Therapeutic vaccine-induced plasma cell differentiation is defective in the presence of persistently high HBsAg levels.

BACKGROUND & AIMS: Mechanisms behind the impaired response of antigen-specific B cells to therapeutic vaccination in chronic hepatitis B virus (HBV) infection remain unclear. The development of vaccines or strategies to overcome this obstacle is vital for advancing the management of chronic hepatitis B. METHODS: A mouse model, denominated as E6F6-B, was engineered to feature a knock-in of a B-cell receptor (BCR) that specifically recognizes HBsAg. This model served as a valuable tool for investigating the temporal and spatial dynamics of humoral responses following therapeutic vaccination under continuous antigen exposure. Using a suite of immunological techniques, we elucidated the differentiation trajectory of HBsAg-specific B cells post-therapeutic vaccination in HBV carrier mice. RESULTS: Utilizing the E6F6-B transfer model, we observed a marked decline in antibody-secreting cells 2 weeks after vaccination. A dysfunctional and atypical pre-plasma cell population (BLIMP-1+ IRF4+ CD40- CD138- BCMA-) emerged, manifested by sustained BCR signaling. By deploying an antibody to purge persistent HBsAg, we effectively prompted the therapeutic vaccine to provoke conventional plasma cell differentiation. This resulted in an enhanced anti-HBs antibody response and facilitated HBsAg clearance. CONCLUSIONS: Sustained high levels of HBsAg limit the ability of therapeutic hepatitis B vaccines to induce the canonical plasma cell differentiation necessary for anti-HBs antibody production. Employing a strategy combining antibodies with vaccines can surmount this altered humoral response associated with atypical pre-plasma cells, leading to improved therapeutic efficacy in HBV carrier mice. IMPACT AND IMPLICATIONS: Therapeutic vaccines aimed at combatting HBV encounter suboptimal humoral responses in clinical settings, and the mechanisms impeding their effectiveness have remained obscure. Our research, utilizing the innovative E6F6-B mouse transfer model, reveals that the persistence of HBsAg can lead to the emergence of an atypical pre-plasma cell population, which proves to be relevant to the potency of therapeutic HBV vaccines. Targeting the aberrant differentiation process of these atypical pre-plasma cells stands out as a critical strategy to amplify the humoral response elicited by HBV therapeutic vaccines in carrier mouse models. This discovery suggests a compelling avenue for further study in the context of human chronic hepatitis B. Encouragingly, our findings indicate that synergistic therapy combining HBV-specific antibodies with vaccines offers a promising approach that could significantly advance the pursuit of a functional cure for HBV.

Evolution of the SARS-CoV-2 Omicron Variants: Genetic Impact on Viral Fitness.

Over the last three years, the pandemic of COVID-19 has had a significant impact on people's lives and the global economy. The incessant emergence of variant strains has compounded the challenges associated with the management of COVID-19. As the predominant variant from late 2021 to the present, Omicron and its sublineages, through continuous evolution, have demonstrated iterative viral fitness. The comprehensive elucidation of the biological implications that catalyzed this evolution remains incomplete. In accordance with extant research evidence, we provide a comprehensive review of subvariants of Omicron, delineating alterations in immune evasion, cellular infectivity, and the cross-species transmission potential. This review seeks to clarify the underpinnings of biology within the evolution of SARS-CoV-2, thereby providing a foundation for strategic considerations in the post-pandemic era of COVID-19.

Micronanoparticled risedronate exhibits potent vaccine adjuvant effects.

