Chemical synthesis of a 28 kDa full-length PET degrading enzyme ICCG by the removable backbone modification strategy.

Chemical protein synthesis offers a powerful way to access otherwise-difficult-to-obtain proteins such as mirror-image proteins. Although a large number of proteins have been chemically synthesized to date, the acquisition to proteins containing hydrophobic peptide fragments has proven challenging. Here, we describe an approach that combines the removable backbone modification strategy and the peptide hydrazide-based native chemical ligation for the chemical synthesis of a 28 kDa full-length PET degrading enzyme IGGC (a higher depolymerization efficiency of variant leaf-branch compost cutinase (LCC)) containing hydrophobic peptide segments. The synthetic ICCG exhibits the enzymatic activity and will be useful in establishing the corresponding mirror-image version of ICCG.

Validation of healthcare professional proxy-reported children's International Mucositis Evaluation Scale.

OBJECTIVE: The objective was to describe the reliability and validity of the healthcare professional proxy-report version of the Children's International Mucositis Evaluation Scale (ChIMES). METHODS: We included pediatric patients who were between 4 and 21 years of age and scheduled to undergo hematopoietic cell transplantation. Mucositis was evaluated by trained healthcare professionals who scored ChIMES, the World Health Organization oral toxicity scale, mouth, and throat pain visual analogue scale, National Cancer Institute-Common Terminology Criteria and the Oral Mucositis Daily Questionnaire. Measures were completed daily and evaluated on days 7-17 post-stem cell infusion for this analysis. Psychometric properties examined were internal consistency, test-retest reliability (days 13 and 14), and convergent construct validity. RESULTS: There were 192 participants included. Cronbach's alpha was 0.90 for ChIMES Total Score and 0.93 for ChIMES Percentage Score. Test-retest reliability were as follows: intraclass correlation coefficient (ICC) 0.82 (95% confidence interval (CI) 0.77-0.85) for ChIMES Total Score and ICC 0.82 (95% CI 0.77-0.86) for ChIMES Percentage Score. In terms of construct validation, all correlations between measures met or exceeded those hypothesized (all p < 0.05). CONCLUSIONS: The healthcare professional proxy-report version of ChIMES is reliable and valid for children and adolescents undergoing hematopoietic cell transplantation.

[Effects of shell composition in shell-core structured nanoparticles on oral physiological barrier and bioavailability].

The present study prepared shell-core nanoparticles comprising poly(lactic-co-glycolic acid)(PLGA) cores encapsulated by shells composed of mixed lipids(Lipoid S100 and DSPE-PEG 2000) or polymer F127 to investigate the effects of shell composition on overcoming physiological barriers of gastrointestinal mucus and intestinal epithelial cells and improving bioavailability.The results are expected to provide references for the research on the improvement of the oral bioavailability of Chinese medicine by nanocar-riers. Silibinin(SLB) was used as a model drug to prepare PLGA nanoparticles coated with the shell of mixed lipids(SLB-LPNs) or F127(SLB-FPNs) via a modified nanoprecipitation method.Transmission electron microscopy showed that both LPNs and FPNs were spherical with a core-shell structure.The average particle sizes of SLB-LPNs and SLB-FPNs were(94.13±2.23) and(95.42±4.91) nm, respectively.The Zeta potential values were(-39.3±2.8) and(-17.0±0.2) mV, respectively.X-ray diffraction analysis revealed the presence of SLB in the two types of nanoparticles in a molecular or amorphous state.The ability of nanoparticles to cross both the mucus and epithelial barriers were evaluated using the cellular internalization kinetics assay.LPNs showed a higher rate of cell internalization than FPNs, indicating that LPNs could penetrate the mucus layer and become internalized by cells more rapidly.As revealed by the in vivo pharmacokinetic assay in rats with SLB suspension as the reference, the relative oral bioavailability of SLB-LPNs and SLB-FPNs was 400.37% and 923.31%, respectively.The effect of SLB-FPNs in improving oral bioavailability was more significant than that of SLB-LPNs.In summary, shell composition can influence the ability of nanoparticles to overcome oral physiological bar-riers, such as the mucus layer and intestinal epithelial cells, and improve oral bioavailability.Shell-core structured nanoparticles are promising nanocarriers for oral drug delivery systems.

