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Efficient formation of excited triplet states on metal-free photosensitizer dyads, bodipy-phenoxazine (BDP-PXZ) and tetramethylbodipy-phenoxazine (TMBDP-PXZ), was investigated using ab initio calculations. We revealed the reason why two different triplet transient species, 3 CT and 3 BDP, can co-exist only for BDP-PXZ as observed in the previous study with the TR-EPR measurements. It was found that the state mixing of 3 CT enables the transition from 1 CT to 3 CT and 3 BDP states only for BDP-PXZ. This mixing effect is commonly seen in the singlet states of twisted intermolecular charge transfer molecules, though the key factor that determines the mixing of the excited states of the dyes was found to be the electron-donating ability of the substituents rather than their steric hindrance. This mechanism was corroborated by comparing the spin polarization ratio of the triplet spin-sublevels measured by TR-EPR with the theoretical predictions. The spin polarization ratio of the triplets should contain information about the transition via intersystem crossing, e.g. the twisted angle of two chromophores of the dyad, and thus it can be a powerful tool to analyze the molecular mechanism of photochemical processes at the electronic structure level. These insights on the molecular structures' effect provided by this theoretical study would be a compass to molecular design of metal-free triplet photosensitizers.

Photon upconversion (UC) from red or near-infrared (NIR) light to blue light is promising for in vivo optogenetics. However, the examples of in vivo optogenetics have been limited to lanthanide inorganic UC nanoparticles, and there have been no examples of optogenetics without using heavy metals. Here the first example of in vivo optogenetics using biocompatible heavy metal-free TTA-UC nanoemulsions is shown. A new organic TADF sensitizer, a boron difluoride curcuminoid derivative modified with a bromo group, can promote intersystem crossing to the excited triplet state, significantly improving TTA-UC efficiency. The TTA-UC nanoparticles formed from biocompatible surfactants and methyl oleate acquire water dispersibility and remarkable oxygen tolerance. By combining with genome engineering technology using the blue light-responding photoactivatable Cre-recombinase (PA-Cre), TTA-UC nanoparticles promote Cre-reporter EGFP expression in neurons in vitro and in vivo. The results open new opportunities toward deep-tissue control of neural activities based on heavy metal-free fully organic UC systems., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

ConspectusQuantum sensing leverages quantum properties to enhance the sensitivity and resolution of sensors beyond their classical sensing limits. Quantum sensors, such as diamond defect centers, have been developed to detect various physical properties, including magnetic fields and temperature. However, the spins of defects are buried within dense solids, making it difficult for them to strongly interact with molecular analytes. Therefore, nanoporous materials have been implemented in combination with electron spin center of molecules (molecular qubits) to produce quantum chemosensors that can distinguish various chemical substances. Molecular qubits have a uniform structure, and their properties can be precisely controlled by changing their chemical structure. Metal-organic frameworks (MOFs) are suitable for supporting molecular qubits because of their high porosity, structural regularity, and designability. Molecular qubits can be inserted in the MOF structures or adsorbed as guest molecules. The qubits in the MOF can interact with analytes upon exposure, providing an effective and tunable sensing platform.In this Account, we review the recent progress in qubit-MOF hybrids toward the realization of room-temperature quantum chemosensing. Molecular qubits can be introduced in controlled concentrations at targeted positions by exploiting metal ions, ligands, or guests that compose the MOF. Heavy metal-free organic chromophores have several outstanding features as molecular qubits; namely, they can be initialized by light irradiation and exhibit relatively long coherence times of submicroseconds to microseconds, even at room temperature. One detection method involves monitoring the hyperfine interaction between the electron spins of the molecular qubits and the nuclear spins of the analyte incorporated in the pore. There is also an indirect detection method that relies on the motional change in molecular qubits. If the motion of the molecular qubit changes with the adsorption of the analyte, it can be detected as a change in the spin relaxation process. This mechanism is unique to qubits exposed in nanopores, not observed in conventional qubits embedded in dense solids.By maximizing the guest recognition ability of MOFs and the environmental sensitivity of qubits, quantum chemosensing that recognizes specific chemical species in a highly selective and sensitive manner may be possible. It is difficult to distinguish between diverse chemical species by employing only one combination of MOF and qubit, but by creating arrays of different qubit-MOF hybrids, it would become possible to distinguish between various analytes based on pattern recognition. Inspired by the human olfactory mechanism, we propose the use of multiple qubit-MOF hybrids and pattern recognition to identify specific molecules. This system represents a quantum version of olfaction, and thus we propose the concept of a "quantum nose." Quantum noses may be used to recognize biometabolites and biomarkers and enable new medical diagnostic technologies and olfactory digitization.

The integration of multiple chromophore units into a single molecule is expected to improve the performance of photon upconversion based on triplet-triplet annihilation (TTA-UC) that can convert low energy photons to higher energy photons at low excitation intensity. In this study, a macrocyclic parallel dimer of 9,10-diphenylanthracene (DPA) with a precisely parallel orientation, named MPD-2, is synthesized, and its TTA-UC properties are investigated. MPD-2 shows a green-to-blue TTA-UC emission in the presence of a triplet sensitizer, platinum octaethylporphyrin (PtOEP). Compared to monomeric DPA, MPD-2 results in an enhancement of the spin statistical factor of TTA and a decrease in the excitation light intensity due to the intramolecular TTA process. The obtained structure-property relationship provides important information for the further improvement of TTA-UC properties., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Co-published by University of Science and Technology of China and American Chemical Society.)