Micro/Nano-scale particles are widely used as vaccine adjuvants to enhance immune response and improve antigen stability. While aluminum salt is one of the most common adjuvants approved for human use, its immunostimulatory capacity is suboptimal. In this study, we modified risedronate, an immunostimulant and anti-osteoporotic drug, to create zinc salt particle-based risedronate (Zn-RS), also termed particulate risedronate. Compared to soluble risedronate, micronanoparticled Zn-RS adjuvant demonstrated increased recruitment of innate cells, enhanced antigen uptake locally, and a similar antigen depot effect as aluminum salt. Furthermore, Zn-RS adjuvant directly and quickly stimulated immune cells, accelerated the formulation of germinal centers in lymph nodes, and facilitated the rapid production of antibodies. Importantly, Zn-RS adjuvant exhibited superior performance in both young and aged mice, effectively protecting against respiratory diseases such as SARS-CoV-2 challenge. Consequently, particulate risedronate showed great potential as an immune-enhancing vaccine adjuvant, particularly beneficial for vaccines targeting the susceptible elderly.

Effect of enhanced recovery after surgery with multidisciplinary collaboration on nursing outcomes after total knee arthroplasty.

BACKGROUND: There is a lack of studies on the effects of enhanced recovery after surgery (ERAS) with multidisciplinary collaboration on the nursing outcomes of total knee arthroplasty (TKA). AIM: To explore the effect of ERAS with multidisciplinary collaboration on nursing outcomes after TKA. METHODS: We retrospectively analyzed the clinical data of 80 patients who underwent TKA at a tertiary hospital between January 2021 and December 2022. The patients were divided into two groups according to the nursing mode: the ERAS group (n = 40) received ERAS with multidisciplinary collaboration, and the conventional group (n = 40) received routine nursing. The following indicators were compared between the two groups: length of hospital stay, hospitalization cost, intraoperative blood loss, hemoglobin level 24 h after surgery, visual analog scale (VAS) score for pain, range of motion (ROM) of the knee joint, Hospital for Special Surgery (HSS) knee score, and postoperative complications. RESULTS: The ERAS group had a significantly shorter length of hospital stay, lower hospitalization cost, less intraoperative blood loss, higher hemoglobin level 24 h after surgery, lower VAS score for pain, higher knee joint ROM, and higher HSS knee score than the conventional group (all P < 0.05). There was no significant difference in the incidence of postoperative complications between the two groups (P > 0.05). CONCLUSION: Multidisciplinary collaboration with ERAS can reduce blood loss, shorten hospital stay, and improve knee function in patients undergoing TKA.

Insights into the fate and properties of organic halamines during ultraviolet irradiation: Implications for drinking water safety.

Organic halamines compounds present a significant threat to the safety of drinking water due to their potential toxicity and stability. While Ultraviolet (UV) disinfection is commonly used for water treatment, its specific effects on organic halamines and the underlying mechanisms remain poorly understood. In this study, we investigated eight amino acid-derived organic chlor- and bromamines as representative compounds. Our findings revealed that organic halamines have a slow hydrolysis rate (<10-3 M-1 s-1) and can persist in water for extended periods (30-2000 min). However, their disinfection efficacy against Staphylococcus aureus and their ability to degrade micropollutants like carbamazepine were found to be limited. Interestingly, under UV irradiation, the N-X bonds in organic halamines were observed to break, leading to accelerated decomposition and the generation of abundant free radicals. These free radicals synergistically facilitated the removal of micropollutants and the inactivation of pathogenic microorganisms. It is worth noting that this transformation of organic halamines during UV disinfection resulted in a slight increase in the concentrations of nitrogenous disinfection byproducts. These findings shed light on the behavior and characteristics of organic halamines during UV disinfection processes, providing crucial insights for effectively managing drinking water quality impacted by these compounds. By understanding the implications of organic halamines, we can refine water treatment strategies and ensure the safety of drinking water supplies.

Intranasal influenza-vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response in hamsters.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and "anatomical escape" characteristics threaten the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. Here we investigate immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants in hamsters. Intranasal delivery of dNS1-RBD induces innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrains the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (Il6, Il1b, and Ifng) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden.

Combination therapy of therapeutic antibody and vaccine or entecavir in HBV carrier mice.

