Effect of exogenous oestrogen treatment frequency on induction of artificial lactation in pseudopregnant sows.

In this study, we examined whether the frequency of exogenous oestrogen treatment affects the induction of artificial lactation and milk production. Furthermore, we analysed changes in milk components obtained from artificially lactating sows. Pseudopregnant induced by treatment with 30 mg of estradiol dipropionate (EDP) on Day 10 (Day 0 = the last day of estrus) were divided into three groups: those administered 5 mg of EDP once on Day 39 (n = 5), twice on Days 32 and 39 (n = 5) and three times on Days 25, 32 and 39 (n = 6). All animals were treated with prostaglandin F2α (PGF2α) on Day 46 for induced lactation. Artificial lactation was induced in 66.7%-80.0% of sows, and the EDP treatment frequency before PGF2α administration had no significant effect on either the induction rate of artificial lactation or the milk yield during the experimental period. The milk composition (levels of crude protein, crude fat, crude ash, lactose and immunoglobulin) did not differ among the groups. In conclusion, the number of EDP treatments prior to PGF2α administration had no effect on either the efficiency of artificial lactation induction or milk production.

Ultrathin metasurface on a 100†nm-thick dielectric membrane absorbs infrared rays.

Flat optics based on metasurfaces produce unprecedented two-dimensional planar optical elements that cannot be developed with naturally occurring materials. However, it remains to be shown whether metasurfaces on ultrathin dielectric membranes can be adopted in a broad range of optical elements as flat optics. Here we demonstrate that a fabricated ultrathin metasurface composed of double-sided metal structures on a 100 nm-thick SiNx membrane absorbs infrared rays with a high absorptance of 97.1% at 50.1 THz. This ultrathin metasurface and its fabrication method would be a welcome contribution to a wide range of trailblazing applications, including ultrathin absorbers for imaging and light detection and ranging (LIDAR), directivity control of thermal radiation, and polarization control of vacuum ultraviolet light.

Protein S-nitrosylation is involved in valproic acid-promoted neuronal differentiation of adipose tissue-derived stem cells.

Neuronal differentiation of adipose tissue-derived stem cells (ASCs) is greatly promoted by valproic acid (VPA) with cAMP elevating agents thorough NO signaling pathways, but its mechanism is not fully understood. In the present study, we investigate the involvement of protein S-nitrosylation in the VPA-promoted neuronal differentiation of ASCs. The whole amount of S-nitrosylated protein was increased by the treatment with VPA alone for three days in ASCs. An inhibitor of thioredoxin reductase (TrxR), auranofin, further increased the amount of S-nitrosylated protein and enhances the VPA-promoted neuronal differentiation in ASCs. On the contrary, another inhibitor of TrxR, dinitrochlorobenzene, inhibited the VPA-promoted neuronal differentiation in ASCs even with cAMP elevating agents, which was accompanied by unexpectedly decreased S-nitrosylated protein. It was considered from these results that increased protein S-nitrosylation is involved in VPA-promoted neuronal differentiation of ASCs. By the proteomic analysis of S-nitrosylated protein in VPA-treated ASCs, no identified proteins could be specifically related to VPA-promoted neuronal differentiation. The identified proteins, however, included those involved in the metabolism of substances regulating neuronal differentiation, such as aspartate and glutamate.

Three-dimensional flat bands in pyrochlore metal CaNi2.

Electronic flat-band materials host quantum states characterized by a quenched kinetic energy. These flat bands are often conducive to enhanced electron correlation effects and emergent quantum phases of matter1. Long studied in theoretical models2-4, these systems have received renewed interest after their experimental realization in van der Waals heterostructures5,6 and quasi-two-dimensional (2D) crystalline materials7,8. An outstanding experimental question is if such flat bands can be realized in three-dimensional (3D) networks, potentially enabling new materials platforms9,10 and phenomena11-13. Here we investigate the C15 Laves phase metal CaNi2, which contains a nickel pyrochlore lattice predicted at a model network level to host a doubly-degenerate, topological flat band arising from 3D destructive interference of electronic hopping14,15. Using angle-resolved photoemission spectroscopy, we observe a band with vanishing dispersion across the full 3D Brillouin zone that we identify with the pyrochlore flat band as well as two additional flat bands that we show arise from multi-orbital interference of Ni d-electrons. Furthermore, we demonstrate chemical tuning of the flat-band manifold to the Fermi level that coincides with enhanced electronic correlations and the appearance of superconductivity. Extending the notion of intrinsic band flatness from 2D to 3D, this provides a potential pathway to correlated behaviour predicted for higher-dimensional flat-band systems ranging from tunable topological15 to fractionalized phases16.

