Recognition Receptor for Methylated Arginine at the Single Molecular Level.

Among the various types of post-translational modifications (PTMs), methylation is the simple functionalized one that regulates the functions of proteins and affects interactions of protein-protein and protein-DNA/RNA, which will further influence diverse cellular processes. The methylation modification has only a slight effect on the size and hydrophobicity of proteins or peptides, and it cannot change their net charges at all, so the methods for recognizing methylated protein are still limited. Here, we designed a recognition receptor consisting of a α-hemolysin (α-HL) nanopore and polyamine decorated γ-cyclodextrin (am8γ-CD) to differentiate the methylation of peptide derived from a heterogeneous nuclear ribonucleoprotein at the single molecule level. The results indicate that the modification of a methyl group enhances the interaction between the peptide and the recognition receptor. The results of molecular simulations were consistent with the experiments; the methylated peptide interacts with the receptor strongly due to the more formation of hydrogen bonds. This proposed strategy also can be used to detect PTM in real biological samples and possesses the advantages of low-cost and high sensitivity and is label-free. Furthermore, the success in the construction of this recognition receptor will greatly facilitate the investigation of pathogenesis related to methylated arginine.

Current oscillations from bipolar nanopores for statistical monitoring of hydrogen evolution on a confined electrochemical catalyst.

Taking advantage of bipolar electrochemistry and a glass nanopipette, continuous single bubbles can be controlled which are generated and detached from a nanometer-sized area of confined electrochemical catalysts. The observed current oscillations offer opportunities to rapidly collect data for the statistical analysis of single-bubble generation on and departure from the catalysts.

SIRT2 Deficiency Aggravates Diet-Induced Nonalcoholic Fatty Liver Disease through Modulating Gut Microbiota and Metabolites.

Non-alcoholic fatty liver disease (NAFLD), characterized by excessive lipid accumulation in hepatocytes, is an increasing global healthcare burden. Sirtuin 2 (SIRT2) functions as a preventive molecule for NAFLD with incompletely clarified regulatory mechanisms. Metabolic changes and gut microbiota imbalance are critical to the pathogenesis of NAFLD. However, their association with SIRT2 in NAFLD progression is still unknown. Here, we report that SIRT2 knockout (KO) mice are susceptible to HFCS (high-fat/high-cholesterol/high-sucrose)-induced obesity and hepatic steatosis accompanied with an aggravated metabolic profile, which indicates SIRT2 deficiency promotes NAFLD-NASH (nonalcoholic steatohepatitis) progression. Under palmitic acid (PA), cholesterol (CHO), and high glucose (Glu) conditions, SIRT2 deficiency promotes lipid deposition and inflammation in cultured cells. Mechanically, SIRT2 deficiency induces serum metabolites alteration including upregulation of L-proline and downregulation of phosphatidylcholines (PC), lysophosphatidylcholine (LPC), and epinephrine. Furthermore, SIRT2 deficiency promotes gut microbiota dysbiosis. The microbiota composition clustered distinctly in SIRT2 KO mice with decreased Bacteroides and Eubacterium, and increased Acetatifactor. In clinical patients, SIRT2 is downregulated in the NALFD patients compared with healthy controls, and is associated with exacerbated progression of normal liver status to NAFLD to NASH in clinical patients. In conclusion, SIRT2 deficiency accelerates HFCS-induced NAFLD-NASH progression by inducing alteration of gut microbiota and changes of metabolites.

LSD1-Demethylated LINC01134 Confers Oxaliplatin Resistance Through SP1-Induced p62 Transcription in HCC.

