Investigation of unidirectional coupling of dipole emitters in valley photonic heterostructure waveguides.

Photonic heterostructure has recently become a promising platform to study topological photonics with the introduction of mode width degree of freedom (DOF). However, there is still a lack of comprehensive analysis on the coupling of dipole emitters in photonic heterostructures, which constrains the development of on-chip quantum optics based on chiral dipole sources. We systematically analyze the unidirectional coupling mechanism between dipole emitters and valley photonic heterostructure waveguides (VPHWs). With the eigenmode calculations and full-wave simulations, the Stokes parameters are obtained to compare the coupling performance of two types of valley-interface VPHWs. Simulation results show that compared to the zigzag interface with inversion symmetry, the strategy of bearded interface with glide symmetry is easier to realize high-efficiency coupling. By adjusting the position and chirality of dipole emitters in VPHWs, the transmission of light reverses with guided modes coupled to different directions. Furthermore, a topological beam modulator is realized based on VPHWs, which maintains the robustness to large-area potential barriers and sharp corners. Our work supplies a powerful guide for chiral light-matter interaction, which is expected to be applied to increasingly compact and efficient on-chip optical platforms in the future.

Nd:YVO4/YVO4 cascaded Raman laser pumped dual-wavelength signal wave MgO:PPLN-OPO with wide range adjustable wavelength interval.

This article presents a dual-wavelength signal wave output system capable of generating a broad range of adjustable wavelength intervals. The setup involved the creation of a dual-wavelength cascaded Raman laser featuring composite cavities operating at 1176 nm and 1313 nm. Experimental investigations were carried out on an external cavity MgO:PPLN-OPO driven by the cascaded Raman laser. By setting the crystal polarization period to 27.6-34.4 µm and the temperature to 50-130°C, adjustable tunable output of dual-wavelength signal wave at 1176 nm-MgO:PPLN-OPO (1550-2294 nm) and 1313 nm-MgO:PPLN-OPO (1768-2189 nm) was achieved with a wavelength interval of 0-218 nm. Under the conditions of a period of 34.4 µm, temperature of 90°C, and an incident Raman power of 2.6 W, the highest conversion efficiency of Raman to dual-wavelength signal wave (2212, 2182 nm) was 34.2%. Furthermore, the maximum output power of dual-wavelength signal wave was recorded at 1.02 W with an incident Raman power of 3.33 W.

Regulation of ROS in myeloid-derived suppressor cells through targeting fatty acid transport protein 2 enhanced anti-PD-L1 tumor immunotherapy.

Despite the remarkable success and efficacy of immune checkpoint blockade (ICB) therapy against the PD-1/PD-L1 axis, it induces sustained responses in a sizeable minority of cancer patients due to the activation of immunosuppressive factors such as myeloid-derived suppressor cells (MDSCs). Inhibiting the immunosuppressive function of MDSCs is critical for successful cancer ICB therapy. Interestingly, lipid metabolism is a crucial factor in modulating MDSCs function. Fatty acid transport protein 2 (FATP2) conferred the function of PMN-MDSCs in cancer via the upregulation of arachidonic acid metabolism. However, whether regulating lipid accumulation in MDSCs by targeting FATP2 could block MDSCs reactive oxygen species (ROS) production and enhance PD-L1 blockade-mediated tumor immunotherapy remains unexplored. Here we report that FATP2 regulated lipid accumulation, ROS, and immunosuppressive function of MDSCs in tumor-bearing mice. Tumor cells-derived granulocyte macrophage-colony stimulating factor (GM-CSF) induced FATP2 expression in MDSCs by activation of STAT3 signaling pathway. Pharmaceutical blockade of FATP2 expression in MDSCs by lipofermata decreased lipid accumulation, reduced ROS, blocked immunosuppressive activity, and consequently inhibited tumor growth. More importantly, lipofermata inhibition of FATP2 in MDSCs enhanced anti-PD-L1 tumor immunotherapy via the upregulation of CD107a and reduced PD-L1 expression on tumor-infiltrating CD8+T-cells. Furthermore, the combination therapy blocked MDSC's suppressive role on T- cells thereby enhanced T-cell's ability for the production of IFN-γ. These findings indicate that FATP2 plays a key role in modulating lipid accumulation-induced ROS in MDSCs and targeting FATP2 in MDSCs provides a novel therapeutic approach to enhance anti-PD-L1 cancer immunotherapy.

