FMRP phosphorylation modulates neuronal translation through YTHDF1.

RNA-binding proteins (RBPs) control messenger RNA fate in neurons. Here, we report a mechanism that the stimuli-induced neuronal translation is mediated by phosphorylation of a YTHDF1-binding protein FMRP. Mechanistically, YTHDF1 can condense with ribosomal proteins to promote the translation of its mRNA targets. FMRP regulates this process by sequestering YTHDF1 away from the ribosome; upon neuronal stimulation, FMRP becomes phosphorylated and releases YTHDF1 for translation upregulation. We show that a new small molecule inhibitor of YTHDF1 can reverse fragile X syndrome (FXS) developmental defects associated with FMRP deficiency in an organoid model. Our study thus reveals that FMRP and its phosphorylation are important regulators of activity-dependent translation during neuronal development and stimulation and identifies YTHDF1 as a potential therapeutic target for FXS in which developmental defects caused by FMRP depletion could be reversed through YTHDF1 inhibition.

Selective PPARγ modulator diosmin improves insulin sensitivity and promotes browning of white fat.

Peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of adipocyte differentiation, glucolipid metabolism, and inflammation. Thiazolidinediones are PPARγ full agonists with potent insulin-sensitizing effects, whereas their oral usage is restricted because of unwanted side effects, including obesity and cardiovascular risks. Here, via virtual screening, microscale thermophoresis analysis, and molecular confirmation, we demonstrate that diosmin, a natural compound of wide and long-term clinical use, is a selective PPARγ modulator that binds to PPARγ and blocks PPARγ phosphorylation with weak transcriptional activity. Local diosmin administration in subcutaneous fat (inguinal white adipose tissue [iWAT]) improved insulin sensitivity and attenuated obesity via enhancing browning of white fat and energy expenditure. Besides, diosmin ameliorated inflammation in WAT and liver and reduced hepatic steatosis. Of note, we determined that iWAT local administration of diosmin did not exhibit obvious side effects. Taken together, the present study demonstrated that iWAT local delivery of diosmin protected mice from diet-induced insulin resistance, obesity, and fatty liver by blocking PPARγ phosphorylation, without apparent side effects, making it a potential therapeutic agent for the treatment of metabolic diseases.

High-Throughput-Methyl-Reading (HTMR) assay: a solution based on nucleotide methyl-binding proteins enables large-scale screening for DNA/RNA methyltransferases and demethylases.

Epigenetic therapy has significant potential for cancer treatment. However, few small potent molecules have been identified against DNA or RNA modification regulatory proteins. Current approaches for activity detection of DNA/RNA methyltransferases and demethylases are time-consuming and labor-intensive, making it difficult to subject them to high-throughput screening. Here, we developed a fluorescence polarization-based 'High-Throughput Methyl Reading' (HTMR) assay to implement large-scale compound screening for DNA/RNA methyltransferases and demethylases-DNMTs, TETs, ALKBH5 and METTL3/METTL14. This assay is simple to perform in a mix-and-read manner by adding the methyl-binding proteins MBD1 or YTHDF1. The proteins can be used to distinguish FAM-labelled substrates or product oligonucleotides with different methylation statuses catalyzed by enzymes. Therefore, the extent of the enzymatic reactions can be coupled with the variation of FP binding signals. Furthermore, this assay can be effectively used to conduct a cofactor competition study. Based on the assay, we identified two natural products as candidate compounds for DNMT1 and ALKBH5. In summary, this study outlines a powerful homogeneous approach for high-throughput screening and evaluating enzymatic activity for DNA/RNA methyltransferases and demethylases that is cheap, easy, quick, and highly sensitive.

Hierarchical MoN@NiFe-LDH Heterostructure Nanowire Array for Highly Efficient Electrocatalytic Hydrogen Evolution.

The slow charge transfer and high energy barrier are the key restrictions of cost-effective electrocatalysts for hydrogen production. A hierarchical heterostructure of MoN@NiFe-layered double hydroxides (LDH) is developed, with NiFe-LDH nanosheets supported on MoN nanowire arrays. The as-prepared MoN@NiFe-LDH exhibits a remarkably high performance on hydrogen production in alkaline medium, which is close to the benchmark Pt/C. The theoretical computations indicate that MoN@NiFe-LDH has a metallic character inherited from MoN, which gives rise to the promoted charge transfer. Furthermore, the adsorption intensity of intermediates on MoN@NiFe-LDH is optimized and thereby the energy barrier is diminished. This work demonstrates the significance of constructing heterostructure for boosting the charge transfer and reducing the energy barrier, which can shed light on the development of highly efficient and low-cost electrocatalyst for hydrogen production.

