Demonstration of 120 Gbit/s turbulence-resilient coherent optical communication employing cylindrical vector beam multiplexing.

Free space optical (FSO) communication has gained widespread attention due to its advantages, including high confidentiality, high communication capacity, and no limitation of spectrum. One of the great challenges in FSO communication is the transmission performance degradation in atmospheric turbulence channel due to wavefront distortion and scintillation. Here, we proposed and experimentally demonstrated a 120 Gbit/s vector beam multiplexed coherent optical communication system with turbulence-resilient capacity. Four multiplexed vector beams, each carrying a 30 Gbit/s quadrature phase-shift keying signal, propagate through different turbulence conditions. The influence of turbulence channel on the vector beam impairments is experimentally investigated. Under the weaker turbulence conditions, the system bit error rates are below the forward error correction threshold of 3.8 × 10-3. In comparison with the Gaussian mode, the communication interruption probability of the vector beams system decreases from 36% to 12%-18% under stronger turbulence conditions.

Combined strategies for effective cancer immunotherapy with a novel anti-CD47 monoclonal antibody.

CD47 is a widely expressed cell-surface protein that regulates phagocytosis mediated by cells of the innate immune system, such as macrophages and dendritic cells. CD47 serves as the ligand for a receptor on these innate immune cells, signal regulatory protein (SIRP)-α, which in turn inhibits phagocytosis. Several targeted CD47 therapeutic antibodies have been investigated clinically; however, how to improve its therapeutic efficacy remains unclear. Herein, we developed a CD47 blocking antibody, named IBI188, that could specifically block the CD47-SIRP-α axis, which transduces the "don't eat me" signal to macrophages. In vitro phagocytosis assays demonstrated the pro-phagocytosis ability of IBI188. Furthermore, several in vivo models were chosen to evaluate the anti-tumor efficacy of IBI188. IBI188 treatment upregulated cell movement- and inflammation-related genes in macrophages. Synergism was observed when combined with an anti-CD20 therapeutic antibody, whose function depends on antibody-dependent cellular cytotoxicity/phagocytosis (ADCC/ADCP). CD47 expression was evaluated following azacytidine (AZA) treatment, a standard-of-care for patients with multiple myeloma; enhanced anti-tumor efficacy was observed in the combination group in AML xenograft models. Notably, IBI188 treatment increased vascular endothelial growth factor-A (VEGF-A) levels in a solid tumor model, and combined treatment with an anti-VEGF-A antibody and IBI188 resulted in an enhanced anti-tumor effect. These data indicate that IBI188 is a therapeutic anti-CD47 antibody with anti-tumor potency, which can be enhanced when used in combination with standard-of-care drugs for cancer treatment.

URI1 suppresses irradiation-induced reactive oxygen species (ROS) by activating autophagy in hepatocellular carcinoma cells.

Radiotherapy has been extensively applied in cancer treatment. However, this treatment is ineffective in Hepatocellular carcinoma (HCC) due to lack of radiosensitivity. Unconventional prefoldin RPB5 interactor 1 (URI1) exhibits characteristics similar to those oncoproteins, which promotes survival of cancer cells. As a consequence of the irradiation, the levels of endogenous reactive oxygen species (ROS) rise. In the current study, we analyzed the role of URI1 in the control of ROS levels in HepG2 cells. Upon URI1 overexpression, HepG2 cells significantly suppressed irradiation-induced ROS, which may help cells escape from oxidative toxicity. And our data demonstrated that overexpression of URI1 not only resulted in an increase of autophagic flux, but also resulted in an further increased capacity of autophagy to eliminate ROS. It indicated that URI1 suppressed irradiation-induced ROS through activating autophagy. Moreover, URI1 activated autophagy by promoting the activities of AMP-activated protein kinase (AMPK). Results showed that overexpression of URI1 increased the phosphorylation of AMPKα at the Thr172 residue and the activated-AMPK promoted the phosphorylation of forkhead box O3 (FOXO3) at the Ser253 residue, which significantly induced autophagy. Taken together, our findings provide a mechanism that URI1 suppresses irradiation-induced ROS by activating autophagy through AMPK/FOXO3 signaling pathway. These new molecular insights will provide an important contribution to our better understanding about irradiation insensitivity of HCC.

PD-L1/LAG-3 bispecific antibody enhances tumor-specific immunity.

