Integrating TCGA and Single-Cell Sequencing Data for Hepatocellular Carcinoma: A Novel Glycosylation (GLY)/Tumor Microenvironment (TME) Classifier to Predict Prognosis and Immunotherapy Response.

The major liver cancer subtype is hepatocellular carcinoma (HCC). Studies have indicated that a better prognosis is related to the presence of tumor-infiltrating lymphocytes (TILs) in HCC. However, the molecular pathways that drive immune cell variation in the tumor microenvironment (TME) remain poorly understood. Glycosylation (GLY)-related genes have a vital function in the pathogenesis of numerous tumors, including HCC. This study aimed to develop a GLY/TME classifier based on glycosylation-related gene scores and tumor microenvironment scores to provide a novel prognostic model to improve the prediction of clinical outcomes. The reliability of the signatures was assessed using receiver operating characteristic (ROC) and survival analyses and was verified with external datasets. Furthermore, the correlation between glycosylation-related genes and other cells in the immune environment, the immune signature of the GLY/TME classifier, and the efficacy of immunotherapy were also investigated. The GLY score low/TME score high subgroup showed a favorable prognosis and therapeutic response based on significant differences in immune-related molecules and cancer cell signaling mechanisms. We evaluated the prognostic role of the GLY/TME classifier that demonstrated overall prognostic significance for prognosis and therapeutic response before treatment, which may provide new options for creating the best possible therapeutic approaches for patients.

Analysis of 3 Surgical Approaches for the Treatment of Cerebrospinal Fluid Otorrhea: A Case Series Report.

Background: This case series report aimed to present three surgical approaches used for the treatment of cerebrospinal fluid (CSF) otorrhea, providing less invasive surgical options for managing this condition. Methods: Clinical data of 26 patients with CSF otorrhea, who underwent treatment using three surgical methods between June 2012 and June 2022, were retrospectively analyzed. The study collected information on patients' basic demographic characteristics, chief complaints, location of the defect, results of otorrhea endoscopic examination, findings from skull base thin-slice computed tomography (CT) examination, and causes of CSF otorrhea. Postoperative outcomes of CSF otorrhea were followed up. Results: Among the 26 cases of CSF otorrhea, there were 13 (50%) males and 13 (50%) females who underwent treatment using the three surgical methods. The etiology of CSF otorrhea included 10 (38%) cases of spontaneous CSF otorrhea, including 2 (8%) cases of congenital inner ear deformity and 8 (31%) cases without obvious inducement. Additionally, there were 5 (19%) cases of trauma, 6 (23%) cases of cholesteatoma complications, 3 (12%) cases of postoperative complications of brain tumor, 1 (4%) case of radiotherapy, and 1 (4%) case of a malignant tumor. A total of 12 (46%) cases of CSF otorrhea were treated by local repair of the defect. Furthermore, 3 (12%) cases underwent local repair of the defect combined with sealing of the tympanic sinus entrance, while 11 (42%) cases underwent local repair of the defect combined with sealing of the eustachian tube and the external auditory canal. No recurrence of CSF otorrhea was observed during the 6-month to 10-year follow-up period after surgery. Conclusion: The three methods for CSF otorrhea, including local defect repair, local defect repair combined with sealing of the tympanic sinus entrance, and sealing of the eustachian tube and the external auditory canal, demonstrated successful outcomes in appropriately selected patients.

Single-cell transcriptome analysis reveals the metabolic changes and the prognostic value of malignant hepatocyte subpopulations and predict new therapeutic agents for hepatocellular carcinoma.