Molecular Insights into the Improved Bioactivity of Interferon Conjugates Attached to a Helical Polyglutamate.

Attaching polymers, especially polyethylene glycol (PEG), to protein drugs has emerged as a successful strategy to prolong circulation time in the bloodstream. The hypothesis is that the flexible chain wobbles on the protein's surface, thus resisting potential nonspecific adsorption. Such a theoretical framework may be challenged when a helical polyglutamate is used to conjugate with target proteins. In this study, we investigated the structure-activity relationships of polyglutamate-interferon conjugates P(EG3Glu)-IFN using molecular simulations. Our results show that the local crowding effect induced by oligoethylene glycols (i.e., EG3) is the primary driving force for helix formation in P(EG3Glu), and its helicity can be effectively increased by reducing the free volume of the two termini. Furthermore, it was found that the steric hindrance induced by IFN is not conductive to the helicity of P(EG3Glu) but contributes to its dominant orientation relative to interferon. The orientation of IFN relative to the helical P(EG3Glu) can help to protect the protein drug from neutralizing antibodies while maintaining its bioactivity. These findings suggest that the helical structure and its orientation are critical factors to consider when updating the theoretical framework for protein-polymer conjugates.

ERRα contributes to HDAC6-induced chemoresistance of osteosarcoma cells.

Chemotherapy resistance is an important problem for clinical therapy of osteosarcoma (OS). The potential effects of histone deacetylases (HDACs) on OS chemoresistance are studied. The expression of HDACs in OS cells resistance to doxorubicin (Dox) and cisplatin (CDDP) is checked. Among 11 members of HDACs, levels of HDAC6 are significantly upregulated in OS cells resistance to Dox and CDDP. Inhibition of HDAC6 via its specific inhibitor ACY1215 restores chemosensitivity of OS-resistant cells. Further, HDAC6 directly binds with estrogen-related receptors alpha (ERRα) to regulate its acetylation and protein stability. Inhibition of ERRα further strengthens ACY1215-increased chemosensitivity of OS-resistant cells. Mechanistically, K129 acetylation is the key residue for HDAC6-regulated protein levels of ERRα. Collectively, we find that ERRα contributes to HDAC6-induced chemoresistance of OS cells. Inhibition of HDAC6/ERRα axis might be a potential approach to overcome chemoresistance and improve therapy efficiency for OS treatment. 1. HDAC6 was significantly upregulated in Dox and CDDP resistant OS cells; 2. Inhibition of HDAC6 can restore chemosensitivity of OS cells; 3. HDAC6 binds with ERRα at K129 to decrease its acetylation and increase protein stability; 4. ERRα contributes to HDAC6-induced chemoresistance of OS cells.

Association between different MAP levels and 30-day mortality in sepsis patients: a propensity-score-matched, retrospective cohort study.

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by the infection-related host response disorder. Adequate mean arterial pressure is an important prerequisite of tissue and organ perfusion, which runs through the treatment of sepsis patients, and an appropriate mean arterial pressure titration in the early-stage correlates to the positive outcome of the treatment. Therefore, in the present study, we aimed to elucidate the relationship between early mean arterial pressure levels and short-term mortality in sepsis patients. METHODS: We included all suspected sepsis patients from MIMIC-III database with average mean arterial pressure ≥ 60 mmHg on the first day of intensive care unit stay. Those patients were then divided into a permissive low-mean arterial pressure group (60-65 mmHg) and a high-mean arterial pressure group (> 65 mmHg). Multivariate Cox regression analysis was conducted to analyze the relationship between MAP level and 30-day, 60-day, and 100-day mortality of suspected sepsis patients in the two groups. Propensity score matching, inverse probability of treatment weighing, standardized mortality ratio weighting, PA weighting, overlap weighting, and doubly robust analysis were used to verify our results. RESULTS: A total of 14,031 suspected sepsis patients were eligible for inclusion in our study, among which 1305 (9.3%) had an average first-day mean arterial pressure of 60-65 mmHg, and the remaining 12,726 patients had an average first-day mean arterial pressure of more than 65 mmHg. The risk of 30-day mortality was reduced in the high mean arterial pressure group compared with the permissive low-mean arterial pressure group (HR 0.67 (95% CI 0.60-0.75; p < 0.001)). The higher mean arterial pressure was also associated with lower 60-day and 100-day in-hospital mortality as well as with shorter duration of intensive care unit stay. Patients in the high-mean arterial pressure group also had more urine output on the first and second days of intensive care unit admission. CONCLUSIONS: After risk adjustment, the initial mean arterial pressure of above 65 mmHg was associated with reduced short-term mortality, shorter intensive care unit stay, and higher urine volume in the first two days among patients with sepsis.