BACKGROUND AND AIMS: Oxaliplatin (OXA) is one of the most common chemotherapeutics in advanced hepatocellular carcinoma (HCC), the resistance of which poses a big challenge. Long noncoding RNAs (lncRNAs) play vital roles in chemoresistance. Therefore, elucidating the underlying mechanisms and identifying predictive lncRNAs for OXA resistance is needed urgently. METHODS: RNA sequencing (RNA-seq) and fluorescence in situ hybridization (FISH) were used to investigate the OXA-resistant (OXA-R) lncRNAs. Survival analysis was performed to determine the clinical significance of homo sapiens long intergenic non-protein-coding RNA 1134 (LINC01134) and p62 expression. Luciferase, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and chromatin isolation by RNA purification (ChIRP) assays were used to explore the mechanisms by which LINC01134 regulates p62 expression. The effects of LINC01134/SP1/p62 axis on OXA resistance were evaluated using cell viability, apoptosis, and mitochondrial function and morphology analysis. Xenografts were used to estimate the in vivo regulation of OXA resistance by LINC01134/SP1/p62 axis. ChIP, cell viability, and xenograft assays were used to identify the demethylase for LINC01134 up-regulation in OXA resistance. RESULTS: LINC01134 was identified as one of the most up-regulated lncRNAs in OXA-R cells. Higher LINC01134 expression predicted poorer OXA therapeutic efficacy. LINC01134 activates anti-oxidative pathway through p62 by recruiting transcription factor SP1 to the p62 promoter. The LINC01134/SP1/p62 axis regulates OXA resistance by altering cell viability, apoptosis, and mitochondrial homeostasis both in vitro and in vivo. Furthermore, the demethylase, lysine specific demethylase 1 (LSD1) was responsible for LINC01134 up-regulation in OXA-R cells. In patients with HCC, LINC01134 expression was positively correlated with p62 and LSD1 expressions, whereas SP1 expression positively correlated with p62 expression. CONCLUSIONS: LSD1/LINC01134/SP1/p62 axis is critical for OXA resistance in HCC. Evaluating LINC01134 expression in HCC will be effective in predicting OXA efficacy. In treatment-naive patients, targeting the LINC01134/SP1/p62 axis may be a promising strategy to overcome OXA chemoresistance.

FOXO3A-induced LINC00926 suppresses breast tumor growth and metastasis through inhibition of PGK1-mediated Warburg effect.

Phosphoglycerate kinase 1 (PGK1), a critical component of the glycolytic pathway, relates to the development of various cancers. However, the mechanisms of PGK1 inhibition and physiological significance of PGK1 inhibitors in cancer cells are unclear. Long non-coding RNAs (lncRNAs) play a vital role in tumor growth and progression. Here, we identify a lncRNA LINC00926 that negatively regulates PGK1 expression and predicts good clinical outcome of breast cancer. LINC00926 downregulates PGK1 expression through the enhancement of PGK1 ubiquitination mediated by E3 ligase STUB1. Moreover, hypoxia inhibits LINC00926 expression and activates PGK1 expression largely through FOXO3A. FOXO3A/LINC00926/PGK1 axis regulates breast cancer glycolysis, tumor growth, and lung metastasis both in vitro and in vivo. In breast cancer patients, LINC00926 expression is negatively correlated with PGK1 and positively correlated with FOXO3A expression. Our work established FOXO3A/LINC00926/PGK1 as a critical axis to regulate breast cancer growth and progression. Targeting PGK1 or supplement of LINC00926 or FOXO3A could be potential therapeutic strategies in breast cancer.

Biomimetic Molecular Clamp Nanopores for Simultaneous Quantifications of NAD+ and NADH.

NADH/NAD+ is pivotal to fundamental biochemistry research and molecular diagnosis, but recognition and detection for them are a big challenge at the single-molecule level. Inspired by the biological system, here, we designed and synthesized a biomimetic NAD+/NADH molecular clamp (MC), octakis-(6-amino-6-deoxy)-γ-cyclomaltooctaose, and harbored in the engineered α-HL(M113R)7 nanopore, forming a novel single-molecule biosensor. The single-molecule measurement possesses high selectivity and a high signal-to-noise ratio, allowing to simultaneously recognize and detect for sensing NADH/NAD+ and their transformations.

Crowding-Induced DNA Translocation through a Protein Nanopore.

A crowded cellular environment is highly associated with many significant biological processes. However, the effect of molecular crowding on the translocation behavior of DNA through a pore has not been explored. Here, we use nanopore single-molecule analytical technique to quantify the thermodynamics and kinetics of DNA transport under heterogeneous cosolute PEGs. The results demonstrate that the frequency of the translocation event exhibits a nonmonotonic dependence on the crowding agent size, while both the event frequency and translocation time increase monotonically with increasing crowder concentration. In the presence of PEGs, the rate of DNA capture into the nanopore elevates 118.27-fold, and at the same time the translocation velocity decreases from 20 to 120 µs/base. Interestingly, the impact of PEG 4k on the DNA-nanopore interaction is the most notable, with up to ΔΔG = 16.27 kJ mol-1 change in free energy and 764.50-fold increase in the binding constant at concentration of 40% (w/v). The molecular crowding effect will has broad applications in nanopore biosensing and nanopore DNA sequencing in which the strategy to capture analyte and to control the transport is urgently required.