Induction of apoptosis in hematological cancer cells by dorsomorphin correlates with BAD upregulation.

AMPK is generally a tumor suppressor. However, once cancer arises, AMPK becomes a tumor promoter instead, driving cancer development. For such AMPK-driven cancers, AMPK blockade may be a valuable therapeutic strategy. Here we show that AMPK is upregulated in a variety of hematological cancers and plays key roles in maintaining viability of tumor cells. Blockade of AMPK signaling by dorsomorphin markedly induces apoptosis in Jurkat, K562 cell lines as well as primary cancerous B cells. Mechanistically, dorsomorphin significantly upregulates the expression of BAD, a pro-apoptotic member of the Bcl-2 gene family involved in initiating apoptosis. Reduction of BAD expression by RNA interference prevents apoptosis in response to AMPK inhibition. Thus, our data found BAD integrates the pro-apoptotic effects of dorsomorphin and provided novel insights into the mechanisms by which AMPK facilitates survival signaling in hematologic tumor cells.

Evolution of the Raman beam quality in a folded-coupled-cavity Nd:YVO4/YVO4 Raman laser.

An end-pumped actively $Q$Q-switched ${\rm Nd}\!:\!{{\rm YVO}_4}/{{\rm YVO}_4}$Nd:YVO4/YVO4 Raman laser with a folded coupled cavity is demonstrated to study the evolution of Raman beam quality. The theoretical mechanism of the beam cleanup effect of stimulated Raman scattering is analyzed. The beam quality ($M^2$M2) of the Raman beam and the fundamental beams before and after the Raman conversion are measured experimentally. The results show that with the incident pump power increasing, the ${M^2}$M2 of the fundamental beam increases from 1.85 to 3.08, while the ${M^2}$M2 of the Raman beam increases from 1.21 to 1.69. The beam quality of the Raman laser and its degradation are better than that of the fundamental laser.

Vaccination with a DNA vaccine encoding CD317-targeting HBs antigen elicits enhanced immunity in mice.

BACKGROUND: Conventional hepatitis B virus (HBV) vaccines fail to induce protective antibody titers in 5-10% of immune-competent vaccines. Therefore, safe and effective HBV vaccines are still clinically needed. METHODS: In this study, we developed a plasmid DNA vaccine encoding CD317 single-chain fragment variable (α317scFv) linked with the hepatitis B surface antigen (HBsAg) and detected the humoral and cellular immune responses elicited by this vaccine in BALB/c mice. RESULTS: Vaccination with this fusion DNA vaccine in BALB/c mice induced more robust antiviral T cell and antibody immunity against HBsAg. Compared with mice vaccinated with control vaccine encoding HBsAg, the level of serum-circulating anti-HBsAg antibody (HBsAb) was nearly double in fusion DNA-vaccinated mice. More interesting, splenic lymphocytes isolated from fusion DNA-vaccinated mice showed more potent proliferation and IFN-γ production after being re-stimulated with recombinant HBsAg in vitro. And not only that, the cytotoxicity of fusion DNA vaccine-sensitized splenocytes was ∼3-fold higher than that of controls. CONCLUSION: Taken together, our results reveal that the fusion DNA vaccine can induce more effective immunological protection against HBV, and is a promising candidate for preventing HBV infection.

Dynamic Stark induced vortex momentum of hydrogen in circular fields.

