GSDMD protects intestinal epithelial cells against bacterial infections through its N-terminal activity impacting intestinal immune homeostasis.

The intestinal mucosal barrier serves as a vital guardian for gut health, maintaining a delicate equilibrium between gut microbiota and host immune homeostasis. Recent studies have found the intricate roles of Gasdermin D (GSDMD), a key executioner of pyroptosis downstream of the inflammasome, within the intestine, including controlling colitis in intestinal macrophage and the regulatory function in goblet cell mucus secretion. Thus, the exact role and nature of GSDMD's regulatory function in maintaining intestinal immune homeostasis and defending against pathogens remain elucidation. Here, we uncover that GSDMD plays a key role in defending against intestinal Citrobacter rodentium infection, with high expression in intestinal epithelial and lamina propria myeloid cells. Our results show that GSDMD specifically acts in intestinal epithelial cells to fight the infection, independently of its effects on antimicrobial peptides or mucin secretion. Instead, the resistance is mediated through GSDMD's N-terminal fragments, highlighting its importance in intestinal immunity. However, the specific underlying mechanism of GSDMD N-terminal activity in protection against intestinal bacterial infections still needs further study to clarify in the future.

Ferroptosis: Iron-mediated cell death linked to disease pathogenesis.

Ferroptosis is an iron-mediated regulatory cell death pattern characterized by oxidative damage. The molecular regulating mechanisms are related to iron metabolism, lipid peroxidation, and glutathione metabolism. Additionally, some immunological signaling pathways, such as the cyclic GMP-AMP synthase-stimulator ofinterferon genes axis, Janus kinase-signal transducer and activator of transcription 1 axis, and transforming growth factor beta 1-Smad3 axis may also participate in the regulation of ferroptosis. Studies have shown that ferroptosis is closely related to many diseases such as cancer, neurodegenerative diseases, inflammatory diseases, and autoimmune diseases. Considering the pivotal role of ferroptosis-regulating signaling in the pathogenesis of diverse diseases, the development of ferroptosis inducers or inhibitors may have significant clinical potential for the treatment of the aforementioned conditions.

ECSIT facilitates memory CD8+ T cell development by mediating fumarate synthesis during viral infection and tumorigenesis.

Memory CD8+ T cells play a crucial role in infection and cancer and mount rapid responses to repeat antigen exposure. Although memory cell transcriptional programmes have been previously identified, the regulatory mechanisms that control the formation of CD8+ T cells have not been resolved. Here we report ECSIT as an essential mediator of memory CD8+ T cell differentiation. Ablation of ECSIT in T cells resulted in loss of fumarate synthesis and abrogated TCF-1 expression via demethylation of the TCF-1 promoter by the histone demethylase KDM5, thereby impairing memory CD8+ T cell development in a cell-intrinsic manner. In addition, ECSIT expression correlated positively with stem-like memory progenitor exhausted CD8+ T cells and the survival of patients with cancer. Our study demonstrates that ECSIT-mediated fumarate synthesis stimulates TCF-1 activity and memory CD8+ T cell development during viral infection and tumorigenesis and highlights the utility of therapeutic fumarate analogues and PD-L1 inhibition for tumour immunotherapy.

Synthesis of spherical CaO pellets incorporated with Mg, Y, and Ce inert carriers for CO2 capture.

Sintering and elutriation are two main problems of the calcium looping process for high-temperature CO2 capture. In the process of CO2 capture, the operation temperature is generally higher than the Taman temperature, resulting in the agglomeration and sintering of the sorbents. The traditional sorbent powers need to be granulated for practical application in a circulating fluidized bed to avoid elutriation. By using a new agar-assisted technology to granulate CaO powder incorporated with Mg, Y, and Ce inert supports, the problems of sintering and elutriation can be mitigated within one step. The incorporated inert supports are uniformly dispersed in the CaO/CaCO3 particles as an inert scaffold, and the inert scaffold is used as a skeleton to resist sintering, alleviate its agglomeration phenomenon, and keep the specific surface area to a certain extent. The Ce-incorporated CaO pellets have been proven to exhibit the best carbonation conversion and sorption capacity. The sorption capacity of 10% CeO2-incorporated CaO pellets reached 0.574 g CO2/g sorbent, more than 43% higher than that of the pure CaO pellets. In addition, the effects of the solid-liquid ratio during the preparation stage on CO2 performance were also investigated, demonstrating that a solid-liquid ratio of 1:5 was the optimal ratio to produce satisfying sorbents. The mitigated sintering and achieved spherical CaO pellets greatly promote the practical application of the calcium looping process for CO2 capture.

