Human cytomegalovirus infection impairs neural differentiation via repressing sterol regulatory element binding protein 2-mediated cholesterol biosynthesis.

Congenital human cytomegalovirus (HCMV) infection is a major cause of abnormalities and disorders in the central nervous system (CNS) and/or the peripheral nervous system (PNS). However, the complete pathogenesis of neural differentiation disorders caused by HCMV infection remains to be fully elucidated. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells (MSCs) with a high proliferation and neurogenic differentiation capacity. Since SHEDs originate from the neural crest of the early embryonic ectoderm, SHEDs were hypothesized to serve as a promising cell line for investigating the pathogenesis of neural differentiation disorders in the PNS caused by congenital HCMV infection. In this work, SHEDs were demonstrated to be fully permissive to HCMV infection and the virus was able to complete its life cycle in SHEDs. Under neurogenic inductive conditions, HCMV infection of SHEDs caused an abnormal neural morphology. The expression of stem/neural cell markers was also disturbed by HCMV infection. The impairment of neural differentiation was mainly due to a reduction of intracellular cholesterol levels caused by HCMV infection. Sterol regulatory element binding protein-2 (SREBP2) is a critical transcription regulator that guides cholesterol synthesis. HCMV infection was shown to hinder the migration of SREBP2 into nucleus and resulted in perinuclear aggregations of SREBP2 during neural differentiation. Our findings provide new insights into the prevention and treatment of nervous system diseases caused by congenital HCMV infection.

Controllable Blue Shift and Enhancement Emission during the Gradually Increasing Molecular Weight of Polyacrylamide.

Nonconventional luminescent polymers have become research hotspots due to their advantages such as persistent room temperature phosphorescence (p-RTP) emission and strong film-forming properties. It is proven that the molecular weight (MW) of such luminescent polymers has a significant impact on their emission over a large range, generally with a red shift as the MW increases. Herein, four controllable MW polyacrylamides are prepared via reversible addition-fragmentation chain transfer polymerization (RAFT), and their photoluminescence quantum yield and p-RTP lifetimes gradually increase with the increasing MW. The emission of p-RTP gradually shifts blue with increasing MW, which is likely due to the gradually changing interactions between the electron-rich portion in RAFT reagent and the increasing acrylamide (AM) units in the molecular chain. These can be reasonably explained through small angle X-ray scattering, the clustering-triggered emission (CTE) mechanism, and supported by theoretical calculations. Powder with controllable p-RTP capability has the potential for strategic anti-counterfeiting encryption. The above results not only promote the development of the CTE mechanism toward more precise explanations but also provide new ideas for the preparation of nonconventional luminescent polymers with controllable p-RTP emission performance.

Nonadjacent Wireless Electrotherapy for Tissue Repair by a 3D-Printed Bioresorbable Fully Soft Triboelectric Nanogenerator.

Electrotherapy is a promising tissue repair technique. However, electrotherapy devices are frequently complex and must be placed adjacent to injured tissue, thereby limiting their clinical application. Here, we propose a general strategy to facilitate tissue repair by modulating endogenous electric fields with nonadjacent (approximately 44 mm) wireless electrotherapy through a 3D-printed entirely soft and bioresorbable triboelectric nanogenerator based stimulator, without any electrical accessories, which has biomimetic mechanical properties similar to those of soft tissue. In addition, the feasibility of using the stimulator to construct an electrical double layer with tissue for nonadjacent wireless electrotherapy was demonstrated by skin and muscle injury models. The treated groups showed significantly improved tissue repair compared with the control group. In conclusion, we developed a promising electrotherapy strategy and may inspire next-generation electrotherapy for tissue repair.

Combined impacts of microplastics and cadmium on the liver function, immune response, and intestinal microbiota of crucian carp (Carassius carassius).

Microplastics (MPs) and the heavy metal cadmium (Cd) have attracted global attention for their toxicological interactions in aquatic organisms. The purpose of this investigation was evaluating the effect of MPs (1 mg L-1) and Cd (5 mg L-1) on the liver function, immune response of crucian carp (Carassius carassius) after 96 h exposure, and intestinal microbiota after 21 days, respectively. Co-exposure to MPs and Cd significantly enhanced MP accumulation in the liver of the crucian carp compared to the accumulation with exposure to MPs alone. Co-exposure to MPs and Cd triggered notable histopathological alterations accompanied by increased hepatic cell necrosis and inflammation, and was associated with higher aspartate aminotransferase and alanine aminotransferase levels, lower superoxide dismutase and catalase activity levels, but higher malondialdehyde content and total antioxidant capacity in the liver. Moreover, the combined treatment of MPs and Cd led to the up-regulated transcription of genes related to immune response, such as interleukin 8 (il-8), il-10, il-1ß, tumor necrosis factor-α, and heat shock protein 70, both in the liver and spleen. Co-exposure to MPs and Cd reduced the variety and abundance of the intestinal microbiota in the crucian carp. Our research indicates that the combined exposure to MPs and Cd may exert synergistic toxic effects on crucian carp, which could impede the sustainable growth of the aquaculture industry and pose potential risks to food safety.

