IL-27 disturbs lipid metabolism and restrains mitochondrial activity to inhibit γδ T17 cell-mediated skin inflammation.

IL-17+ γδ T cells (γδ T17) are kick-starters of inflammation due to their strict immunosurveillance of xenobiotics or cellular damages and rapid response to pro-inflammatory stimulators. IL-27 is a well-recognized pleiotropic immune regulator with potent inhibitory effects on type 17 immune responses. However, its actions on γδ T17 mediated inflammation and the underlying mechanisms are less well understood. Here we find that IL-27 inhibits the production of IL-17 from γδ T cells. Mechanistically, IL-27 promotes lipolysis while inhibits lipogenesis, thus reduces the accumulation of lipids and subsequent membrane phospholipids, which leads to mitochondrial deactivation and ensuing reduction of IL-17. More importantly, Il27ra deficient γδ T cells are more pathogenic in an imiquimod-induced murine psoriasis model, while intracutaneous injection of rmIL-27 ameliorates psoriatic inflammation. In summary, this work uncovered the metabolic basis for the immune regulatory activity of IL-27 in restraining γδ T17 mediated inflammation, which provides novel insights into IL-27/IL-27Ra signaling, γδ T17 biology and the pathogenesis of psoriasis.

Immune-Ageing Evaluation of Peripheral T and NK Lymphocyte Subsets in Chinese Healthy Adults.

Ageing is often accompanied with a decline in immune system function, resulting in immune ageing. Numerous studies have focussed on the changes in different lymphocyte subsets in diseases and immunosenescence. The change in immune phenotype is a key indication of the diseased or healthy status. However, the changes in lymphocyte number and phenotype brought about by ageing have not been comprehensively analysed. Here, we analysed T and natural killer (NK) cell subsets, the phenotype and cell differentiation states in 43,096 healthy individuals, aged 20-88 years, without known diseases. Thirty-six immune parameters were analysed and the reference ranges of these subsets were established in different age groups divided into 5-year intervals. The data were subjected to random forest machine learning for immune-ageing modelling and confirmed using the neural network analysis. Our initial analysis and machine modelling prediction showed that naïve T cells decreased with ageing, whereas central memory T cells (Tcm) and effector memory T cells (Tem) increased cluster of differentiation (CD) 28-associated T cells. This is the largest study to investigate the correlation between age and immune cell function in a Chinese population, and provides insightful differences, suggesting that healthy adults might be considerably influenced by age and sex. The age of a person's immune system might be different from their chronological age. Our immune-ageing modelling study is one of the largest studies to provide insights into 'immune-age' rather than 'biological-age'. Through machine learning, we identified immune factors influencing the most through ageing and built a model for immune-ageing prediction. Our research not only reveals the impact of age on immune parameter differences within the Chinese population, but also provides new insights for monitoring and preventing some diseases in clinical practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00106-0.

Relationship between histone demethylase LSD family and development and prognosis of gastric cancer.

Objective: to elucidate the correlation between histone demethylase and gastric cancer. Research object: histone demethylase and gastric cancer. Results: As one of the important regulatory mechanisms in molecular biology and epigenetics, histone modification plays an important role in gastric cancer including downstream gene expression regulation and epigenetics effect. Both histone methyltransferase and histone demethylases are involved in the formation and maintaining different of histone methylation status, which in turn through a variety of vital molecules and signaling pathways involved in the recognition of histone methylation modification caused by the downstream biological process, eventually participate in the regulation of chromatin function, and with a variety of important physiological activities, especially closely related to the occurrence of gastric cancer and embryonic development. Conclusion: This paper intends to review the research progress in this field from the aspects of histone methylation modification and the protein structure, catalytic mechanism and biological function of the important histone demethylases LSD1 and LSD2, in order to provide the theoretical reference for further understanding and exploration of histone demethylases in development and prognosis of gastric cancer.

Peripheral immune characteristics of hepatitis B virus-related hepatocellular carcinoma.