Background: The development of HCC is often associated with extensive metabolic disturbances. Single cell RNA sequencing (scRNA-seq) provides a better understanding of cellular behavior in the context of complex tumor microenvironments by analyzing individual cell populations. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data was employed to investigate the metabolic pathways in HCC. Principal component analysis (PCA) and uniform manifold approximation and projection (UMAP) analysis were applied to identify six cell subpopulations, namely, T/NK cells, hepatocytes, macrophages, endothelial cells, fibroblasts, and B cells. The gene set enrichment analysis (GSEA) was performed to explore the existence of pathway heterogeneity across different cell subpopulations. Univariate Cox analysis was used to screen genes differentially related to The Overall Survival in TCGA-LIHC patients based on scRNA-seq and bulk RNA-seq datasets, and LASSO analysis was used to select significant predictors for incorporation into multivariate Cox regression. Connectivity Map (CMap) was applied to analysis drug sensitivity of risk models and targeting of potential compounds in high risk groups. Results: Analysis of TCGA-LIHC survival data revealed the molecular markers associated with HCC prognosis, including MARCKSL1, SPP1, BSG, CCT3, LAGE3, KPNA2, SF3B4, GTPBP4, PON1, CFHR3, and CYP2C9. The RNA expression of 11 prognosis-related differentially expressed genes (DEGs) in normal human hepatocyte cell line MIHA and HCC cell lines HCC-LM3 and HepG2 were compared by qPCR. Higher KPNA2, LAGE3, SF3B4, CCT3 and GTPBP4 protein expression and lower CYP2C9 and PON1 protein expression in HCC tissues from Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases. The results of target compound screening of risk model showed that mercaptopurine is a potential anti-HCC drug. Conclusion: The prognostic genes associated with glucose and lipid metabolic changes in a hepatocyte subpopulation and comparison of liver malignancy cells to normal liver cells may provide insight into the metabolic characteristics of HCC and the potential prognostic biomarkers of tumor-related genes and contribute to developing new treatment strategies for individuals.

Corrigendum: Single-cell transcriptome analysis reveals the metabolic changes and the prognostic value of malignant hepatocyte subpopulations and predict new therapeutic agents for hepatocellular carcinoma.

[This corrects the article DOI: 10.3389/fonc.2023.1104262.].

Autotaxin (ATX) inhibits autophagy leading to exaggerated disruption of intestinal epithelial barrier in colitis.

Inflammatory bowel disease (IBD) is an immune-mediated disease. Autotaxin (ATX) is associated with increased inflammatory molecules, however, its effect on IBD is not well understood. Autophagy plays an important role in IBD, whether ATX and autophagy act in concert in IBD remains unknown. This study is to explore the possible mechanisms of ATX affecting autophagy leading to the disruption of intestinal epithelial barrier, thereby exacerbating colitis. The expression of ATX was upregulated in UC patients and dextran sulfate sodium (DSS)-induced colitis mice. Here, we described that providing an ATX inhibitor during DSS colitis increased autophagy and ameliorated colonic inflammation. Conversely, intrarectal administration with recombinant (r)ATX increased colitis and decreased autophagy. This pro-colitic effect was attenuated in mice treated with rapamycin, resulting in increased autophagy activity and mild colitis. Moreover, the inhibitory effect of rATX on autophagy was confirmed in vitro and was reversed by the addition of rapamycin. The damaging effects of ATX on epithelial barrier function were reversed by ATX inhibitor or rapamycin treatment. In sum, our results show that ATX can inhibit autophagy through the mTOR pathway, resulting in exaggerated damage to the intestinal epithelial barrier during colitis. These findings suggest that ATX may be a key pro-colitic factor, and represent a potential therapeutic target for treating IBD in the future.

Self-paced Multi-view Learning for CT-based severity assessment of COVID-19.

Prior studies for the task of severity assessment of COVID-19 (SA-COVID) usually suffer from domain-specific cognitive deficits. They mainly focus on visual cues based on single cognitive functions but fail to reconcile the valuable information from other alternative views. Inspired by the cognitive process of radiologists, this paper shifts naturally from single-symptom measurements to a multi-view analysis, and proposes a novel Self-paced Multi-view Learning (SPML) framework for automated SA-COVID. Specifically, the proposed SPML framework first comprehensively aggregates multi-view contexts in lung infection with different measure paradigms, i.e., Global Feature Branch, Texture Feature Branch, and Volume Feature Branch. In this way, multiple-perspective clues are taken into account to reflect the most essential pathological manifestation on CT images. To alleviate small-sample learning problems, we also introduce an optimization with self-paced learning strategy to cognitively increase the characterization capabilities of training samples by learning from simple to complex. In contrast to traditional batch-wise learning, a pure self-paced way can further guarantee the efficiency and accuracy of SPML when dealing with small and biased samples. Furthermore, we construct a well-established SA-COVID dataset that contains 300 CT images with fine annotations. Extensive experiments on this dataset demonstrate that SPML consistently outperforms the state-of-the-art baselines. The SA-COVID dataset is publicly released at https://github.com/YishuLiu/SA-COVID.

New insights of anaerobic performance, antibiotic resistance gene removal, microbial community structure: applying graphite-based materials in wet anaerobic digestion.