Chronic infection with the hepatitis B virus (HBV) is a leading causes of liver cirrhosis and hepatocellular carcinoma. However, managing HBV treatments is challenging due to the lack of effective monotherapy. Here, we present two combination approaches, both of which aim to target and enhance the clearance of HBsAg and HBV-DNA. The first approach involves the use of antibodies to continuously suppress HBsAg, followed by the administration of a therapeutic vaccine in a sequential manner. This approach results in better therapeutic outcomes compared to the use of these treatments individually. The second approach involves combining antibodies with ETV, which effectively overcomes the limitations of ETV in suppressing HBsAg. Thus, the combination of therapeutic antibodies, therapeutic vaccines, and other existing drugs is a promising strategy for the development of novel strategies to treat hepatitis B.

Molecular insights towards changing behaviors of organic matter in a full-scale water treatment plant using FTICR-MS.

The changing behavior of organic matter in a full-scale water treatment process was characterized based on the three-dimensional excitation-emission matrix (3D-EEM) and Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). Polyaluminum chloride (PAC) as a coagulant can help to effectively remove soluble microbial by-products-like and aromatic protein-like substances during coagulation and sedimentation, corresponding to tannin and coagulated aromatic regions. The leakage of soluble microbial products during sand filtration resulted in an increase in the intensity of biomass-like regions. Nitrogen-containing compounds have higher weighted average value of double bond equivalents (DBEw) and the modified aromaticity index (AImod-w) than nitrogen-free compounds. Water treatment can preferentially remove unsaturated nitrogen-containing compounds with more O atoms and higher-oxidation-state carbon. The dissolved organic carbon (DOC) and UV254 were not correlated well with changes in nitrogen-containing compounds due to the preferential removal of nitrogen-containing compounds. This study revealed the specificity of organic matter removal during water treatment, and it was helpful in optimizing treatment processes for various raw water to ensure water quality.

Predictive models for the aqueous phase reactivity of inorganic radicals with organic micropollutants.

Single-electron transfer (SET) is one of the most common reaction mechanisms for degrading organic micropollutants (OMPs) in advanced oxidation processes. We collected 300 SET reactions (CO3•-, SO4•-, Cl2•-, and Br2•--mediated) and calculated three key parameters for understanding the SET mechanism: aqueous phase free energies of activation (ΔG‡), free energies of reactions (ΔG), and orbital energy gaps of reactants (EOMPsHOMO-ERadiLUMO). Then, we classified the OMPs according to their structure, developed and evaluated linear energy relationships of the second-order rate constants (k) with ΔG‡, ΔG, or EOMPsHOMO-ERadiLUMO in each class. Considering that a single descriptor cannot capture all the chemical diversity, we combined ΔG‡, ΔG, and EOMPsHOMO-ERadiLUMO as inputs to develop multiple linear regression (MLR) models. Chemical classification is critical to the linear model described above. However, OMPs usually have multiple functional groups, making the classification challenging and uncertain. Therefore, we tried machine learning algorithms to predict k values without chemical classification. We found that decision trees (R2 = 0.88-0.95) and random forest (R2 = 0.90-0.94) algorithms show better performance on the prediction of the k values, whereas boosted tree algorithm cannot make an accurate prediction (R2 = 0.19-0.36). Overall, our study provides a powerful tool to predict the aqueous phase reactivity of OMP to certain radicals without the need for chemical classification.

Apolipoprotein H induces sex-specific steatohepatitis and gut dysbiosis during chronic hepatitis B infection.

Apolipoprotein H (APOH) is involved in lipid metabolism and functions as an acute-phase protein during hepatitis B virus (HBV) infection. Herein, we explored whether APOH acts on the development of fatty liver upon chronic HBV infection. Serum APOH level was significantly lower in cirrhosis patients than in healthy controls or patients with chronic infection. It showed sex bias, with elevated levels in female patients with chronic infection. Also, serum APOH levels were negatively correlated with HBV surface antigen (HBsAg) but positively correlated with albumin and triglyceride levels. In In vitro HBV infection model, HBV upregulated APOH expression in a non-temporal manner, and HBsAg levels were elevated by silencing APOH. RNA sequencing (RNA-seq) demonstrated bidirectional expression of APOH, which impacted the immunoregulation upon infection or the metabolic regulation in HepG2.2.15 cells. Then, ApoH -/- mice with persistent HBV replication displayed steatohepatitis and gut microbiota dysbiosis with synergistic sex differences. Our study deciphers the roles of APOH in chronic liver diseases.