Natto extract inhibits infection caused by the Aujeszky's disease virus in mice.

Aujeszky's disease virus (ADV), also known as Suid alphaherpesvirus 1, which mainly infects swine, causes life-threatening neurological disorders. This disease is a serious global risk factor for economic losses in the swine industry. The development of new anti-ADV drugs is highly anticipated and required. Natto, a traditional Japanese fermented food made from soybeans, is a well-known health food. In our previous study, we confirmed that natto has the potential to inhibit viral infections by severe acute respiratory syndrome coronavirus 2 and bovine alphaherpesvirus 1 through their putative serine protease(s). In this study, we found that an agent(s) in natto functionally impaired ADV infection in cell culture assays. In addition, ADV treated with natto extract lost viral infectivity in the mice. We conducted an HPLC gel-filtration analysis of natto extract and molecular weight markers and confirmed that Fraction No. 10 had ADV-inactivating ability. Furthermore, the antiviral activity of Fraction No. 10 was inhibited by the serine protease inhibitor 4-(2-Aminoethyl) benzene sulfonyl fluoride hydrochloride (AEBSF). These results also suggest that Fraction No. 10, adjacent to the 12.5 kDa peak of the marker in natto extract, may inactivate ADV by proteolysis. Our findings provide new avenues of research for the prevention of Aujeszky's disease.

Prebiotic effect of poly-D-3-hydroxybutyrate prevents dyslipidemia in obese mice.

Obesity is a global health problem caused by genetic, environmental, and psychological factors and is associated with various health disorders. As such, there is a growing focus on the prevention of obesity and related diseases. The gut microbiota plays a crucial role in these diseases and has become a therapeutic target. Prebiotics, such as poly-d-3-hydroxybutyric acid (PHB), have gained attention for their potential to alter the gut microbiota, promote beneficial bacterial growth, and alleviate obesity. In this study, we examined the prebiotic effects of PHB in obese mice. We found that, in C57BL/6N mice, PHB reduced blood lipid levels. Analysis of the intestinal microflora also revealed an increase in short-chain fatty acid-producing bacteria. When PHB was administered to obese mice, subcutaneous fat and dyslipidemia were reduced, and the number of beneficial bacteria in the intestinal microflora increased. Furthermore, fatty degradation and oxidative stress were suppressed in the liver. PHB regulates gut bacterial changes related to obesity and effectively inhibits dyslipidemia, suggesting that it could be a prebiotic agent for curing various obesity-related diseases. In summary, PHB increases the beneficial gut microbiota, leading to an alleviation of obesity-associated dyslipidemia.

Effect of pseudopregnancy duration in nonpregnant sows on induced lactation.

This study was conducted to examine the effects of different pseudopregnancy periods in nonpregnant sows on artificial lactation induction efficiency and milk composition. Sixteen pseudopregnant sows (n = 4 per group) were treated with 5 mg of estradiol dipropionate at 28 (Group D38), 35 (Group D45), 42 (Group D52), and 49 (Group D59) days after the end of estrus, followed by prostaglandin F2α as 0.175-mg cloprostenol twice at 12 h intervals 10 days later. The overall success rate of lactation induction was 81.3%. The lactation rates were significantly higher in Groups D38, D45, and D59 (100.0%) than in Group D52 (25.0%). The milk immunoglobulin (Ig) G concentration was significantly higher in Group D38 than in Group D59. However, IgA levels and milk compositions (protein, ash, and lactose) did not differ among the groups. Lactation induction was successful between 38 and 59 days of pseudopregnancy. Apart from IgG, pseudopregnancy length did not affect milk components from 38 to 59 days of pseudopregnancy.