Low-dose and same day use of polyethylene glycol improves image of video capsule endoscopy: A multi-center randomized clinical trial.

BACKGROUND AND AIM: Clear visualization of the small bowel is a requirement for satisfactory video capsule endoscopy (VCE). The aim of this study was to identify the optimal dose and timing of polyethylene glycol (PEG) for small bowel preparation before VCE. METHODS: A total of 410 patients were enrolled in this prospective randomized trial. All patients fasted for 12 h and ingested 320 mg simethicone 30 min before swallowing the capsule. Patients were randomized into five groups: Group A (no PEG), Group B (1-L PEG, 12 h before VCE), Group C (2-L PEG, 12 h before VCE), Group D (1-L PEG, 4 h before VCE), and Group E (2-L PEG, 4 h before VCE). The primary endpoint was small bowel visualization quality (SBVQ), and the secondary endpoints were patient acceptability and diagnosis rate of VCE. RESULTS: Excellent SBVQ was achieved in 27 (32.5%) of Group A, 38 (46.3%) of Group B, 40 (48.2%) of Group C, 55 (66.3%) of Group D, and 43 (54.4%) of Group E. The percentage of excellent SBVQ in Group D was significantly more than in Group A (66.3% vs 32.5%, P < 0.001), and diagnostic rate in the distal segment was higher (28.9% vs 10.8%, P = 0.0035). Patient acceptance of 1-L PEG was better than of 2-L PEG (P < 0.005). CONCLUSION: Small bowel cleansing with 1-L PEG given 4 h before VCE was the optimal preparation for visualization of the bowel and patient acceptance (ClinicalTrials.gov, ID: NCT02486536).

NIR-Activated "OFF/ON" Photodynamic Therapy by a Hybrid Nanoplatform with Upper Critical Solution Temperature Block Copolymers and Gold Nanorods.

Photodynamic therapy (PDT) is a promising treatment modality for cancer treatment owing to its minimally invasive nature and negligible drug resistance. However, the disadvantages of conventional photosensitizers including universal aggregation-caused quenching (ACQ) effect or nonselective activation are still major hurdles for PDT clinical application. Herein, a new strategy for flexible manipulating photosensitizers in effective quenching and quick recovery of photoactivation is presented by introducing porphyrin units into upper critical solution temperature (UCST) block copolymer decorated gold nanorods (AuNR-P(AAm-co-AN-co-TPP)-b-PEG). The UCST block copolymer can achieve a self-quenching effect to make the porphyrin photosensitizers in the "Off" state by π-π stacking and hydrogen bonding interactions at physiological temperature, which greatly minimizes the nonselective phototoxicity of the photosensitizers to meet the requirement of phototherapy protected from sunlight. After the immigration of AuNR-P(AAm-co-AN-co-TPP)-b-PEG nanoparticles into the tumor tissue and the internalization by cancer cells, the UCST polymer chains can be extended under the local heating of AuNRs by NIR light irradiation, and then porphyrin photosensitizers are turned "On" to dramatically boost the PDT efficiency. Therefore, the process of PDT could be well manipulated in the "Off/On" state by the hybrid nanoplatform with UCST block copolymers and AuNRs, which will open new horizons for clinical treatments of PDT.

Comprehensive analysis of the relationship between yield stress and dewatering performance in sludge conditioning: Insights from various treatment methods.

