The transcription regulator ID3 maintains tumor-specific memory CD8+ T cells in draining lymph nodes during tumorigenesis.

During tumorigenesis, the recently identified tumor-specific memory T cells in draining lymph nodes (TdLN-TTSM cells) play a pivotal role in tumor repression that gives rise to progenitor exhausted T (TPEX) cells and further replenishes tumor-specific CD8+ T cells residing in the tumor microenvironment (TME). However, how TTSM cells are maintained in TdLN is largely unknown. Here, we show that the transcription regulator ID3 (inhibitor of DNA binding 3) is highly expressed by TTSM cells compared with other CD8+ T cell subsets. The deficiency of ID3 significantly interrupts the maintenance of TTSM and TPEX cells, resulting in decreased tumor-infiltrating CD8+ T cells and impaired tumor control. Consistent with this, overexpression of ID3 in CD8+ T cells increases the TTSM cell population and enhances the anti-tumor immune response.

A Review of Hydroxylated and Methoxylated Brominated Diphenyl Ethers in Marine Environments.

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs) are present in the marine environment worldwide. Both OH-PBDEs and MeO-PBDEs are known natural products, whereas OH-PBDEs may also be metabolites of PBDEs. There is growing concern regarding OH-PBDEs as these compounds seem to be biological active than PBDEs. In the present study, we reviewed the available data on the contamination of OH/MeO-PBDEs in the marine environment worldwide, including seawater, marine sediment, marine plants, invertebrates, fish, seabirds and mammals. Bioaccumulation and biomagnification of OH/MeO-PBDEs in the marine food web were summarized as well. This study also proposes the future research of OH/MeO-PBDEs, including the production and the synthesis pathway of OH/MeO-PBDEs, the toxicokinetics of OH/MeO-PBDEs and the toxicology and human exposure risk assessment.

Bioaccumulation and Biomagnification of Hexabromocyclododecane in Marine Biota from China: A Review.

Hexabromocyclododecane (HBCD) was listed in Annex A of the Stockholm Convention on Persistent Organic Pollutants for its persistence, bioaccumulation and toxicity, and pose significant adverse effects on natural environments and human health. HBCDs are ubiquitously found in marine environments worldwide and can be biomagnified in marine organisms with a high trophic level. In the present study, we reviewed the available data on contamination of HBCDs in the marine biota from China, including mollusks, crustaceans, fish and mammals. Bioaccumulation and biomagnification of HBCDs in the marine food web were summarized as well. This study also prospected the future research of HBCDs, including the transport and fluxes of HBCDs to and within the marine environment, the biomagnification of HBCDs in different ecosystems, and the metabolism of HBCDs in different marine species.

Targeted Nanobubbles of PD-L1 mAb Combined with Doxorubicin as a Synergistic Tumor Repressor in Hepatocarcinoma.

Purpose: Ultrasound nanobubbles (NBs) can kill tumor cells, mediated by their effects of cavitation and acoustic perforation through ultrasound, while as novel drug carriers, biomaterial-modified NBs release drugs at a target region. In this work, the ultrasound NBs bridged by biotin-streptavidin were prepared simultaneously to be loaded with both programmed death ligand 1 monoclonal antibody (PD-L1 mAb) and doxorubicin (DOX), which are immune checkpoint inhibitors (ICIs) and chemotherapeutic agents, to synergize immunotherapy and chemotherapy combined with sonodynamic therapy (SDT). Methods: The PD-L1 mAb/DOX NBs, using bridging affinity biotin (BRAB) technology as a bridge, were prepared by thin-film hydration and mechanical oscillation for the targeted delivery of biotinylated PD-L1 mAb and DOX. Characterization and pharmacokinetic studies of PD-L1 mAb/DOX NBs were performed in vitro and in vivo. The antitumor effect of ultrasound-mediated PD-L1 mAb/DOX-NBs was studied in the subcutaneously transplanted tumor of the H22 hepatoma model, and the mechanism of synergistic tumor repression was investigated. Results: The data of in vitro targeting experiments, contrast-enhanced ultrasound imaging (CEUS), in vivo imaging of the small animals imaging system (IVIS), and frozen sections showed that PD-L1 mAb/DOX-NBs have well-targeted aggregation in the tumor. By observing tumor inhibition rate, tissue cell apoptosis, and apoptosis-related gene and protein expression, the PD-L1 mAb/DOX-NBs group showed the best immunotherapy effects, and its tumor volume and mass inhibition rates were about 69.64% and 75.97%, respectively (P < 0.01). Therefore, blocking the PD-1/PD-L1 pathway could improve immune cells' tumor-killing ability. Antitumor immune cytokines were further enhanced when combined with DOX-induced tumor cell apoptosis and immunogenic cell death (ICD). Conclusion: In summary, ultrasound-mediated PD-L1 mAb/DOX-NBs showed significant synergistic antitumor effects, providing a potential combined immunotherapy strategy for HCC.

