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Abstract The overlapping metabolic reprogramming of cancer and immune cells is a putative determinant of the antitumor immune response in cancer. Increased evidence suggests that cancer metabolism not only plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune response through both the release of metabolites and affecting the expression of immune molecules, such as lactate, PGE2, arginine, etc. Actually, this energetic interplay between tumor and immune cells leads to metabolic competition in the tumor ecosystem, limiting nutrient availability and leading to microenvironmental acidosis, which hinders immune cell function. More interestingly, metabolic reprogramming is also indispensable in the process of maintaining self and body homeostasis by various types of immune cells. At present, more and more studies pointed out that immune cell would undergo metabolic reprogramming during the process of proliferation, differentiation, and execution of effector functions, which is essential to the immune response. Herein, we discuss how metabolic reprogramming of cancer cells and immune cells regulate antitumor immune response and the possible approaches to targeting metabolic pathways in the context of anticancer immunotherapy. We also describe hypothetical combination treatments between immunotherapy and metabolic intervening that could be used to better unleash the potential of anticancer therapies.

A low-complexity adaptive equalizer including equalization, rotation of state of polarization (RSOP) tracking, and phase recovery is proposed for coherent optical polarization-division-multiplexing (PDM) quadrature phase-shifting keying (QPSK) transmission system. A conventional N-tap 2 × 2 butterfly finite impulse response filter is simplified to two N-tap filters and a 1-tap 2 × 2 filter. Two N-tap filters could compensate for inter-symbol interference and residual chromatic dispersion based on the same error cost function from the power sum of two polarization coupling constant modulus signals. 1-tap 2 × 2 filter which works on the nonlinear principal component analysis (NPCA) criterion is designed for joint polarization demultiplexing and phase recovery. NPCA is proved to not only void the singularity problem in the constant modulus algorithm (CMA) but also has faster tracking capability. Two kinds of adaptive equalizers using least mean squares NPCA (LMS-NPCA) and recursive least squares NPCA (RLS-NPCA) are compared in our simulation and experiment. In an experiment of 112 Gb/s PDM-QPSK transmission over 50 km standard single-mode fiber, the proposed two schemes have better transmission performance at RSOP speed of 1 Mrad/s and 5 Mrad/s compared to the conventional CMA and Viterbi-Viterbi phase estimation (VVPE) scheme. The reduced complexity of the proposed schemes is more than 40%.

Volterra equalizer (VE) is a well-known and effective algorithm to deal with the linear and nonlinear distortions in optical interconnect, but the high computational complexity hinders its practical application. Generally, sparse VEs based on ℓ1- or ℓ0-regularization are good ways to reduce the complexity by discarding some inessential taps. However, a tap threshold needs to be chosen in these sparse VEs like the threshold-based pruned retraining VE (TR-VE) to decide the discarded taps. And this tap threshold should be adjusted fine to balance the reduced complexity and equalization performance, especially when the testing environments alter. Thus, the reduced complexity in these sparse VEs may fluctuate. To address this issue, a robust and stable complexity reduced sparse VE using ℓ0-regularization (ℓ0 -SR-VE) is proposed in this paper. The recursive least square (RLS) algorithm is used to replace the least mean square algorithm for the faster convergence speed and better equalization performance. The complexity of this equalizer depends on its parameters but not the tap threshold. Once the equalizer parameters are determined, the complexity would not change with the system characteristics, contributing to higher practicability. In our experiment, a 150 Gbit/s PAM8 signal transmission system based on intensity modulation and direct detection (IMDD) is achieved, and a dual-drive Mach-Zehnder modulator for optical single-sideband signal generation is used to mitigate the power fading effect. The experimental results show that with the help of ℓ0-SR-VE, the reduced complexity percentage is stable at 66.18% compared with the RLS-based VE, even after 75 km standard single-mode fiber (SSMF) transmission. By using this equalizer, 4×150 Gbit/s PAM8 signals have also been successfully transmitted over 30 km SSMF at C-band. The reduced complexity variation of ℓ0 -TR-VE is >20%, but the reduced complexity of the proposed ℓ0-SR-VE is stable at 60% even after 30 km SSMF for all four lanes.

Abstract The correct folding is a key process for a protein to acquire its functional structure and conformation. Prefoldin is a well-known chaperone protein that regulates the correct folding of proteins. Prefoldin plays a crucial role in the pathogenesis of common neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease). The important role of prefoldin in emerging fields (such as nanoparticles, biomaterials) and tumors has attracted widespread attention. Also, each of the prefoldin subunits has different and independent functions from the prefoldin complex. It has abnormal expression in different tumors and plays an important role in tumorigenesis and development, especially c-Myc binding protein MM-1. MM-1 can inhibit the activity of c-Myc through various mechanisms to regulate tumor growth. Therefore, an in-depth analysis of the complex functions of prefoldin and their subunits is helpful to understand the mechanisms of protein misfolding and the pathogenesis of diseases caused by misfolded aggregation.