Application of Biomedical Microspheres in Wound Healing.

Tissue injury, one of the most common traumatic injuries in daily life, easily leads to secondary wound infections. To promote wound healing and reduce scarring, various kinds of wound dressings, such as gauze, bandages, sponges, patches, and microspheres, have been developed for wound healing. Among them, microsphere-based tissue dressings have attracted increasing attention due to the advantage of easy to fabricate, excellent physicochemical performance and superior drug release ability. In this review, we first introduced the common methods for microspheres preparation, such as emulsification-solvent method, electrospray method, microfluidic technology as well as phase separation methods. Next, we summarized the common biomaterials for the fabrication of the microspheres including natural polymers and synthetic polymers. Then, we presented the application of the various microspheres from different processing methods in wound healing and other applications. Finally, we analyzed the limitations and discussed the future development direction of microspheres in the future.

Feasibility study on Ti-15Mo-7Cu with low elastic modulus and high antibacterial property.

Titanium and titanium alloy with low density, high specific strength, good biological, excellent mechanical compatibility and easy to process have been widely used in the medical materials, but their application in orthopedics and dentistry often face bacterial infection, corrosion failure and stress shielding. In this paper, Ti-15Mo-7Cu (TM-7Cu) alloy was prepared by high vacuum non-consumable electric arc melting furnace and then treated by solution and aging treatment. The microstructure, mechanical properties, antibacterial properties and cytocompatibility were studied by X-ray diffraction, microhardness tester, electrochemical working station, antibacterial test and Live/Dead staining technology. The results have shown that the heat treatment significantly influenced the phase transformation, the precipitation of Ti2Cu phase, the elastic modulus and the antibacterial ability. With the extension of the aging time, the elastic modulus slightly increased and the antibacterial rate obviously increased. TM-7Cu alloy with a low elastic modulus of 83GPa and a high antibacterial rate of > 93% was obtained. TM-7Cu alloy showed no cytotoxicity to MC3T3. It was suggested that TM-7Cu might be a highly competitive medical material.

Molecular Origin of the Biologically Accelerated Mineralization of Hydroxyapatite on Bacterial Cellulose for More Robust Nanocomposites.

Biomineralization generates hierarchically structured minerals with vital biological functions in organisms. This strategy has been adopted to construct complex architectures to achieve similar functionalities, mostly under chemical environments mimicking biological components. The molecular origin of the biofacilitated mineralization process is elusive. Herein, we describe the mineralization of hydroxyapatite (HAp) accompanying the biological secretion of nanocellulose by Acetobacter xylinum. In comparison with mature cellulose, the newly biosynthesized cellulose molecules greatly accelerate the nucleation rate and facilitate the uniform distribution of HAp crystals, thereby generating composites with a higher Young modulus. Both simulations and experiments indicate that the biological metabolism condition allows the easier capture of calcium ions by the more abundant hydroxyl groups on the glucan chain before the formation of hydrogen bonding, for the subsequent growth of HAp crystals. Our work provides more insights into the biologically accelerated mineralization process and presents a different methodology for the generation of biomimetic nanocomposites.

Antibacterial Vancomycin@ZIF-8 Loaded PVA Nanofiber Membrane for Infected Bone Repair.