In this paper, we report our numerical simulation on the symmetry distortion and mechanism of the vortex-shaped momentum distribution of hydrogen atom by taking into account of the dynamic Stark effect. By deploying the strong field approximation (SFA) theory, we performed extensive simulation on the momentum pattern of hydrogen ionized by two time-delayed oppositely circularly polarized attosecond pulses. We deciphered that this distortion is originated from the temporal characteristics of the dynamic Stark phase which is nonlinear in time.

High-performance second-Stokes generation of a Nd:YVO4/YVO4 Raman laser based on a folded coupled cavity.

We report an actively Q-switched Nd:YVO4/YVO4 intracavity Raman laser at second-Stokes wavelength of 1313.6 nm, which is capable of operating efficiently under pulse repetition frequency higher than 80 kHz. A folded coupled cavity is adopted to optimize the fundamental and the Stokes resonators individually and make full use of the high pump intensity on the Raman crystal. With relatively high output coupling of 82% at 1313 nm, the average output power of 5.16 W at 1313 nm is achieved under the incident pump power of 36.7 W. The cascaded Raman emission at both the first- and second-Stokes wavelength of 1176 and 1313 nm is investigated to discuss the optimization of the second-Stokes generation.

10.3-W actively Q-switched Nd:YVO4/YVO4 folded coupled-cavity Raman laser at 1176 nm.

We report herein an efficient actively Q-switched Nd:YVO4/YVO4 intracavity Raman laser operating at 1176 nm. Factors such as resonator geometry and pumping scheme are optimized to strengthen the power scalability and the conversion efficiency of the intracavity Raman laser. With a folded coupled cavity adopted to make full use of the high pump intensity on the Raman crystal, the first-order Stokes output of 10.32 W at 1176 nm is achieved under the incident pump power of 39 W and pulse repetition frequency of 160 kHz. The corresponding optical efficiency reaches 26.4%, and even higher efficiency of 27.8% is obtained at lower incident pump of 34.4 W.

9.80-W and 0.54-mJ actively Q-switched Nd:YAG/Nd:YVO4 hybrid gain intracavity Raman laser at 1176 nm.

Here we propose an efficient diode-end-pumped actively Q-switched 1176-nm Nd:YAG/Nd:YVO4 hybrid gain intracavity Raman laser. By virtue of the construction of a coaxial double crystal, the laser not only can operate efficiently at low pulse repetition frequencies (PRFs), thereby realizing relatively high-energy and high-peak-power pulsed output, but also is capable of generating a high average output power at high PRFs. A maximum pulse energy of 0.54 mJ for the 1176-nm Stokes light is achieved at the PRF of 10 kHz, and the maximum average output power up to 9.80 W is obtained at the PRF of 100 kHz, while the incident pump power is 42.0 W.

Tunable amplified spontaneous emission in graphene quantum dots doped cholesteric liquid crystals.

Graphene quantum dots (GQDs) have received much research attention, because of their useful structure and optical absorption/emission. We report the tunable amplified spontaneous emission (ASE) in GQD-doped cholesteric liquid crystal (CLC), which to the best of our knowledge has not been previously observed. The GQDs are uniformly dispersed with a weight ratio of 0.5 wt.% in CLC. Under optical excitation, typical ASE is triggered in the system at pump energies greater than 1.25 mJ cm-2. The emission peak at the long wavelength edge of the photonic bandgap shifts from 662 to 669 nm, as the working temperature is increased from 50 to 90 °C. The preparation of the combined GQDs and CLC is simple and low-cost, and the resulting material is photostable and non-toxic. Combining the GQD gain material with the self-assembled CLC resonator has potential in the fabrication of ASE source and laser devices.

TIPE2 protein prevents injury-induced restenosis in mice.