Understanding the relationship between sludge yield stress (σy) and dewatering performance is essential for optimizing sludge conditioning processes. This study systematically investigates the effects of various conditioning methods-including thermal hydrolysis (TH), freezing/thawing (FT), anaerobic digestion (AD), polyaluminum chloride (PAC), polyacrylamide (PAM), and Fenton treatment (Fenton)-on sludge yield stress and its correlation with dewatering efficiency. Using linear regression, partial least squares regression (PLSR), and correlation heatmap analyses, we reveal significant variations in the correlation between σy and dewatering indexes, including moisture content (Mc), capillary suction time (CST), and bound water proportion (Wb/Wt), depending on the conditioning method and intensity. Under FT and PAM conditioning, σy shows a strong negative linear correlation with dewatering performance, with Pearson's r values exceeding -0.880, indicating that a decrease in σy corresponds to improved dewatering efficiency. Conversely, AD conditioning exhibits a positive linear correlation, with r values up to 0.993, suggesting that an increase in σy correlates with reduced dewatering efficiency. For TH, PAC, and Fenton treatments, the correlation between σy and dewatering metrics is highly sensitive to changes in treatment intensity. In the PLSR analysis, the VIP values, which quantify the importance of each predictor variable, indicate that Wb/Wt in TH conditioning (VIP = 1.649) and CST in PAC (VIP = 1.309) and Fenton (VIP = 1.299) conditioning strongly influence σy. This study highlights the significant impact of conditioning methods and intensities on the correlation between σy and dewatering performance. While σy provides valuable insights as a predictive indicator, its predictive power is limited in more complex conditioning scenarios. Therefore, optimizing conditioning intensity and incorporating multiple rheological parameters are essential for achieving superior sludge dewatering outcomes.

Thermo-reversible gelation of atactic poly(methyl methacrylate) in poly(ethylene glycol) oligomers.

The temperature-concentration behavior of physical gel by atactic poly(methyl methacrylate) (aPMMA) in poly(ethylene glycol) oligomer (PEG400) was investigated. A liquid-liquid demixing interferes with a glass transition during cooling. The combination of demixing and T g leads to the formation of amorphous gels at low temperature. We suggest that the gelation of aPMMA/PEG400 is a glassy gel, in which short-range attractive depletion interaction in the polymer/oligomer system was the driving force at molecular level.

A clinically translatable kit for MRI/NMI dual-modality nanoprobes based on anchoring group-mediated radiolabeling.

Magnetic resonance imaging (MRI)/nuclear medicine imaging (NMI) dual-modality imaging based on radiolabeled nanoparticles has been increasingly exploited for accurate diagnosis of tumor and cardiovascular diseases by virtue of high spatial resolution and high sensitivity. However, significant challenges exist in pursuing truly clinical applications, including massive preparation and rapid radiolabeling of nanoparticles. Herein, we report a clinically translatable kit for the convenient construction of MRI/NMI nanoprobes relying on the flow-synthesis and anchoring group-mediated radiolabeling (LAGMERAL) of iron oxide nanoparticles. First, homogeneous iron oxide nanoparticles with excellent performance were successfully obtained on a large scale by flow synthesis, followed by the surface anchoring of diphosphonate-polyethylene glycol (DP-PEG) to simultaneously render the underlying nanoparticles biocompatible and competent in robust labeling of radioactive metal ions. Moreover, to enable convenient and safe usage in clinics, the DP-PEG modified nanoparticle solution was freeze-dried and sterilized to make a radiolabeling kit followed by careful evaluations of its in vitro and in vivo performance and applicability. The results showed that 99mTc labeled nanoprobes are effectively obtained with a labeling yield of over 95% in 30 minutes after simply injecting Na[99mTcO4] solution into the kit. In addition, the Fe3O4 nanoparticles sealed in the kit can well stand long-term storage even for 300 days without deteriorating the colloidal stability and radiolabeling yield. Upon intravenous injection of the as-prepared radiolabeled nanoprobes, high-resolution vascular images of mice were obtained by vascular SPECT imaging and magnetic resonance angiography, demonstrating the promising clinical translational value of our radiolabeling kit.