Network pharmacology analysis and experimental validation of Anemarrhenae Rhizoma in treating Alzheimer's disease. / çŸ¥æ¯æ²»ç–—é˜¿å°”èŒ¨æµ·é»˜ç— ç½‘ç»œè¯ç†å­¦ç ”ç©¶åŠå®žéªŒéªŒè¯.

OBJECTIVES: To explore the mechanism of Anemarrhenae Rhizoma in treatment of Alzheimer's Disease (AD). METHODS: The active ingredients and targets of Anemarrhenae Rhizoma for treatment of AD were screened with network pharmacology methods, the protein-protein interaction (PPI) network was constructed and the core targets were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriching analysis was performed. The peripheral blood lymphocytes were extracted and lymphoblastoid cell lines (LCL) were constructed and an in vitro cell model of LCL-SKNMC was established. MTT and CCK-8 methods were used to quantify SKNMC/LCL cells, 2 ´, 7 ´-dichlorodihydrofluorescein diacetate (DCFH-DA) probe was used to detect reactive oxygen species (ROS), and immunofluorescence staining was used to detect the generation of Aß1-42 in a co-cultured model. Western blotting was used to detect protein expression in the co-culture model. The lifespan of N2 nematodes was observed under oxidative stress, normal state, and heat stress; ROS generated by N2 nematodes was detected by DCFH-DA probes. The paralysis time of CL4176 N2 nematodes was evaluated by paralysis assay, and Aß deposition in the pharynx was detected by Thioflavin S staining. RESULTS: Through network pharmacology, 15 potential active ingredients and 103 drug-disease targets were identified. PPI analysis showed that the Anemarrhenae Rhizoma might play anti-AD roles through albumin, Akt1, tumor necrosis factor, epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), mammalian target of rapamycin (mTOR), amyloid precursor protein (APP) and other related targets. KEGG analysis showed that the pharmacological effects of Anemarrhenae Rhizoma might involve the biological processes of Alzheimer's disease, endocrine resistance, insulin resistance; and neuroactive ligand-receptor interaction, phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, calcium signaling pathway, AGE-RAGE signaling pathway in diabetes complications, neurotrophic factor signaling pathway and others. The in vitro cell experiments showed that Anemarrhenae Rhizoma was able to reduce the production of ROS and Aß1-42 (both P<0.01), inhibit the expression of ß-secretase 1 (BACE1), APP and Aß1-42 proteins (all P<0.05), up-regulate the expression of p-PI3K/PI3K, p-AKT/AKT, p-GSK3ß/GSK3ß in SKNMC cells (all P<0.05). The in vivo studies further confirmed that Anemarrhenae Rhizoma prolonged the lifespan of C. elegans under stress and normal conditions, reduced the accumulation of ROS and the toxicity of Aß deposition. CONCLUSIONS: Anemarrhenae Rhizoma may reduce the production of Aß in AD and inhibit its induced oxidative stress, which may be achieved by regulating the PI3K/Akt/GSK-3ß pathway.

ECSIT Is a Critical Factor for Controlling Intestinal Homeostasis and Tumorigenesis through Regulating the Translation of YAP Protein.

The intestinal epithelium is the fastest renewing tissue in mammals and its regenerative process must be tightly controlled to minimize the risk of dysfunction and tumorigenesis. The orderly expression and activation of Yes-associated protein (YAP) are the key steps in driving intestinal regeneration and crucial for intestinal homeostasis. However, the regulatory mechanisms controlling this process remain largely unknown. Here, it is discovered that evolutionarily conserved signaling intermediate in Toll pathways (ECSIT), a multi-functional protein, is enriched along the crypt-villus axis. Intestinal cell-specific ablation of ECSIT results in the dysregulation of intestinal differentiation unexpectedly accompanied with enhanced YAP protein dependent on translation, thus transforming intestinal cells to early proliferative stem "-like" cells and augmenting intestinal tumorigenesis. Loss of ECSIT leads to metabolic reprogramming in favor of amino acid-based metabolism, which results in demethylation of genes encoding the eukaryotic initiation factor 4F pathway and their increased expression that further promotes YAP translation initiation culminating in intestinal homeostasis imbalance and tumorigenesis. It is also shown that the expression of ECSIT is positively correlated with the survival of patients with colorectal cancer. Together, these results demonstrate the important role of ECSIT in regulating YAP protein translation to control intestinal homeostasis and tumorigenesis.

