Immune Regulatory Networks and Therapy of γδ T Cells in Liver Cancer: Recent Trends and Advancements.

The roles of γδ T cells in liver cancer, especially in the potential function of immunotherapy due to their direct cytotoxic effects on tumor cells and secretion of important cytokines and chemokines, have aroused research interest. This review briefly describes the basic characteristics of γδ T cells, focusing on their diverse effects on liver cancer. In particular, different subtypes of γδ T cells have diverse or even opposite effects on liver cancer. We provide a detailed description of the immune regulatory network of γδ T cells in liver cancer from two aspects: immune components and nonimmune components. The interactions between various components in this immune regulatory network are dynamic and pluralistic, ultimately determining the biological effects of γδ T cells in liver cancer. We also integrate the current knowledge of γδ T-cell immunotherapy for liver cancer treatment, emphasizing the potential of these cells in liver cancer immunotherapy.

The immune response of hepatocellular carcinoma after locoregional and systemic therapies: The available combination option for immunotherapy.

Hepatocellular carcinoma (HCC) is associated with a highly heterogeneous immune environment that produces an immune response to various locoregional treatments (LRTs), which in turn affects the effectiveness of immunotherapy. Although LRTs still dominate HCC therapies, 50-60% of patients will ultimately be treated with systemic therapies and might receive those treatments for the rest of their life. TACE, SIRT, and thermal ablation can dramatically increase the immunosuppressive state of HCC, a condition that can be addressed by combination with immunotherapy to restore the activity of lymphocytes and the secretion of cellular immune factors. Immune treatment with locoregional and systemic treatments has dramatically changed the management of HCC. In this review, we examine the research on the changes in the immune microenvironment after locoregional or systemic treatment. We also summarize the regulation of various immune cells and immune factors in the tumor microenvironment and discuss the different infiltration degrees of immune cells and factors on the prognosis of HCC to better compare the efficacy between different treatment methods from the perspective of the tumor microenvironment. This information can be used to help develop treatment options for the upcoming new era of HCC treatment in the future.

Integrated proteogenomic characterization reveals an imbalanced hepatocellular carcinoma microenvironment after incomplete radiofrequency ablation.

BACKGROUND: Efforts to precisely assess tumor-specific T-cell immune responses still face major challenges, and the potential molecular mechanisms mediating hepatocellular carcinoma (HCC) microenvironment imbalance after incomplete radiofrequency ablation (iRFA) are unclear. This study aimed to provide further insight into the integrated transcriptomic and proteogenomic landscape and identify a new target involved in HCC progression following iRFA. METHODS: Peripheral blood and matched tissue samples were collected from 10 RFA-treated HCC patients. Multiplex immunostaining and flow cytometry were used to assess local and systemic immune responses. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were explored via transcriptomic and proteogenomic analyses. Proteinase-3 (PRTN3) was identified in these analyses. And then, the ability of PRTN3 to predict overall survival (OS) was assessed in 70 HCC patients with early recurrence after RFA. In vitro CCK-8, wound healing and transwell assays were conducted to observe interactions between Kupffer cells (KCs) and HCC cells induced by PRTN3. The protein levels of multiple oncogenic factors and signaling pathway components were detected by western blotting. A xenograft mouse model was built to observe the tumorigenic effect of PRTN3 overexpression on HCC. RESULTS: Multiplex immunostaining revealed no immediate significant change in local immune cell counts in periablational tumor tissues after 30 min of iRFA. Flow cytometry showed significantly increased levels of CD4+ T cells, CD4+CD8+ T cells, and CD4+CD25+CD127- Tregs and significantly decreased the levels of CD16+CD56+ natural killer cells on day 5 after cRFA (p < 0.05). Transcriptomics and proteomics revealed 389 DEGs and 20 DEPs. Pathway analysis showed that the DEP-DEGs were mainly enriched in the immunoinflammatory response, cancer progression and metabolic processes. Among the DEP-DEGs, PRTN3 was persistently upregulated and closely associated with the OS of patients with early recurrent HCC following RFA. PRTN3 expressed in KCs may affect the migration and invasion of heat stress-treated HCC cells. PRTN3 promotes tumor growth via multiple oncogenic factors and the PI3K/AKT and P38/ERK signaling pathways. CONCLUSIONS: This study provides a comprehensive overview of the immune response and transcriptomic and proteogenomic landscapes of the HCC milieu induced by iRFA, revealing that PRTN3 promotes HCC progression after iRFA. TRIAL REGISTRATION: ChiCTR2200055606, http://www.chictr.org.cn/showproj.aspx?proj=32588 .