Alleviating Oxidative Injury of Myocardial Infarction by a Fibrous Polyurethane Patch with Condensed ROS-Scavenging Backbone Units.

Excessive reactive oxygen species (ROS) generated after myocardial infarction (MI) result in the oxidative injury in myocardium. Implantation of antioxidant biomaterials, without the use of any type of drugs, is very appealing for clinical translation, leading to the great demand of novel biomaterials with high efficiency of ROS elimination. In this study, a segmented polyurethane (PFTU) with a high density of ROS-scavenging backbone units is synthesized by the reaction of poly(thioketal) dithiol (PTK) and poly(propylene fumarate) diol (PPF) (soft segments), thioketal diamine (chain extender), and 1,6-hexamethylene diisocyanate (HDI). Its chemical structure is verified by gel permeation chromatography (GPC), 1 H nuclear magnetic resonance (1 H NMR) spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The electrospun composite PFTU/gelatin (PFTU/Gt) fibrous patches show good antioxidation capacity and ROS-responsive degradation in vitro. Implantation of the PFTU/gelatin patches on the heart tissue surface in MI rats consistently decreases the ROS level, membrane peroxidation, and cell apoptosis at the earlier stage, which are not observed in the non-ROS-responsive polyurethane patch. Inflammation and fibrosis are also reduced in the PFTU/gelatin-treated hearts, resulting in the reduced left ventricular remodeling and better cardiac functions postimplantation for 28 d.

Effect of polytetrafluoroethylene nanoplastics on combined inhibition of ciprofloxacin and bivalent copper on nitrogen removal, sludge activity and microbial community in sequencing batch reactor.

The work aimed to explore effects of polytetrafluoroethylene nanoplastics on joint inhibitions of ciprofloxacin and bivalent copper on the nitrogen removal in a sequencing batch reactor and its potential mechanisms. The addition of bivalent copper and/or ciprofloxacin reduced the ammonia nitrogen elimination rate with or without polytetrafluoroethylene nanoplastics. Adsorption kinetics and thermodynamics showed the binary bivalent copper and ciprofloxacin promoted their adsorptions by polytetrafluoroethylene nanoplastics. Polytetrafluoroethylene nanoplastics enhanced combined toxicities of ciprofloxacin and bivalent copper to sludge activities and microbial community involved into nitrification and denitrification due to the adsorption of ciprofloxacin and bivalent copper by polytetrafluoroethylene nanoplastics. With or without polytetrafluoroethylene nanoplastics, bivalent copper and/or ciprofloxacin caused more obvious level changes of protein than polysaccharide. This study provides novel insights for understanding the effect of combined heavy metals and antibiotics on the performance in a sequencing batch reactor with the nanoplastics stress.

Puerarin promotes the osteogenic differentiation of rat dental follicle cells by promoting the activation of the nitric oxide pathway.

Puerarin regulates the osteoblast differentiation of umbilical cord mesenchymal stem cells. This study, hereby, explored the effects of puerarin on the osteogenic differentiation of dental follicle cells (DFCs) for the first time. Rat DFCs (rDFCs) were isolated and identified. After the rDFCs were treated by Puerarin and cultured in osteogenic induction medium, the viability, osteogenic differentiation, and the activities of alkaline phosphatase (ALP) and nitric oxide (NO) were detected. Besides, the secretion of cyclic guanosine monophosphate (cGMP) and expressions of collagen I, osteocalcin (OC), osteopontin (OPN), runt-related transcription factor 2 (RUNX2), soluble guanylate cyclase (SGC), and protein kinase G 1 (PKG-1) were further determined or quantified. Puerarin enhanced the viability and osteogenic differentiation, and increased the activities of ALP, NO, and cGMP and the expressions of Collagen I, OC, OPN, RUNX2, SGC, and PKG-1 in rDFCs. After the co-treatment with puerarin and L-NMMA (NO synthase inhibitor), the promotive effects of Puerarin on cell viability, osteogenic differentiation, and the expressions of collagen I, OC, OPN, RUNX2, SGC, and PKG-1 in rDFCs were reversed by L-NMMA. Puerarin boosted the osteogenic differentiation of rDFCs by activating the NO pathway.