Anti-programmed cell death-1 (PD-1)/PD-ligand-1 (PD-L1) treatments are effective in a fraction of patients with advanced malignancies. However, the majority of patients do not respond to it. Resistance to cancer immunotherapy can be mediated by additional immune checkpoints. We hypothesized that co-targeting of PD-L1 and lymphocyte-activation gene 3 (LAG-3) could provide an alternative therapeutic approach. Here, we developed IBI323, a dual blockade bispecific antibody targeting PD-L1 and LAG-3. We assessed the binding affinity, blocking activity, cell bridging effect, and immunomodulation function of IBI323 using in vitro assays. We also evaluated, in two humanized mouse models, anti-tumor effects and antitumor T cell immunity induced by IBI323. IBI323 bound to PD-L1 and LAG-3 with similar potency as its parental antibodies and blocked the interaction of PD-1/PD-L1, CD80/PD-L1, and LAG-3/MHC-II. Moreover, IBI323 mediated the bridging of PD-L1+ cells and LAG-3+ cells and demonstrated superior immune stimulatory activity compared to each parent antibody in mixed leukocyte reaction. In PD-L1/LAG-3 double knock-in mice bearing human PD-L1 knock-in MC38 tumors, IBI323 showed stronger anti-tumor activity compared to each parental antibody. The better antitumor response correlated with increased tumor-specific CD8+ and CD4+ T cells. IBI323 also induced stronger anti-tumor effect against established A375 tumors compared with combination in mice reconstituted with human immune cells. Collectively, these data demonstrated that IBI323 preserved the blockade activities of parental antibodies while processing a novel cell bridging function. Based on the encouraging preclinical results, IBI323 has significant value in further clinical development.

Impact of Equalization-Enhanced Phase Noise on Digital Nonlinearity Compensation in High-Capacity Optical Communication Systems.

Equalization-enhanced phase noise (EEPN) can severely degrade the performance of long-haul optical fiber transmission systems. In this paper, the impact of EEPN in Nyquist-spaced dual-polarization quadrature phase shift keying (DP-QPSK), dual-polarization 16-ary quadrature amplitude modulation (DP-16QAM), and DP-64QAM optical transmission systems is investigated considering the use of electrical dispersion compensation (EDC) and multi-channel digital backpropagation (MC-DBP). Our results demonstrate that full-field DBP (FF-DBP) is more susceptible to EEPN compared to single-channel and partial-bandwidth DBP. EEPN-induced distortions become more significant with the increase of the local oscillator (LO) laser linewidth, and this results in degradations in bit-error-rates (BERs), achievable information rates (AIRs), and AIR-distance products in optical communication systems. Transmission systems using higher-order modulation formats can enhance information rates and spectral efficiencies, but will be more seriously degraded by EEPN. It is found that degradations on AIRs, for the investigated FF-DBP schemes, in the DP-QPSK, the DP-16QAM, and the DP-64QAM systems are 0.07 Tbit/s, 0.11 Tbit/s, and 0.57 Tbit/s, respectively, due to the EEPN with an LO laser linewidth of 1 MHz. It is also seen that the selection of a higher-quality LO laser can significantly reduce the bandwidth requirement and the computational complexity in the MC-DBP.

RMP/URI inhibits both intrinsic and extrinsic apoptosis through different signaling pathways.

The evading apoptosis of tumor cells may result in chemotherapy resistance. Therefore, investigating what molecular events contribute to drug-induced apoptosis, and how tumors evade apoptotic death, provides a paradigm to explain the relationship between cancer genetics and treatment sensitivity. In this study, we focused on the role of RMP/URI both in cisplatin-induced endogenous apoptosis and in TRAIL-induced exogenous apoptosis in HCC cells. Although flow cytometric analysis indicated that RMP overexpression reduced the apoptosis rate of HCC cells treated with both cisplatin and TRAIL, there was a difference in mechanism between the two treatments. Western blot showed that in intrinsic apoptosis induced by cisplatin, the overexpression of RMP promoted the Bcl-xl expression both in vitro and in vivo. Besides, RMP activated NF-κB/p65(rel) through the phosphorylation of ATM. However, in TRAIL-induced extrinsic apoptosis, RMP significantly suppressed the transcription and expression of P53. Moreover, the forced expression of P53 could offset this inhibitory effect. In conclusion, we presumed that RMP inhibited both intrinsic and extrinsic apoptosis through different signaling pathways. NF-κB was distinctively involved in the RMP circumvention of intrinsic apoptosis, but not in the extrinsic apoptosis of HCC cells. RMP might play an important role in defects of apoptosis, hence the chemotherapeutic resistance in hepatocellular carcinoma. These studies are promising to shed light on a more rational approach to clinical anticancer drug design and therapy.