Forsythiaside A attenuates lipopolysaccharide-induced mouse mastitis by activating autophagy and regulating gut microbiota and metabolism.

Mastitis is an inflammatory disease of the mammary gland with a high incidence in lactating animals, significantly impacting their health and breastfeeding. Moreover, mastitis adversely affects milk quality and yield, resulting in substantial economic losses for the dairy farming industry. Forsythiaside A (FTA), a phenylethanol glycoside analog extracted from Forsythia, exhibits notable anti-inflammatory and antioxidant properties. However, its protective effects and specific mechanisms against mastitis remain unclear. In this study, a lipopolysaccharide (LPS)-induced mouse mastitis model was used to investigate the protective effect of FTA on LPS-induced mastitis and its potential mechanism using histological assays, Western blot, qRT-PCR, FITC-albumin permeability test, 16s rRNA gene sequencing analysis and non-targeted metabolomics assays to investigate the protective effect of FTA on LPS-induced mastitis model and its potential mechanism. The results demonstrated that FTA significantly mitigated LPS-induced mouse mastitis by reducing inflammation and apoptosis levels, modulating the PI3K/AKT/mTOR signaling pathways, inducing autophagy, and enhancing antioxidant capacity and the expression of tight junction proteins. Furthermore, FTA increased the abundance of beneficial microbiota while decreasing the levels of harmful microbiota in mice, thus counteracting the gut microbiota disruption induced by LPS stimulation. Intestinal metabolomics analysis revealed that FTA primarily regulated LPS-induced metabolite alterations through key metabolic pathways, such as tryptophan metabolism. This study confirms the anti-inflammatory and antioxidant effects of FTA on mouse mastitis, which are associated with key metabolic pathways, including the restoration of gut microbiota balance and the regulation of tryptophan metabolism. These findings provide a novel foundation for the treatment and prevention of mammalian mastitis using FTA.

Forsythiaside A attenuates mastitis via PINK1/Parkin-mediated mitophagy.

BACKGROUND: Bovine mastitis is the most common animal production disease in the global dairy industry, which affects the health of dairy cows. When bovine mastitis occurs, the mitochondrial metabolism of breast tissue increases, and the relationship between inflammation and mitophagy has become a hot topic for many scholars. The abuse of antibiotics leads to the increase of resistance to bovine mastitis. FTA is one of the main effective components of Forsythia suspensa, which has anti-inflammatory, anti-infection, anti-oxidation and anti-virus pharmacological effects, and has broad application prospects in the prevention and treatment of bovine mastitis. However, the relationship between the anti-inflammatory effects of FTA and mitophagy is still unclear. PURPOSE: This study mainly explores the anti-inflammatory effect of FTA in bovine mastitis and the relationship between mitophagy. METHODS: MAC-T cells and wild-type mice were used to simulate the in vitro and in vivo response of mastitis. After the pretreatment with FTA, CsA inhibitors and siPINK1 were used to interfere with mitophagy, and the mitochondrial function impairment and the expression of inflammatory factors were detected. RESULTS: It was found that pre-treatment with FTA significantly reduced LPS induced inflammatory response and mitochondrial damage, while promoting the expression of mitophagy related factors. However, after inhibiting mitophagy, the anti-inflammatory effect of FTA was inhibited. CONCLUSION: This study is the first to suggest the relationship between the anti-inflammatory effect of FTA and mitophagy. PINK1/Parkin-mediated mitophagy is one of the ways that FTA protects MAC-T cells from LPS-induced inflammatory damage.

Transcriptome sequencing analysis of bovine mammary epithelial cells induced by lipopolysaccharide.

Mastitis in cows is caused by the inflammation of the mammary glands due to an infection by external pathogenic bacteria. Mammary gland epithelial cells, which are in direct contact with the external environment, are responsible for the first line of defense of the mammary gland against pathogenic bacteria, playing an essential role in immune defense. To investigate the mechanism of bovine mammary epithelial cells in the inflammatory process, we treated the cells with LPS for 12 hours and analyzed the changes in mRNA by transcriptome sequencing. The results showed that compared to the control group, the LPS treatment group had 121 up-regulated genes and 18 down-regulated genes. GO and KEGG enrichment analysis revealed that these differential genes were mainly enriched in the IL-17 signaling pathway, Legionellosis, Cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, and other signaling pathways. Furthermore, the expression of GRO1 and CXCL3 mRNAs increased significantly after LPS treatment. These findings provide new insights for the treatment of mastitis in cows in the future.