Singlet fission (SF) is a promising approach in quantum information science because it can generate spin-entangled quintet triplet pairs by photoexcitation independent of temperature. However, it is still challenging to rationally achieve quantum coherence at room temperature, which requires precise control of the orientation and dynamics of triplet pairs. Here we show that the quantum coherence of quintet multiexcitons can be achieved at room temperature by arranging two pentacene chromophores in parallel and in close proximity within a macrocycle. By making dynamic covalent Schiff-base bonds between aldehyde-modified pentacene derivatives, macrocyclic parallel dimer-1 ( MPD-1 ) can be selectively synthesized in a high yield. MPD-1 exhibits fast subpicosecond SF in polystyrene film and generates spin-polarized quintet multiexcitons. Furthermore, the coherence time T 2 of the MPD-1 quintet is as long as 648 ns, even at room temperature. This macrocyclic parallel dimer strategy opens up new possibilities for future quantum applications using molecular multilevel qubits.

We evaluate the accuracy of the quantum inverse (Q-Inv) algorithm, in which the multiplication of Ĥ - k to the reference wave function is replaced by the Fourier transformed multiplication of e -iλ Ĥ , as a function of the integration parameters and the iteration power k for various systems, including H 2 , LiH, BeH 2 and the notorious H 4 molecule at square geometry. We further consider the possibility of employing the Gaussian-quadrature rule as an alternate integration method and compared it to the results employing trapezoidal integration. The Q-Inv algorithm is compared to the inverse iteration method using the Ĥ -1 inverse (I-Iter) and the exact inverse by lower-upper decomposition. Energy values are evaluated as the expectation values of the Hamiltonian. Results suggest that the Q-Inv method provides lower energy results than the I-Iter method up to a certain k , after which the energy increases due to errors in the numerical integration that are dependent on the integration interval. A combined Gaussian-quadrature and trapezoidal integration method proved to be more effective at reaching convergence while decreasing the number of operations. For systems like H 4 , in which the Q-Inv cannot reach the expected error threshold, we propose a combination of Q-Inv and I-Iter methods to further decrease the error with k at lower computational cost. Finally, we summarize the recommended procedure when treating unknown systems.

Quantum sensing has the potential to improve the sensitivity of chemical sensing by exploiting the characteristics of qubits, which are sensitive to the external environment. Modulation of quantum coherence by target analytes can be a useful tool for quantum sensing. Using molecular qubits is expected to provide excellent sensitivity due to the proximity of the sensor to the target analyte. However, many molecular qubits are used at cryogenic temperatures, and how to make molecular qubits respond to specific analytes remains unclear. Here, we propose a material design in which the coherence time changes in response to a variety of analytes at room temperature. We used the photoexcited triplet, which can be initialized at room temperature, as qubits and introduce them to a metal-organic framework that can flexibly change its pore structure in response to guest adsorption. By changing the local molecular density around the triplet qubits by adsorption of a specific analyte, the mobility of the triplet qubit can be changed, and the coherence time can be made responsive., (© 2024. The Author(s).)

Dynamic nuclear polarization (DNP) is a method for achieving high levels of nuclear spin polarization by transferring spin polarization from electrons to nuclei by microwave irradiation, resulting in higher sensitivity in NMR/MRI. In particular, DNP using photoexcited triplet electron spins (triplet-DNP) can provide a hyperpolarized nuclear spin state at room temperature and in low magnetic field. In this review article, we highlight recent developments in materials and instrumentation for the application of triplet-DNP. First, a brief history and principles of triplet-DNP will be presented. Next, important advances in recent years will be outlined: new materials to hyperpolarize water and biomolecules; high-sensitivity solution NMR by dissolution triplet-DNP; and strategies for further improvement of the polarization. In view of these developments, future directions to widen the range of applications of triplet-DNP will be discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality, and its incidence is increasing due to endemic obesity. HCC is sexually dimorphic in both humans and rodents with higher incidence in males, although the mechanisms contributing to these correlations remain unclear. Here, we examined the role of sphingosine kinase 2 (SphK2), the enzyme that regulates the balance of bioactive sphingolipid metabolites, sphingosine-1-phosphate (S1P) and ceramide, in gender specific MASH-driven HCC., Methods: Male and female mice were fed a high fat diet with sugar water, a clinically relevant model that recapitulates MASH-driven HCC in humans followed by physiological, biochemical cellular and molecular analyses. In addition, correlations with increased risk of HCC recurrence were determined in patients., Results: Here, we report that deletion of SphK2 protects both male and female mice from Western diet-induced weight gain and metabolic dysfunction without affecting hepatic lipid accumulation or fibrosis. However, SphK2 deficiency decreases chronic diet-induced hepatocyte proliferation in males but increases it in females. Remarkably, SphK2 deficiency reverses the sexual dimorphism of HCC, as SphK2 -/- male mice are protected whereas the females develop liver cancer. Only in male mice, chronic western diet induced accumulation of the autophagy receptor p62 and its downstream mediators, the antioxidant response target NQO1, and the oncogene c-Myc. SphK2 deletion repressed these known drivers of HCC development. Moreover, high p62 expression correlates with poor survival in male HCC patients but not in females. In hepatocytes, lipotoxicity-induced p62 accumulation is regulated by sex hormones and prevented by SphK2 deletion. Importantly, high SphK2 expression in male but not female HCC patients is associated with a more aggressive HCC differentiation status and increased risk of cancer recurrence., Conclusions: This work identifies SphK2 as a potential regulator of HCC sexual dimorphism and suggests SphK2 inhibitors now in clinical trials could have opposing, gender-specific effects in patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier GmbH.)