Inhibiting Radiative Transition-Mediated Multifunctional Polymeric Nanoplatforms for Highly Efficient Tumor Phototherapeutics.

It is highly desired to explore ideal phototherapeutic nanoplatforms, especially containing satisfactory phototherapeutic agents (PTAs), for potential cancer therapies. Herein, we proposed an effective strategy for designing a highly efficient PTA through inhibiting radiative transition (IRT). Specifically, we developed an ultralow radiative BODIPY derivative (TPA-IBDP) by simply conjugating two triphenylamine units to iodine-substituted BODIPY, which could simultaneously facilitate the nonradiative decay channels of singlet-to-triplet intersystem crossing and intramolecular charge transfer. In comparison to the normal BODIPY compound, TPA-IBDP exhibited an outstanding singlet oxygen yield (31.8-fold) and a higher photothermal conversion efficiency (PCE; over 3-fold), respectively, benefiting from the extended π-conjugated donor-to-accepter (D-A) structure and the heavy atom effect. For tumor phototherapy using TPA-IBDP, TPA-IBDP was conjugated with a H2O2-responsive amphiphilic copolymer POEGMA10-b-[PBMA5-co-(PS-N3)2] to construct a multifunctional phototherapeutic BODIPY-based nanoplatform (PB). PB produced abundant singlet oxygen (1O2) and heat along with negligible fluorescence emission under near-infrared laser irradiation. Additionally, PB could generate a GSH-depletion scavenger (quinone methide, QM) after reacting with the abundant intracellular H2O2 in tumor for the cooperative enhancement of IRT-mediated phototherapy. We envision that this highly efficient multifunctional phototherapeutic nanoplatform cooperated by GSH-depletion could be a valuable paradigm for tumor treatments.

Site-Specific PEGylation of Anti-Mesothelin Recombinant Immunotoxins Increases Half-life and Antitumor Activity.

Recombinant immunotoxins (RIT) are chimeric proteins containing an Fv that binds to tumor cells, fused to a fragment of Pseudomonas exotoxin (PE) that kills the cell. Their efficacy is limited by their short half-life in the circulation. Chemical modification with polyethylene glycol (PEG) is a well-established method to extend the half-lives of biologics. Our goal was to engineer RITs with an increase in half-life and high cytotoxic activity. We introduced single cysteines at different locations in five anti-mesothelin RITs and employed site-specific PEGylation to conjugate them to 20-kDa PEG. Because our previous PEGylation method using ß-mercaptoethanol reduction gave poor yields of PEG-modified protein, we employed a new method using tris(2-carboxyethyl)phosphine to reduce the protein and could PEGylate RITs at approximately 90% efficiency. The new proteins retained 19% to 65% of cytotoxic activity. Although all proteins are modified with the same PEG, the radius of hydration varies from 5.2 to 7.1, showing PEG location has a large effect on protein shape. The RIT with the smallest radius of hydration has the highest cytotoxic activity. The PEGylated RITs have a 10- to 30-fold increase in half-life that is related to the increase in hydrodynamic size. Biodistribution experiments indicate that the long half-life is due to delayed uptake by the kidney. Antitumor experiments show that several PEG-RITs are much more active than unmodified RIT, and the PEG location greatly affects antitumor activity. We conclude that PEGylation is a useful approach to improve the half-life and antitumor activity of RITs.

[Spectroscopy study of binding mechanisms and molecular recognition of methamidophos-specific moleculary imprinted polymer].

