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While group-2 innate lymphoid cells (ILC2s) are highly proliferative in allergic inflammation, the removal of overactivated ILC2s in allergic diseases has not been investigated. We previously showed that chronic airway allergy induces “exhausted-like” dysfunctional ILC2s expressing T cell immunoreceptor with Ig and ITIM domains (TIGIT). However, the physiological relevance of these cells in chronic allergy remains elusive. To precisely identify and monitor TIGIT+ ILC2s, we generated TIGIT lineage tracer mice. Chronic allergy stably induced TIGIT+ ILC2s, which were highly activated, apoptotic, and were quickly removed from sites of chronic allergy. Transcripts from coding genes were globally suppressed in the cells, possibly due to reduced chromatin accessibility. Cell death in TIGIT+ ILC2s was enhanced by interactions with CD155 expressed on macrophages, whereas genetic ablation of Tigit or blockade by anti-TIGIT antagonistic antibodies promoted ILC2 survival, thereby deteriorating chronic allergic inflammation. Our work demonstrates that TIGIT shifts the fate of ILC2s toward activation-induced cell death, which could present a new therapeutic target for chronic allergies.

The controlling nutritional status (CONUT) score is a simplified nutritional index calculated from serum albumin, total cholesterol, and total lymphocyte count. This study evaluated the prognostic impact of the CONUT score on overall survival (OS) in patients with peripheral T-cell lymphoma (PTCL). A multicenter, retrospective cohort study including 99 patients with PTCL was conducted. The CONUT score was significantly higher in the non-survivor group (median 5, range 0-12) than in the survivor group (median 3, range 0-11

Chip-scale optical devices operated at wavelengths shorter than communication wavelengths, such as LiDAR for autonomous driving, bio-sensing, and quantum computation, have been developed in the field of photonics. In data processing involving optical devices, modulators are indispensable for the conversion of electronic signals into optical signals. However, existing modulators have a high half-wave voltage-length product (VπL) which is not sufficient at wavelengths below 1000 nm. Herein, we developed a significantly efficient optical modulator which has low VπL of 0.52 V·cm at λ = 640 nm using an electro-optic (EO) polymer, with a high glass transition temperature (Tg = 164 °C) and low optical absorption loss (2.6 dB/cm) at λ = 640 nm. This modulator is not only more efficient than any EO-polymer modulator reported thus far, but can also enable ultra-high-speed data communication and light manipulation for optical platforms operating in the ranges of visible and below 1000 nm infrared.

In this mini-review, recent progress of the evaluation of the first hyperpolarizability (β) and the second hyperpolarizability (γ) by hyper-Rayleigh scattering (HRS) or second harmonic scattering (...

Volume-regulated anion channels (VRACs) mediate Cl- and organic solute efflux from vertebrate cells and are essential for cell volume homeostasis. VRACs are heteromeric assemblies of LRRC8A-E proteins with unknown stoichiometries. Homomeric LRRC8A and LRRC8D channels have a hexameric structure. However, these channels are either non-functional or exhibit abnormal functional properties limiting their utility for structure-function analyses. We circumvented these limitations by developing novel homomeric LRRC8 chimeric channels with physiologically relevant functional properties. We demonstrate here that the LRRC8C-LRRC8A(IL125) chimera comprising LRRC8C and 25 amino acids unique to the first intracellular loop (IL1) of LRRC8A has a heptameric structure like that of homologous pannexin channels. Membrane lipids are a key structural element of the channel and are located between subunits and occluding the channel pore. Our results suggest that native VRAC/LRRC8 channels are heptamers and that associated lipids are likely essential for normal channel gating and regulation.

Swelling-activated volume-regulated anion channels (VRACs) are heteromeric channels comprising LRRC8A and at least one other LRRC8 paralog. Cryoelectron microscopy (cryo-EM) structures of nonnative LRRC8A and LRRC8D homohexamers have been described. We demonstrate here that LRRC8A homohexamers poorly recapitulate VRAC functional properties. Unlike VRACs, LRRC8A channels heterologously expressed in Lrr8c−/− HCT116 cells are poorly activated by low intracellular ionic strength (µ) and insensitive to cell swelling with normal µ. Combining low µ with swelling modestly activates LRRC8A, allowing characterization of pore properties. VRACs are strongly inhibited by 10 µM 4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1 H-inden-5-yl)oxy]butanoic acid (DCPIB) in a voltage-independent manner. In contrast, DCPIB block of LRRC8A is weak and voltage sensitive. Cryo-EM structures indicate that DCPIB block is dependent on arginine 103. Consistent with this, LRRC8A R103F mutants are insensitive to DCPIB. However, an LRRC8 chimeric channel in which R103 is replaced by a leucine at the homologous position is inhibited ∼90% by 10 µM DCPIB in a voltage-independent manner. Coexpression of LRRC8A and LRRC8C gives rise to channels with DCPIB sensitivity that is strongly µ dependent. At normal intracellular µ, LRRC8A + LRRC8C heteromers exhibit strong, voltage-independent DCPIB block that is insensitive to R103F. DCPIB inhibition is greatly reduced and exhibits voltage dependence with low intracellular µ. The R103F mutation has no effect on maximal DCPIB inhibition but eliminates voltage dependence under low µ conditions. Our findings demonstrate that the LRRC8A cryo-EM structure and the use of heterologously expressed LRRC8 heteromeric channels pose significant limitations for VRAC mutagenesis-based structure-function analysis. Native VRAC function is most closely mimicked by chimeric LRRC8 homomeric channels.