Enhanced formation of haloacetonitriles during chlorination with bromide: Unveiling the important roles of organic bromamines.

The formation of brominated disinfection byproducts (Br-DBPs) is an emerging issue in drinking water disinfection because its toxicity is tens to hundreds of times higher than that of chlorinated analogues and because of the widespread presence of bromide in source water. However, the mechanism and pathways of Br-DBPs formation remain unclear. In this study, we used glycine, alanine, and serine as model precursors and observed that brominated haloacetonitriles (Br-HANs) were more likely to be formed than brominated trihalomethanes. The results showed that there is not only one important way to HAN formation in the presence of bromide. We propose that organic bromamines, similar to organic chloramines, play a significant role in the formation of Br-HANs. Both the experimental and theoretical results confirmed that the decay of organic bromamines was faster than that of organic chloramines, which verified our assumption. The effect of the pH was investigated to further confirm the role of organic bromamines. In addition, we found that the formation of Br-HANs was significantly inhibited when monochloramine was used as a disinfectant, because the formation of organic bromamines was blocked. However, the formation of Br-HANs was promoted during the UV/chlorine process because of the faster decay of organic bromamines under UV photolysis. Overall, our study reveals the formation mechanism of Br-HANs and provides an alternative method to prevent Br-HAN formation.

Insight into the mechanisms of trichloronitromethane formation by vacuum ultraviolet: QSAR model and FTICR-MS analysis.

Vacuum ultraviolet (VUV) photolysis is recognized as an environmental-friendly treatment process. Nitrate (NO3-) and natural organic matter (NOM) are widely present in water source. We investigated trichloronitromethane (TCNM) formation during chlorination after VUV photolysis, because TCNM is an unregulated highly toxic disinfection byproduct. In this study: (1) we found reactive nitrogen species that is generated under VUV photolysis of NO3- react with organic matter to form nitrogen-containing compounds and subsequently form TCNM during chlorination; (2) we found the mere presence of 0.1 mmol/L NO3- can result in the formation of up to 63.96 µg/L TCNM; (3) we found the changes in pH (6.0-8.0), chloride (1-4 mmol/L), and bicarbonate (1-4 mmol/L) cannot effectively diminish TCNM formation; and, (4) we established the quantitative structure-activity relationship (QSAR) model, which indicated a linear relationship between TCNM formation and the Hammett constant (σ) of model compounds; and, (5) we characterized TCNM precursors in water matrix after VUV photolysis and found 1161 much more nitrogen-containing compounds with higher aromaticity were generated. Overall, this study indicates more attention should be paid to reducing the formation risk of TCNM when applying VUV photolysis process at scale.

Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine.

SARS-CoV-2 spread in humans results in continuous emergence of new variants, highlighting the need for vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation-patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x) that contains key regions and residues across multiple SAR-CoV-2 variants. STFK1628x demonstrated high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine composed of STFK and STFK1628x elicited high titers of broad-spectrum neutralizing antibodies to 19 circulating SARS-CoV-2 variants, including Omicron sublineages BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5. Furthermore, this vaccine conferred robust protection against intranasal challenges by either SARS-CoV-2 ancestral strain or immune-evasive Beta and Omicron BA.1. Strikingly, vaccination with the bivalent vaccine in hamsters effectively blocked within-cage virus transmission of ancestral SARS-CoV-2, Beta variant, and Omicron BA.1 to unvaccinated sentinels. Thus, our study provided insight and antigen candidates for the development of next-generation COVID-19 vaccines.