Natural restoration alters soil microbial community structure, but has contrasting effects on the diversity of bacterial and fungal assemblages in salinized grasslands.

Natural restoration has often been considered an effective measure for rehabilitating degraded ecosystems. However, its impact on the structure and diversity of soil microbial communities, particularly within a salinized grassland during its restoration succession, remains unclear. In this study, we examined the effects of natural restoration on the Shannon-Wiener diversity index, Operational Taxonomic Units (OTU) richness, and structure of the soil microbial community of a sodic-saline grassland in China using high-throughput amplicon sequencing data from representative successional chronosequences. Our results indicated that natural restoration resulted in a significant mitigation of the grassland salinization (pH from 9.31 to 8.32 and electrical conductivity from 393.33 to 136.67 µs·cm-1) and a significant alteration of the soil microbial community structure of the grassland (p < 0.01). However, the effects of natural recovery differed in terms of the abundance and diversity of bacteria and fungi. For example, the relative abundance of the bacterial phyla Acidobacteria increased by 116.45 % in the topsoil and 339.03 % in the subsoil, while that of the fungal phyla Ascomycota decreased by 8.86 % in the topsoil and 30.18 % in the subsoil. There was no significant effect of restoration on bacterial diversity, but fungal diversity increased by 15.02 % in the Shannon-Wiener index and 62.20 % in the OTU richness in the topsoil. Model-selection analysis further corroborated that the alteration of the soil microbial structure by natural restoration may be due to the fact that the bacteria could adapt to the alleviated salinized grassland soil and the fungi could adapt to the improved soil fertility of the grasslands. Overall, our results contribute to an in-depth understanding of the impacts of natural restoration on soil microbial diversity and community structure in salinized grasslands during the long-term successional course. This may also help to apply natural restoration as a greener practice option for managing degraded ecosystems.

Pore reconstruction mechanism of wheat straw-templated Li4SiO4 pellets for CO2 capture.

The traditional Li4SiO4-based CO2 sorbent pellets prepared from mechanical granulation methods usually presented densified microstructures. Hence, wheat straw, an agricultural waste featured with huge production and low cost, was used as porosity creator to improve the microstructures and CO2 capture performance of Li4SiO4 pellets. The results indicated that wheat straw effectively enhanced the cyclic CO2 sorption capacity of the pellets. In particular, 30 wt% wheat straw-templated Li4SiO4 pellets (LA-WS30) exhibited the capacity of ~0.15 g/g that is almost twice as high as that of unmodified pellets. The enriched porosity and improved porous structures resulted from the quick release of burning gases was considered as the main reason for the performance enhancement. In addition, the alkaline (K and Na) salts in wheat straw played a positive role in CO2 sorption of Li4SiO4 pellets due to the reduced diffusion resistance. However, the pore plugging of residual wheat straw ashes after high-temperature treatment decreased the contact areas and, thus, led to the capacity reduction. To conclude, the comprehensive performance of wheat straw-templated Li4SiO4 pellets is the result of the combined effects of porosity creation, alkali doping and pore plugging by ashes.

The Gasdermin D N-terminal fragment acts as a negative feedback system to inhibit inflammasome-mediated activation of Caspase-1/11.

Inflammatory pathways usually utilize negative feedback regulatory systems to prevent tissue damage arising from excessive inflammatory response. Whether such negative feedback mechanisms exist in inflammasome activation remains unknown. Gasdermin D (GSDMD) is the pyroptosis executioner of downstream inflammasome signaling. Here, we found that GSDMD, after its cleavage by caspase-1/11, utilizes its RFWK motif in the N-terminal ß1-ß2 loop to inhibit the activation of caspase-1/11 and downstream inflammation in a negative feedback manner. Furthermore, an RFWK motif-based peptide inhibitor can inhibit caspase-1/11 activation and its downstream substrates GSDMD and interleukin-1ß cleavage, as well as lipopolysaccharide-induced sepsis in mice. Collectively, these findings provide a demonstration of the N-terminal fragment of GSDMD as a negative feedback regulator controlling inflammasome activation and a detailed delineation of the underlying inhibitory mechanism.