A new methamidophos-specific molecularly imprinted polymer (MIP) was synthesized based on non-covalent interaction. The complexes formed between MAP and MAA were evaluated by 1H NMR, FTIR and UV spectrometry. The MAP-MAA complexes of 1 : 2 mole ratio were obtained by cooperative hydrogen bonding and the complexes possessed better stabilization (K = 2.894 x 10(6) L2 x mol(-2). The Infrared spectrometry differences of the MIPs before and after saturated with MAP further indicated that there were carboxyl functional groups in the MIP, which could interact with the template by cooperative hydrogen bonding specifically.

Raman tracking the activity of urease in saliva for healthcare.

The detection of urease activity in the oral cavity is considered to be an efficient way to prevent dental caries and also to screen for helicobacter pylori infection. Herein, a rapid surface enhanced Raman scattering (SERS) method is proposed to determine the activity of urease by using inositol hexaphosphate (IP6) stabilized silver nanoparticles (AgNPs@IP6) as an efficient SERS-active substrate. The determination was achieved by monitoring the SERS peak intensity of urea at 1003 cm-1. With urease increase, the response of urea at 1003 cm-1 decreases gradually, indicating the two has good correlation. A linear relationship between the absolute value of signal drop and urease concentration is observed in a range from 2.35 to 37.5 µg/mL. In addition, the rapid SERS method was used to evaluate the activity of urease in real sample of saliva without any pretreatment, exhibiting a promising potential for biomedical application.

NIR-Triggered "OFF/ON" Photodynamic Therapy through a Upper Critical Solution Temperature Block Copolymer.

Activatable photodynamic therapy (A-PDT) has attracted great attention in precision medicine, which can be activated by endogenous or exogenous stimuli to selectively produce reactive oxygen species (ROS) at the disease site. Thermal responsive polymers with a lower critical solution temperature (LCST) have normally been utilized for constructing A-PDT system. Herein, we fabricated a photothermal activatable photosensitizer (A-PS) by the combination of thermal responsive porphyrin-containing P(AAm-co-AN-co-TPP)-b-POEGMA amphiphilic block copolymer with an upper critical solution temperature (UCST) of 42 °C and a cyanine dye of IR780. The photoactivity of porphyrin units could be severely inhibited by IR780 due to the fluorescence resonance energy transfer (FRET) from TPP to IR780 during blood circulation process ("OFF" state). After an uptake by A549 cells and then irradiated with 808 nm laser, A-PS nanoparticles were subsequently dissociated owing to the increased local temperature above the UCST of the polymer chains by excellent photothermal conversion of IR780, resulting in the enhanced photoactivity of TPP ("ON" state) and the remarkable antitumor effect. Therefore, the UCST-based A-PS extended the biological application of thermal responsive polymers, which may provide a new insight into the design of smart cancer therapeutic systems.

GSH-Activatable NIR Nanoplatform with Mitochondria Targeting for Enhancing Tumor-Specific Therapy.

Developing smart photosensitizers that are sensitive to tumor-specific signals for minimal side effects and enhanced antitumor efficacy is a tremendous challenge for tumor phototherapies. Herein, we construct a nanoplatform with glutathione (GSH)-activatable and mitochondria-targeted pro-photosensitizer encapsulated by ultrasensitive pH-responsive polymer for achieving imaging-guided tumor-specific photodynamic therapy (PDT). The GSH-activatable pro-photosensitizer, di-cyanine (DCy7), has been synthesized where two cyanine moieties are covalently conjugated by a disulfide bond, and the hydrophobic DCy7 is further encapsulated with an amphiphilic pH-responsive diblock copolymer POEGMA-b-PDPA to form P@DCy7 nanoparticles. Upon endocytosis by cancer cells, P@DCy7 nanoparticles dissociate at endosome first and then DCy7 is released to cytoplasm and subsequently activated by the high concentration of GSH, finally targets mitochondria for organelle-targeted PDT. Moreover, intracellular antioxidant GSH is consumed during the activation procedure that is beneficial to efficient PDT. These P@DCy7 nanoparticles display selective phototoxicity against tumor cells (HepG2 or 4T1 cells) over normal cells (BEAS-2B cells) in vitro, and their GSH-activatable enhanced PDT efficacy is further confirmed in tumor-bearing mice. Thus, P@DCy7 nanoparticles allow for accurate and highly efficient PDT with minimal side effects, providing an attractive nanoplatform for organelle-targeted precise PDT.