A well-matched marriage of immunotherapy and radiofrequency ablation to reduce the relapse and progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains a health challenge with increasing incidence worldwide. Radiofrequency ablation (RFA) is a potentially curative option for patients with early-stage HCC. However, the high rate of tumor recurrence limits long-term survival when the tumors are larger than 2 cm and undergoing insufficient RFA (iRFA). Notably, in situ tumor necrosis due to thermal ablation is assumed to be a source of antigens that induce antitumor immunity. Therefore, mounting studies and trials have attempted to provide a rational and effective therapeutic strategy combining RFA and immunotherapy to treat HCC. Nowadays, many controversies and challenges with this combined therapeutic strategy remain to be resolved, such as the indications for adjuvant immunotherapy along with RFA in early HCC, the sequence of the two treatments in advanced HCC, and the optimal timing of immunotherapy before or after RFA. In addition, individualized treatment strategies need to be perfected for patients with HCC.

Thermally assisted efficient electrochemical lithium extraction from simulated seawater.

Extracting lithium electrochemically from seawater has the potential to resolve any future lithium shortage. However, electrochemical extraction only functions efficiently in high lithium concentration solutions. Herein, we discovered that lithium extraction is temperature and concentration dependent. Lithium extraction capacity (i.e., the mass of lithium extracted from the source solutions) and speed (i.e., the lithium extraction rate) in electrochemical extraction can be increased significantly in heated source solutions, especially at low lithium concentrations (e.g., < 3 mM) and high Na+/Li+ molar ratios (e.g., >1000). Comprehensive material characterization and mechanistic analyses revealed that the improved lithium extraction originates from boosted kinetics rather than thermodynamic equilibrium shifts. A higher temperature (i.e., 60 oC) mitigates the activation polarization of lithium intercalation, decreases charge transfer resistances, and improves lithium diffusion. Based on these understandings, we demonstrated that a thermally assisted electrochemical lithium extraction process could achieve rapid (36.8 mg g-1 day-1) and selective (51.79% purity) lithium extraction from simulated seawater with an ultrahigh Na+/Li+ molar ratio of 20,000. The integrated thermally regenerative electrochemical cycle can harvest thermal energy in heated source solutions, enabling a low electrical energy consumption (11.3-16.0 Wh mol-1 lithium). Furthermore, the coupled thermal-driven membrane process in the system can also produce freshwater (13.2 kg m-2 h-1) as a byproduct. Given abundant low-grade thermal energy availability, the thermally assisted electrochemical lithium extraction process has excellent potential to realize mining lithium from seawater.

Carbon/iron by-product from catalytic methane decomposition as recyclable Fenton catalyst for pollutant degradation.

Direct catalytic decomposition of methane (CDM) has been studied as a possible emission-free hydrogen production route for over 100 years. However, the high cost of catalyst regeneration limits its practical applications. Here, we demonstrate that the solid by-product from CDM using Fe ore catalysts comprising carbon nano onions encapsulated with magnetic Fe cores (Fe@C) can serve as efficient and recyclable Fenton catalysts for pollutant degradation. Fe@C/H2O2 has better performance than FeSO4/H2O2 at similar Fe concentrations and can be used to decompose various pollutants. Mechanistic studies reveal that graphitic carbon layers and encapsulated Fe0 contribute to their high catalytic activity. Further, Fe@C can be easily recovered from an aqueous solution and reused due to the encapsulated magnetic Fe particles. Over three reused cycles, Fe@C/H2O2 only yields 1/8 of Fe sludges compared to FeSO4/H2O2, significantly reducing Fe sludge treatment costs. Overall, Fe@C demonstrates excellent application potentials in water and wastewater treatment, making H2 production via CDM economically more viable.

Temporal trends and source apportionment of water pollution in Honghu Lake, China.