Esculetin improves murine mastitis induced by streptococcus isolated from bovine mammary glands by inhibiting NF-κB and MAPK signaling pathways.

Cow mastitis, caused by Streptococcus infection of the mammary glands, is a common clinical disease that can lead to decreased milk quality and threaten animal welfare and performance. Esculetin (ESC) is a coumarin with anti-inflammatory and anti-asthmatic effects. However, whether ESC has therapeutic effects on mastitis remains unexplored. This study was conducted to investigate the protective effect of ESC against murine mastitis caused by Streptococcus isolated from bovine mammary glands and elucidate the underlying mechanisms. Streptococcus uberis was used to construct a mouse model of mastitis. The results showed that the mice exhibited edema and thickening of the acinar wall with inflammatory infiltration after S. uberis treatment. Intraperitoneal injection of ESC significantly reduced inflammatory cell infiltration, restored normal physiological function, and inhibited the production of the inflammatory cytokines interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analysis revealed that ESC reduced P38 phosphorylation, further inhibited the influence of mammary Streptococcus on cytoplasmic translocation of nuclear factor-κB (P65), and inhibited the transcriptional activation of P65, thus inhibiting the generation of inflammatory cells. Collectively, ESC may inhibit mitogen-activated protein kinase and nuclear factor-κB, thereby highlighting its potential for the treatment and prevention of mastitis.

Forsythoside A regulates autophagy and apoptosis through the AMPK/mTOR/ULK1 pathway and alleviates inflammatory damage in MAC-T cells.

Dairy cow mastitis is the most common disease encountered in dairy farming. Lipopolysaccharides (LPS), among the major virulence-related factors produced by Escherichia coli, stimulate mammary gland inflammation and cause its damage, thereby affecting milk yield and quality. Forsythoside A (FTA) is among the main active components of forsythia. Recent pharmacological studies have demonstrated that FTA possesses anti-inflammatory, antiviral, antioxidant, and other biological activities. This study investigated the effects of the FTA-activated AMP-activated protein kinase (AMPK) signaling pathway on LPS-induced autophagy, apoptosis, and inflammatory damage in bovine mammary epithelial (MAC-T) cells. Cell activity was measured using the Cell Counting Kit 8. Moreover, real-time quantitative polymerase chain reaction and western blot analyses were used to detect expression levels of autophagic, apoptotic, and inflammatory factors, as well as those of oxidative stress-related genes and proteins. The annexin-FITC/PI assay and immunofluorescence assay were used to detect the apoptosis rate and LC3B expression, respectively. We found that FTA attenuated LPS-induced inhibition of MAC-T cell proliferation, reduced mRNA expression of related inflammatory factors, relieved oxidative stress, and exerted protective effects on MAC-T cells. Additionally, FTA activated autophagy, attenuated inhibition of autophagy flow, and inhibited apoptosis. Autophagy and apoptosis were mainly regulated through the AMPK/mTOR/ULK1 pathway. The aforementioned FTA-induced effects were inhibited by the administration of Compound C (CC; an AMPK inhibitor). Taken together, these results indicate that FTA can alleviate LPS-induced inflammation and oxidative stress in MAC-T cells, attenuate impairments in autophagy, and inhibit apoptosis. However, these effects were blocked by CC, which suggests that FTA inhibits LPS-induced autophagy, apoptosis, and inflammatory damage in MAC-T cells by activating the AMPK pathway.

Manipulating the fluorescence of exciton-plasmon hybrids in the strong coupling regime with dual resonance enhancements.