IGF2BP1-regulated expression of ERRα is involved in metabolic reprogramming of chemotherapy resistant osteosarcoma cells.

Doxorubicin (Dox) is the standard treatment approach for osteosarcoma (OS), while acquired drug resistance seriously attenuates its treatment efficiency. The present study aimed to investigate the potential roles of metabolic reprogramming and the related regulatory mechanism in Dox-resistant OS cells. The results showed that the ATP levels, lactate generation, glucose consumption and oxygen consumption rate were significantly increased in Dox-resistant OS cells compared with parental cells. Furthermore, the results revealed that the increased expression of estrogen-related receptor alpha (ERRα) was involved in metabolic reprogramming in chemotherapy resistant OS cells, since targeted inhibition of ERRα restored the shifting of metabolic profiles. Mechanistic analysis indicated that the mRNA stability, rather than ERRα transcription was markedly increased in chemoresistant OS cells. Therefore, it was hypothesized that the 3'-untranslated region of ERRα mRNA was methylated by N6-methyladenine, which could further recruit insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress mRNA decay and increase mRNA stability. IGF2BP1 knockdown downregulated ERRα and reversed the metabolic alteration of resistant OS cells. Additionally, the oncogenic effect of the IGF2BP1/ERRα axis on Dox-resistant OS cells was verified by in vitro and in vivo experiments. Clinical analysis also revealed that the expression levels of IGF2BP1 and ERRα were associated with the clinical progression of OS. Collectively, the current study suggested that the IGF2BP1/ERRα axis could regulate metabolic reprogramming to contribute to the chemoresistance of OS cells.

Sequence Effect of Peptide-Based Materials on Delivering Interferon-α (IFN-α): A Molecular Dynamic Perspective.

Peptide-based biomaterials exhibit great potentials in developing drug delivery platforms due to their biocompatibility and biodegradability beyond poly(ethylene glycol). How different amino acids in peptides used for delivery play their roles is still unclear at the microscopic level. This work compared the assembly behaviors of a series of peptides around interferon-α (IFN-α). Through all-atom molecular simulations, the sequence effect of peptides on delivering interferon-α was quantitively characterized. The hydrophobic elastin-like peptide (VPGAG)n preferred to self-aggregate into dense clusters, rather than encapsulate IFN-α. The hydrophilic zwitterionic peptides with repeating unit "KE" tended to phase-separate from IFN-α in the mixture. In contrast, peptides with a hybrid sequence, i.e., (VPKEG)n, exhibited the highest contact preference, and the formed protective shell endowed IFN-α with better thermal stability and stealth property and achieved a subtle balance between protecting IFN-α and subsequent releasing. Further energy decomposition analysis revealed that the positively charged Lys contributed most to the binding affinity while the negatively charged Glu contributed most to the hydrophilic property of peptide-based materials. In summary, this article reveals why peptides composed of repeating hydrophobic and charged residues could be a potential choice for delivering therapeutic proteins in the form of solution.