Simultaneous High-Resolution Detection of Bioenergetic Molecules using Biomimetic-Receptor Nanopore.

A novel artificial receptor, heptakis-[6-deoxy-6-(2-hydroxy-3-trimethylammonion-propyl) amino]-beta-cyclomaltoheptaose, with similar functions of mitochondrial ADP/ATP carrier protein, was synthesized and harbored in the engineered α-HL (M113R)7 nanopore, forming a single-molecule biosensor for sensing bioenergetic molecules and their transformations. The strategy significantly elevates both selectivity and signal-to-noise, which enables simultaneous recognition and detection of ATP, ADP, and AMP by real-time single-molecule measurement.

Nanopore Single-Molecule Analysis of Metal Ion-Chelator Chemical Reaction.

Metal ions play critical roles in wide range of biochemical and physiological processes, but they can cause toxicity if excessive ingestion or misregulation. Chelating agents offer an efficient mean for metal ions intoxication and therapeutics of diseases. Studies on metal ion-chelator interactions are important for understanding the reaction mechanism and developing new specific metal chelator drugs. However, it remains a significant challenge to detect the metal ion-chelator interactions at the molecular level. Here, we report a label-free nanopore sensing approach that enables single-molecule investigation of the complexation process. We demonstrate that the chemical reaction between Cu2+ and carboxymethyl-ß-cyclodextrin (CMßCD) in a nanoreactor is completely different from in the bulk solution. The formation constant (Kf = 4.70 × 104 M-1) increases 14 417-fold in the nanopore than that in the bulk solution (Kf = 3.26 M-1). The bioavailable CMßCD as a natural derivative with higher affinity for Cu2+ could be used in the safe medicinal removal of toxic metal. On the basis of the different ionic current signatures across an α-hemolysin (α-HL) mutant (M113N)7 nanopore lodged with a CMßCD adaptor in the presence and absence of Cu2+, the reversible molecular binding events to CMßCD can be in situ recorded and the single-molecule thermodynamic and kinetic information can be obtained. Interestly, we found that the Cu2+ binding leads to the increase of the channel current, rather than the blocking as usual nanopore experiment. The uncommon (on/off) characteristic could be very useful for fabricating the nanodevice. Furthermore, the unique nanopore sensor can provide a highly sensitive approach for detecting metal ions.

Metal-organic complex-functionalized protein nanopore sensor for aromatic amino acids chiral recognition.

Chiral recognition at single-molecule level for small active molecules is important, as exhibited by many nanostructures and molecular assemblies in biological systems, but it presents a significant challenge. We report a simple and rapid sensing strategy to discriminate all enantiomers of natural aromatic amino acids (AAA) using a metal-organic complex-functionalized protein nanopore, in which a chiral recognition element and a chiral recognition valve were equipped. A trifunctional molecule, heptakis-(6-deoxy-6-amino)-ß-cyclodextrin (am7ßCD), was non-covalently lodged within the nanopore of an α-hemolysin (αHL) mutant, (M113R)7-αHL. Copper(ii) ion reversibly bonds to the amino group of am7ßCD to form an am7ßCD-CuII complex, which allowed chiral recognition for each enantiomer in the mixture of AAA by distinct current signals. The CuII plugging valve plays a crucial rule that holds chiral molecules in the nanocavity for a sufficient registering time. Importantly, six enantiomers of all nature AAA could be simultaneously recognized at one time. Enantiomeric excess (ee) could also be accurately detected by this approach. It should be possible to generalize this approach for sensing of other chiral molecules.

[Preparation of Human Serum Albumin Micro/Nanotubes].

In this research, protein micro/nanotubes were fabricated by alternate layer-by-layer (LbL) assembly of human serum albumin (HSA) and polyethyleneimine (PEI) into polycarbonate (PC) membranes. The experimental conditions of pH values, ionic strength, the depositions cycles and the diameter of porous membrane were discussed. The morphology and composition of tubes were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), fourier transform infrared spectroscopy (FTIR) and energy dispersive spectroscopy (EDS). The results show that pH and ionic strength of the solution are the key factors that influence the effect of assembly. Micro/nanotubes with good opening hollow tubular structure were obtained when pH 7.4 HSA solution and pH 10.3 PEI solution without NaCl were used in synthesis procedure. The outer diameter of tube was dependent on the PC template, thus the micro/nanotubes size was controlled by the wall thickness, which can be adjusted by the number of layers of the HSA and PEI deposited along the pore walls. To avoid the thin wall being damaged in dissolving the template and vacuum drying, the PEI/HSA bilayer number should not be less than 3. The polar solvent N,N-dimethylformamide (DMF) can dissolve PC template to release the micro/nanotubes.