The addition of carbonaceous materials into anaerobic digestion (AD) has gained widespread attention due to their significant effects on anaerobic performance and antibiotic resistance gene (ARG) removal. This study selected graphite, graphene, and graphene oxide (GO) as additives to investigate variations in AD performance, ARG removal, microbial community diversity and structure in wet AD systems. The results indicated that the addition of graphite-based materials in wet AD systems could increase degradation of solid organic matters by 0.91%-3.41% and utilization of soluble organic fractions by 10.43%-13.67%, but could not stimulate methane production. After the addition of graphite and graphene, ARG removal rates were effectively increased to 90.85% and 94.22%, respectively. However, the total ARG removal rate was reduced to 77.46% with the addition of GO. In addition, the microbial diversity in the wet AD process was enhanced with the addition of GO only, graphite and graphene led to a reduction in it. As for bacterial community, graphite and graphene increased the abundance of Thermotogae from 43.43% to 57.42% and 58.74%, while GO increased the abundance of Firmicute from 49.90% to 56.27%. For the archaeal community, the proportion of hydrogenotrophic methanogens was improved when adding each graphite-based material; however, only GO increased Methanosaeta that was acetoclastic methanogens. Finally, methanogens were found as the ARG host, and ARGs that belong to the same subtype might exist in the same host bacteria.

Highly Sensitive, Flow Cytometry-Based Measurement of Intestinal Permeability in Models of Experimental Colitis.

BACKGROUND & AIMS: Increased intestinal permeability is seen in a variety of inflammatory conditions such as enteric infections and inflammatory bowel disease. Because barrier function can provide a key biomarker of disease severity, it often is assayed in animal models. A common methodology involves gavaging mice with fluorescein isothiocyanate-conjugated dextran (FITC-D), followed by cardiac puncture to assay plasma fluorescence on a spectrophotometer. Although the FITC-D method is relatively simple, its sensitivity is limited and enables only a single measurement because the test requires killing the subject. Herein, we describe a novel flow cytometry-based method of intestinal permeability measurement based on detection of orally gavaged ovalbumin (OVA) that leaks out of the gut. Our approach uses minute blood volumes collected from the tail vein, permitting repeated testing of the same subject at multiple time points. By comparing this assay against the gold standard FITC-D method, we show the expanded utility of our OVA assay in measuring intestinal permeability. METHODS: We directly compared our OVA assay against the FITC-D assay by co-administering both probes orally to the same animals and subsequently using their respective methodologies to measure intestinal permeability by detecting probe levels in the plasma. Permeability was assessed in mice genetically deficient in intestinal mucus production or glycosylation. In addition, wild-type mice undergoing dextran sodium sulfate-induced colitis or infected by the enteric bacterial pathogen Citrobacter rodentium also were tested. RESULTS: The OVA assay showed very high efficacy in all animal models of intestinal barrier dysfunction tested. Besides identifying intestinal barrier dysfunction in mice with impaired mucin glycosylation, the assay also allowed for repeated tracking of intestinal permeability within the same animal over time, providing data that cannot be easily acquired with other currently applied methods. CONCLUSIONS: The OVA assay is a highly sensitive and effective method of measuring intestinal permeability in mouse models of barrier dysfunction and experimental colitis.

Zinc finger myeloid Nervy DEAF-1 type (ZMYND) domain containing proteins exert molecular interactions to implicate in carcinogenesis.

Morphogenesis and organogenesis in the low organisms have been found to be modulated by a number of proteins, and one of such factor, deformed epidermal auto-regulatory factor-1 (DEAF-1) has been initially identified in Drosophila. The mammalian homologue of DEAF-1 and structurally related proteins have been identified, and they formed a family with over 20 members. The factors regulate gene expression through association with co-repressors, recognition of genomic marker, to exert histone modification by catalyze addition of some chemical groups to certain amino acid residues on histone and non-histone proteins, and degradation host proteins, so as to regulate cell cycle progression and execution of cell death. The formation of fused genes during chromosomal translocation, exemplified with myeloid transforming gene on chromosome 8 (MTG8)/eight-to-twenty one translocation (ETO) /ZMYND2, MTG receptor 1 (MTGR1)/ZMYND3, MTG on chromosome 16/MTGR2/ZMYND4 and BS69/ZMYND11 contributes to malignant transformation. Other anomaly like copy number variation (CNV) of BS69/ZMYND11 and promoter hyper methylation of BLU/ZMYND10 has been noted in malignancies. It has been reported that when fusing with Runt-related transcription factor 1 (RUNX1), the binding of MTG8/ZMYND2 with co-repressors is disturbed, and silencing of BLU/ZMYND10 abrogates its ability to inhibition of cell cycle and promotion of apoptotic death. Further characterization of the implication of ZMYND proteins in carcinogenesis would enhance understanding of the mechanisms of occurrence and early diagnosis of tumors, and effective antitumor efficacy.

Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction.

Hyperglycemia and type 2 diabetes (T2D) are caused by failure of pancreatic beta cells. The role of the gut microbiota in T2D has been studied, but causal links remain enigmatic. Obese individuals with or without T2D were included from two independent Dutch cohorts. Human data were translated in vitro and in vivo by using pancreatic islets from C57BL6/J mice and by injecting flagellin into obese mice. Flagellin is part of the bacterial locomotor appendage flagellum, present in gut bacteria including Enterobacteriaceae, which we show to be more abundant in the gut of individuals with T2D. Subsequently, flagellin induces a pro-inflammatory response in pancreatic islets mediated by the Toll-like receptor (TLR)-5 expressed on resident islet macrophages. This inflammatory response is associated with beta-cell dysfunction, characterized by reduced insulin gene expression, impaired proinsulin processing and stress-induced insulin hypersecretion in vitro and in vivo in mice. We postulate that increased systemically disseminated flagellin in T2D is a contributing factor to beta-cell failure in time and represents a novel therapeutic target.

Performance enhancement and population structure of denitrifying phosphorus removal system over redox mediator at low temperature.

The development of denitrifying polyphosphate accumulating organisms (DPAOs) presents a strategy to carbon competition between denitrifying bacteria and phosphorus removing bacteria. However, low temperature inhibits the rate of enzyme-catalyzed and substrate diffusion during denitrifying phosphorus removal (DPR). Therefore, the present study assessed the addition of NQS (100 µmol/L) for enhancing the removal of TP and TN in DPR reactors operated at alternating anaerobic and anoxic phases and different influent phosphate concentrations. The results showed that the removal efficiency of TP and TN in NQS-DPR system at 10 °C were 99.9% and 42.0%, respectively, which were 2.1 and 2.0 times higher than that of DPR system. Adding NQS significantly alleviated the increase of pH under anoxic condition and decreased the ORP value of the reactor, which in turn enhanced the PHAs accumulation process. The determination of functional genes (nirK, narG and phoD) showed that Dechloromonas, Lentimicrobium, and Terrimonas were the dominant functional bacteria in NQS-DPR system at 10 °C with the relative abundance of 3.09%, 2.99% and 2.28%, respectively. This study can provide valuable information for the effects of the addition of the redox mediator on denitrifying phosphorus removal technology.

Radical and non-radical cooperative degradation in metal-free electro-Fenton based on nitrogen self-doped biochar.

To achieve sustainable metal-free electron-Fenton, N self-doped biochar air-cathode (BCAC) was prepared by pyrolyzing coffee residues. During the pyrolysis process, the endogenous N transformed from edge-doping to graphite-doping. Particularly, N vacancies started to evolve when the peak temperature exceeded 700 °C. A high Tetracycline removal rate of 70.42% was obtained on the BCAC at the current density of 4 mA cm-2. Quenching tests incorporated with ESR spectroscopy were adopted to identify the specific oxidants produced on the cathode. The results showed that •OH (37.36%), •O2- (29.67%) and 1O2 (24.17%) played comparable role in the tetracycline removal, suggesting the coexist of radical and non-radical oxidants in our electro-Fenton system. According to the structure characterization and the DFT calculation, graphitic N was suggested as the critical site for H2O2 generation, and both graphitic N and pyridinic N were electroactive sites for H2O2 activation to •OH. Graphitic N and N vacancies with stronger capabilities in O2 adsorption and electron-trapping were proposed as the electroactive sites for 1O2 and •O2- formation. This work predicts a novel electro-Fenton process with cooperative radical and non-radical degradation on N self-doped carbonaceous catalysts at a mild condition, which is extremely meaningful for boosting sustainable electro-Fenton technology.

CRISPR/Cas12a-based electrochemical biosensor for highly sensitive detection of cTnI.