Arsenic trioxide increases apoptosis of SK-N-BE (2) cells partially by inducing GPX4-mediated ferroptosis.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial tumor in central nervous system threatening children's health with limited therapeutic options. Arsenic trioxide (ATO) has been identified the cytotoxicity in NB cells but the potential mechanism remains unclear. In this study, we attempted to obtain some insight into the mechanisms of cell death induced by ATO in NB cells. METHODS AND RESULTS: Proteomic analyses found that ATO can affect the signaling pathway associated with ferroptosis, including the upregulation of iron absorption (FTL, FTH1, HO-1), ferritinophagy (LC3, P62, ATG7, NCOA4) and modifier of glutathione synthesis (GCLM); downregulation of glutamine synthetase (GS) and GPX4, which was the critical inhibitor of ferroptosis. Western blot analysis revealing GPX4 expression in SK-N-BE (2) cells decreased after treatment with ATO (7.3 µM), resulting in a loss of GPX4 activity. Furthermore, Ferroptosis inhibitor ferrostatin-1 partially blocked ATO-induced cell death. CONCLUSIONS: Our study revealed that ATO may induce ferroptosis in neuroblastoma cell SK-N-BE (2) by facilitating the downregulation of GPX4, ultimately resulting in iron-dependent oxidative death.

Incidence of postoperative symptomatic spinal epidural hematoma requiring surgical evacuation: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to determine the incidence of symptomatic spinal epidural hematoma (SSEH) following spine surgery. METHODS: We systematically searched for all relevant articles that mentioned the incidence of SSEH following the spine surgery published in the PubMed, Embase, and Cochrane Library databases through March 2022 and manually searched the reference lists of included studies. The Newcastle-Ottawa quality assessment scale (NOS) was used to assess the quality of the included studies. A fixed-effects or random-effects model was performed to calculate the pooled incidence of the totality and subgroups based on the heterogeneity. The potential publication bias was assessed by Egger's linear regression and a funnel plot. Sensitivity analysis was also conducted. RESULTS: A total of 40 studies were included in our meta-analysis based on our inclusion and exclusion criteria. The overall pooled incidence of SSEH was 0.52% (95% CI 0.004-0.007). In the subgroup analysis, the pooled incidence of SSEH in males and females was 0.86% (95% CI 0.004-0.023) and 0.68% (95% CI 0.003-0.017). Among the different indications, a higher incidence (2.9%, 95% CI 0.006-0.084) was found in patients with deformity than degeneration (1.12%, 95% CI 0.006-0.020) and tumor (0.30%, 95% CI 0.006-0.084). For different surgical sites, the incidences of SSEH in cervical, thoracic and lumbar spine were 0.32% (95% CI 0.002-0.005), 0.84% (95% CI 0.004-0.017) and 0.63% (95% CI 0.004-0.010), respectively. The incidences of SSEH in anterior and posterior approach were 0.24% (95% CI 0.001-0.006) and 0.70% (95% CI 0.004-0.011), respectively. The pooled incidence of SSEH was five times higher with minimally invasive surgery (1.94%, 95% CI 0.009-0.043) than with open surgery (0.42%, 95% CI 0.003-0.006). Delayed onset of SSEH had a lower incidence of 0.16% (95% CI 0.001-0.002) than early onset. There were no significant variations in the incidence of SSEH between patients who received perioperative anticoagulation therapy and those who did not or did not report getting chemopreventive therapy (0.44%, 95% CI 0.006-0.084 versus 0.42%, 95% CI 0.003-0.006). CONCLUSION: We evaluated the overall incidence proportion of SSEH after spine surgery and performed stratified analysis, including sex, surgical indication, site, approach, minimally invasive surgery, and delayed onset of SSEH. Our research would be helpful for patients to be accurately informed of their risk and for spinal surgeons to estimate the probability of SSEH after spine surgery.

Identification and analyses of inhibitors targeting apolipoprotein(a) kringle domains KIV-7, KIV-10, and KV provide insight into kringle domain function.

Increased plasma concentrations of lipoprotein(a) (Lp(a)) are associated with an increased risk for cardiovascular disease. Lp(a) is composed of apolipoprotein(a) (apo(a)) covalently bound to apolipoprotein B of low-density lipoprotein (LDL). Many of apo(a)'s potential pathological properties, such as inhibition of plasmin generation, have been attributed to its main structural domains, the kringles, and have been proposed to be mediated by their lysine-binding sites. However, available small-molecule inhibitors, such as lysine analogs, bind unselectively to kringle domains and are therefore unsuitable for functional characterization of specific kringle domains. Here, we discovered small molecules that specifically bind to the apo(a) kringle domains KIV-7, KIV-10, and KV. Chemical synthesis yielded compound AZ-05, which bound to KIV-10 with a Kd of 0.8 µm and exhibited more than 100-fold selectivity for KIV-10, compared with the other kringle domains tested, including plasminogen kringle 1. To better understand and further improve ligand selectivity, we determined the crystal structures of KIV-7, KIV-10, and KV in complex with small-molecule ligands at 1.6-2.1 Å resolutions. Furthermore, we used these small molecules as chemical probes to characterize the roles of the different apo(a) kringle domains in in vitro assays. These assays revealed the assembly of Lp(a) from apo(a) and LDL, as well as potential pathophysiological mechanisms of Lp(a), including (i) binding to fibrin, (ii) stimulation of smooth-muscle cell proliferation, and (iii) stimulation of LDL uptake into differentiated monocytes. Our results indicate that a small-molecule inhibitor targeting the lysine-binding site of KIV-10 can combat the pathophysiological effects of Lp(a).