Tetramethylammonium-filled protein nanopore for single-molecule analysis.

Nanopore technology, as the simplest and most inexpensive single-molecule tool, is being intensively developed. In nanopore stochastic sensing, KCl and NaCl have traditionally been employed as pore-filled electrolytes for recording the change of ion conductance in nanopores triggered by analyte translocation through the pore. However, some challenges limit its further advance. Here we used tetramethylammonium (TMA) chloride, instead of KCl, as a novel analysis system for nanopores. Some unique nanopore characteristics were observed: (1) The stability of the planar lipid bilayer for embedding the protein pores was elevated at least 6 times. (2) The TMA-Cl system could effectively reduce the noise of single-channel recording. (3) It was easy to control the insertion of protein pores into the lipid bilayer, and the formed single nanopore could last for a sufficiently long time. (4) TMA-Cl could be used as a DNA speed bump in the nanopore to slow DNA translocation speed. (5) The capacity of the nanopore capture of DNA (capture rate) increased significantly and simultaneously increased the translocation time of DNA in the pore. (6) The TMA-filled nanopore could discriminate between various polynucleotides.

Nanopore single-molecule analysis of DNA-doxorubicin interactions.

Anticancer activity and toxicity of doxorubicin (Dox) are associated with its DNA intercalation. To understand the role in gene regulation and the drug mechanism, it is a challenge to detect the DNA-Dox interaction at the single-molecule level without the use of laborious, time-consuming labeling assays and an error-prone amplification method. Here, we utilized the simplest and cheapest, yet highly sensitive, single-molecule nanopore technology to investigate the DNA-Dox interaction and explore in situ the intercalative reaction kinetics. Distinctive electronic signal patterns between DNA and the DNA-Dox complex allow protein nanopore to readily detect the changes in structure and function of DNA. After Dox insertion, nanopore unzipping time of DNA was elevated 10-fold while the blocking current decreased, demonstrating the higher affinity of the DNA-Dox complex (formation constant K(f) = 3.09 × 10(5) M(-1)). Continuous rapid nanopore detection in real time displayed that Dox intercalation in DNA is a two-state dynamic process: fast binding and slow conformational adaption. The nanopore platform provides a powerful tool for studying small molecule-biomacromolecule interactions and paves the way for novel applications aimed at drug screening and functional analysis.

Construct validity of the Chinese version of the Self-care of Heart Failure Index determined using structural equation modeling.

BACKGROUND: The Self-care of Heart Failure Index (SCHFI) is an empirically tested instrument for measuring the self-care of patients with heart failure. OBJECTIVE: The aim of this study was to develop a simplified Chinese version of the SCHFI and provide evidence for its construct validity. METHODS: A total of 182 Chinese with heart failure were surveyed. A 2-step structural equation modeling procedure was applied to test construct validity. RESULTS: Factor analysis showed 3 factors explaining 43% of the variance. Structural equation model confirmed that self-care maintenance, self-care management, and self-care confidence are indeed indicators of self-care, and self-care confidence was a positive and equally strong predictor of self-care maintenance and self-care management. Moreover, self-care scores were correlated with the Partners in Health Scale, indicating satisfactory concurrent validity. CONCLUSION: The Chinese version of the SCHFI is a theory-based instrument for assessing self-care of Chinese patients with heart failure.

Establishing mainstream partial nitrification in the membrane aerated biofilm reactor by limiting the oxygen concentration in the biofilm.