Proliferation of vascular smooth muscle cells (VSMCs) plays an important role in restenosis, a disease characterized by smooth muscle cell hyperplasia and neointimal formation. How proliferation signals are controlled to avoid restenosis is not fully understood. Here we report that TIPE2, the tumor necrosis factor (TNF) α-induced protein 8-like 2 (TNFAIP8L2), suppresses injury-induced restenosis by inhibiting VSMCs proliferation. TIPE2 was significantly upregulated in VSMCs in response to PDGF-BB stimuli and injury. Enforced TIPE2 expression significantly suppressed VSMCs proliferation and cell cycle progression, whereas TIPE2 deficiency in VSMCs promoted cell proliferation and upregulated the expression of Cyclins D1 and D3. TIPE2 likely regulated VSMC proliferation via Rac1-STAT3 and ERK1/2 signaling pathways. It blocked STAT3 activation and nuclear translocation in a Rac1-dependent manner. As a result, TIPE2-deficient VSMCs exhibited enhanced proliferation whereas TIPE2-deficient mice developed more severe restenosis in response to vascular injury. Conversely, adenovirus-mediated gene transfer of TIPE2 significantly reduced injury-induced restenosis in mice. These results indicate that TIPE2 plays a suppressive role in injury-induced restenosis and may serve as a new therapeutic target for treating the disease.

Efficient phase-matching for difference frequency generation with pump of Bessel laser beams.

A type of phase matching for difference frequency generation with Bessel-type pump beams is proposed. In this geometry, the phase matching is achieved in a cone around the laser path by properly controlling the beam profile. An experimental case that 1.5THz generation with ~2µm lasers pumped bulk GaAs crystal is considered. Calculations of the energy conversion characteristics are performed based on a semi-analytical model. The results indicate that this configuration could relax the phase matching condition in a wide range of nonlinear crystals and pump wavelengths.

Random lasing in a colloidal quantum dot-doped disordered polymer.

We report random lasing in colloidal quantum dots (CQDs) doped disordered polymer. The CdSe/ZnS core-shell CQDs are dispersed in hybrid polymer including two types of monomers with different rates of polymerization. After UV curing, spatially localized random resonators are formed owing to long range refractive-index fluctuations in inhomogeneous polymer with gain. Upon the optical excitation, random lasing action is triggered above the threshold of 7mJ/cm2. Through the investigation on the spectral characteristics of random laser, the wavelengths of random lasers strongly depend on pump position, which confirms that random laser modes originate from spatially localized resnonators. According to power Fourier transform of emission spectrum, the average size of equivalent micro resonators is attributed to be 50 µm. The proposed method provides a facile route to develop random lasers based on CQDs, showing potential applications on random fiber laser and laser displays.

High performance PbSe colloidal quantum dot vertical field effect phototransistors.

Here, vertical field effect phototransistors (VFEPTs) based on lead selenide colloidal quantum dots (PbSe CQDs) for infrared photo detection were investigated, using Au/Ag nanowires as the source transparent electrode. VFEPTs have the advantage of easy fabrication of ultrashort channel length devices, as the channel length is simply determined here by the PbSe CQDs active layer's thickness (260 nm). In ultrashort channels, photo-excited carriers quickly (in nanoseconds) transfer to the drain. As soon as a hole (electron) reaches the drain, a hole (electron) is replenished from the source. Accordingly, multiple holes circulate in the ultrashort channel following a single electron-hole photo generation. As a result, the device exhibits superior photoconductive properties over the lateral structure. PbSe CQD VFEPTs show ambipolar operation under low voltage down to one volt at room temperature. Moreover, high photo responsivity and high specific detectivity of 2 × 10(4) A W(-1) and 7 × 10(12) Jones are also achieved in the devices under 808 nm laser illumination. The transparent electrode-based near infrared VFEPTs prepared through this self-assembly solution process show promise for applications in electronics and photoelectronics.

Enhanced amplified spontaneous emission in a quantum dot-doped polymer-dispersed liquid crystal.