Flexible and Filter-Free Color-Imaging Sensors with Multicomponent Perovskites Deposited Using Enhanced Vapor Technology.

Halide perovskites are promising photoactive materials for filter-free color-imaging sensors owing to their outstanding optoelectronic properties, tunable bandgaps, and suitability for large-scale fabrication. However, producing patterned perovskite films of sufficiently high quality for such applications poses a challenge for existing fabrication methods: using solution processes to prepare patterned perovskite films is complicated, while evaporation methods often result in perovskite photodetectors with limited performance. In this paper, the authors report the development of an improved evaporation method in which substrates are treated with a brominated (3-aminopropyl) triethoxysilane self-assembled monolayer to improve the properties of the patterned perovskite films. The resulting perovskite photodetectors exhibit significantly enhanced photosensitivity and long-term stability (exceeding 100 days). Additionally, the polymer substrates facilitate device flexibility. Finally, perovskites comprising three different halide components, each with a different bandgap, are integrated into a device array using the developed evaporation technology, yielding sensors that enable the discrimination of red, green, and blue colors. Thus, the flexible photosensor arrays can generate colorful images closely resembling perceived patterns, demonstrating reliable color imaging. Therefore, this study successfully demonstrates filter-free color-imaging by integrating high-performance patterned and multicomponent perovskite photodetectors, highlighting the potential of such detectors for advanced optoelectronic applications, including hyperspectral imaging.

Discovery of a novel 53BP1 inhibitor through AlphaScreen-based high-throughput screening.

Tumor suppressor p53-binding protein 1 (53BP1), a tantem tudor domain (TTD) protein, takes part in DNA Damage Repair (DDR) pathways through the specific recognition of lysine methylation on histones. The dysregulation of 53BP1 is closely related to the development of many diseases including cancer. Moreover, recent studies found that deficiency of 53BP1 could increase the efficiency of precise CRISPR/Cas9 genome editing. Thus, discovery of inhibitor is beneficial to the study of biological functions of 53BP1 and the application of CRISPR/Cas9 genome editing. UNC2170 and its derivatives have been reported as 53BP1 targeted small molecular inhibitors with modest activities. Hence, to discover better 53BP1 inhibitors, we conducted an AlphaScreen assay based high-throughput screening (HTS) and identified a novel and effective 53BP1-TTD inhibitor DP308 which disrupts the binding between 53BP1 and H4K20me2 peptide with an IC50 value of 1.69 ± 0.73 µM. Both Microscale Themophoresis (MST) and Surface Plasmon Resonance (SPR) assays confirmed the direct binding between DP308 and 53BP1-TTD protein with binding affinity (Kd) of about 2.7 µM. Molecular docking studies further suggested that DP308 possibly occupies the H4K20me2 binding pocket of the 53BP1-TTD aromatic cage. These results demonstrated that DP308 is a promising small molecule inhibitor for further optimization towards a more potent chemical probe of 53BP1. Additionally, it could be a potential valuable tool for applying to gene editing therapy by increasing the efficiency of CRISPR/Cas9 genome editing.

Identification of novel GPR81 agonist lead series for target biology evaluation.

GPR81 is a novel drug target that is implicated in the control of glucose and lipid metabolism. The lack of potent GPR81 modulators suitable for in vivo studies has limited the pharmacological characterization of this lactate sensing receptor. We performed a high throughput screen (HTS) and identified a GPR81 agonist chemical series containing a central acyl urea scaffold linker. During SAR exploration two additional new series were evolved, one containing cyclic acyl urea bioisosteres and another a central amide bond. These three series provide different selectivity and physicochemical properties suitable for in-vivo studies.