Group 2 innate lymphoid cells (ILC2s) reside in peripheral tissues such as the lungs, skin, nasal cavity, and gut and provoke innate type 2 immunity against allergen exposure, parasitic worm infection, and respiratory virus infection by producing TH2 cytokines. Recent advances in understanding ILC2 biology revealed that ILC2s can be trained by IL-33 or allergic inflammation, are long-lived, and mount memory-like type 2 immune responses to any other allergens afterwards. In contrast, IL-33, together with retinoic acid, induces IL-10-producing immunosuppressive ILC2s. In this review, we discuss how the allergic cytokine milieu and other immune cells direct the generation of trained ILC2s with immunostimulatory or immunosuppressive recall capability in allergic diseases and infections associated with type 2 immunity. The molecular mechanisms of trained immunity by ILCs and the physiological relevance of trained ILC2s are also discussed.

D-band (110–170 GHz) antenna-coupled optical modulators with electro-optic (EO) polymer waveguides and non-coplanar patch antennas were fabricated using a poled EO polymer film transfer method. A carrier-to-sideband ratio (CSR) of 42.3 dB corresponding to an optical phase shift of 15.3 mrad was obtained by irradiating 150 GHz electromagnetic waves with an irradiation power density of 34.3 W/m2. Our devices and fabrication method have great potential for achieving highly efficient wireless-to-optical signal conversion in radio-over-fiber (RoF) systems.

We have developed silicon-photonic modulators with electro-optic polymer embedded silicon ladder-slot waveguide. 3-dB bandwidth calculated from RC product is estimated to be over 400 GHz. Fabricated modulators exhibited a half-voltage-length product (V π L) of 3.3 Vmm.

In this study, W-band (75–110 GHz) antenna-coupled optical modulators with a cyclo-olefin polymer (COP) lower cladding, an electro-optic (EO) polymer waveguide, and a gap-embedded patch antenna array were fabricated using a transfer and bonding method of a poled EO polymer film. A carrier-to-sideband ratio (CSR) of 56 dB corresponding to an optical phase shift of 3 mrad was obtained under irradiation with 100 GHz electromagnetic waves with a power of 12.8 W/m2. Our devices have the potential to achieve highly efficient wireless–optical signal conversion in radio-over-fiber (RoF) systems.

Optical phased arrays (OPAs), which manipulate an optical beam by controlling the phase of light, are optical devices characterized by high speed, small size, light weight, and high reliability that make various applications possible. In this study, an eight-channel-waveguide OPA using an electro-optic (EO) polymer for phase control was fabricated. Very high-speed optical beam scanning with a frequency of 2 MHz was demonstrated by applying a driving waveform superimposing sinusoidal and rectangular-wave voltages. Furthermore, the EO polymer OPA can be operated with a low total-operation power consumption of 0.38 mW at a scanning speed of 500 kHz.

The controlling nutritional status (CONUT) is a simplified nutritional index calculated from serum albumin, total cholesterol, and the total lymphocyte count. Although the CONUT score is an independent prognostic factor in several hematological malignancies, the prognostic impact of the CONUT score in peripheral T-cell lymphoma (PTCL) is unclear. This study evaluated the prognostic impact of the CONUT score on overall survival (OS) in patients with PTCL. A multicentre, retrospective, cohort study including 99 patients with PTCL was conducted. The CONUT score was significantly higher in the non-survivor group (median 5, range 0-12) than in the survivor group (median 3, range 0-11) (P = 0.026). The CONUT score was an independent prognostic factor in a multivariable Cox proportional hazards model (hazard ratio 1.118, 95% confidence interval 1.020-1.225, P = 0.017). The Cox proportional hazards model with restricted cubic spline showed an S-shaped relationship between the CONUT score and OS. No significant effect-modification by the International Prognostic Index (IPI) was observed, and the CONUT score affected the prognosis of PTCL regardless of the IPI (P for interaction = 0.208). In conclusion, the CONUT score is an independent prognostic factor in patients with PTCL irrespective of IPI categories.

Stark effect is usually ignored because large effect is observed only at a wavelength where absorption is large. However, we found that contribution of the Stark effect is not negligible in the measurement of EO coefficient r even at a wavelength where the absorption is relatively small. Large Stark effect is useful for terahertz (THz) wave detection. The advantages of THz wave detection by the Stark effect is the wide bandwidth and simple optical geometry. Utilizing the Stark effect in EO polymers provides us with a wide variety of applications for electromagnetic wave detection.