Enhanced trichloronitromethane formation during chlorine-UV treatment of nitrite-containing water by organic amines.

This study explored the risk of trichloronitromethane (TCNM) formation during chlorination of the nitrite-containing water after pre-chlorination and subsequent UV irradiation (i.e., the chlorine-UV process). The competitive reaction between amino acid (AA) and NO2- for chlorine produced organic chloramine and reduced the oxidation from NO2- to NO3-, resulting in a significant enhancement of TCNM in the presence of AA (>5.52 µg L-1) as compared to the absence of AA (0.42 µg L-1). The generation of HO• during UV photolysis of organic chloramines was confirmed. Among the process parameters, pre-chlorination time (from 5 min to 30 min) had no significant effect on TCNM formation; the highest TCNM formation occurred at pH 7 (from pH 6 to pH 8); prolonged UV irradiation time (from 5 min to 30 min) and increased chlorine to AA ratio (Cl2:AA) (from 1 to 3) decreased the TCNM formation. The hydroxylated, chlorinated and nitrosated products were detected. The quantum chemical calculation results indicated the attack of NO2• was more likely to occur at the meta and para positions of benzoic acid (BZA), because of the steric hindrance of the carboxylic group in BZA to the ortho position. Based on the results of the toxicity assessment, pre-chlorination with a higher chlorine dosage could be an effective method of controlling both TCNM formation and acute toxicity. Overall, the results of this study contributed to the understanding of the TCNM formation mechanism as well as optimizing the parameters of the chlorine-UV process to reduce the risk of TCNM formation.

The neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2.

Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.

Impact of pre-oxidation on the formation of byproducts in algae-laden water disinfection: Insights from fluorescent and molecular weight.

Pre-oxidation has been reported to be an effective way to remove algal cells in water, but the released algal organic matter (AOM) could be oxidized and lead to the increment in disinfection by-product (DBP) formation. The relationship between pre-oxidation and AOM-derived DBP formation needs to be approached more precisely. This study compared the impact of four pre-oxidants, ozone (O3), chlorine dioxide (ClO2), potassium permanganate (KMnO4) and sodium hypochlorite (NaClO), on the formation of nitrogenous (N-) and carbonaceous (C-) DBPs in AOM chlorination. The characterization (fluorescent properties, molecular weight distribution and amino acids concentration) on AOM samples showed that the characterization properties variations after pre-oxidation were highly dependent on the oxidizing ability of oxidants. The disinfection experiments showed that O3 increased DBP formation most significantly, which was consistent with the result of characterization properties variations. Then canonical correspondent analysis (CCA) and Pearson's correlation analysis were conducted based on the characterization data and DBP formation. CCA indicated that C-DBPs formation was highly dependent on fluorescent data. The formation of haloacetic acids (HAAs) had a positive correlation with aromatic protein-like component while trichloromethane (TCM) had a positive correlation with fulvic acid-like component. Pearson's correlation analysis showed that low molecular weight fractions were favorable to form N-DBPs. Therefore, characterization data could provide the advantages in the control of DBP formation, which further revealed that KMnO4 and ClO2 were better options for removing algal cells as well as limiting DBP formation.

A Bacterially Expressed SARS-CoV-2 Receptor Binding Domain Fused With Cross-Reacting Material 197 A-Domain Elicits High Level of Neutralizing Antibodies in Mice.

The Coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented public health crisis worldwide. Although several vaccines are available, the global supply of vaccines, particularly within developing countries, is inadequate, and this necessitates a need for the development of less expensive, accessible vaccine options. To this end, here, we used the Escherichia coli expression system to produce a recombinant fusion protein comprising the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; residues 319-541) and the fragment A domain of Cross-Reacting Material 197 (CRM197); hereafter, CRMA-RBD. We show that this CRMA-RBD fusion protein has excellent physicochemical properties and strong reactivity with COVID-19 convalescent sera and representative neutralizing antibodies (nAbs). Furthermore, compared with the use of a traditional aluminum adjuvant, we find that combining the CRMA-RBD protein with a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH-002C-Ac) leads to stronger humoral immune responses in mice, with 4-log neutralizing antibody titers. Overall, our study highlights the value of this E. coli-expressed fusion protein as an alternative vaccine candidate strategy against COVID-19.