The successful fabrication of the cTnI detection platform is very meaningful for instant diagnosis of the myocardialinjury and related cardiovascular diseases (CVDs). In this research work, the magnetic nanoparticles and aptamer collaboration with the Cas12a/crRNA are used for the electrochemical detection of cTnI. The aptamer is hybridized with its partially complementary DNA (probe 2, P2) and then is modified on the magnetic nanoparticles. In the presence of cTnI, the cTnI combines with the aptamer and P2 is released. The released P2 is hybridized with the crRNA and the trans-cleavage activity of CRISPR/Cas12a is triggered. Therefore, the methylene blue-modified DNA (probe1, P1) on the surface of the electrode is cleaved, resulting in the decrease of the electrochemical signal. Based on the synergy effect of the high specific target recognition of aptamer, target-specifically triggering trans-cleavage activity of CRISPR/Cas12a, as well as good separation ability of magnetic nanoparticles, the developed electrochemical biosensor enables to detect cTnI with high specificity and sensitivity. The detection limit is low down to 10 pg/mL with a linear range from 100 pg/mL to 50000 pg/mL. The developed sensing platform was successfully applied for the detection of cTnI in human serum. This fabricated CRISPR/Cas12a-based electrochemical biosensor can offer a valuable tool for the diagnosis, prognosis, and treatment of patient with CVDs.

Type VI secretion systems of pathogenic and commensal bacteria mediate niche occupancy in the gut.

The type VI secretion system (T6SS) is a contractile nanomachine widely distributed among pathogenic and commensal Gram-negative bacteria. The T6SS is used for inter-bacterial competition to directly kill competing species; however, its importance during bacterial infection in vivo remains poorly understood. We report that the murine pathogen Citrobacter rodentium, used as a model for human pathogenic Escherichia coli, harbors two functional T6SSs. C. rodentium employs its T6SS-1 to colonize the murine gastrointestinal tract by targeting commensal Enterobacteriaceae. We identify VgrG1 as a C. rodentium T6SS antibacterial effector, which exhibits toxicity in E. coli. Conversely, commensal prey species E. coli Mt1B1 employs two T6SSs of its own to counter C. rodentium colonization. Collectively, these data demonstrate that the T6SS is a potent weapon during bacterial competition and is used by both invading pathogens and resident microbiota to fight for a niche in the hostile gut environment.

Construction of cleaner production management system in China: mode innovation of cleaner production.

This study is based on the practice of cleaner production (CP) audits in more than 300 enterprises. After reviewing 1484 CP options, it is found that 82.5% of the options are directly and indirectly related to management. Moreover, there are common problems such as the poor sustainability of CP audit results. This shows that enterprise management plays a significant role in implementing CP options. Based on these, this study proposes a new concept of cleaner production management (CPM) system, and draws lessons from the modern environmental management theory and method to establish the framework of CPM system. This system combines the theory and method of CP with the management system of enterprises and presents the CPM requirements in the current enterprise management system, which mainly includes CPM responsibilities, CP objectives, CPM indexes, CP energy resources management, CP process control, CP product management, CPM inspections, and CP performance evaluation. The characteristic of the proposed system is to construct a modern information-based CPM system. With highly systematic, concise structure, and easy operability, this system not only simplifies and improves the CP work in enterprises and reduces several tedious tasks such as document preparation, but also enhance the enterprise management efficiency and motivate the willingness of employees to participate in CP. Innovated and developed for CP implementation, the system has been implemented and applied in Chinese enterprises, and the implementation and application have obvious effects on improving production level as well as environmental and economic benefits.

Synergy of developed micropores and electronic structure defects in carbon-doped boron nitride for CO2 capture.

With the aim of relieving the serious environmental and climate issues arising from excessive emission of anthropogenic CO2, extensive solid absorbents have been developed for CO2 capture. Among them, porous boron nitride (BN) is considered an ideal candidate due to its high specific surface area, abundant structural defects, low density, and outstanding chemical inertness. Herein, BN absorbents were synthesized from pyrolysis of melamine-boric acid precursors, and the effect of pyrolysis temperature (900, 1000, 1050 and 1100 °C) on the properties and performances was investigated. Various characterizations were performed to evaluate the physicochemical properties and CO2 uptake capacities of BN absorbents. The result demonstrated that a carbon-doped BN structure was achieved instead of a pure BN material, and the carbonization degree was enhanced with the increase of pyrolysis temperatures. BN absorbent pyrolyzed at 1100 °C exhibited the highest CO2 adsorption capacity of 3.71 mmol/g (273 K). The reason should be that the doping of carbon in the framework of BN contributed to the formation of abundant micropores, which enhanced the physical adsorption by offering more adsorption sites. At the same time, more negative charges on BN were induced by structural defects, which favored the chemical adsorption of CO2 by invoking charge-induced chemisorption interaction. This study clarified the role of pore structure and electronic structure defects in CO2 adsorption capacity of carbon-doped BN, which would open up more spacious avenues for the development of promising BN-based absorbents, or even catalysts.