Strong couplings between molecular excitons and metal plasmons bring advantages to effectively manipulate the optical properties of hybrid systems, including both absorption and fluorescence. In contrast to absorption behaviours, which have been quite well understood and can be categorized into different regimes such as Fano dip and Rabi splitting, the characteristics of fluorescence in strongly coupled hybrids remain largely unexplored. Quenching instead of the enhancement of fluorescence is usually observed in the corresponding experiments, and a theoretical model to deal with this phenomenon is still lacking. Herein, we demonstrate a largely enhanced fluorescence in a hybrid system with Cy5 dye molecules strongly coupled to Ag nanoparticle films, signified by the huge Rabi splitting absorption spectra. The plexciton Rabi splitting of the hybrids can be tuned from 320 meV to as large as 750 meV by adjusting both plasmon strength and molecular concentration. Moreover, when the excitation and emission wavelengths are respectively tuned to be resonant with the two Rabi peaks, the hybrid acting as a plexcitonic dual resonant antenna exhibits an enhanced fluorescence 44 times larger than that of the free dye molecule. We also develop a theoretical model to simultaneously study the characteristics of both the absorption and emission spectra, including the peak shifting and strength. These findings offer a new strategy to design and fabricate plexcitonic devices with tunable optical responses and efficient fluorescence.

Synthesis of Au/CdSe Janus Nanoparticles with Efficient Charge Transfer for Improving Photocatalytic Hydrogen Generation.

Metal-semiconductor heterostructures integrate multiply functionalities beyond those of their individual counterparts. Great efforts have been devoted to synthesize heterostructures with controlled morphologies for the applications ranging from photocatalysis to photonic nanodevices. Beyond the morphologies, the interface between two counterparts also significantly influences the performance of the heterostructures. Here, we synthesize Au/CdSe Janus nanostructures consisting of two half spheres of Au and CdSe separated by a flat and high-quality interface. Au/CdSe with other morphologies could also be prepared by adjusting the overgrowth conditions. The photocatalytic hydrogen generation of the Au/CdSe Janus nanospheres is measured to be 3.9 times higher than that of the controlled samples with CdSe half-shells overgrown on the Au nanospheres. The highly efficient charge transfer across the interface between Au and CdSe contributes to the improved photocatalytic performance. Our studies may find the applications in the design of heterostructures with highly efficient photocatalytic activity.

Highly tunable nonlinear response of Au@WS2 hybrids with plasmon resonance and anti-Stokes effect.

We synthesize Au@WS2 hybrid nanobelts and investigate their third-order nonlinear responses mediated by a strong anti-Stokes effect. By using the femtosecond Z-scan technique and tuning the excitation photon energy (Eexc), we find the sign reversals of both nonlinear absorption coefficient ß and nonlinear refractive index γ to be around 1.60 eV, which is prominently higher than the bandgap (1.35 eV) of WS2 bulk owing to the strong anti-Stokes processes around the bandgap of the indirect semiconductors. The saturable absorption and self-defocusing of the WS2 nanobelts are significantly enhanced by the plasmon resonance of the Au nanoparticles when Eexc > 1.60 eV. But the excited state absorption assisted by the anti-Stokes processes and the self-focusing observed at Eexc < 1.60 eV are suppressed by the surface plasmon. Furthermore, by using population rate equations, we theoretically analyze the sign reversals of both ß and γ and reveal the physical mechanism of the unique nonlinear responses of the hybrids with the plasmon resonance and anti-Stokes effect. These observations enrich the understanding of the nonlinear processes and interactions between the plasmon and exciton and are helpful for developing nonlinear optical nanodevices.

Pure magnetic-quadrupole scattering and efficient second-harmonic generation from plasmon-dielectric hybrid nano-antennas.

We theoretically demonstrate that pure magnetic quadrupole (MQ) scattering is achieved via the excitation of anapole modes and Fano resonance in noble metal (Au or Ag) and high refractive index dielectric (AlGaAs) hybrid nano-antennas. In Au-AlGaAs hybrid nano-antennas, electric anapole and magnetic anapole modes are observed, leading to the suppressions of electric and magnetic dipoles. Introducing gain material to AlGaAs nanodisk to increase the strength of electric quadrupole (EQ) Fano resonance leads to the suppression of EQ scattering. Then, ideal MQ scattering is achieved at the wavelength of total scattering cross-section dip. The increase of signal-to-noise ratio of MQ results in the great enhancement of near-field inside AlGaAs nanodisk. Additionally, the strong MQ resonance exhibits great capability for boosting second-harmonic generation by proper mode matching. These findings achieved in subwavelength geometries have important implications for functional metamaterials and nonlinear photonic nanodevices.