The proliferation of nitrite oxidizing bacteria (NOB) still remains as a major challenge for nitrogen removal in mainstream wastewater treatment process based on partial nitrification (PN). This study investigated different operational conditions to establish mainstream PN for the fast start-up of membrane aerated biofilm reactor (MABR) systems. Different oxygen controlling strategies were adopted by employing different influent NH4+-N loads and oxygen supply strategies to inhibit NOB. We indicated the essential for NOB suppression was to reduce the oxygen concentration of the inner biofilm and the thickness of aerobic biofilm. A higher NH4+-N load (7.4 g-N/(m2·d)) induced higher oxygen utilization rate (14.4 g-O2/(m2·d)) and steeper gradient of oxygen concentration, which reduced the thickness of aerobic biofilm. Employing closed-end oxygen supply mode exhibited the minimum concentration of oxygen to realize PN, which was over 46% reduction of the normal open-end oxygen mode. Under the conditions of high NH4+-N load and closed-end oxygen supply mode, the microbial community exhibited a comparative advantage of ammonium oxidizing bacteria over NOB in the aerobic biofilm, with a relative abundance of Nitrosomonas of 30-40% and no detection of Nitrospira. The optimal fast start-up strategy was proposed with open-end aeration mode in the first 10 days and closed-end mode subsequently under high NH4+-N load. The results revealed the mechanism of NOB inhibition on the biofilm and provided strategies for a quick start-up and stable mainstream PN simultaneously, which poses great significance for the future application of MABR.

Virological and Mitochondriopathogical Characteristics of the SARS-CoV-2 Omicron XBB.1.16 Spike.

The emergence of XBB.1.16 has gained rapid global prominence. Previous studies have elucidated that the infection of SARS-CoV-2 induces alterations in the mitochondrial integrity of host cells, subsequently influencing the cellular response to infection. In this study, we compared the differences in infectivity and pathogenicity between XBB.1.16 and the parental Omicron sublineages BA.1 and BA.2 and assessed their impact on host mitochondria. Our findings suggest that, in comparison with BA.1 and BA.2, XBB.1.16 exhibits more efficient spike protein cleavage, more efficient mediating syncytia formation, mild mitochondriopathy, and less pathogenicity. Altogether, our investigations suggest that, based on the mutation of key sites, XBB.1.16 exhibited enhanced infectivity but lower pathogenicity. This will help us to further investigate the biological functions of key mutation sites.

Free ammonia-free nitrous acid based partial nitrification in sequencing batch membrane aerated biofilm reactor.

Membrane aerated biofilm reactor (MABR) has attracted a lot of attention as an energy-efficient integrated nitrogen removing technology in recent years. However, it is lacking of understanding to realize stable partial nitrification in MABR because of its unique oxygen transfer mode and biofilm structure. In this study, free ammonia (FA) and free nitrous acid (FNA) based control strategies for partial nitrification with low NH4+-N concentration were proposed in a MABR of sequencing batch mode. The MABR was operated for over 500 days under different influent NH4+-N concentrations. With the influent NH4+-N of around 200 mg-N/L, partial nitrification could be established with relatively low concentration of FA (0.4-2.2 mg-N/L) which suppressed nitrite oxidizing bacteria (NOB) on the biofilm. With lower influent NH4+-N concentration of around 100 mg-N/L, the FA concentration was lower and strengthened suppression strategies based on FNA were needed. With the final pH of operating cycles below 5.0, the FNA produced in the sequencing batch MABR could stabilize partial nitrification by eliminating NOB on the biofilm. Since the activity of ammonia oxidizing bacteria (AOB) was lower without the blow-off of dissolved carbon dioxide in the bubbleless MABR, longer hydraulic retention time was required to reach a low pH for high concentration of FNA to suppress NOB. After exposures to FNA, the relative abundance of Nitrospira was decreased by 94.6%, while the abundance of Nitrosospira increased greatly which became another dominant AOB genus in addition to Nitrosomonas.

Enhanced E6AP-mediated ubiquitination of ENO1 via LINC00663 contributes to radiosensitivity of breast cancer by regulating mitochondrial homeostasis.

Radiotherapy has shown measurable efficacy in breast cancer (BC). Elucidating the mechanisms and developing effective strategies against resistance, which is a major challenge, is crucial. Mitochondria, which regulate homeostasis of the redox environment, have emerged as a radiotherapeutic target. However, the mechanism via which mitochondria are controlled under radiation remains elusive. Here, we identified alpha-enolase (ENO1), as a prognostic marker for the efficacy of BC radiotherapy. ENO1 enhances radio-therapeutic resistance in BC via reducing the production of reactive oxygen species (ROS) and apoptosis in vitro and in vivo through modulation of mitochondrial homeostasis. Moreover, LINC00663 was identified as an upstream regulator of ENO1, which regulates radiotherapeutic sensitivity by downregulating ENO1 expression in BC cells. LINC00663 regulates ENO1 protein stability by enhancing the E6AP-mediated ubiquitin-proteasome pathway. In BC patients, LINC00663 expression is negatively correlated with ENO1 expression. Among patients treated with IR, those who did not respond to radiotherapy expressed lower levels of LINC00663 than those sensitive to radiotherapy. Our work established LINC00663/ENO1 critical to regulate IR-resistance in BC. Inhibition of ENO1 with a specific inhibitor or supplement of LINC00663 could be potential sensitizing therapeutic strategies for BC.