The power conversion efficiency (PCE) of organic photovoltaics (OPVs) has reached more than 19% due to the rapid development of non-fullerene acceptors (NFAs). To compete with the PCEs (26%) of commercialized silicon-based inorganic photovoltaics, the drawback of OPVs should be minimized. This drawback is the intrinsic large loss of open-circuit voltage; however, a general approach to this issue remains elusive. Here, we report a discovery regarding highly efficient NFAs, specifically ITIC. We found that charge-transfer (CT) and charge dissociation (CD) can occur even in a neat ITIC film without the donor layer. This is surprising, as these processes were previously believed to take place exclusively at donor/acceptor heterojunctions. Femtosecond time-resolved visible to mid-infrared measurements revealed that in the neat ITIC layers, the intermolecular CT immediately proceeds after photoirradiation (<0.1 ps) to form weakly-bound excitons with a binding energy of 0.3 eV, which are further dissociated into free electrons and holes with a time-constant of 56 ps. Theoretical calculations indicate that stacking faults in ITIC ( i.e. , V-type molecular stacking) induce instantaneous intermolecular CT and CD in the neat ITIC layer. In contrast, J-type stacking does not support such CT and CD. This previously unknown pathway is triggered by the larger dipole moment change on the excited state generated at the lower symmetric V-type molecular stacking of ITIC. This is in sharp contrast with the need of sufficient energy offset for CT and CD at the donor-acceptor heterojunction, leading to the significant voltage loss in conventional OPVs. These results demonstrate that the rational molecular design of NFAs can increase the local dipole moment change on the excited state within the NFA layer. This finding paves the way for a groundbreaking route toward the commercialization of OPVs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Organic crystals are a promising class of materials for various optical applications. However, it has been challenging to make macroscopic organic crystals with bicontinuous porosity that are applicable to flow chemistry. In this study, a new class of porous materials, cm-scale crystalline organic monoliths (COMs) with bicontinuous porosity, are synthesized by replicating the porous structure of silica monolith templates. The COMs composed of p -terphenyl can take up more than 30 wt% of an aqueous solution, and the photophysical properties of the p -terphenyl crystals are well maintained in the COMs. The relatively high surface area of the COMs can be exploited for efficient Dexter energy transfer from triplet sensitizers on the pore surface. The resulting triplet excitons in the COMs encounter and annihilate, generating upconverted UV emission. The COMs would open a new avenue toward applications of organic crystals in flow photoreaction systems., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Bending inherently planar π-cores consisting of only six-membered rings has traditionally been challenging because a powerful transformation is required to compensate for the significant strain energy associated with bending. Herein, we demonstrate that sulfur extrusion can achieve substantial molecular bending of a perylene structure to form a substructure of a Vögtle belt, a proposed yet hitherto elusive carbon nanotube fragment. Bent perylene bisimide (PBI) derivatives were synthesized through a double-sulfur-extrusion reaction from the corresponding sulfur-containing V-shaped precursors with an internal alkyl tether. The effect of bending the inherently planar PBI core, which is a recent topic of interest for the design of advanced organic electronic and optoelectronic materials, was investigated systematically. Increasing the curvature leads to a red shift in the absorption and emission spectra, while the fluorescence quantum yields remain high. This stands in contrast with the nonemissive features of previously reported nonplanar PBI derivatives based on conjugative tethers. Detailed photophysical measurements indicated that the increasing curvature with shorter alkyl tethers (i) slightly facilitates intersystem crossing and (ii) significantly suppresses the internal conversion in the excited state of the present bent PBI derivatives. The latter characteristics originate from the restricted dynamic motion associated with the charge-transfer (CT) character between the core chromophores and the N -aryl units.

Metal-organic frameworks (MOFs) integrated with molecular qubits are promising for quantum sensing. In this study, a new UiO-type MOF with a 5,12-diazatetracene (DAT)-containing ligand is synthesized, and the radicals generated in the MOF exhibit high stability and a relatively long coherence time ( T 2 ) responsive to the introduction of various guest molecules.

An efficient algorithm for compressing a given many-body potential energy surface (PES) of molecular systems into a grid-based matrix product operator (MPO) is proposed. The PES is once represented by a full-dimensional or truncated many-body expansion form, which is obtained by ab initio calculations at each grid mesh point, and then all terms in the expansion are compressed and merged into a single MPO while maintaining the bond dimension of the MPO as small as possible. It was shown that the ab initio PES of the H 2 CO was compressed by more than 2 orders of magnitude in the size of the site operators without loss of accuracy. By the use of grid basis, the tensor rank of the site operators of the MPO is reduced from four to three due to the diagonal nature of the position-dependent operators on grid basis, which significantly reduces the computational cost of the tensor contractions required in the real and imaginary time evolution of the matrix product state (MPS) wave functions with the grid-based MPO (Grid-MPO) Hamiltonian. Similar to other grid-based methods, Grid-MPO is easily applicable to any kinds of potentials of molecular systems, such as analytical empirical model potentials expressed by position operators and ab initio potentials, if the values at the grid points are available. Using the Grid-MPO combined with the MPS, we calculated the time correlation function of the Eigen cation H 3 O + ( H 2 O ) 3 to predict the infrared spectrum and compared with the experimental and the previous theoretical studies. The actual scaling with the size of systems was examined for the multidimensional Henon-Heiles Hamiltonian. It was shown that the method is considerably accelerated by the graphic processing unit (GPU) because the sizes of site operators were kept small and all tensors were able to be stored on the VRAM of a GPU.

A method to predict the D tensor in the molecular frame with multiconfigurational wave functions in large active space was proposed, and the spin properties of the lowest triplets of aromatic molecules were examined with full-π active space; such calculations were challenging because the size of active space grows exponentially with the number of π electrons. In this method, the exponential growth of complexity is resolved by the density matrix renormalization group (DMRG) algorithm. From the D tensor, we can directly determine the direction of the magnetic axes and the ZFS parameters, D - and E -values, of the phenomenological spin Hamiltonian with their signs, which are not usually obtained in ESR experiments. The method using the DMRG-CASSCF wave function can give correct results even when the sign of D - and E -values is sensitive to the accuracy of the prediction of the D tensor and existing methods fail to predict the correct magnetic axes.