Honghu Lake, the largest shallow lake in Jianghan Plain of China, is essential for maintaining ecosystem functioning in this region. However, water pollution and high disturbance are seriously threatening the ecological security of this lake. To explore the causes of water quality fluctuations in Honghu Lake, the water quality index method (CCME-WQI), multivariate statistical, and source apportionment techniques were adopted to characterize temporal trends in lake water quality (2004-2017), identify the main driving factors of water quality indicators, and quantify the contribution of various pollution sources. Besides, the water periods of the lake have been reclassified due to the seasonal variation of rainfall in the study area. The results of CCME-WQI showed that the water quality in Honghu Lake initially improved over 2004-2011, with better water quality in the wet period than in the dry periods, while the results over 2012-2017 were found to be opposite. Correlation analysis identified untreated industrial wastewater (UIW) as the main pollution source affecting CODMn concentrations in Honghu Lake, while untreated domestic sewage discharge (UDS) was identified as the main pollution source affecting BOD and F. coli concentrations. The main pollution sources affecting nutrient indicators were rainfall and enclosure aquaculture (EA). Principal component analysis (PCA) combined with absolute principal component score-multiple linear regression model (APCS-MLR) further appointed the source contribution of each pollution source to water quality indicators. The results showed that EA in 2012 was reduced by 81% compared with 2004, resulting in the contribution of EA to NH3-N, TP, and TN decreased by 0.2 mg L-1, 0.039 mg L-1, and 0.37 mg L-1, respectively. Compared with 2012, UIW was reduced by 65% in 2016, resulting in the contribution of UIW to CODMn decreased by 1.17 mg L-1. In addition, compared with 2004, UDS decreased by 85% in 2016, and the contribution of UDS to BOD and F. coli decreased by 0.7 mg L-1 and 887 cfu L-1, respectively. Based on the results of APCS-MLR, it was predicted that the concentrations of COD and TP in Honghu Lake would meet the water quality requirements after 2017. However, the rainfall non-point source pollution must be further controlled to achieve the desired level of TN concentration. This study provided an accurate method for analyzing lake water pollution, and the results can provide a valuable reference for optimizing water quality management and pollution control strategies within Honghu Lake.

Thermo-osmosis-Coupled Thermally Regenerative Electrochemical Cycle for Efficient Lithium Extraction.

Lithium (Li) production based on the soda evaporation process is time-consuming and unsustainable. The emerging electrochemical Li extraction is time-efficient but requires high-concentration Li sources and significant electrical energy input. Here, we demonstrate a fast, energy-saving, and environment-friendly Li production process by coupling a thermally regenerative electrochemical cycle (TREC) using lithium manganese oxide (LMO) and nickel hexacyanoferrate (NiHCF) electrodes with poly(vinylidene fluoride) membrane-based thermo-osmosis (denoted as TO-TREC). The characterization of LMO and NiHCF electrodes confirmed that the relatively high temperature of TO-TREC has negligible adverse effects on the ion intercalation in LMO and NiHCF electrodes. The LMO/NiHCF pair has a positive temperature coefficient of 0.843 mV K-1. In the TO-TREC process, Li ions are selectively extracted from a Li-containing brine warmed by low-grade heat and then released into a room-temperature recovery solution such as LiCl with a production rate of 50-60 mmol Li+ m-2 h-1. Li source solutions are concentrated by thermo-osmosis simultaneously, making it possible to utilize previously unusable Li-containing sources, such as concentrated brines from desalination plants and industrial effluents. Besides, the TREC harvests thermal energy from the heated brine, saving >20% of electrical energy compared to conventional electrochemical methods. The new process shows the potential to meet the growing global Li demands for many applications.

2D Material Based Advanced Membranes for Separations in Organic Solvents.

2D materials have shown high potentials for fabricating next-generation membranes. To date, extensive studies have focused on the applications of 2D material membranes in gas and aqueous media. Recently, compelling opportunities emerge for 2D material membranes in separation applications in organic solvents because of their unique properties, such as ultrathin mono- to few-layers, outstanding chemical resistance toward organic solvents. Hence, this review aims to provide a timely overview of the current state-of-the-art of 2D material membranes focusing on their applications in organic solvent separations. 2D material membranes fabricated using graphene materials and a few representative nongraphene-based 2D materials, including covalent organic frameworks and MXenes, are summarized. The key membrane design strategies and their effects on separation performances in organic solvents are also examined. Last, several perspectives are provided in terms of the critical challenges for 2D material membranes, including standardization of membrane performance evaluation, improving understandings of separation mechanisms, managing the trade-off of permeability and selectivity, issues related to application versatility, long-term stability, and fabrication scalability. This review will provide a useful guide for researchers in creating novel 2D material membranes for advancing new separation techniques in organic solvents.