigment.

Competing Interests: The authors report no conflicts of interest.

Chromophore cis/trans photoisomerization is a fundamental process in chemistry and in the activation of many photosensitive proteins. A major task is understanding the effect of the protein environment on the efficiency and direction of this reaction compared to what is observed in the gas and solution phases. In this study, we set out to visualize the hula twist (HT) mechanism in a fluorescent protein, which is hypothesized to be the preferred mechanism in a spatially constrained binding pocket. We use a chlorine substituent to break the twofold symmetry of the embedded phenolic group of the chromophore and unambiguously identify the HT primary photoproduct. Through serial femtosecond crystallography, we then track the photoreaction from femtoseconds to the microsecond regime. We observe signals for the photoisomerization of the chromophore as early as 300 fs, obtaining the first experimental structural evidence of the HT mechanism in a protein on its femtosecond-to-picosecond timescale. We are then able to follow how chromophore isomerization and twisting lead to secondary structure rearrangements of the protein β-barrel across the time window of our measurements.

Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are common complications of CLL. The optimal treatment of steroid refractory AIHA/PRCA is not well established. We conducted a multicenter study of ibrutinib and rituximab in patients with relapsed/refractory to steroids AIHA/PRCA and underlying CLL. Protocol included induction (ibrutinib 420 mg/day and rituximab, 8 weekly and 4 monthly infusions) and maintenance phase with ibrutinib alone until progression or unacceptable toxicity. Fifty patients were recruited (44-warm AIHA, 2-cold AIHA, 4-PRCA). After the induction 34 patients (74%) have achieved complete response, 10 (21.7%) partial response. Median time to hemoglobin normalization was 85 days. With regards to CLL response 9 (19%) patients have achieved CR, 2 (4%) patients-stabilization and 39 (78%)-PR. The median follow-up was 37.56 months. In AIHA group 2 patients had a relapse. Among 4 patients with PRCA 1 patient did not respond, and 1 patient had a relapse after CR, 2 remained in CR. The most common adverse events were neutropenia (62%), infections (72%), gastrointestinal complications (54%). In conclusion ibrutinib in combination with rituximab is an active second-line treatment option for patients with relapsed or refractory AIHA/PRCA and underlying CLL., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Here, we present DNA aptamers capable of specific binding to glial tumor cells in vitro , ex vivo , and in vivo for visualization diagnostics of central nervous system tumors. We selected the aptamers binding specifically to the postoperative human glial primary tumors and not to the healthy brain cells and meningioma, using a modified process of systematic evolution of ligands by exponential enrichment to cells; sequenced and analyzed ssDNA pools using bioinformatic tools and identified the best aptamers by their binding abilities; determined three-dimensional structures of lead aptamers (Gli-55 and Gli-233) with small-angle X-ray scattering and molecular modeling; isolated and identified molecular target proteins of the aptamers by mass spectrometry; the potential binding sites of Gli-233 to the target protein and the role of post-translational modifications were verified by molecular dynamics simulations. The anti-glioma aptamers Gli-233 and Gli-55 were used to detect circulating tumor cells in liquid biopsies. These aptamers were used for in situ , ex vivo tissue staining, histopathological analyses, and fluorescence-guided tumor and PET/CT tumor visualization in mice with xenotransplanted human astrocytoma. The aptamers did not show in vivo toxicity in the preclinical animal study. This study demonstrates the potential applications of aptamers for precise diagnostics and fluorescence-guided surgery of brain tumors., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Purpose: Anorectoplasty and pull-through procedure can be performed with extensive mobilization or tension anastomosis, which can compromise bowel blood perfusion. We aimed to analyze the hypoxia biomarker values and histopathological findings in both conditions to correlate the occurrence of anal stenosis and defecation disorders in experimental models., Methods: We created anorectal reconstruction models with impaired vascularization of the anorectum (group I) and tension anastomosis (group II) in rats. A third group of animals underwent sham operation (group III) and another as controls (group IV). Hypoxia biomarker values were assessed in all groups. The histopathological changes on the postoperative days 3 and 35, anal stenosis and defecation disorders on day 35 were compared., Results: Hypoxia biomarker values confirmed postoperative ischemia in groups I-III compared to control. Group I and II rats had a similarly pronounced ischemia with histopathologic changes in the anorectum on the postoperative day 3 and accompanied by severe fibrosis on day 35. Compared to the sham operation, both groups showed defecation disorders with significant anal stenoses., Conclusion: Extensive rectal mobilization to about the same extent as tension anastomosis has a major impact on postoperative rectal ischemia, resulting in severe fibrotic changes in the anorectum and defecation disorders in the long term., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The strong light-matter coupling regime, in which excitations of materials hybridize with excitations of confined light modes into polaritons, holds great promise in various areas of science and technology. A key aspect for all applications of polaritonic chemistry is the relaxation into the lower polaritonic states. Polariton relaxation is speculated to involve two separate processes: vibrationally assisted scattering (VAS) and radiative pumping (RP), but the driving forces underlying these two mechanisms are not fully understood. To provide mechanistic insights, we performed multiscale molecular dynamics simulations of tetracene molecules strongly coupled to the confined light modes of an optical cavity. The results suggest that both mechanisms are driven by the same molecular vibrations that induce relaxation through nonadiabatic coupling between dark states and polaritonic states. Identifying these vibrational modes provides a rationale for enhanced relaxation into the lower polariton when the cavity detuning is resonant with specific vibrational transitions.