Solid-state materials with improved light-to-energy conversions in organic photovoltaics and in optoelectronics are expected to be developed by realizing efficient triplet-triplet annihilation (TTA) by manipulating the spin conversion processes to the singlet state. In this study, we elucidate the spin conversion mechanism for delayed fluorescence by TTA from a microscopic view of the molecular conformations. We examine the time evolution of the electron spin polarization of the triplet-pair state (TT state) in an amorphous solid-state system exhibiting highly efficient up-conversion emission by using time-resolved electron paramagnetic resonance. We clarified that the spin-state population of the singlet TT increased through the spin interconversion from triplet and quintet TT states during exciton diffusion with random orientation dynamics between the two triplets for the modulation of the exchange interaction, achieving a high quantum yield of up-conversion emission. This understanding provides us with a guide for the development of efficient light-to-energy conversion devices utilizing TTA.

A series of ferrocene(Fc)-bridged pentacene(Pc)-dimers [Fc-Ph(2,n)-(Pc) 2 : n=number of phenylene spacers] were synthesized to examine the tortional motion effect of Fc-terminated phenylene linkers on strongly coupled quintet multiexciton ( 5 TT) formation through intramolecular singlet fission (ISF). Fc-Ph(2,4)-(Pc) 2 has a relatively small electronic coupling and large conformational flexibility according to spectroscopic and theoretical analyses. Fc-Ph(2,4)-(Pc) 2 exhibits a high-yield 5 TT together with quantitative singlet TT ( 1 TT) generation through ISF. This demonstrates a much more efficient ISF than those of other less flexible Pc dimers. The activation entropy in 1 TT spin conversion of Fc-Ph(2,4)-(Pc) 2 is larger than those of the other systems due to the larger conformational flexibility associated with the torsional motion of the linkers. The torsional motion of linkers in 1 TT is attributable to weakened metal-ligand bonding in the Fc due to hybridization of the hole level of Pc to Fc in 1 TT unpaired orbitals., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

A series of metal-organic frameworks (MOFs) assembled with diazatetracene (DAT)-based linkers were synthesized and characterized. Despite different chromophore orientations and spacings, photoinduced persistent radicals were generated in all the MOFs, and their spin-lattice relaxation time ( T 1 ) and spin-spin relaxation time ( T 2 ) were found to be relatively long even at room temperature. The generality of long T 1 and T 2 values of photogenerated radicals in the chromophore-assembled MOFs provides a new platform towards quantum sensing applications.

Singlet fission can generate an exchange-coupled quintet triplet pair state 5 TT, which could lead to the realization of quantum computing and quantum sensing using entangled multiple qubits even at room temperature. However, the observation of the quantum coherence of 5 TT has been limited to cryogenic temperatures, and the fundamental question is what kind of material design will enable its room-temperature quantum coherence. Here, we show that the quantum coherence of singlet fission-derived 5 TT in a chromophore-integrated metal-organic framework can be over hundred nanoseconds at room temperature. The suppressed motion of the chromophores in ordered domains within the metal-organic framework leads to the enough fluctuation of the exchange interaction necessary for 5 TT generation but, at the same time, does not cause severe 5 TT decoherence. Furthermore, the phase and amplitude of quantum beating depend on the molecular motion, opening the way to room-temperature molecular quantum computing based on multiple quantum gate control.

Herein, we give an overview of several less explored structural and optical characterization techniques useful for biomaterials. New insights into the structure of natural fibers such as spider silk can be gained with minimal sample preparation. Electromagnetic radiation (EMR) over a broad range of wavelengths (from X-ray to THz) provides information of the structure of the material at correspondingly different length scales (nm-to-mm). When the sample features, such as the alignment of certain fibers, cannot be characterized optically, polarization analysis of the optical images can provide further information on feature alignment. The 3D complexity of biological samples necessitates that there be feature measurements and characterization over a large range of length scales. We discuss the issue of characterizing complex shapes by analysis of the link between the color and structure of spider scales and silk. For example, it is shown that the green-blue color of a spider scale is dominated by the chitin slab's Fabry-Pérot-type reflectivity rather than the surface nanostructure. The use of a chromaticity plot simplifies complex spectra and enables quantification of the apparent colors. All the experimental data presented herein are used to support the discussion on the structure-color link in the characterization of materials.

Microlens arrays (MLAs) which are increasingly popular micro-optical elements in compact integrated optical systems were fabricated using a femtosecond direct laser write (fs-DLW) technique in the low-shrinkage SZ2080 TM photoresist. High-fidelity definition of 3D surfaces on IR transparent CaF 2 substrates allowed to achieve ∼50% transmittance in the chemical fingerprinting spectral region 2-5 μm wavelengths since MLAs were only ∼10 μm high corresponding to the numerical aperture of 0.3 (the lens height is comparable with the IR wavelength). To combine diffractive and refractive capabilities in miniaturised optical setup, a graphene oxide (GO) grating acting as a linear polariser was also fabricated by fs-DLW by ablation of a 1 μm-thick GO thin film. Such an ultra-thin GO polariser can be integrated with the fabricated MLA to add dispersion control at the focal plane. Pairs of MLAs and GO polarisers were characterised throughout the visible-IR spectral window and numerical modelling was used to simulate their performance. A good match between the experimental results of MLA focusing and simulations was achieved.

Current immunotherapies aim to modulate the balance among different immune cell populations, thereby controlling immune reactions. However, they often cause immune overactivation or over-suppression, which makes them difficult to control. Thus, it would be ideal to manipulate immune cells at a local site without disturbing homeostasis elsewhere in the body. Recent technological developments have enabled the selective targeting of cells and tissues in the body. Photo-targeted specific cell therapy has recently emerged among these. Near-infrared photoimmunotherapy (NIR-PIT) has surfaced as a new modality for cancer treatment, which combines antibodies and a photoabsorber, IR700DX. NIR-PIT is in testing as an international phase III clinical trial for locoregional recurrent head and neck squamous cell carcinoma (HNSCC) patients (LUZERA-301, NCT03769506), with a fast-track designation by the United States Food and Drug Administration (US-FDA). In Japan, NIR-PIT for patients with recurrent head and neck cancer was conditionally approved in 2020. Although NIR-PIT is commonly used for cancer therapy, it could also be exploited to locally eliminate certain immune cells with antibodies for a specific immune cell marker. This strategy can be utilized for anti-allergic therapy. Herein, we discuss the recent technological advances in local immunomodulation technology. We introduce immunomodulation technology with NIR-PIT and demonstrate an example of the knockdown of regulatory T cells (Tregs) to enhance local anti-tumor immune reactions.