Upregulation of the JAK-STAT pathway promotes maturation of human embryonic stem cell-derived cardiomyocytes.

The immature characteristics and metabolic phenotypes of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) restrict their applications for disease modeling, drug discovery, and cell-based therapy. Leveraging on the metabolic shifts from glycolysis to fatty acid oxidation as CMs mature, a human hexokinase1-GFP metabolic reporter cell line (H7 HK1-GFP) was generated to facilitate the isolation of fetal or more matured hPSC-CMs. RNA sequencing of fetal versus more matured CMs uncovered a potential role of interferon-signaling pathway in regulating CM maturation. Indeed, IFN-γ-treated CMs resulted in an upregulation of the JAK-STAT pathway, which was found to be associated with increased expression of CM maturation genes, shift from MYH6 to MYH7 expression, and improved sarcomeric structure. Functionally, IFN-γ-treated CMs exhibited a more matured electrophysiological profile, such as increased calcium dynamics and action potential upstroke velocity, demonstrated through calcium imaging and MEA. Expectedly, the functional improvements were nullified with a JAK-STAT inhibitor, ruxolitinib.

Fasting increases microbiome-based colonization resistance and reduces host inflammatory responses during an enteric bacterial infection.

Reducing food intake is a common host response to infection, yet it remains unclear whether fasting is detrimental or beneficial to an infected host. Despite the gastrointestinal tract being the primary site of nutrient uptake and a common route for infection, studies have yet to examine how fasting alters the host's response to an enteric infection. To test this, mice were fasted before and during oral infection with the invasive bacterium Salmonella enterica serovar Typhimurium. Fasting dramatically interrupted infection and subsequent gastroenteritis by suppressing Salmonella's SPI-1 virulence program, preventing invasion of the gut epithelium. Virulence suppression depended on the gut microbiota, as Salmonella's invasion of the epithelium proceeded in fasting gnotobiotic mice. Despite Salmonella's restored virulence within the intestines of gnotobiotic mice, fasting downregulated pro-inflammatory signaling, greatly reducing intestinal pathology. Our study highlights how food intake controls the complex relationship between host, pathogen and gut microbiota during an enteric infection.

Application of co-pyrolysis biochar for the adsorption and immobilization of heavy metals in contaminated environmental substrates.

Heavy metal pollution has been considered as a serious threat to the environment and human in the past decades due to its toxic and unbiodegradable properties. Recently, extensive studies have been carried out on the removal of heavy metals, and various adsorption materials have been successfully developed. Among, biochar is a promising option because of its advantages of various biomass sources, abundant microporous channels and surface functional groups, as well as its attractive economic feasibility. However, the application of pristine biochar is limited by its low adsorption capacity and nonregenerative property. Co-pyrolysis biochar, produced from the pyrolysis of biomass with the addition of another biomass or non-biomass precursor, is potential in overcoming the limitation of pristine biochar and achieving superior performance for heavy metal adsorption and immobilization. Therefore, this article summarizes the recent advances in development and applications of co-pyrolysis biochar for adsorption and immobilization of various heavy metals in contaminated environmental substrates. In details, the production, characteristics and advantages of co-pyrolysis biochar are initially presented. Subsequently, the adsorption behaviors and mechanisms of different heavy metals (including Hg, Zn, Pb, Cu, Cd, Cr, As, etc.) in flue gas and wastewater by co-pyrolysis biochar are reviewed, as well as factors influencing their adsorption capacities. Meanwhile, the immobilization of heavy metals in both biochar itself and contaminated soils by co-pyrolysis biochar is discussed. Finally, the limitations of current studies and future prospects are proposed. It aims at providing a guideline for the exploitation and application of cost-effective and environmental-friendly co-pyrolysis biochar in the decontamination of environmental substrates.