Photoactivation of bacteriophytochrome involves a cis-trans photoisomerization of a biliverdin chromophore, but neither the precise sequence of events nor the direction of the isomerization is known. Here, we used nonadiabatic molecular dynamics simulations on the photosensory protein dimer to resolve the isomerization mechanism in atomic detail. In our simulations the photoisomerization of the D ring occurs in the counterclockwise direction. On a subpicosecond time scale, the photoexcited chromophore adopts a short-lived intermediate with a highly twisted configuration stabilized by an extended hydrogen-bonding network. Within tens of picoseconds, these hydrogen bonds break, allowing the chromophore to adopt a more planar configuration, which we assign to the early Lumi-R state. The isomerization process is completed via helix inversion of the biliverdin chromophore to form the late Lumi-R state. The mechanistic insights into the photoisomerization process are essential to understand how bacteriophytochrome has evolved to mediate photoactivation and to engineer this protein for new applications.

Aptamers are short, single-stranded DNA or RNA oligonucleotide molecules that function as synthetic analogs of antibodies and bind to a target molecule with high specificity. Aptamer affinity entirely depends on its tertiary structure and charge distribution. Therefore, length and structure optimization are essential for increasing aptamer specificity and affinity. Here, we present a general optimization procedure for finding the most populated atomistic structures of DNA aptamers. Based on the existed aptamer LC-18 for lung adenocarcinoma, a new truncated LC-18 (LC-18t) aptamer LC-18t was developed. A three-dimensional (3D) shape of LC-18t was reported based on small-angle X-ray scattering (SAXS) experiments and molecular modeling by fragment molecular orbital or molecular dynamic methods. Molecular simulations revealed an ensemble of possible aptamer conformations in solution that were in close agreement with measured SAXS data. The aptamer LC-18t had stronger binding to cancerous cells in lung tumor tissues and shared the binding site with the original larger aptamer. The suggested approach reveals 3D shapes of aptamers and helps in designing better affinity probes., Competing Interests: The authors declare no competing interests., (© 2021.)

Bacterial phytochrome photoreceptors usually belong to two-component signaling systems which transmit environmental stimuli to a response regulator through a histidine kinase domain. Phytochromes switch between red light-absorbing and far-red light-absorbing states. Despite exhibiting extensive structural responses during this transition, the model bacteriophytochrome from Deinococcus radiodurans (DrBphP) lacks detectable kinase activity. Here, we resolve this long-standing conundrum by comparatively analyzing the interactions and output activities of DrBphP and a bacteriophytochrome from Agrobacterium fabrum (Agp1). Whereas Agp1 acts as a conventional histidine kinase, we identify DrBphP as a light-sensitive phosphatase. While Agp1 binds its cognate response regulator only transiently, DrBphP does so strongly, which is rationalized at the structural level. Our data pinpoint two key residues affecting the balance between kinase and phosphatase activities, which immediately bears on photoreception and two-component signaling. The opposing output activities in two highly similar bacteriophytochromes suggest the use of light-controllable histidine kinases and phosphatases for optogenetics., (© 2021. The Author(s).)