The N-methyl-D-aspartate receptors (NRs) in hippocampal CA3 are crucial for the synaptic transmission and plasticity within the CA3 recurrent circuit, which supports the hippocampal functions, such as pattern completion, and reverberatory association of sensory inputs. Previous study showed that synchronous activation of distinct cell populations in CA3, which correspond to distinct events, associated independent events, suggesting that the recurrent circuit expressing NRs in CA3 mediates the artificial association of memory events stored in CA3 ensembles. However, it is still unclear whether CA3 NRs are crucial for the artificial association of memory events stored in the CA3 ensembles. Here we report that the triple transgenic mice (cfos-tTA/KA1-Cre/NR1 flox/flox), which specifically lack NRs in the CA3 cell ensembles, showed impairment in artificial association between two events, which in control mice triggered artificial association. This result indicates that NRs in the hippocampal CA3 are required for the artificial association of memory events stored in the CA3 cell ensembles., (© 2023. The Author(s).)

Stem cell therapy plays an important role in regenerative therapy; however, there is little information on the in vivo dynamics of transplanted stem cells and the influence of the inflammation of affected tissues or organs on these dynamics. In this study, we revealed real-time dynamics of transplanted adipose tissue-derived stem cells (ASCs) and the influence of the inflammatory states on these dynamics in acute liver failure mice. Quantum dots (QDs) labeling did not affect the cytokine profile of ASCs, and intravenously transplanted ASCs labeled with QDs could be detected in real time with high efficiency without laparotomy. Until 30 min after ASC transplantation, no marked differences in the behavior or accumulation of transplanted ASCs in the liver were observed among the three groups with different degrees of liver damage (normal, weak, and strong). However, significant differences in the engraftment rate of transplanted ASCs in the liver were observed among the three groups from 4 h after transplantation. The engraftment rate was inversely correlated with the extent of the liver damage. These data suggested that QDs are useful for in vivo real-time imaging of transplanted cells, and the inflammatory state of tissues or organs may affect the engraftment rate of transplanted cells.

The hippocampus must be capable of sorting and integrating multiple sensory inputs separately but simultaneously. However, it remains to be elucidated how the hippocampus executes these processes simultaneously during learning. Here we found that synchrony between conditioned stimulus (CS)-, unconditioned stimulus (US)- and future retrieval-responsible cells occurs in the CA1 during the reverberatory phase that emerges after sensory inputs have ceased, but not during CS and US inputs. Mutant mice lacking N-methyl-D-aspartate receptors (NRs) in CA3 showed a cued-fear memory impairment and a decrease in synchronized reverberatory activities between CS- and US-responsive CA1 cells. Optogenetic CA3 silencing at the reverberatory phase during learning impaired cued-fear memory. Thus, the hippocampus uses reverberatory activity to link CS and US inputs, and avoid crosstalk during sensory inputs., (© 2022. The Author(s).)

Active recall of short-term memory (STM) is known to last for a few hours, but whether STM has long-term functions is unknown. Here we show that STM can be optogenetically retrieved at a time point during which natural recall is not possible, uncovering the long-term existence of an STM engram. Moreover, re-training within 3 days led to natural long-term recall, indicating facilitated consolidation. Inhibiting offline CA1 activity during non-rapid eye movement (NREM) sleep, N-methyl-D-aspartate receptor (NMDAR) activity, or protein synthesis after first exposure to the STM-forming event impaired the future re-exposure-facilitated consolidation, which highlights a role of protein synthesis, NMDAR and NREM sleep in the long-term storage of an STM trace. These results provide evidence that STM is not completely lost within hours and demonstrates a possible two-step STM consolidation, first long-term storage as a behaviorally inactive engram, then transformation into an active state by recurrence within 3 days., (© 2022. The Author(s).)

Background: Light-based therapies are promising for treating diseases including cancer, hereditary conditions, and protein-related disorders. However, systems, methods, and devices that deliver light deep inside the body are limited. This study aimed to develop an endovascular therapy-based light illumination technology (ET-BLIT), capable of providing deep light irradiation within the body., Methods: The ET-BLIT system consists of a catheter with a single lumen as a guidewire and diffuser, with a transparent section at the distal end for thermocouple head attachment. The optical light diffuser alters the emission direction laterally, according to the optical fibre's nose-shape angle. If necessary, after delivering the catheter to the target position in the vessel, the diffuser is inserted into the catheter and placed in the transparent section in the direction of the target lesion., Findings: ET-BLIT was tested in an animal model. The 690-nm near-infrared (NIR) light penetrated the walls of blood vessels to reach the liver and kidneys without causing temperature increase, vessel damage, or blood component alterations. NIR light transmittance from the diffuser to the detector within the organ or vessel was approximately 30% and 65% for the renal and hepatic arteries, respectively., Interpretation: ET-BLIT can be potentially used in clinical photo-based medicine, as a far-out technology. ET-BLIT uses a familiar method that can access the whole body, as the basic procedure is comparable to that of endovascular therapy in terms of sequence and technique. Therefore, the use of the ET-BLIT system is promising for many light-based therapies that are currently in the research phase., Funding: Supported by Programme for Developing Next-generation Researchers (Japan Science and Technology Agency); JSPS KAKENHI (18K15923, 21K07217); JST-CREST (JPMJCR19H2); JST-FOREST-Souhatsu (JPMJFR2017); The Uehara Memorial Foundation; Yasuda Memorial Medical Foundation; Mochida Memorial Foundation for Medical and Pharmaceutical Research; Takeda Science Foundation; The Japan Health Foundation; Takahashi Industrial and Economic Research Foundation; AICHI Health Promotion Foundation; and Princess Takamatsu Cancer Research Fund., Competing Interests: Declaration of interests Nothing to declare., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objective: Bronchoscopy is an airborne particle-generating procedure. However, few methods for safe bronchoscopy have been developed. To reduce airborne particles during bronchoscopy, we created an 'e-mask', which is a simple, disposable mask for patients. Our objective was to evaluate the e-mask's protective ability against airborne particles and to assess respiratory adverse events and complications., Methods: Patients with stage 2-4 chronic obstructive pulmonary disease were excluded. We performed visualization and quantifying experiments on airborne particles with and without the e-mask. We prospectively evaluated whether wearing the e-mask during bronchoscopy was associated with the incidence of patients requiring >5 L/min oxygen to maintain >90% oxygen saturation, and patients with >45 mm Hg end-tidal carbon dioxide (EtCO 2 ) elevation, in addition to complications, compared to historical controls., Results: In the visualization experiment, more than ten thousand times of airborne particles were generated without the e-mask than with the e-mask. The volume of airborne particles was significantly reduced with the e-mask, compared to that without the e-mask (p = 0.011). Multivariate logistic regression analysis revealed that wearing the e-mask had no significant effect on the incidence of patients requiring >5 L/min oxygen to maintain >90% oxygen saturation, (p = 0.959); however, wearing the e-mask was a significant factor in >45 mm Hg EtCO 2 elevation (p = 0.026). No significant differences in complications were observed between the e-mask and control groups (5.8% vs. 2.5%, p = 0.395)., Conclusion: Wearing the e-mask during bronchoscopy significantly reduced the generation of airborne particles during bronchoscopy without increasing complications., (© 2022 Asian Pacific Society of Respirology.)