Largely enhanced photocatalytic hydrogen production rate of CdS/(Au-ReS2) nanospheres by the dielectric-plasmon hybrid antenna effect.

In this study, we synthesized CdS/(Au-ReS2) nanospheres that have highly efficient photocatalytic hydrogen production activity induced by dielectric-plasmon hybrid antenna resonance. As the diameter (D) of ReS2 nanospheres consisting of 2D nanosheets increases from 114 ± 11 to 218 ± 25 nm, the resonance wavelength of the ReS2 dielectric antenna is tuned from 380 to 620 nm and the hydrogen production rate for the CdS/(Au-ReS2) nanospheres increases by more than 1.85 times and reaches a value as high as 3060 µmol g-1 h-1, with a 9% weight percentage of Au. Due to the enhancements of the local electromagnetic field and excitation energy transfer by the ReS2-Au dielectric-plasmon hybrid antenna, the hydrogen production rate for the CdS/(Au-ReS2) nanospheres (D = 218 ± 25 nm) is 797, 319, 105 and 12 times larger than that for pure ReS2, Au-ReS2, CdS, and CdS-ReS2, respectively. Additionally, the persistence and reusability measurements indicate a favorable stability of CdS/(Au-ReS2). These results provide a strategy to prepare a new class of dielectric-plasmon hybrid antennas consisting of 2D materials and metal nanoparticles, which have promise in applications ranging from photocatalysis to nonlinear optics.

Coupling Resonances of Surface Plasmon in Gold Nanorod/Copper Chalcogenide Core-Shell Nanostructures and Their Enhanced Photothermal Effect.

Dual plasmonic Au@Cu2-x S core-shell nanorods (NRs) have been fabricated by using a hydrothermal method and plasmon-coupled effect between the Au core and Cu2-x S shell in the near-infrared (NIR) region. The extinction spectrum of Au@Cu2-x S NRs is dominated by the surface plasmon resonance (SPR) of the Cu2-x S shell, the transverse surface plasmon resonance (TSPR), and the longitudinal surface plasmon resonance (LSPR) of the Au NRs. With the Cu2-x S shell increasing (fixed Au NRs), the TSPR peak slightly redshifts and the LSPR and SPR peaks blueshift, owing to competition between the redshift of the refractive index effect and blueshift from the plasmon coupled effect. Although, for Au@Cu2 S NRs, only TSPR and LSPR peaks can be seen and a redshift arises with the increasing Cu2 S shell thickness, implying that no plasmonic coupling between Au NRs and Cu2 S shell occurred. The extinction spectrum of the Au@Cu2-x S NRs with three coupled resonance peaks is simulated by using the FDTD method, taking into account the electron-transfer effect. The dispersion properties of the coupling of Au@Cu2-x S NRs with the LSPR of the initial Au core are studied experimentally by changing the length of the Au NRs, which are explained theoretically by the coupled harmonic oscillator model. The calculated coupled coefficients between SPR of the Cu2-x S shell and LSPR of the Au NRs is 180 meV, which is much stronger than that of TSPR of Au NRs of 55 meV. Finally, the enhanced photothermal effect of Au@Cu2-x S NRs has been demonstrated.

Enhanced Second Harmonic Generation by Mode Matching in Gain-assisted Double-plasmonic Resonance Nanostructure.

We theoretically study the gain-assisted double plasmonic resonances to enhance second harmonic generation (SHG) in a centrosymmetric multilayered silver-dielectric-gold-dielectric (SDGD) nanostructure. Introducing gain media into the dielectric layers can not only compensate the dissipation and lead to giant amplification of surface plasmons (SPs), but also excite local quadrupolar plasmon which can boost SHG by mode matching. Specifically, as the quadrupolar mode dominates SHG in our nanostructure, under the mode matching condition, the intensity of second harmonic near-field can be enhanced by 4.43 × 102 and 1.21 × 105 times when the super-resonance is matched only at the second harmonic (SH) frequency or fundamental frequency, respectively. Moreover, the intensity of SHG near-field is enhanced by as high as 6.55 × 107 times when the nanostructure is tuned to double super-resonances at both fundamental and SH frequencies. The findings in this work have potential applications in the design of nanosensors and nanolasers.

