Interleukin-35 Dampens CD8+ T Cells Activity in Patients With Non-viral Hepatitis-Related Hepatocellular Carcinoma

Interleukin (IL)-35 is a newly identified IL-12 cytokine family member, which has been demonstrated to induce immunotolerance by suppression of CD8+ T cells function in chronic viral hepatitis. However, the role of IL-35 in modulating CD8+ T cells activity in non-viral hepatitis-related hepatocellular carcinoma (HCC) was not fully elucidated. Forty-four patients with non-viral hepatitis-related HCC and 20 healthy individuals were enrolled. Serum IL-35 concentration was measured by ELISA. CD8+ T cells were purified from peripheral bloods and liver tissues. mRNA expression of cytotoxic/inhibitory molecules in CD8+ T cells with IL-35 stimulation was semi-quantified by real-time PCR. Direct and indirect contact co-culture systems of CD8+ T cells and HCC cell lines were set up. The modulatory function of IL-35 on peripheral and liver-resident CD8+ T cells was assessed by measurement of lactate dehydrogenase release and cytokine production in the co-culture supernatants. Serum IL-35 was notably elevated in HCC patients, while effective anti-tumor therapies down-regulated IL-35 concentration. Recombinant IL-35 stimulation suppressed cytotoxicity and proinflammatory cytokine secretion of peripheral and liver-resident CD8+ T cells in direct and indirect contact co-culture systems. This process was accompanied by reduction of perforin expression and interferon-γ production, as well as programmed death-1 and cytotoxic T-lymphocyte-associated protein 4 elevation in CD8+ T cells. The current data suggested that IL-35 inhibited both cytolytic and non-cytolytic function of CD8+ T cells to non-viral hepatitis-related HCC probably via repression of perforin expression. IL-35 might be considered to be one of the therapeutic targets for patients with HCC

Reduced circulating interleukin 35 is associated with enhanced peripheral T cell function in primary biliary cholangitis

Interleukin 35 (IL-35) mediates immunosuppression of T cells in autoimmune diseases. T cells play an important role in primary biliary cholangitis (PBC) with incompletely elucidated pathogenesis. Thus, we aimed to investigate the role of IL-35 regulation on T cells in PBC patients. Fifty-one PBC patients and 28 controls were enrolled in this study. Plasma IL-35 level was measured. Purified peripheral CD4+ and CD8+ T cells were stimulated with exogenous IL-35 to investigate their functional phenotypes. IL-35-treated CD8+ T cells were cultured with human intrahepatic biliary epithelial cell line to determine the cytotoxicity of CD8+ T cells from PBC patients. Plasma IL-35 concentration was lower in PBC patients and negatively correlated with alkaline phosphatase. CD4+ T cells from PBC patients exhibited elevated transcription factor expressions and cytokine secretion, whereas CD8+ T cells produced increased cytotoxic molecules and cytokines. In vitro IL-35 stimulation suppressed the production of IL-17 and IL-22 by CD4+ T cells from PBC patients. CD8+ T cells treated with IL-35 mediated reduced target cell death in the direct contact co-culture system in PBC patients. This process was accompanied by reduced production of cytotoxic molecules and cytokines and increased expressions of immune checkpoint receptors in CD8+ T cells. Reduced circulating IL-35 might be insufficient to suppress T cell function, leading to the immune dysregulation in PBC patients

Comparative Genomic Analysis of Latilactobacillus curvatus and L. sakei

In this study, the genomes of 19 Latilactobacillus curvatus and 40 L. sakei strains were comparatively analyzed. Average nucleic acid identity (ANI) and genome-wide colinearity indicated that the genomes of L. curvatus and L. sakei had weak nucleotide sequence homology, allowing them to be used as indicators to distinguish the two species. Pangenomes for these species were constructed, whose core gene functions were annotated. The results showed that the core genomes of L. curvatus and L. sakei were mainly involved in their basic metabolism. Analysis of individual genomes of the strains revealed that 1) both L. curvatus and L. sakei contained a wide range of genes encoding glycoside hydrolases, which are abundant genetic resources for catabolizing and metabolizing dietary fiber such as polysaccharides, lactose utilization, and lignocellulose; 2) antibiotic resistance genes were annotated in the genomes of three strains, which originate from horizontal gene transfer; 3) the unique arginine deiminase pathway of L. sakei, the serine dehydratase and guanine deaminase pathways of L. curvatus, and the glutamate decarboxylase pathway of several strains were identified, revealing that the acid tolerance mechanisms of these two species are different; and 4) genes encoding cold stress proteins were discovered, which endow the two species with good cold processing properties. Moreover, the genomes of some L. sakei strains contained gene clusters related to the biosynthesis of lactocin S and condensin. In conclusion, this study established taxonomic criteria for the two species and information on individual differences between their strains, which will provide a basis for the study of the physiological, biochemical, molecular genetic mechanisms of L. curvatus and L. sakei and their industrial applications

Protective Roles of Gadd45 and MDM2 in Blueberry Anthocyanins Mediated DNA Repair of Fragmented and Non-Fragmented DNA Damage in UV-Irradiated HepG2 Cells