Porphyrins are variously substituted tetrapyrrolic macrocycles, with wide-ranging biological and chemical applications derived from metal chelation in the core and the 18π aromatic surface. Under suitable conditions, the porphyrin framework can deform significantly from regular planar shape, owing to steric overload on the porphyrin periphery or steric repulsion in the core, among other structure modulation strategies. Adopting this nonplanar porphyrin architecture allows guest molecules to interact directly with an exposed core, with guest-responsive and photoactive electronic states of the porphyrin allowing energy, information, atom and electron transfer within and between these species. This functionality can be incorporated and tuned by decoration of functional groups and electronic modifications, with individual deformation profiles adapted to specific key sensing and catalysis applications. Nonplanar porphyrins are assisting breakthroughs in molecular recognition, organo- and photoredox catalysis; simultaneously bio-inspired and distinctly synthetic, these molecules offer a new dimension in shape-responsive host-guest chemistry. In this review, we have summarized the synthetic methods and design aspects of nonplanar porphyrin formation, key properties, structure and functionality of the nonplanar aromatic framework, and the scope and utility of this emerging class towards outstanding scientific, industrial and environmental issues.

Polarisation analysis of light-matter interactions established for propagating optical far-fields is now extended into an evanescent field as demonstrated in this study using an attenuated total reflection (ATR) setup and a synchrotron source at THz frequencies. Scalar intensity E 2 , rather than a vector E -field, is used for absorbance analysis of the s- and p-components of the linearly polarised incident light. Absorption and phase changes induced by the sample and detected at the transmission port of the ATR accessory revealed previously non-accessible anisotropy in the absorption-dispersion properties of the sample probed by the evanescent optical near-field. Mapping of the sample's anisotropy perpendicular to its surface by the non-propagating light field is validated and the cos 2   θ absorbance dependence was observed for the angle θ , where θ = 0° is aligned with the sample's surface. A four-polarisation method is presented for the absorbance mapping and a complimentary retardance spectrum is retrieved from the same measurement of the angular dependence of transmittance in structurally complex poly-hydroxybutyrate (PHB) and poly-L-lactic acid (PLLA) samples with amorphous and banded-spherulite (radially isotropic) crystalline regions. A possibility of all 3D mapping of anisotropy (polarisation tomography) is outlined.

Ideal cancer treatments specifically target and eradicate tumor cells without affecting healthy cells. Therefore, antibody-based therapies that specifically target cancer antigens can be considered ideal cancer therapies. Antibodies linked with small-molecule drugs (i.e., antibody-drug conjugates [ADCs]) are widely used in clinics as antibody-based therapeutics. However, because tumors express antigens heterogeneously, greater target specificity and stable binding of noncleavable linkers in ADCs limit their antitumor effects. To overcome this problem, strategies, including decreasing the binding strength, conjugating more drugs, and targeting tumor stroma, have been applied, albeit with limited success. Thus, further technological advancements are required to remotely control the ADCs. Here, we described a drug that is photo-releasable from an ADC created via simple double conjugation and its antitumor effects both on target and nontarget tumor cells. Specifically, noncleavable T-DM1 was conjugated with IR700DX to produce T-DM1-IR700. Although T-DM1-IR700 itself is noncleavable, with NIR-light irradiation, it can release DM1-derivatives which elicited antitumor effect in vitro mixed culture and in vivo mixed tumor model which are mimicking heterogeneous tumor-antigen expression same as real clinical tumors. This cytotoxic photo-bystander effect occurred in various types mixed cultures in vitro, and changing antibodies also exerted photo-bystander effects, suggesting that this technology can be used for targeting various specific cancer antigens. These findings can potentially aid the development of strategies to address challenges associated with tumor expression of heterogeneous antigen., Competing Interests: Kazuhide Sato and Kazuomi Takahashi have a patent pending. The other authors declare no conflicts of interest., (© 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of The American Institute of Chemical Engineers.)