Magnetic Fano resonance-induced second-harmonic generation enhancement in plasmonic metamolecule rings.

The "artificial magnetic" resonance in plasmonic metamolecules extends the potential application of magnetic resonance from terahertz to optical frequency bypassing the problem of magnetic response saturation by replacing the conduction current with the ring displacement current. So far, the magnetic Fano resonance-induced nonlinearity enhancement in plasmonic metamolecule rings has not been reported. Here, we use the magnetic Fano resonance to enhance second-harmonic generation (SHG) in plasmonic metamolecule rings. In the spectra of the plasmonic metamolecule, an obvious Fano dip appears in the scattering cross section, while the dip does not appear in the absorption cross section. It indicates that at the Fano dip the radiative losses are suppressed, while the optical absorption efficiency is at a high level. The largely enhanced SHG signal is observed as the excitation wavelength is adjusted at the magnetic Fano dip of the plasmonic metamolecule rings with stable and tunable magnetic responses. We also compare the magnetic Fano dip with the electric case to show its advantages in enhancing the fundamental and second harmonic responses. Our research provides a new thought for enhancing optical nonlinear processes by magnetic modes.

Plasmon-Modulated Excitation-Dependent Fluorescence from Activated CTAB Molecules Strongly Coupled to Gold Nanoparticles.

Excitation-dependent fluorophores (EDFs) have been attracted increasing attention owing to their high tunability of emissions and prospective applications ranging from multicolor patterning to bio-imaging. Here, we report tunable fluorescence with quenching dip induced by strong coupling of exciton and plasmon in the hybrid nanostructure of CTAB* EDFs and gold nanoparticles (AuNPs). The quenching dip in the fluorescence spectrum is tuned by adjusting excitation wavelength as well as plasmon resonance and concentration of AuNPs. The observed excitation-dependent emission spectra with quenching dip are theoretically reproduced and revealed to be induced by resonant energy transfer from multilevel EDFs with wider width channels to plasmonic AuNPs. These findings provide a new approach to prepare EDF molecules and a strategy to modulate fluorescence spectrum via exciton-to-plasmon energy transfer.

Plasmon-assisted site-selective growth of Ag nanotriangles and Ag-Cu2O hybrids.

We report a plasmon-assisted growth of metal and semiconductor onto the tips of Ag nanotriangles (AgNTs) under light irradiation. The site-selective growth of Ag onto AgNTs are firstly demonstrated on the copper grids and amine-coated glass slides. As the irradiation time increases, microscopic images indicate that AgNTs gradually touch with each other and finally "weld" tip-to-tip together into the branched chains. Meanwhile, the redshift of plasmon band is observed in the extinction spectra, which agrees well the growth at the tips of AgNTs and the decrease of the gaps between the adjacent nanotriangles. We also synthesize AgNT-Cu2O nanocomposites by using a photochemical method and find that the Cu2O nanoparticles preferably grow on the tips of AgNTs. The site-selective growth of Ag and Cu2O is interpreted by the local field concentration at the tips of AgNTs induced by surface plasmon resonance under light excitation.

Transport properties of a single plasmon interacting with a hybrid exciton of a metal nanoparticle-semiconductor quantum dot system coupled to a plasmonic waveguide.

The transport properties of a single plasmon interacting with a hybrid system composed of a semiconductor quantum dot (SQD) and a metal nanoparticle (MNP) coupled to a one-dimensional surface plasmonic waveguide are investigated theoretically via the real-space approach. We considered that the MNP-SQD interaction leads to the formation of a hybrid exciton and the transmission and reflection of a single incident plasmon could be controlled by adjusting the frequency of the classical control field applied to the MNP-SQD hybrid nanosystem, the kinds of MNPs and the background media. The transport properties of a single plasmon interacting with such a hybrid nanosystem discussed here could find applications in the design of next-generation quantum devices, such as single-photon switching and nanomirrors, and in quantum information processing.