Mechanical Properties and Biological Behavior of 3D Matrices Produced by Electrospinning from Protein-Enriched Polyurethane.

Properties of matrices manufactured by electrospinning from solutions of polyurethane Tecoflex EG-80A with gelatin in 1,1,1,3,3,3-hexafluoroisopropanol were studied. The concentration of gelatin added to the electrospinning solution was shown to influence the mechanical properties of matrices: the dependence of matrix tensile strength on protein concentration is described by a bell-shaped curve and an increase in gelatin concentration added to the elasticity of the samples. SEM, FTIR spectroscopy, and mechanical testing demonstrate that incubation of matrices in phosphate buffer changes the structure of the fibers and alters the polyurethane-gelatin interactions, increasing matrix durability. The ability of the matrices to maintain adhesion and proliferation of human endothelial cells was studied. The results suggest that matrices made of 3% polyurethane solution with 15% gelatin (wt/wt) and treated with glutaraldehyde are the optimal variant for cultivation of endothelial cells.

[Spectroscopy and XPS studies on molecular recognition of a molecularly imprinted cotinine-specific polymer].

In the present study, molecular imprinting technique was used to develop a method based on noncovalent interaction for the systhesis of a cotinine-specific polymer. The molecular recognition characteristics of the template polymer were evaluated by UV, IR, XPS and 1H NMR. The results indicated that the interactions should be cooperative hydrogen bonds produced by self-assembling of the template and the monomer. The stoichiometric mole ratio of COT-MAA complex is 1 : 2. Furthermore, nitrogen atom of the pyridine ring and oxygen atom of the lactam group in cotinine molecular are hydrogen-bond acceptors, being the predominant binding sites interacting with the functional monomer.

Optimal use of polyethylene glycol for preparation of small bowel video capsule endoscopy: a network meta-analysis.

OBJECTIVE: Standardized strategy of bowel preparation before video capsule endoscopy (VCE) remains controversial. This study aimed to assess the ideal dose of PEG, based on small bowel visualization quality (SBVQ), diagnostic yield (DY), and complete rate (CR) of VCE using a network meta-analysis (NMA) of randomized controlled trials (RCTs). METHODS: This NMA included RCTs comparing any of the following bowel preparation interventions for VCE: fasting overnight ("Fast"), 1 liter PEG ("PEG 1L"), 2-liter PEG ("PEG 2L"), or 4-liter PEG ("PEG 4L"). The authors searched papers in PubMed, Cochrane Library, and Embase as of June 2016. The cumulative ranking (SUCRA) probabilities to rank different doses of PEG and Fast were used. RESULTS: The search engine provided 102 studies. Nine RCTs including 982 patients were incorporated into this analysis. All studies showed low risk of bias of blinding. SUCRA provided an initial ranking among these strategies, in which PEG 2 L showed the best score in SBVQ (PEG 2 L, 89.4%; PEG 1 L, 62.5%; PEG 4 L, 44.0%; Fast, 4.1%) and DY (PEG 2 L, 74.6%; PEG 1 L 28.1%; PEG 4 L 65.9%; Fast 31.4%) of VCE. No significant difference was shown in the analysis of CR. CONCLUSIONS: This study recommends PEG 2 L as the ideal dose, which may improve the SBVQ of VCE and, therefore, diagnostic accuracy. Multi-center randomized controlled trials are required to verify these findings.