Gasdermin D restricts anti-tumor immunity during PD-L1 checkpoint blockade.

Tumor microenvironments (TMEs) require co-operation of innate and adaptive immune cells, which influence tumor progression and immunotherapy. Caspase-activated gasdermins facilitate tumor death and promote anti-tumor immunity. How pyroptosis in immune cells affects the TME remains unclear. TME expression of gasdermin D (GSDMD) is highly expressed in antigen-presenting cells (APCs) and correlates with immune checkpoint signatures. Through conditional deletion of GSDMD, we demonstrate that GSDMD in TME APCs restricts anti-tumor immunity during PD-L1 inhibition. Loss of GSDMD in APCs enhances interferon-stimulated genes (ISGs), thereby promoting CD8+ T cell activation in a cGAS-dependent manner. Moreover, pharmacological inhibition of GSDMD-mediated pyroptosis and PD-L1 improve anti-tumor immunity, highlighting the potential of combining GSDMD/PD-L1 inhibition for immunotherapy as a therapeutic strategy.

An improved automated diatom detection method based on YOLOv5 framework and its preliminary study for taxonomy recognition in the forensic diatom test.

The diatom test is a forensic technique that can provide supportive evidence in the diagnosis of drowning but requires the laborious observation and counting of diatoms using a microscopy with too much effort, and therefore it is promising to introduce artificial intelligence (AI) to make the test process automatic. In this article, we propose an artificial intelligence solution based on the YOLOv5 framework for the automatic detection and recognition of the diatom genera. To evaluate the performance of this AI solution in different scenarios, we collected five lab-grown diatom genera and samples of some organic tissues from drowning cases to investigate the potential upper/lower limits of the capability in detecting the diatoms and recognizing their genera. Based on the study of the article, a recall score of 0.95 together with the corresponding precision score of 0.9 were achieved on the samples of the five lab-grown diatom genera via cross-validation, and the accuracy of the evaluation in the cases of kidney and liver is above 0.85 based on the precision and recall scores, which demonstrate the effectiveness of the AI solution to be used in drowning forensic routine.

Microglial AIM2 alleviates antiviral-related neuro-inflammation in mouse models of Parkinson's disease.

Inflammasome involvement in Parkinson's disease (PD) has been intensively investigated. Absent in melanoma 2 (AIM2) is an essential inflammasome protein known to contribute to the development of several neurological diseases. However, a specific role for AIM2 in PD has not been reported. In this study, we investigated the effect of AIM2 in the N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD model by use of various knockout and bone marrow chimeric mice. The mechanism of action for AIM2 in PD was assessed by RNA-sequencing and in vitro primary microglial transfection. Results were validated in the A30P transgenic mouse model of PD. In the MPTP mouse model, AIM2 activation was found to negatively regulate neuro-inflammation independent of the inflammasome. Microglial AIM2 deficiency exacerbated behavioral and pathological features of both MPTP-induced and transgenic PD mouse models. Mechanistically, AIM2 reduced cyclic GMP-AMP synthase (cGAS)-mediated antiviral-related inflammation by inhibition of AKT-interferon regulatory factor 3 (IRF3) phosphorylation. These results demonstrate microglial AIM2 to inhibit the antiviral-related neuro-inflammation associated with PD and provide for a foundation upon which to identify new therapeutic targets for treatment of the disease.

Evaluation of Inspection Efficiency of Diatom Artificial Intelligence Search System Based on Scanning Electron Microscope.

OBJECTIVES: To explore the application values of diatom artificial intelligence (AI) search system in the diagnosis of drowning. METHODS: The liver and kidney tissues of 12 drowned corpses were taken and were performed with the diatom test, the view images were obtained by scanning electron microscopy (SEM). Diatom detection and forensic expert manual identification were carried out under the thresholds of 0.5, 0.7 and 0.9 of the diatom AI search system, respectively. Diatom recall rate, precision rate and image exclusion rate were used to detect and compare the efficiency of diatom AI search system. RESULTS: There was no statistical difference between the number of diatoms detected in the target marked by the diatom AI search system and the number of diatoms identified manually (P>0.05); the recall rates of the diatom AI search system were statistically different under different thresholds (P<0.05); the precision rates of the diatom AI system were statistically different under different thresholds(P<0.05), and the highest precision rate was 53.15%; the image exclusion rates of the diatom AI search system were statistically different under different thresholds (P<0.05), and the highest image exclusion rate was 99.72%. For the same sample, the time taken by the diatom AI search system to identify diatoms was only 1/7 of that of manual identification. CONCLUSIONS: Diatom AI search system has a good application prospect in drowning cases. Its automatic diatom search ability is equal to that of experienced forensic experts, and it can greatly reduce the workload of manual observation of images.