Hsa-LINC02418/mmu-4930573I07Rik regulated by METTL3 dictates anti-PD-L1 immunotherapeutic efficacy via enhancement of Trim21-mediated PD-L1 ubiquitination.

BACKGROUND: Limited response to programmed death ligand-1 (PD-L1)/programmed death 1 (PD-1) immunotherapy is a major hindrance of checkpoint immunotherapy in non-small cell lung cancer (NSCLC). The abundance of PD-L1 on the tumor cell surface is crucial for the responsiveness of PD-1/PD-L1 immunotherapy. However, the negative control of PD-L1 expression and the physiological significance of the PD-L1 inhibition in NSCLC immunotherapy remain obscure. METHODS: Bioinformatics analysis was performed to profile and investigate the long non-coding RNAs that negatively correlated with PD-L1 expression and positively correlated with CD8+T cell infiltration in NSCLC. Immunofluorescence, in vitro PD-1 binding assay, T cell-induced apoptosis assays and in vivo syngeneic mouse models were used to investigate the functional roles of LINC02418 and mmu-4930573I07Rik in regulating anti-PD-L1 therapeutic efficacy in NSCLC. The molecular mechanism of LINC02418-enhanced PD-L1 downregulation was explored by immunoprecipitation, RNA immunoprecipitation (RIP), and ubiquitination assays. RIP, luciferase reporter, and messenger RNA degradation assays were used to investigate the m6A modification of LINC02418 or mmu-4930573I07Rik expression. Bioinformatics analysis and immunohistochemistry (IHC) verification were performed to determine the significance of LINC02418, PD-L1 expression and CD8+T cell infiltration. RESULTS: LINC02418 is a negative regulator of PD-L1 expression that positively correlated with CD8+T cell infiltration, predicting favorable clinical outcomes for patients with NSCLC. LINC02418 downregulates PD-L1 expression by enhancing PD-L1 ubiquitination mediated by E3 ligase Trim21. Both hsa-LINC02418 and mmu-4930573I07Rik (its homologous RNA in mice) regulate PD-L1 therapeutic efficacy in NSCLC via Trim21, inducing T cell-induced apoptosis in vitro and in vivo. Furthermore, METTL3 inhibition via N6-methyladenosine (m6A) modification mediated by YTHDF2 reader upregulates hsa-LINC02418 and mmu-4930573I07Rik. In patients with NSCLC, LINC02418 expression is inversely correlated with PD-L1 expression and positively correlated with CD8+T infiltration. CONCLUSION: LINC02418 functions as a negative regulator of PD-L1 expression in NSCLC cells by promoting the degradation of PD-L1 through the ubiquitin-proteasome pathway. The expression of LINC02418 is regulated by METTL3/YTHDF2-mediated m6A modification. This study illuminates the underlying mechanisms of PD-L1 negative regulation and presents a promising target for improving the effectiveness of anti-PD-L1 therapy in NSCLC.

Effects of aromatherapy on fatigue, quality of sleep and quality of life in patients with inflammatory bowel disease: A feasibility study.

BACKGROUND: Fatigue, poor sleep quality and poor quality of life (QoL) are recognised as common problems for patients with inflammatory bowel disease (IBD). This study aimed to evaluate feasibility and effect of aromatherapy on these problems in patients with IBD. METHODS: Seventy IBD patients from a tertiary hospital in China were randomly assigned to an intervention group and a control group. During the 8-week intervention, the intervention group received aromatherapy through the skin and by inhalation, and the control group received routine nursing care. All patients were administered questionnaires at two sessions-the Multidimensional Fatigue Inventory, the Inflammatory Bowel Disease Questionnaire and the Pittsburgh Sleep Quality Index-before and after the intervention. The clinical trial registration number is ChiCTR2100045889. RESULTS: Postintervention fatigue and sleep problems were relieved in the intervention group compared with the control group (P < 0.05). Moreover, QoL scores improved significantly in the intervention group (P < 0.05). CONCLUSION: These results suggested that aromatherapy may be an effective complementary treatment method to relieve fatigue and sleep problems and improve quality of life in IBD patients.