Differential expression of desmin in the uterine myometrium and cervix as a possible mechanism for successful parturition in rats.

Expression of desmin, an intermediate filament, in the myometrium and cervix were investigated in peripartum rats (full term day 22 of pregnancy (DP22)). Des mRNA was expressed in lesser amounts in the cervix at peripartum (DP17 and 21, and day of birth 1 (DB1)), compared to those in the cervixes of ovariectomized rats. Immunohistochemical analysis revealed that desmin protein was diffusely present in the myometrium, and locally in the epithelium of the cervix. Western blot analysis showed that desmin protein levels in the myometrium increased 4- to 6-fold at DP17, 21 and DB1, and decreased rapidly at DB2 to the basal level observed in ovariectomized or non-pregnant rats. In contrast, cervical desmin protein levels increased approximately 10-fold at DP21 compared to those in ovariectomized rats, but decreased rapidly at DB1, indicating its decrease at parturition and an inconsistency between mRNA and protein expression. The administration of 17ß-estradiol to ovariectomized rats increased desmin protein levels in the myometrium and cervix after 24 h. S-nitrosylated desmin protein was detected in the myometrium and cervix at DP21. The mRNA expression of inducible nitric oxide synthase was consistent with the expression of desmin protein. Thus, desmin, which is regulated by estradiol, is differentially expressed in the myometrium and cervix at peripartum possibly for successful pregnancy and parturition. In the cervix, desmin protein expression seems to be regulated by estradiol at the translational level. S-nitrosylation of desmin may have a potential role in the peripartum uterus.

Complementary mRNA expression of enzymes producing nitric oxide and prostaglandin in ductus arteriosus with respect to their role in maintaining patency.

mRNA expression of molecules related to the activity of nitric oxide or prostaglandin E2, the critical regulators maintaining the ductus arteriosus patency, was examined in rat ductus arteriosus at preterm (days 18.5 and 19.5 of pregnancy) and near term (days 20.5 and 21.5). The endothelial nitric oxide synthase mRNA level increased transiently at preterm and then decreased at near term. The cyclooxygenase 2 mRNA increased gradually from near-term to the term complementary to the reduced endothelial nitric oxide synthase mRNA. These results suggest that the role shift between nitric oxide and prostaglandin E2 in maintaining ductus arteriosus patency at preterm and near term may be due to complementary expression changes of endothelial nitric oxide synthase and cyclooxygenase 2 at the transcriptional level.

The novel sustained 3-hydroxybutyrate donor poly-D-3-hydroxybutyric acid prevents inflammatory bowel disease through upregulation of regulatory T-cells.

Inflammatory bowel disease (IBD) is a chronic persistent intestinal disorder, with ulcerative colitis and Crohn's disease being the most common. However, the physio-pathological development of IBD is still unknown. Therefore, research on the etiology and treatment of IBD has been conducted using a variety of approaches. Short-chain fatty acids such as 3-hydroxybutyrate (3-HB) are known to have various physiological activities. In particular, the production of 3-HB by the intestinal microflora is associated with the suppression of various inflammatory diseases. In this study, we investigated whether poly-D-3-hydroxybutyric acid (PHB), a polyester of 3-HB, is degraded by intestinal microbiota and works as a slow-release agent of 3-HB. Further, we examined whether PHB suppresses the pathogenesis of IBD models. As long as a PHB diet increased 3-HB concentrations in the feces and blood, PHB suppressed weight loss and histological inflammation in a dextran sulfate sodium-induced IBD model. Furthermore, PHB increased the accumulation of regulatory T cells in the rectum without affecting T cells in the spleen. These results indicate that PHB has potential applications in treating diseases related to the intestinal microbiota as a sustained 3-HB donor. We show for the first time that biodegradable polyester exhibits intestinal bacteria-mediated bioactivity toward IBD. The use of bioplastics, which are essential materials for sustainable social development, represents a novel approach to diseases related to dysbiosis, including IBD.