Cross-species tropism and antigenic landscapes of circulating SARS-CoV-2 variants.

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) may alter viral host tropism and affect the activities of neutralizing antibodies. Here, we investigated 153 RBD mutants and 11 globally circulating variants of concern (VOCs) and variants of interest (VOIs) (including Omicron) for their antigenic changes and cross-species tropism in cells expressing 18 ACE2 orthologs. Several RBD mutations strengthened viral infectivity in cells expressing ACE2 orthologs of non-human animals, particularly those less susceptible to the ancestral strain. The mutations surrounding amino acids (aas) 439-448 and aa 484 are more likely to cause neutralization resistance. Strikingly, enhanced cross-species infection potential in the mouse and ferret, instead of the neutralization-escape scores of the mutations, account for the positive correlation with the cumulative prevalence of mutations in humans. These findings present insights for potential drivers of circulating SARS-CoV-2 variants and provide informative parameters for tracking and forecasting spreading mutations.

UV-induced activation of organic chloramine: Radicals generation, transformation pathway and DBP formation.

Organic chloramines of little disinfection efficacy commonly exist in disinfection process (chlor(am)ination) due to the wide presence of organic amines in water, of which N-chlorodimethylamine (CDMA) is a typical one. For the first time, UV photolysis for the activation of CDMA was investigated. UV photolysis caused the cleavage of N-Cl bond in CDMA to form Cl• and subsequently HO•, both of which are dominant contributors to the destruction of model contaminant bisphenol A (BPA). Typical spectra of HO• were detected by electron paramagnetic resonance (EPR) experiments, while spectra of reactive nitrogen species (RNS) were not detected during UV photolysis of CDMA. The increase of pH (6.0-8.0), HCO3-/CO32-, Cl- and nature organic matter inhibited the degradation of BPA. We proposed pathways of CDMA and BPA degradation based on the identified transformation products. UV photolysis of CDMA and BPA reduced the formation of N-nitrosodimethylamine (NDMA) at pH 8.0, but increased the formation of trichloronitromethane (TCNM) at pH 7.0 and 8.0. The increasing toxicity and the formation of TCNM and NDMA gave us a hint that formation of organic chloramines should be concerned.

Molecular insights into formation of nitrogenous disinfection byproducts from algal organic matter in UV-LEDs/chlorine process based on FT-ICR analysis.

Eutrophication is a globally concerned issue, which brings algal cells and algal organic matter (AOM) into drinking water treatment plants. AOM is an important branch of nitrogenous disinfection byproduct (N-DBP) precursors. The variation of AOM composition in UV-LEDs/chlorine process, and its relationship with N-DBP formation still remain much uncertainty. Herein, we used fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to investigate AOM transformation in UV-LEDs/chlorine process, with UV285 and UV365 as light source, and screen for typical precursors of N-DBPs. We found that more nitrogen-containing compounds were generated after UV-LEDs/chlorine process, leading to the larger formation of N-DBPs in postchlorination. Compounds such as lignin, proteins, and amino sugars tends to be oxidized by reactive species in UV-LEDs/chlorine process. Further, compounds with higher O/C and higher weighted average double bond equivalence (DBEw) are easier to form N-DBPs, including dichloroacetonitrile and trichloronitromethane. Also, influence factors including pH, UV fluence, post-chlorination time and bromide concentration on N-DBP formation were evaluated. The results show that N-DBP formation generally followed the order of UV285/chlorine-postchlorination, UV365/chlorine-postchlorination, and direct chlorination. Our study provides comprehensive information on N-DBP formation from AOM in UV-LEDs/chlorine-postchlorination from molecular levels.