Quantum dot-doped polymer-dispersed liquid crystals (QD-PDLCs) were prepared by photoinitiated polymerization and sealed in capillary tubes. The concentration of QDs in the PDLC was 1 wt%. Amplified spontaneous emission (ASE) of the quantum dot-doped polymer-dispersed liquid crystals was observed with 532 nm wavelength laser excitation. The threshold for ASE was 6 mJ cm(-2), which is much lower than that for homogeneous quantum dot-doped polymer (25 mJ cm(-2)). The threshold for ASE was dramatically enhanced when the working temperature exceeded the clearing point of the liquid crystal; this result demonstrates that multi-scattering caused by the liquid crystals effectively improved the path length or dwell time of light in the gain region, which played a key role in decreasing the threshold for ASE.

Efficient 914-nm Nd:YVO4 laser under double-end polarized pumping.

We report herein the enhancement of output power and optical efficiency of a quasi-three-level Nd:YVO4 laser through a double-end polarized pumping scheme, which improves the usually insufficient pump absorption of the short laser gain medium with low doping concentration, and meanwhile alleviates the influence of thermal effect. 17.7 W laser output at 914 nm is obtained under the launched 808-nm pump of 53.0 W, corresponding to an optical efficiency of 33.4%.

Enhanced atherosclerosis in TIPE2-deficient mice is associated with increased macrophage responses to oxidized low-density lipoprotein.

Atherosclerosis has been widely recognized as an inflammatory disease of the arterial wall in which macrophages play a major role. Yet, how macrophage-mediated pathology is regulated during atherosclerosis is poorly understood. TNF-α-induced protein 8-like 2 (TIPE2, also known as TNFAIP8L2) is highly expressed in resting macrophages and can negatively regulate inflammation through inhibiting immune receptor signaling. We report in this article that TIPE2 plays a crucial atheroprotective role likely by regulating macrophage responses to oxidized low-density lipoprotein (ox-LDL). TIPE2-deficient macrophages treated with ox-LDL produced more oxidative stress and proinflammatory cytokines, and exhibited heightened activation of the JNK, NF-κB, and p38 signaling pathways. As a consequence, TIPE2 deficiency in bone marrow-derived cells exacerbated atherosclerosis development in Ldlr(-/-) mice fed a high-fat diet. Importantly, ox-LDL markedly downregulated TIPE2 mRNA and protein levels in macrophages, suggesting that ox-LDL mediates atherosclerosis by TIPE2 inhibition. These results indicate that TIPE2 is a new inhibitor of atherosclerosis and a potential drug target for treating the disease.

5.2-W high-repetition-rate eye-safe laser at 1525 nm generated by Nd:YVO4₋YVO4stimulated Raman conversion.

We report herein an efficient eye-safe Raman laser, which is based upon Nd:YVO4₋YVO4 and in-band pumped by a wavelength-locked laser diode array at 878.6 nm. By virtue of mitigated thermal load and improved pump absorption, a maximum average output power of 5.2 W at 1525 nm is obtained under the incident pump power of 30.6 W with the pulse repetition frequency of 140 kHz, corresponding to an optical efficiency of 17.0%.

Immunological dynamics in MASH: from landscape analysis to therapeutic intervention.

Metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH), is a multifaceted liver disease characterized by inflammation and fibrosis that develops from simple steatosis. Immune and inflammatory pathways have a central role in the pathogenesis of MASH, yet, how to target immune pathways to treat MASH remains perplexed. This review emphasizes the intricate role that immune cells play in the etiology and pathophysiology of MASH and highlights their significance as targets for therapeutic approaches. It discusses both current strategies and novel therapies aimed at modulating the immune response in MASH. It also highlights challenges in liver-specific drug delivery, potential off-target effects, and difficulties in targeting diverse immune cell populations within the liver. This review is a comprehensive resource that integrates current knowledge with future perspectives in the evolving field of MASH, with the goal of driving forward progress in medical therapies designed to treat this complex liver disease.