Organic electro-optic (EO) polymers have attracted much attention to their potential use of the optical interconnection for faster data communication. Photochemical stability is a crucial problem to be solved for using in commercial systems. We investigated the photochemical stability of the EO polymers under irradiation of a laser at the O-band (1310 nm) to reveal the factors of photodegradation and to obtain a good estimate for the operating lifetime of the devices. Based on the results obtained, we will discuss the effects of excited singlet oxygen on the photochemical stability of the EO polymers.

We have been investigating an optical phased array (OPA) using an electro-optic (EO) polymer, that can control the shape and direction of an optical beam at high speed. In this study, we propose an OPA which consists of hybrid waveguides with organic and inorganic optical core materials. By applying the taper structure to the inorganic core at the connection part, we inproved coupling efficiency.

In Beyond 5G wireless communication, it is expected that the radio over fiber (RoF) technology that transmits signal waveforms of terahertz waves (0.1-10 THz) using optical fibers will be important. In this research, we fabricated optical modulators consisting of the patch antenna arrays and electro-optic (EO) polymer waveguides, aiming to develop a device that directly modulates light by irradiating electromagnetic waves in the W band (75-110 GHz). We also prototyped a device structure with a ground electrode to improve the efficiency of the electromagnetic wave detection.

Various alkyl-methylimidazolium ionic liquids (ILs) were inspected using infrared spectroscopy in the middle frequency range. In the 1050–1200 cm–1 range, there is a skeletal vibrational mode accompanied with a large in-plane +C(2)–H bending motion and +C(4)–H and +C(5)–H motions, and in the 1500–1650 cm–1 range, there are two skeletal vibrational modes with in-plane +C(4,5)–H bending motions. Interestingly, in both ranges, we found that skeletal vibrational modes with a large in-plane +C(2)–H bending motion and in-plane +C(4,5)–H bending motions are insensitive to increases in the basicity of anions or the strengthening of hydrogen bond-type interactions, and the behaviors are completely different from those in the +C–H stretching vibrational modes in the 3000–3200 cm–1 range and the skeletal vibrational modes with large out-of-plane +C–H motions in the 700–950 cm–1 range. Furthermore, in alkyl-methylimidazolium tetrafluoroborate [Cnmim+][BF4–] ILs, we found that absorption due to the (threefold) degenerate vibrational mode of [BF4–] was observed as a broad absorption band with three splitting peaks in the 900–1150 cm–1 range as a result of local symmetry breaking due to the cation–anion interactions.

Follicular lymphoma (FL) is an indolent lymphoma that often transforms into a high-grade lymphoma, mostly diffuse large B-cell lymphoma. A case of FL suggested to transform into plasmablastic lymphoma is presented. A 59-year-old man was admitted to our hospital because of right lower abdominal pain and vomiting. Computed tomography showed a mass in the ileocecum. Colonoscopy showed a mass with an ulcer in the ascending colon, and surgery was performed. Immunohistochemical staining of the biopsied mass showed infiltrated lymphocytes that were positive for CD38, CD45, CD138, and λ chain, and negative for CD4, CD5, CD8, CD10, CD20, CD56, and κ chain. Flow cytometric analysis of the ascites showed similar results. FISH analyses performed using lymph node biopsy specimens, ascite fluid and pleural effusion fluid identified the presence of an IGH/BCL2 translocation. FL was suggested to transform into PBL. Although the patient received three courses of R-CHOP chemotherapy and salvage chemotherapy, the patient died because of lymphoma progression less than 6 months after the diagnosis of PBL. Transformation of FL to PBL is highly unusual. The lack of a standard treatment for PBL results in the poor outcome of this entity. Novel therapeutic approaches are needed.

The 700-950 cm-1 range in infrared spectroscopy was investigated for various imidazolium-based ionic liquids (ILs). Two main vibrational modes of the methylimidazolium cation exist in this region. At 700-800 cm-1, there is an out-of-plane +C(2)-H and +C(4,5)-H bending mode with a larger motion of +C(4,5)-H in the imidazolium ring, whereas at 800-950 cm-1, there is an out-of-plane +C(2)-H and +C(4,5)-H bending mode with a larger motion of +C(2)-H in the imidazolium ring. The molar-concentration-normalized absorbance spectrum of the former band at 700-800 cm-1, which is related to the bending mode with a large +C(4,5)-H motion in the imidazolium ring, is not particularly sensitive to the interactions with anions. The molar-concentration-normalized absorbance spectrum of the latter band at 800-950 cm-1 was nearly identical for ILs that have methylimidazolium cations with carbon chains of different lengths and the same anions. The band shape of the latter band, which is related to the bending mode with a large out-of-plane +C(2)-H bending motion, was highly sensitive to the interactions with anions and, interestingly, both blue- and red-shifted tendencies in the spectrum for each system were observed.