Advances and Prospects of Ultrasound Targeted Drug Delivery Systems Using Biomaterial-modified Micro/Nanobubbles for Tumor Therapy.

The incidence of malignant tumors is rising rapidly and tends to be in the younger, which has been one of the most important factors endangering the safety of human life. Ultrasound micro/nanobubbles, as a noninvasive and highly specific antitumor strategy, can reach and destroy tumor tissue through their effects of cavitation and acoustic perforation under the guidance of ultrasound. Meanwhile, micro/nanobubbles are now used as a novel drug carrier, releasing drugs at a target region, especially on the prospects of biomaterial-modified micro/nanobubbles as a dual modality for drug delivery and therapeutic monitoring. Successful evaluation of the sonoporation mechanism(s), ultrasound parameters, drug type, and dose will need to be addressed before translating this technology for clinical use. Therefore, this paper collects the literature on the experimental and clinical studies of ultrasound biomaterial-modified micro/nanobubbles therapy in vitro and in vivo in recent years.

[Molecular chaperones facilitate soluble expression of recombinant non-toxic mutant CRM197 of diphtheria toxin in Escherichia coli].

Diphtheria toxin is an ADP-ribosyltransferase toxic to human cells. Mutation of the active site in its catalytic domain eliminates the toxicity, but retains its immunogenicity. A non-toxic mutant of diphtheria toxin known as CRM197 protein has become an ideal carrier protein for conjugate vaccines. CRM197 can further improve its immunogenicity by cross-linking with other antigens, so it has good potential to find broad applications. Unfortunately, inclusion bodies are easily formed during the expression of recombinant CRM197 protein in Escherichia coli, which greatly reduces its yield. In order to address this problem, pG-KJE8 vector carrying molecular chaperones and plasmid pET28a-CRM197, were co-expressed in Escherichia coli. The results showed that the recombinant CRM197 protein was successfully expressed and appeared largely in inclusion bodies. The molecular chaperones DnaK, DnaJ, GrpE, GroES and GroEL5 expressed can facilitate correct and rapid folding of CRM197. Furthermore, it can also improve the recovery rate of soluble CRM197 protein. The soluble expression of CRM197 was maximized upon addition of 1.0 mmol/L IPTG, 0.5 mg L-arabinose, 5.0 ng/mL tetracycline and induction at 20oC for 16 h. The soluble CRM197 protein shows good immunoreactivity, demonstrating the molecular chaperones expressed from pG-KJE8 facilitated the soluble expression of CRM197 protein in E. coli.

Social distance influences the outcome evaluation of cooperation and conflict: Evidence from event-related potentials.

Previous research shows that social distance plays an important role in promoting cooperation and that subtle cues that reduce social distance increase the tendency to cooperate. However, it is unclear how social distance influences our outcome evaluation of cooperative and conflict feedback. The present study investigated the influence of social distance on cooperative and conflict behavior and the evaluation process of the cooperative and conflict outcomes, using the event-related potentials (ERPs) technique. We recorded ERPs from 14 normal adults playing a social game task against a friend and a stranger. The results showed that the FRN (Feedback Related Negativity) and P300 were affected by the opponent's choice to cooperate or aggress; however, only the P300 was affected by social distance. Specifically, when the opponent chose to cooperate, the feedback elicited a smaller FRN and a larger P300 amplitude; and compared with playing against friends, the P300 had a larger amplitude when participants gaming with strangers. Our results indicate that at the early stage of the evaluation of cooperation and conflict outcomes, individuals may initially and quickly encode the valence of outcomes, judging whether an outcome is consistent with their expectations. However, at the late stage, which involves a top-down cognitive appraisal process, some social factors, such as social distance, may moderate processing of attention resource allocation of feedback about outcomes, and of higher-level motivation/affective appraisal.