Deriving the slip-front propagation velocity with slip-dependent and slip-velocity-dependent friction laws via the use of the linear marginal stability hypothesis.

We investigate analytically and numerically the determining factors of the slip front propagation (SFP) velocity. The slip front has two forms characterized by an intruding or extruding front. We assume a one-dimensional viscoelastic medium on a rigid and fixed substrate, and we employ the friction law depending on the slip and slip velocity. Despite this dependency potentially being nonlinear, we use the linear marginal stability hypothesis, which linearizes the governing equation for the slip, to investigate the intruding and extruding front velocities. The analytically obtained velocities are found to be consistent with the numerical computation where we assume the friction law depends nonlinearly on both the slip and slip velocity. This implies that the linearized friction law is sufficient to capture the dominant features of SFP behavior.

Hydrogen sulfide potently promotes neuronal differentiation of adipose tissue-derived stem cells involving nitric oxide-mediated signaling cascade with the aid of cAMP-elevating agents.

Neuronal differentiation of adipose tissue-derived stem cells (ASCs) is potently promoted by valproic acid (VPA) through a gaseous signaling molecule, nitric oxide (NO). Here, we investigated the involvement of hydrogen sulfide (H2S), another gaseous signaling molecule, in neuronal differentiation of ASCs. VPA-promoted neuronal differentiation of ASCs was accompanied by increased intracellular H2S and sulfane sulfur with increased mRNA expression of enzymes synthesizing sulfane sulfur including cystathionine ß-synthase (CBS), of which inhibition reduced the differentiation efficiency. H2S donors, GYY4137 (GYY) or NaHS, potently promoted neuronal differentiation of ASCs when cAMP-elevating agents, dibutyryl cyclic adenosine monophosphate and isobutyl methyl-xanthine, were added as neuronal induction medium (NIM). Neuronal differentiation of ASCs promoted by NaHS or GYY was accompanied by Ca2+ entry and increased mRNA expression of voltage-gated Ca2+ channels. NaHS or GYY also increased mRNA expression of enzymes of the NO-citrulline cycle including inducible NO synthase (iNOS). It was concluded from these results that H2S potently promoted differentiation of ASCs into neuronal cells expressing functional voltage-gated Ca2+ channels with the aid of cAMP-elevating agents, involving NO-mediated signaling cascade. These effects of H2S were also considered as a partial mechanism for the VPA-promoted neuronal differentiation of ASCs.

Valproic acid promotes differentiation of adipose tissue-derived stem cells to neuronal cells selectively expressing functional N-type voltage-gated Ca2+ channels.

The differentiation of adipose tissue-derived stem cells (ASCs) to neuronal cells is greatly promoted by valproic acid (VPA), and is synergistically enhanced by the following treatment with neuronal induction medium (NIM) containing cAMP-elevating agents. In the present study, we investigated the synergism between VPA and NIM in neuronal differentiation of ASCs, assessed by the expression of neurofilament medium polypeptide (NeFM), with respect to Ca2+ entry. VPA (2 mM) treatment for 3 days followed by NIM for 2 h synergistically increased the incidence of neuronal cells differentiated from ASCs to an extent more than VPA alone treatment for 6 days, shortening the time required for the differentiation. VPA increased intracellular Ca2+ and the mRNAs of voltage-gated Ca2+ channels, Cacna1b (Cav2.2) and Cacna1h (Cav3.2), in ASCs. Inward currents through Ca2+ channels were evoked electrophysiologically at high voltage potential in ASCs treated with VPA. NIM reduced the mRNAs of NeFM and Cacna1b in VPA-promoted neuronal differentiation of ASCs. It was concluded that functional N-type voltage-gated Ca2+ channels (Cav2.2) are selectively expressed in VPA-promoted neuronal differentiation of ASCs. NIM seems to enhance the mRNA translation of molecules required for the differentiation. Neuronal cells obtained from ASCs by this protocol will be used as a cell source for regenerative therapy of neurological disorders associated with altered Cav2.2 activity.