Peer reviewe

Protective Roles of Gadd45 and MDM2 in Blueberry Anthocyanins Mediated DNA Repair of Fragmented and Non-Fragmented DNA Damage in UV-Irradiated HepG2 Cells

Peer reviewe

TR-SDTN: Trust Based Efficient and Scalable Routing in Hostile Social DTNs

A delay tolerant network (DTN) presents a new communication model, which uses a store-carry-forward approach to deliver messages due to the nature of the network. With the development of the mobile internet, the research on DTNs becomes a hot topic. One critical issue in the DTNs with social characteristics is that there could exist selfish and malicious nodes which block important data and as a result intentionally disturb the communication. Although there are many research works which address the issue and adopt various trust models to encourage nodes to forward information, most of them have not considered the social characteristics of the mobile nodes and they have not handled the selfish behaviors and attacks in a systematic way. In view of these defects, we propose a novel solution to address the selfish and security issues in social DTNs. Based on nodes’ social characteristics, a dynamic trust model is proposed to prevent bad-mouthing and ballot stuffing attacks and the Shannon entropy function is introduced to avoid blackhole and greyhole attacks. The simulation results show that our proposed scheme can significantly improve the performance of social DTNs. And the simulation is proved to be consistent with the results from theoretical analysis.Published versio

CCS-DTN : clustering and network coding-based efficient routing in social DTNs

With the development of mobile Internet, wireless communication via mobile devices has become a hot research topic, which is typically in the form of Delay Tolerant Networks (DTNs). One critical issue in the development of DTNs is routing. Although there is a lot research work addressing routing issues in DTNs, they cannot produce an advanced solution to the comprehensive challenges since only one or two aspects (nodes’ movements, clustering, centricity and so on) are considered when the routing problem is handled. In view of these defects in the existing works, we propose a novel solution to address the routing issue in social DTNs. By this solution, mobile nodes are divided into different clusters. The scheme, Spray and Wait, is used for the intra-cluster communication while a new forwarding mechanism is designed for the inter-cluster version. In our solution, the characteristics of nodes and the relation between nodes are fully considered. The simulation results show that our proposed scheme can significantly improve the performance of the routing scheme in social DTNs.Published versio

Holocene climate events inferred from modern and fossil pollen records in Butuo Lake, Eastern Qinghai–Tibetan Plateau

Expansion of the spatial coverage of pollen data is essential to improve understanding of Holocene climate variation. To address this, we collected 25 surface and 72 fossil samples from Butuo Lake in the eastern Qinghai-Tibetan Plateau, China. We reconstructed the vegetation history of the region through detrended correspondence analysis (DCA) of the pollen data. Based on the results of this analysis, we divided the samples into five pollen zones (alpine sparse cushion vegetation, alpine scrub, alpine meadow, montane scrub meadow, and montane coniferous forest) corresponding to the major vegetation types. The observed temporal changes in vegetation (as indicated by the DCA of surface and fossil pollen spectra results, ratios of Artemisia to Cyperaceae (A/Cy), the sum of percentages of dryness indicators (SDI), and percentages of main pollen types) and modern pollen-climate transfer function (developed using the weighted averaging partial least squares regression method (WAPLS)) yield a sensitive record of Holocene monsoonal climate change in the area. During 11,140-8700, 8000-6000, and 5600-1780 cal. yr BP, the climate was wet and the vegetation was dominated by alpine meadow, indicating the occurrence of a strong southwest Asian monsoon that spanned almost the entire Holocene. Notably, two major cold and drought episodes are detected at 8700-8000 and 6000-5600 cal. yr BP, with vegetation dominated by alpine steppe, suggesting that the southwest Asian monsoon was extremely weak during these periods. The data will improve understanding of long-term variations of the southwest Asian monsoon in the region

Holocene climate events inferred from modern and fossil pollen records in Butuo Lake, Eastern Qinghai-Tibetan Plateau

Expansion of the spatial coverage of pollen data is essential to improve understanding of Holocene climate variation. To address this, we collected 25 surface and 72 fossil samples from Butuo Lake in the eastern Qinghai-Tibetan Plateau, China. We reconstructed the vegetation history of the region through detrended correspondence analysis (DCA) of the pollen data. Based on the results of this analysis, we divided the samples into five pollen zones (alpine sparse cushion vegetation, alpine scrub, alpine meadow, montane scrub meadow, and montane coniferous forest) corresponding to the major vegetation types. The observed temporal changes in vegetation (as indicated by the DCA of surface and fossil pollen spectra results, ratios of Artemisia to Cyperaceae (A/Cy), the sum of percentages of dryness indicators (SDI), and percentages of main pollen types) and modern pollen-climate transfer function (developed using the weighted averaging partial least squares regression method (WAPLS)) yield a sensitive record of Holocene monsoonal climate change in the area. During 11,140-8700, 8000-6000, and 5600-1780 cal. yr BP, the climate was wet and the vegetation was dominated by alpine meadow, indicating the occurrence of a strong southwest Asian monsoon that spanned almost the entire Holocene. Notably, two major cold and drought episodes are detected at 8700-8000 and 6000-5600 cal. yr BP, with vegetation dominated by alpine steppe, suggesting that the southwest Asian monsoon was extremely weak during these periods. The data will improve understanding of long-term variations of the southwest Asian monsoon in the region