Pyroptosis, and its Role in Central Nervous System Disease.

Pyroptosis is an inflammatory form of cell death executed by transmembrane pore-forming proteins known as gasdermins and can be activated in an inflammasome-dependent or -independent manner. Inflammasome-dependent pyroptosis is triggered in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) and has emerged as an important player in the pathogenesis of multiple inflammatory diseases, mainly by releasing inflammatory contents. More recently, numerous studies have revealed the intricate mechanisms of pyroptosis and its role in the development of neuroinflammation in central nervous system (CNS) diseases. In this review, we summarize current understandings of the molecular and regulatory mechanisms of pyroptosis. In addition, we discuss how pyroptosis can drive different forms of neurological diseases and new promising therapeutic strategies targeting pyroptosis that can be leveraged to treat neuroinflammation.

Harpagide alleviate neuronal apoptosis and blood-brain barrier leakage by inhibiting TLR4/MyD88/NF-κB signaling pathway in Angiotensin II-induced microglial activation in vitro.

Angiotensin II, the effector peptide of the renin-angiotensin system, is not only a pivotal peptide implicated in the regulation of blood pressure but also a key mediator of the inflammatory processes that play an important role in the pathology of hypertension-related cSVD. Harpagide is the major bioactive constituent of Scrophulariae Radix widely used in traditional Chinese medicine for numerous diseases including hypertension. The present study aimed to investigate the effect of harpagide on Ang II-induced neuroinflammation and the potential mechanism. Pretreated with harpagide or resatorvid (the TLR4 pathway inhibitor), BV2 cells were treated with Ang II or LPS (the TLR4 activator). NO, pro-inflammatory cytokines, the proteins on TLR4/MyD88/NF-κB signaling pathway and the expression of CD86, CD206, TREM2 in BV2 cells were detected respectively. Subsequently, the effects of harpagide on neurotoxicity and BBB destruction triggered by Ang II-induced neuroinflammation were investigated in the co-cultures of BV2 microglia/HT22 hippocampal neurons, BV2 microglia/bEnd.3 endotheliocyte and BV2 microglia/BBB monolayer model. We found that Ang II converted microglia into M1 state and resulted in neuroinflammation through activating TLR4/MyD88/NF-κB signaling pathway. It also triggered the imbalance of TLR4/TREM2 in microglia. Ang II-mediated inflammation microglia further led to neuronal apoptosis and BBB damage. Harpagide showed the effect of alleviating Ang II-mediated neuroinflammation as well as the resulting neurotoxicity and BBB destruction through inhibiting the TLR4/MyD88/NF-κB pathway. The anti-inflammatory and neuroprotective effect of harpagide suggested that it might be a potential therapeutic strategy in hypertensive cSVD.

RNF31 mediated ubiquitination of A20 aggravates inflammation and hepatocyte apoptosis through the TLR4/MyD88/NF-κB signaling pathway.

Inflammatory cytokine storm is one of the main pathogenesis of acute liver injury, and accumulating evidence suggests that the E3 ubiquitin ligase ring finger protein 31 (RNF31) plays an important regulatory role in the activation of inflammatory pathways. We found that RNF31 expression was up-regulated in lipopolysaccharide (LPS)-treated HL-7702 cells. Western blotting results showed decreased expression of RNF31 and total ubiquitinated proteins after transfection of si-RNF31. The results of MTT assay indicated that cell viability was enhanced. Flow cytometry analysis showed that cell apoptosis and ROS content was decreased, and ELISA assay results exhibited that the inflammatory factors secretion was reduced. Interestingly, A20 protein expression was inhibited as RNF31 expression was upregulated. On this basis, we performed co-immunoprecipitation assays and found that RNF31 could interact with A20. Actinomycin tracing and proteasome inhibition experiments showed that RNF31 degrades A20 through the proteasome pathway. Furthermore, overexpression of A20 enhanced cell viability, reduced apoptosis, and inhibited ROS generation and inflammatory factor secretion. Mechanistic studies revealed that RNF31 was able to degrade A20, which affected the inflammatory response and hepatocyte apoptosis mediated by the toll like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/nuclear transcription factor-κB (NF-κB) signaling pathway. Moreover, knockdown of RNF31 attenuated the inflammatory response induced by d-Gal/LPS in mice with acute liver injury. In conclusion, RNF31 degrades A20 by ubiquitination and activates the TLR4/MyD88/NF-κB signaling pathway to aggravate acute liver injury.