The cytoplasmic domain of receptor tyrosine kinases (RTKs) plays roles as a kinase and a protein scaffold; however, the allocation of these two functions is not fully understood. Here, we analyzed the assembly of the transmembrane (TM)-juxtamembrane (JM) region of EGFR, one of the best studied members of RTKs, by combining single-pair fluorescence resonance energy transfer (FRET) imaging and a nanodisc technique. The JM domain of EGFR contains a threonine residue (T654) that is phosphorylated after ligand association. We observed that the TM-JM peptides of EGFR form anionic lipid-induced dimers and cholesterol-induced oligomers. The two forms involve distinct molecular interactions, with a bias toward oligomer formation upon threonine phosphorylation. We further analyzed the functions and oligomerization of whole EGFR molecules, with or without a substitution of T654 to alanine, in living cells. The results suggested an autoregulatory mechanism in which T654 phosphorylation causes a switch of the major function of EGFR from kinase-activating dimers to scaffolding oligomers., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

THz band-pass filters were fabricated by femtosecond-laser ablation of 25-μm-thick micro-foils of stainless steel and Kapton film, which were subsequently metal coated with a ∼70 nm film, closely matching the skin depth at the used THz spectral window. Their spectral performance was tested in transmission and reflection modes at the Australian Synchrotron's THz beamline. A 25-μm-thick Kapton film performed as a Fabry-Pérot etalon with a free spectral range (FSR) of 119 cm-1, high finesse Fc≈17, and was tuneable over ∼10μm (at ∼5 THz band) with β=30∘ tilt. The structure of the THz beam focal region as extracted by the first mirror (slit) showed a complex dependence of polarisation, wavelength and position across the beam. This is important for polarisation-sensitive measurements (in both transmission and reflection) and requires normalisation at each orientation of linear polarisation.

The conventional treatment of thoracic tumors includes surgery, anticancer drugs, radiation, and cancer immunotherapy. Light therapy for thoracic tumors has long been used as an alternative; conventional light therapy also called photodynamic therapy (PDT) has been used mainly for early-stage lung cancer. Recently, near-infrared photoimmunotherapy (NIR-PIT), which is a completely different concept from conventional PDT, has been developed and approved in Japan for the treatment of recurrent and previously treated head and neck cancer because of its specificity and effectiveness. NIR-PIT can apply to any target by changing to different antigens. In recent years, it has become clear that various specific and promising targets are highly expressed in thoracic tumors. In combination with these various specific targets, NIR-PIT is expected to be an ideal therapeutic approach for thoracic tumors. Additionally, techniques are being developed to further develop NIR-PIT for clinical practice. In this review, NIR-PIT is introduced, and its potential therapeutic applications for thoracic cancers are described.

When processing current sensory inputs, animals refer to related past experiences. Current information is then incorporated into the related neural network to update previously stored memories. However, the neuronal mechanism underlying the impact of memories of prior experiences on current learning is not well understood. Here, we found that a cellular ensemble in the posterior parietal cortex (PPC) that is activated during past experience mediates an interaction between past and current information to update memory through a PPC-anterior cingulate cortex circuit in mice. Moreover, optogenetic silencing of the PPC ensemble immediately after retrieval dissociated the interaction without affecting individual memories stored in the hippocampus and amygdala. Thus, a specific subpopulation of PPC cells represents past information and instructs downstream brain regions to update previous memories., (© 2022. The Author(s).)

Elimination of cancerous cells by the immune system is an important mechanism of protection from cancer, however, its effectiveness can be reduced owing to development of resistance and evasion. To understand the systemic immune response in advanced untreated primary colorectal cancer, we analyze immune subtypes and immune evasion via neoantigen-related mechanisms. We identify a distinctive cancer subtype characterized by immune evasion and very poor overall survival. This subtype has less clonal highly expressed neoantigens and high chromosomal instability, resulting in adaptive immune resistance mediated by the immune checkpoint molecules and neoantigen presentation disorders. We also observe that neoantigen depletion caused by immunoediting and high clonal neoantigen load are correlated with a good overall survival. Our results indicate that the status of the tumor microenvironment and neoantigen composition are promising new prognostic biomarkers with potential relevance for treatment plan decisions in advanced CRC., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Bioluminescence imaging (BLI) enables real-time imaging in vitro and in vivo; it is widely used in laboratories. In vitro, the bioluminescence is commonly used as a reporter for the transfection. In vivo, BLI is employed to evaluate cell expression, migration, and proliferation inside animal bodies and visualize specific cells in various fields. Here, this chapter introduces BLI protocols for assaying the efficacy of in vivo BLI in monitoring cancer treatment using mice orthotopic models., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Near infrared photoimmunotherapy (NIR-PIT) is a molecularly targeted treatment for cancers achieved by injecting a conjugate of IRDye700DX ® (IR700), a water-soluble silicon phthalocyanine derivative in the near infrared, and a monoclonal antibody that targets cancer cell antigens. NIR-PIT is a highly specific treatment with few side effects that results in rapid immunogenic cell death. Despite it being a very effective and innovative therapy, there are a few challenges preventing full implementation in clinical practice. These include the limits of near infrared light penetration, selection of targets, concerns about tumor lysis syndrome and drug costs. However, NIR-PIT has been approved by the regulatory authorities in Japan, allowing for exploration of how to mitigate challenges while maximizing the benefits of this treatment modality.

Polarisation analysis in the mid-infrared fingerprint region was carried out on thin (∼1 μm) Si and SiO 2 films evaporated via glancing angle deposition (GLAD) method at 70∘ to the normal. Synchrotron-based infrared microspectroscopic measurements were carried out on the Infrared Microspectroscopy (IRM) beamline at Australian Synchrotron. Specific absorption bands, particularly Si-O-Si stretching vibration, was found to follow the angular dependence of ∼cos2θ, consistent with the absorption anisotropy. This unexpected anisotropy stems from the enhanced absorption in nano-crevices, which have orientation following the cos2θ angular dependence as revealed by Fourier transforming the image of the surface of 3D columnar films and numerical modeling of light field enhancement by sub-wavelength nano-crevices.