Background: Liver cancer is the sixth most common cancer worldwide and the third leading cause of cancer-related death. As a chronic liver disease, many studies have shown that the immune response plays a key role in the progression of liver cancer. Chronic hepatitis B virus (HBV) infection is one of the high-risk factors for HCC, accounting for 50%-80% of HCC cases worldwide, and little is known about the immune status of HBV associated hepatocellular carcinoma (HBV-HCC), therefore, we aimed to explore the changes in peripheral immunity in patients with HBV-HCC. Methods: In this study, patients with HBV-HCC (n=26), patients with hepatitis B-related cirrhosis (HBV-LC) (n=31) and healthy volunteers (n=49) were included. The lymphocytes and their subpopulation phenotypes in peripheral blood were characterized. In addition, we explored the effect of viral replication on peripheral immunity in patients with HCC and analyzed the circulating immunophenotypic characteristics at different stages of HCC with flow cytometry. Results: Firstly, our results showed that the percentages of total αß T cells in the peripheral blood of HBV-HCC patients was significantly decreased compared to healthy subjects. Secondly, we found that naïve CD4+ T cells in HBV-HCC patients were significantly reduced, terminally differentiated CD8+ T cells, homing memory CD8+ T cells and Th2 cells were increased in peripheral circulation in HBV-HCC patients. Moreover, in the peripheral blood of HBV-HCC patients, expression of TIGIT on CD4+ T cells and PD-1 on the surface of Vδ 1 T cells was increased. In addition, we found that sustained viral replication resulted in up-regulation of TIM3 expression on CD4+ T cells, and TIM3+ γδ T cells increased in peripheral circulation in patients with advanced HBV-HCC. Conclusion: Our study showed that circulating lymphocytes in HBV-HCC patients exhibited features of immune exhaustion, especially in HCC patients with persistent viral replication and in patients with intermediate and advanced HBV-HCC, including decreased frequency of T cells and elevated expression of inhibitory receptors including TIGIT and TIM3 on CD4+ T cells and γδ T cells. Meanwhile, our research suggests that the combination of CD3+ T cell and CD8+HLADR+CD38+ T cell may be a potential diagnostic indicator for HBV-HCC. These findings could help us to better understand the immune characteristics of HBV-HCC and explore the immune mechanisms and immunotherapy strategies for HBV-HCC.

High-resolution ISAR imaging based on photonic receiving for high-accuracy automatic target recognition.

A scheme of high-resolution inverse synthetic aperture radar (ISAR) imaging based on photonic receiving is demonstrated. In the scheme, the linear frequency modulated (LFM) pulse echoes with 8 GHz bandwidth at the center frequency of 36 GHz are directly sampled with the photonic analog-to-digital converter (PADC). The ISAR images of complex targets can be constructed without detection range swath limitation due to the fidelity of the sampled results. The images of two pyramids demonstrate that the two-dimension (2D) resolution is 3.3 cm × 1.9 cm. Furthermore, the automatic target recognition (ATR) is employed based on the high-resolution experimental dataset under the assistance of deep learning. Despite of the small training dataset containing only 50 samples for each model, the ATR accuracy of three complex targets is still validated to be 95% on a test dataset with the equal number of samples.

Equivalence of photonic sampling to signal holding in channel-interleaved photonic ADCs by controlling photo-detection response.

Substantial interests have been attracted in the use of photonic sampling and electronic digitizing for photonic analog-to-digital converter (PADC). However, the nature of that photo-detection with signal holding effects has not been well established. This paper analyzes the equivalence of photonic sampling to signal holding by controlling photo-detection response. In the frequency domain, the high-frequency components generated by the sampling pulse train are folded back into the Nyquist band resulting the signal holding response when the output is digitized. We proposed an approximate response of the photodetector (PD) to verify the theoretical analysis. It is found that the photonic sampling serves as the conventional switch-based sample-and-hold (S&H) circuit in channel-interleaved photonic analog-to-digital converter. In the experiment, the signal holding directly inhibits the timing mismatch without sophisticated calibrations.

Photonic ADC-based scheme for joint wireless communication and radar by adopting a broadband OFDM shared signal.

We propose and demonstrate a novel, to the best of our knowledge, joint wireless communication and radar system based on a photonic analog-to-digital converter (PADC), which can receive broadband radio-frequency (RF) signals. Owing to this property, a broadband orthogonal frequency division multiplexing (OFDM) shared signal, which owns obvious advantages in communication applications, can be adopted to realize efficient data communication and high-performance target detection simultaneously. In the experiment, a communication rate of 6 Gbit/s is achieved. Inverse synthetic aperture radar (ISAR) imaging is demonstrated with a two-dimensional (2D) resolution of 3.97 cm × 2.94 cm. Finally, it is verified that high-accuracy radial resolution and high-speed communication can be maintained while increasing the pulse repetition period to detect remote target at around 374.6 m.

Photonic analog-to-digital converter powered by a generalized and robust convolutional recurrent autoencoder.

We propose a convolutional recurrent autoencoder (CRAE) to compensate for time mismatches in a photonic analog-to-digital converter (PADC). In contrast of other neural networks, the proposed CRAE is generalized to untrained mismatches and untrained category of signals while remaining robust to system states. We train the CRAE using mismatched linear frequency modulated (LFM) signals with mismatches of 35 ps and 57 ps under one system state. It can effectively compensate for mismatches of both LFM and Costas frequency modulated signals with mismatches ranging from 35 ps to 137 ps under another system state. When the spur-free dynamic range (SFDR) of the unpowered PADC decreases from 10.2 dBc to -3.0 dBc, the SFDR of the CRAE-powered PADC is over 31.6 dBc.