Abstract Tumor microenvironment (TME) is the internal environment in which tumor cells survive, consisting of tumor cells, fibroblasts, endothelial cells, and immune cells, as well as non-cellular components, such as exosomes and cytokines. Exosomes are tiny extracellular vesicles (40-160nm) containing active substances, such as proteins, lipids and nucleic acids. Exosomes carry biologically active miRNAs to shuttle between tumor cells and TME, thereby affecting tumor development. Tumor-derived exosomal miRNAs induce matrix reprogramming in TME, creating a microenvironment that is conducive to tumor growth, metastasis, immune escape and chemotherapy resistance. In this review, we updated the role of exosomal miRNAs in the process of TME reshaping.

Polarization de-multiplexing becomes challenging in Stokes vector-direct detection (SV-DD) systems, especially when the rotation of state of polarization (RSOP) and fiber chromatic dispersion (CD) are induced. To address this issue, an adaptive blind RSOP equalizer based on Stokes space is proposed. After theoretical analysis, it is found that the distribution of transmitted signals in Stokes space keeps a paraboloid. Based on this analysis, an adaptive scheme is proposed to track the symmetry axis of paraboloid for the first time. It is worth noticing that not only CD but also high-order modulation formats could not change the paraboloid distribution. Therefore, our algorithm has strong robustness to CD and good suitability for SV-DD systems with different modulation formats. In our simulation, the conventional Stokes space-based method and the training sequences (TS) method are both evaluated for comparison. The results show that our scheme can track RSOP of 20 Mrad/s and 8 Mrad/s at hard-decision forward error correction threshold in 28 Gbaud 4-level quadrature amplitude modulation (4-QAM) and 16-QAM SV-DD systems after 100 km fiber transmission, respectively. No additional computational complexity is required compared to the conventional Stokes space-based method. Moreover, compared to the TS-based method, there is no need to know the actual channel information, contributing to good flexibility.

RAS-related C3 botulinum toxin substrate 1 (Rac.1) is one of the important members of Rho GTPases. It is well known that Rac1 is a cytoskeleton regulation protein that regulates cell adhesion, morphology, and movement. Rac1 is highly expressed in different types of tumors, which is related to poor prognosis. Studies have shown that Rac1 not only participates in the tumor cell cycle, apoptosis, proliferation, invasion, migration and angiogenesis, but also participates in the regulation of tumor stem cell, thus promoting the occurrence of tumors. Rac1 also plays a key role in anti-tumor therapy and participates in immune escape mediated by the tumor microenvironment. In addition, the good prospects of Rac1 inhibitors in cancer prevention and treatment are exciting. Therefore, Rac1 is considered as a potential target for the prevention and treatment of cancer. The necessity and importance of Rac1 are obvious, but it still needs further study.

Radiation therapy is a common and acceptable approach for lung cancer. Although the benefit of ionizing radiation (IR) is well-established, cancer cells can still survive via pro-survival and metastasis signaling pathways. Ras related C3 botulinum toxin substrate1 (RAC1), a member of Rho family GTPases, plays important roles in cell migration and survival. In the present study, we investigated the effects of RAC1 on the survival of lung cancer cells treated with irradiation. The results showed RAC1 is overexpressed in lung cancer cells and promoted cell proliferation and survival. Furthermore, IR induced RAC1 expression and activity via the activation of PI3K/AKT signaling pathway, and then enhancing cell proliferation, survival, migration and metastasis and increasing levels of epithelial-to-mesenchymal transition (EMT) markers, which facilitated the cell survival and invasive phenotypes. In addition, overexpression of RAC1 attenuated the efficacy of irradiation, while inhibition of RAC1 enhanced sensitivity of irradiation in xenograft tumors in vivo. Collectively, we further found that RAC1 enhanced radioresistance by promoting EMT via targeting the PAK1-LIMK1-Cofilins signaling in lung cancer. Our finding provides the evidences to explore RAC1 as a therapeutic target for radioresistant lung cancer cells.

Different human leukocyte antigen (HLA) genotypes have been known to be associated with the risk of development of Sjögren's syndrome in different populations, but this association has never been reported in Taiwan. We enrolled 1044 subjects (673 patients, 371 controls) and tested their HLA‐DR genotypes. We found an increased risk of Sjögren's syndrome in patients carrying HLA‐DR8. DR1 and DR14 were associated with increased risk of eye involvement (uveitis, scleritis or optic neuritis), while DR15 was associated with increased risk of interstitial lung disease. DR8 was associated with increased risk of formation of multiple antibodies: anti‐Ro, rheumatoid factor and antinuclear antibodies (ANA) reaching titer 1:80 or above. DR9 was associated with decreased risk of formation of anti‐La antibodies and increased risk of formation of antithyroglobulin antibodies. DR10 was associated with risk of formation of anticyclic citrullinated peptide (anti‐CCP) antibodies, and DR11 was associated with increased risk of formation of anti‐La antibodies. Oral ulcer was found to be negatively associated with anti‐Ro antibodies and with anti‐ENA antibodies. Skin lesions were associated with ANA antibody titer elevation to 1:80 or above. Malignancies of any kind were associated with the presence of cryoglobulin. Females were more likely to be diagnosed at a younger age than males. There was no statistically significant relationship between HLA‐DR genotype and age at disease diagnosis. In patients with Sjögren's syndrome in Taiwan, the presence of HLA‐DR8 appeared to be a risk factor. In addition, we found several associations between HLA‐DR genotype, clinical presentation, and autoantibody status among them. [ABSTRACT FROM AUTHOR]