Heterointerfaces with an epitaxial relationship, self-assembled nanocomposites of Pt(111)/CeO 2 (111) 60°, were successfully formed by simple oxidation of Pt 5 Ce alloy. Oxygen dissolution into the alloy causes spacial periodic compositional perturbation by atomic segregation, specifically, by local diffusion of Pt and Ce atoms. A striped pattern of Pt and CeO 2 with a 4-5 nm periodicity formed through phase transformation of the Pt-rich alloy and oxidation of the Ce-rich alloy, respectively. Notably, a fully epitaxial relationship between the Pt and CeO 2 phases was observed even in the initial stage. With continued annealing, the crystals rotated into an energetically favorable orientation with respect to the remaining (111)Pt//(111)CeO 2 . The alloy oxidation and its resulting nanoscale phase-separation behavior were verified in an ex situ annealing experiment of an alloy specimen, which had been first thinned by a focused ion beam. Changing the oxygen partial pressure to the reaction interface may alter the orientation relationship between the hexagonal close-packed Pt 5 Ce structure and face-centered cubic Pt/CeO 2 structure, thereby altering the growth direction of the separated phases. These findings present a pathway for the self-assembly of epitaxial Pt(111)/CeO 2 (111) interface and are expected to assist the structural design of metal-oxide nanocomposites.

Many studies have investigated the effects of music listening from the viewpoint of music features such as tempo or key by measuring psychological or psychophysiological responses. In addition, technologies for three-dimensional sound field (3D-SF) reproduction and binaural recording have been developed to induce a realistic sensation of sound. However, it is still unclear whether music listened to in the presence of 3D-SF is more impressive than in the absence of it. We hypothesized that the presence of a 3D-SF when listening to music facilitates listeners' moods, emotions for music, and physiological activities such as respiration rate. Here, we examined this hypothesis by evaluating differences between a reproduction condition with headphones (HD condition) and one with a 3D-SF reproduction system (3D-SF condition). We used a 3D-SF reproduction system based on the boundary surface control principle (BoSC system) to reproduce a sound field of music in the 3D-SF condition. Music in the 3D-SF condition was binaurally recorded through a dummy head in the BoSC reproduction room and reproduced with headphones in the HD condition. Therefore, music in the HD condition was auditorily as rich in information as that in the 3D-SF condition, but the 3D-sound field surrounding listeners was absent. We measured the respiration rate and heart rate of participants listening to acousmonium and pipe organ music. The participants rated their felt moods before and after they listened to music, and after they listened, they also rated their felt emotion. We found that the increase in respiration rate, the degree of decrease in well-being, and unpleasantness for both pieces in the 3D-SF condition were greater than in the HD condition. These results suggest that the presence of 3D-SF enhances changes in mood, felt emotion for music, and respiration rate when listening to music., Competing Interests: YO and MKa are employees of NTT Communication Science Laboratories, which is a basic-science research section of Nippon Telegraph and Telephone (NTT) Corporation. There are no pending patents involving the reported research. There are no products in development or marketed products to declare. Thus, the authors adhere to the policies of Frontiers. The remaining 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 © 2021 Ooishi, Kobayashi, Kashino and Ueno.)

Benzo[de]isoquinolino[1,8-gh]quinolinetetracarboxylic diimide (BQQDI) is an n-type organic semiconductor that has shown unique multi-fold intermolecular hydrogen-bonding interactions, leading to aggregated structures with excellent charge transports and electron mobility properties. However, the strong intermolecular anchoring of BQQDI presents challenges for fine-tuning the molecular assembly and improving the semiconducting properties. Herein, we report the design and synthesis of two BQQDI derivatives with phenyl- and cyclohexyl substituents (Ph-BQQDI and Cy 6 -BQQDI), where the two organic semiconductors show distinct molecular assemblies and degrees of intermolecular orbital overlaps. In addition, the difference in their packing motifs leads to strikingly different band structures that give rise to contrasting charge-transport capabilities. More specifically, Cy 6 -BQQDI bearing bulky substituents exhibits isotropic intermolecular orbital overlaps resulting in equal averaged transfer integrals in both π-π stacking directions, even when dynamic disorders are taken into account; whereas Ph-BQQDI exhibits anisotropic averaged transfer integrals in these directions. As a result, Cy 6 -BQQDI shows excellent device performances in both single-crystalline and polycrystalline thin-film organic field-effect transistors up to 2.3 and 1.0 cm 2 V -1 s -1 , respectively., (© 2021. The Author(s).)

Background: Near-infrared photoimmunotherapy (NIR-PIT) is a new modality for treating cancer, which uses antibody-photoabsorber (IRDye700DX) conjugates that specifically bind to target tumor cells. This conjugate is then photoactivated by NIR light, inducing rapid necrotic cell death. NIR-PIT needs a highly expressed targeting antigen on the cells because of its reliance on antibodies. However, using antibodies limits this useful technology to only those patients whose tumors express high levels of a specific antigen. Thus, to propose an alternative strategy, we modified this phototechnology to augment the anticancer immune system by targeting the almost low-expressed immune checkpoint molecules on tumor cells., Methods: We used programmed death-ligand 1 (PD-L1), an immune checkpoint molecule, as the target for NIR-PIT. Although the expression of PD-L1 on tumor cells is usually low, PD-L1 is almost expressed on tumor cells. Intratumoral depletion with PD-L1-targeted NIR-PIT was tested in mouse syngeneic tumor models., Results: Although PD-L1-targeted NIR-PIT showed limited effect on tumor cells in vitro, the therapy induced sufficient antitumor effects in vivo, which were thought to be mediated by the 'photoimmuno' effect and antitumor immunity augmentation. Moreover, PD-L1-targeted NIR-PIT induced antitumor effect on non-NIR light-irradiated tumors., Conclusions: Local PD-L1-targeted NIR-PIT enhanced the antitumor immune reaction through a direct photonecrotic effect, thereby providing an alternative approach to targeted cancer immunotherapy and expanding the scope of cancer therapeutics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)