Discovery of novel CBP bromodomain inhibitors through TR-FRET-based high-throughput screening.

The cAMP-responsive element binding protein (CREB) binding protein (CBP) and adenoviral E1A-binding protein (P300) are two closely related multifunctional transcriptional coactivators. Both proteins contain a bromodomain (BrD) adjacent to the histone acetyl transferase (HAT) catalytic domain, which serves as a promising drug target for cancers and immune system disorders. Several potent and selective small-molecule inhibitors targeting CBP BrD have been reported, but thus far small-molecule inhibitors targeting BrD outside of the BrD and extraterminal domain (BET) family are especially lacking. Here, we established and optimized a TR-FRET-based high-throughput screening platform for the CBP BrD and acetylated H4 peptide. Through an HTS assay against an in-house chemical library containing 20 000 compounds, compound DC_CP20 was discovered as a novel CBP BrD inhibitor with an IC50 value of 744.3 nM. This compound bound to CBP BrD with a KD value of 4.01 µM in the surface plasmon resonance assay. Molecular modeling revealed that DC_CP20 occupied the Kac-binding region firmly through hydrogen bonding with the conserved residue N1168. At the celluslar level, DC_CP20 dose-dependently inhibited the proliferation of human leukemia MV4-11 cells with an IC50 value of 19.2 µM and markedly downregulated the expression of the c-Myc in the cells. Taken together, the discovery of CBP BrD inhibitor DC_CP20 provides a novel chemical scaffold for further medicinal chemistry optimization and a potential chemical probe for CBP-related biological function research. In addition, this inhibitor may serve as a promising therapeutic strategy for MLL leukemia by targeting CBP BrD protein.

Oestrogen-related receptor alpha mediates chemotherapy resistance of osteosarcoma cells via regulation of ABCB1.

Chemotherapy resistance is one of the major challenges for the treatment of osteosarcoma (OS). The potential roles of oestrogenic signals in the chemoresistance of OS cells were investigated. As compare to the parental cells, the doxorubicin and cisplatin (CDDP) resistant OS cells had greater levels of oestrogen-related receptors alpha (ERRα). Targeted inhibition of ERRα by its specific siRNAs or inverse agonist XCT-790 can restore the sensitivity of OS resistant cells to chemotherapy. This might be due to that si-ERRα can decrease the expression of P-glycoprotein (P-gp, encoded by ABCB1), one important ABC membrane transporter for drug efflux. XCT-790 can decrease the transcription and mRNA stability of ABCB1, while had no effect on protein stability of P-gp. ERRα can bind to the transcription factor of SP3 to increase the transcription of ABCB1. Furthermore, XCT-790 treatment decreased the expression of miR-9, which can bind to the 3'UTR of ABCB1 and trigger its decay. Collectively, we found that ERRα can regulate the chemoresistance of OS cells via regulating the transcription and mRNA stability of ABCB1. Targeted inhibition of ERRα might be a potential approach for OS therapy.

Recent Advances in Methylation: A Guide for Selecting Methylation Reagents.

Methylation is a well-known structural modification in organic and medicinal chemistry. This review summarizes recent advances in methylation by categorizing specific methylation reagents. The challenges of mono N-methylation of aliphatic amines and N-methylation of peptides are discussed. This review will be useful for chemists wanting to select the appropriate reagents for methylation chemistry. Based on the large diversity of methylation reagents and their wide scope, this review also broadens perspectives on which strategies to select for utilizing a particular methylation, resulting in an increased flexibility in synthetic route planning.

Protecting Enzymatic Activity via Zwitterionic Nanocapsulation for the Removal of Phenol Compound from Wastewater.

Horseradish peroxidase (HRP) holds great potential in wastewater treatment. However, its instability in harsh environments remains a major issue. Various immobilization technologies were developed to retain enzyme stability at the cost of its effectiveness. We demonstrate that zwitterionic encapsulation of HRP retained both protein stability and activity to a large degree. In a water treatment study, encapsulating HRP into a zwitterionic nanogel resulted in a three-fold increase in the catalytic oxidation efficiency of phenol molecules. In addition, zwitterionic nanocapsules exhibited the best performance when compared with nanocapsules made from other hydrophilic polymers. These results indicated that zwitterionic HRP nanocapsules hold great potential in the decontamination of organic pollutants from wastewater.