The normal development of the glanular urethra is closely related to the normal development of the foreskin. A ventral deficit in the foreskin results with the failure to develop the septum glandis and frenulum, which also form the ventral wall of the glanular and subcoronal urethra. Here we present the anatomical modeling of the foreskin in order to obtain a mucosal collar for the reconstruction of the glanular hypospadias with the GFC technique (Glanular-Frenular-Collar), which can also be used for various purposes to reconstruct the urethra in hypospadias., Competing Interests: Conflicts of interest None., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Photosynthetic reaction centres harvest the energy content of sunlight by transporting electrons across an energy-transducing biological membrane. Here we use time-resolved serial femtosecond crystallography 1 using an X-ray free-electron laser 2 to observe light-induced structural changes in the photosynthetic reaction centre of Blastochloris viridis on a timescale of picoseconds. Structural perturbations first occur at the special pair of chlorophyll molecules of the photosynthetic reaction centre that are photo-oxidized by light. Electron transfer to the menaquinone acceptor on the opposite side of the membrane induces a movement of this cofactor together with lower amplitude protein rearrangements. These observations reveal how proteins use conformational dynamics to stabilize the charge-separation steps of electron-transfer reactions.

Purpose: To investigate the urinary levels of TGF-β1, VEGF, and MCP-1 as potential biomarkers of latent inflammation and fibrosis in the kidney before and 6 months after correction of vesicoureteral reflux (VUR) in children., Methods: A total of 88 patients (mean age 26 months) with VUR were divided into three groups: group A-patients with grades II-III VUR, conservative treatment; group B-patients with grades III-V VUR, endoscopic correction of VUR; group C-patients with grades III-V VUR, ureteral reimplantation after failed endoscopic correction. Control group included 20 healthy children. Biomarker levels were measured by ELISA. 99m Tc-DMSA scintigraphy and renal histology were performed if possible., Results: At admission, TGF-β1 was close to control in all study groups, VEGF increased with severity of the disease, and MCP-1 increased in group C. Six months after correction of VUR, despite clinical and laboratory improvement, TGF-β1 and MCP-1 increased while VEGF decreased compared to the admission values in all groups; no amelioration of renal scarring was detected either by 99m Tc-DMSA scintigraphy or renal histology., Conclusion: The results support our hypothesis that successful correction of VUR is not sufficient to stop or reduce the latent inflammatory and fibrotic processes that have already started in the kidney regardless of the reflux grade and treatment option. Measuring the urinary levels of TGF-β1, VEGF, and MCP-1 may aid in the development of non-invasive, pathophysiologically relevant approach to diagnosis and monitoring of kidney injury and fibrosis in children with VUR.

In this work, we show a proof-of-principle benchtop single-photon light detection and ranging (LIDAR) depth imager at 2.3µm, utilizing superconducting nanowire single-photon detectors (SNSPDs). We fabricate and fiber-couple SNSPDs to exhibit enhanced photon counting performance in the mid-infrared. We present characterization results using an optical parametric oscillator source and deploy these detectors in a scanning LIDAR setup at 2.3µm wavelength. This demonstrates the viability of these detectors for future free-space photon counting applications in the mid-infrared where atmospheric absorption and background solar flux are low.

We report on the investigation of titanium nitride (TiN) thin films deposited via atomic layer deposition (ALD) for microwave kinetic inductance detectors (MKID). Using our in-house ALD process, we have grown a sequence of TiN thin films (thickness 15, 30, 60 nm). The films have been characterised in terms of superconducting transition temperature T c , sheet resistance R s and microstructure. We have fabricated test resonator structures and characterised them at a temperature of 300 mK. At 350 GHz, we report an optical noise equivalent power NEP opt ≈ 2.3 × 10 - 15 W / Hz , which is promising for passive terahertz imaging applications.