Evidence of two-dimensional flat band at the surface of antiferromagnetic kagome metal FeSn.

The kagome lattice has long been regarded as a theoretical framework that connects lattice geometry to unusual singularities in electronic structure. Transition metal kagome compounds have been recently identified as a promising material platform to investigate the long-sought electronic flat band. Here we report the signature of a two-dimensional flat band at the surface of antiferromagnetic kagome metal FeSn by means of planar tunneling spectroscopy. Employing a Schottky heterointerface of FeSn and an n-type semiconductor Nb-doped SrTiO3, we observe an anomalous enhancement in tunneling conductance within a finite energy range of FeSn. Our first-principles calculations show this is consistent with a spin-polarized flat band localized at the ferromagnetic kagome layer at the Schottky interface. The spectroscopic capability to characterize the electronic structure of a kagome compound at a thin film heterointerface will provide a unique opportunity to probe flat band induced phenomena in an energy-resolved fashion with simultaneous electrical tuning of its properties. Furthermore, the exotic surface state discussed herein is expected to manifest as peculiar spin-orbit torque signals in heterostructure-based spintronic devices.

Metalens mounted on a resonant tunneling diode for collimated and directed terahertz waves.

Refraction in materials is a fundamental phenomenon in optics and is a factor in the manipulation of light, such as wavefront shaping and beam control. However, conventional optical lenses incorporated in numerous optical sources are made of naturally occurring materials, and material properties predetermine the lens performance. For the development of terahertz flat optics, we experimentally demonstrate a gradient-refractive-index (GRIN) collimating metalens made of our original reflectionless metasurface with an extremely high refractive index, above 10 at 0.312 THz. The planar collimating metalens converts wide-angle radiation from a resonant tunneling diode (RTD) to a collimated plane wave and enhances the directivity of a single RTD 4.2 times. We also demonstrate directional angle control of terahertz waves by moving the metalens in parallel with the incoming wave. The metalens can be simply integrated with a variety of terahertz continuous-wave (CW) sources for 6G (beyond 5G) wireless communications and imaging in future advanced applications. Flat optics based on high refractive index metasurfaces rather than naturally occurring materials can offer an accessible platform for optical devices with unprecedented functionalities.

Reflectionless metasurface with high refractive index in the terahertz waveband.

Terahertz flat optics is a design concept for replacing conventional three-dimensional bulky optical components with two-dimensional ultra-thin optical components. However, high refractive index materials suitable for flat optics are frequently subject to high Fresnel reflections due to the cumbersome control of the relative permeability it requires. Here we experimentally demonstrate a reflectionless metasurface with a high refractive index of 5.88 + j1.57, extremely low reflectance of 1.3%, high relative permittivity of 6.73 + j0.85, and the high relative permeability of 5.03 + j2.11 at 2.97 THz. The super-fine ink-jet printer using silver paste ink fabricates the metasurface consisting of 80,036 pairs of cut metal wires on both the front and back of a 5 µm-thick polyimide film. The findings also demonstrate that weak conductors as well as good conductors can be used in the design of reflectionless metasurfaces with a high refractive index in the terahertz waveband. The presented metasurface can offer an accessible platform for terahertz flat optics in 6G (beyond 5G) wireless communications and imaging.

Terahertz focusing metalens of reflectionless meta-atoms with negative refractive indices.

Terahertz continuous-wave (CW) sources oscillating around the 1.0 THz band at room temperature have rapidly been developed to bridge the terahertz gap. However, reflectionless metasurfaces suitable for integration with terahertz CW sources as optical components have yet to be developed in the terahertz gap. Here, we propose a terahertz-focusing metalens consisting of reflectionless meta-atoms with a discrete distribution of negative refractive indices from ${-}{1.1}$ to ${-}{2.8}$. The proposed 2D gradient-refractive-index metalens converts an incident terahertz Gaussian beam to a line focus. We also experimentally demonstrate a metasurface of reflectionless meta-atoms with a negative refractive index of ${-}{2.8}$ adopted in the periphery of the metalens. The reflectionless metasurface in the terahertz gap would be a welcome contribution to the rapid growth of terahertz industrial applications with terahertz CW sources. Further, the design approach based on reflectionless meta-atoms with negative refractive indices could be applied to various 2D planar optical components with attractive functionalities such as collimating, arbitrary wavefront shaping, and light vortices.