Plasmonic phase modulator based on novel loss-overcompensated coupling between nanoresonator and waveguide.

We present that surface plasmon polariton, side-coupled to a gain-assisted nanoresonator where the absorption is overcompensated, exhibits a prominent phase shift up to π maintaining the flat unity transmission across the whole broad spectra. Bandwidth of this plasmonic phase shift can be controlled by adjusting the distance between the plasmonic waveguide and the nanoresonator. For a moderate distance, within bandwidth of 100 GHz, the phase shift and transmission are constantly maintained. The plasmonic phase can be shift-keying-modulated by a pumping signal in the gain-assisted nanoresonator. A needed length in our approach is of nanoscale while already suggested types of plasmonic phase modulator are of micrometer scale in length. The energy consumption per bit, which benefits from the nano size of this device, is ideally low on the order of 10 fJ/bit. The controllable plasmonic phase shift can find applications in nanoscale Mach-Zehnder interferometers and other phase-sensitive devices as well as directly in plasmonic phase shift keying modulators.

Tunable plasmon resonance and enhanced second harmonic generation and upconverted fluorescence of hemispheric-like silver core/shell islands.

We investigate tunable plasmon resonance and enhanced second harmonic generation (SHG) and up-converted fluorescence (UCF) of the hemispheric-like silver core/shell islands. The Ag, Ag/Ag2O, and Ag/Ag2O/Ag island films are prepared by using a sputtering technique. The SHG and UCF of the Ag/Ag2O/Ag core/shell islands near the percolating regime is enhanced 2.34 and 3.94 times compared to the sum of two individual counterparts of Ag/Ag2O core/shell and Ag shell islands. The ratio of SHG intensity induced by p- and s-polarization is 0.86 for the initial Ag islands and increase to 1.61 for the Ag/Ag2O/Ag core/shell samples. The tunable intensity ratio of SHG to UCF of the Ag islands treated by thermal and laser annealing processes is also observed. The physical mechanism of the enhanced SHG and UCF in the Ag/Ag2O/Ag core/shell islands is discussed. Our observations provide a new approach to fabricate plasmon-enhanced optical nonlinear nanodevices with tunable SHG and UCF.

Multiple hybridized resonances of IR-806 chromonic molecules strongly coupled to Au nanorods.

Strong coupling of plasmons and molecules generates intriguingly hybridized resonance. The IR-806 molecule is a near-infrared cyanine liquid crystal dye with multiple molecular bands and its tunable absorption spectrum varies dramatically with concentration. In this article, we investigate multiple hybridized resonances of the Au nanorods (AuNRs) strongly coupled to IR-806 molecules. Five hybridized resonance peaks are observed in the extinction spectra of the AuNR@IR-806 hybrids. Two resonance peaks at approximately 840 and 912 nm in the hybrids are reported for the first time. The dependence of the multiple hybridized peaks on the bare plasmon resonance wavelength of AuNRs and the molecular concentration is also demonstrated. The observations presented herein provide a plasmon-molecule coupling route for tuning optical responses of liquid crystal molecules.

Largely enhanced saturable absorption of a complex of plasmonic and molecular-like au nanocrystals.

A saturable absorber is a nonlinear functional material widely used in laser and photonic nanodevices. Metallic nanostructures have prominent saturable absorption (SA) at the plasmon resonance frequency owing to largely enhanced ground state absorption. However, the SA of plasmonic metal nanostructures is hampered by excited-state absorption processes at very high excitation power, which usually leads to a changeover from SA to reversed SA (SA→RSA). Here, we demonstrate tunable nonlinear absorption behaviours of a nanocomplex of plasmonic and molecular-like Au nanocrystals. The SA→RSA process is efficiently suppressed, and the stepwise SA→SA process is fulfilled owing to energy transfer in the nanocomplex. Our observations offer a strategy for preparation of the saturable absorber complex and have prospective applications in liquid lasers as well as one-photon nonlinear nanodevices.