Cadmium-induced toxicity to amphibian tadpoles might be exacerbated by alkaline not acidic pH level.

Heavy metal pollution in natural water bodies generally interacting with other environmental stressors produces toxic effects on aquatic organisms. However, toxicological studies exploring interactive effects of these stressors are still limited. Here, tadpoles of the Zhenhai brown frog (Rana zhenhaiensis) were exposed to a 3 × 3 factorial combination, with three cadmium (Cd) concentrations (0, 10 and 100 µg/L) and three pH levels (5.0, 7.23 and 9.0) throughout the developmental period to assess combined toxic effects of Cd × pH on tadpole growth, development and physiology. Nearly all measured traits [including survival, metamorphosis and abnormality rate, metamorphosis time, post-metamorphic size, hepatic metal content, locomotor performance, antioxidant enzyme activity, and erythrocytic nuclear abnormality (ENA) frequency] were affected by Cd exposure, indicating notable Cd-induced toxicity to R. zhenhaiensis tadpoles. The pH level and its interaction with Cd also had significant impacts on most measured traits, such as survival rate, metamorphosis time, froglet jumping distance, hepatic Cd content, ENA frequency. Acidic (or alkaline) environment itself was toxic to tadpoles. However, high pH (but not low pH) level appeared to exacerbate Cd-induced toxicity to tadpoles. Excess free hydrogen ions under acidic environments might inhibit Cd2+ ions binding to cell surface, which reduced Cd accumulation in tissues. Under alkaline environments, other forms of Cd complexes in the aqueous phase probably contributed to promoting Cd accumulation. Our results indicated that Cd exposure could interact with different pH levels, producing diverse combined toxicities to amphibian larvae.

AIM2 controls microglial inflammation to prevent experimental autoimmune encephalomyelitis.

The role of the PYHIN family member absent in melanoma 2 (AIM2), another important inflammasome sensor, in EAE remains unclear. In this study, we found that AIM2 negatively regulates the pathogenesis of EAE independent of inflammasome activation. AIM2 deficiency enhanced microglia activation and infiltration of peripheral immune cells into the CNS, thereby promoting neuroinflammation and demyelination during EAE. Mechanistically, AIM2 negatively regulates the DNA-PK-AKT3 in microglia to control neuroinflammation synergistically induced by cGAS and DNA-PK. Administration of a DNA-PK inhibitor reduced the severity of the EAE. Collectively, these findings identify a new role for AIM2 in controlling the onset of EAE. Furthermore, delineation of the underlying inflammasome-independent mechanism highlights cGAS and DNA-PK signaling as potential targets for the treatment of heterogeneous MS.

A review on nitrogen transformation in hydrochar during hydrothermal carbonization of biomass containing nitrogen.

Biomass is a type of renewable and sustainable resource that can be used to produce various fuels, chemicals, and materials. Nitrogen (N) in biomass such as microalgae should be reduced if it is used to produce fuels, while the retention of N is favorable if the biomass is processed to yield chemicals or materials with N-containing functional groups. The engineering of the removal and retention of N in hydrochar during hydrothermal carbonization (HTC) of biomass rich in protein is a research hot spot in the past decade. However, the N transformation during HTC has not yet been fully understood. In order to mediate the migration and transformation of N in hydrochar, the present review overviewed i) the characteristics of hydrochar and the original feedstock, ii) the possible N transformation behavior and mechanisms, and iii) the effect of factors such as feedstock and pyrolysis parameters such as temperature on hydrochar N. The high temperature and high protein content promote the dehydration, decarboxylation, and deamination of biomass to produce hydrochar solid fuel with reduced N content, while the Millard and Mannich reactions for lignocellulosic biomass rich in carbohydrate (cellulose, hemicellulose, and lignin) at medium temperatures (e.g., 180-240 °C) significantly promote the enrichment of N in hydrochar. The prediction models can be built based on properties of biomass and the processing parameters for the estimation of the yield and the content of N in hydrochar.