L-NAME, a nitric oxide synthase inhibitor, increases the protein expression of both executioner and inhibitor of apoptosis in the placental bed of mid-to-late pregnant rats.

The involvement of nitric oxide (NO) signaling in apoptosis was examined in the placental bed of mid-to-late pregnant rats. Pregnant rats were treated with l-NAME, a nitric oxide synthase inhibitor, by subcutaneous infusion for 48 hours before the examination at day 13.5, 17.5, or 21.5. l-NAME induced apoptosis in the placental bed to a limited extent at days 13.5 and 17.5, but not at day 21.5. When the placental bed was examined at day 17.5, the protein expression of both executioner (C-Cas3) and inhibitor (XIAP) of apoptosis was increased by l-NAME, but they did not co-localized with apoptosis. It was presumed that placental bed apoptosis induced by l-NAME is regulated through the expression of both executioner and inhibitor, possibly involving protein S-nitrosylation.

Valproic acid up-regulates the whole NO-citrulline cycle for potent iNOS-NO signaling to promote neuronal differentiation of adipose tissue-derived stem cells.

Valproic acid (VPA) remarkably promotes the differentiation of adipose tissue-derived stem cells (ASCs) to mature neuronal cells through nitric oxide (NO) signaling due to up-regulated inducible NO synthase (iNOS) as early as within 3 days. Here, we investigated mechanisms of VPA-promoted neuronal differentiation of ASCs concerning the NO-citrulline cycle, the metabolic cycle producing NO. Cultured rat ASCs were differentiated to mature neuronal cells rich in dendrites and expressing a neuronal marker by treatments with VPA at 2 mM for 3 days and subsequently with the neuronal induction medium for 2 h. Inhibitor (α-methyl-d, l-aspartic acid, MDLA) of arginosuccinate synthase (ASS), a key enzyme of the NO-citrulline cycle, abolishes intracellular NO increase and VPA-promoted neuronal differentiation in ASCs. l-Arginine, the substrate of iNOS, restores the promotion effect of VPA, being against MDLA. Immunocytochemistry showed that ASS and iNOS were increased in ASCs expressing neurofilament medium polypeptide (NeFM), a neuronal marker, by VPA and NIM synergistically. Real-time RT-PCR analysis showed that mRNAs of Ass and arginosuccinate lyase (Asl) in the NO-citrulline cycle were increased by VPA. Chromatin immunoprecipitation assay indicated that Ass and Asl were up-regulated by VPA through the acetylation of their associated histone. From these results, it was considered that VPA up-regulated the whole NO-citrulline cycle, which enabled continuous NO production by iNOS in large amounts for potent iNOS-NO signaling to promote neuronal differentiation of ASCs. This may also indicate a mechanism enabling short-lived NO to function conveniently as a potent signaling molecule that can disappear quickly after its role.

Reflectionless zero refractive index metasurface in the terahertz waveband.

Zero refractive index materials behave electromagnetically as single points despite the finite dimensions because a propagating electromagnetic wave passes with an infinite phase velocity. However, the composition of naturally occurring materials cannot produce a zero refractive index material because any effect of both of the dielectric and magnetic properties would have to vanish (be near zero). In this report, we demonstrate a zero refractive index metasurface with a refractive index of 0.16 + j0.09, the reflectance of 0.7%, and transmittance of 97.3% at 0.505 THz. The measured relative permittivity and relative permeability are 0.18 - j0.10 and 0.004 + j0.16 at 0.505 THz, respectively. Both the relative permittivity and relative permeability simultaneously approach zero at the same frequency, and the dielectric and magnetic properties appear to be absent (vanish) in the artificial material. The zero refractive index metasurface can offer a material platform for terahertz applications with unprecedented functionalities for 6G (beyond 5G) wireless communications, imaging, and security.