Bone substitutes with strong antibacterial properties and bone regeneration effects have an inherent potential in the treatment of severe bone tissue infections, such as osteomyelitis. In this study, vancomycin (Van) was loaded into zeolitic imidazolate framework-8 (ZIF-8) to prepare composite particles, which is abbreviated as V@Z. As a pH-responsive particle, ZIF-8 can be cleaved in the weak acid environment caused by bacterial infection to realize the effective release of drugs. Then, V@Z was loaded into polyvinyl alcohol (PVA) fiber by electrospinning to prepare PVA/V@Z composite bone filler. The drug-loading rate of V@Z was about 6.735%. The membranes exhibited super hydrophilicity, water absorption and pH-controlled Van release behavior. The properties of anti E. coli and S. aureus were studied under the pH conditions of normal physiological tissues and infected tissues (pH 7.4 and pH 6.5, respectively). It was found that the material had good surface antibacterial adhesion and antibacterial property. The PVA/V@Z membrane had the more prominent bacteria-killing effect compared with the same amount of single antibacterial agent containing membrane such as ZIF-8 or Van loaded PVA, and the antibacterial rate was up to 99%. The electrospun membrane had good biocompatibility and can promote MC3T3-E1 cell spreading on it.

The Efficacy of Senna Bowel Preparation for Colonoscopy: A Systematic Review and Meta-analysis.

The quality of bowel preparation is an extremely important determinant of colonoscopy results. However, the efficacy of senna regimens in improving bowel cleanliness is uncertain. We conducted a systematic review and meta-analysis to synthesize data on whether using a senna bowel preparation regimen enhances the bowel cleanliness. We searched Web of Science Core Collection, MEDLINE, PubMed, Embase, Cochrane Library, and Scopus databases (from the inception to August 2021). The primary efficacy outcome was bowel cleanliness. Secondary outcomes included patient compliance, tolerance, and adverse events. Eleven trials fulfilled the inclusion criteria (3,343 patients. Overall, we found no significant differences in bowel cleanliness between the senna regimen and other bowel preparation regimens (odds ratio [95% confidence interval]: 1.02 [0.63, 1.67], p = 0.93). There was significant difference in tolerance (odds ratio [95% confidence interval]: 1.66 [1.08, 2.54], p = .02) and compliance (odds ratio [95% confidence interval]: 3.05 [1.42, 6.55], p = .004). The senna regimen yielded a significantly greater proportion of no nausea (odds ratio [95% confidence interval]: 1.84 [1.45, 2.32]) and vomiting (odds ratio [95% confidence interval]: 1.65 [0.81, 3.35]). Compared with other bowel preparation regimens, the senna regimen may be effective and safe in bowel cleaning before colonoscopy, with superior compliance and tolerance.

Tunable Photoluminescence Properties of Microcrystalline Cellulose with Gradually Changing Crystallinity and Crystal Form.

Nonconventional luminogens with persistent room temperature phosphoresce (p-RTP) are attracting increasing attention owing to their momentous significance and diverse technical applications in optoelectronic and biomedical. So far, the p-RTP emission of some amorphous powders or single crystals has been studied in depth. The p-RTP emission of amorphous and fully crystalline states and their emission properties are widely divergent, while the difference of their p-RTP emission mechanism is still controversial. The relevance between crystallinity change and p-RTP properties is rarely studied. Furthermore, there is almost no research on the photoluminescence (PL) property change and emission mechanism under the crystal form transformation of semi-crystalline polymer. Herein, microcrystalline cellulose (MCC) is chosen as a model compound to explore its crystallinity and the change in luminescence during the crystal form transformation to make up for this gap. By precisely adjusting the crystallinity and crystal cellulose conversion of MCC, the changing trend of quantum efficiency, and p-RTP lifetime is consistent with the change of crystallinity, and the cellulose I may be more beneficial to PL emission than cellulose II. Clustering-triggered emission mechanism can reasonably explain these interesting photophysical processes, which also can be supported by single-crystal analysis and theoretical calculations.

Cemented versus uncemented hemiarthroplasty for the management of femoral neck fractures in the elderly: a meta-analysis and systematic review.

INTRODUCTION: Hemiarthroplasty is commonly used to treat unstable femoral neck fractures in older patients. However, there is no consensus on the use of cement during hemiarthroplasty. Therefore, we performed a systematic review to focus on the outcomes of cemented and uncemented hemiarthroplasty for the treatment of femoral neck fractures in older patients. MATERIALS AND METHODS: Pubmed, Cochrane Central Register of Controlled Trials, and Ovid were searched for studies related comparison of cemented versus uncemented hemiarthroplasty for unstable femoral neck fractures from inception to Jan 20, 2020. The quality of the included randomized controlled trials (RCTs) was assessed using the Cochrane Collaboration tool. The meta-analysis was performed using the RevMan 5.2 software. RESULTS: Eleven RCTs were included in the meta-analysis. Cemented hemiarthroplasty was found to be superior to uncemented arthroplasty with respect to reoperation rate (RR 0.6, 95% CI 0.38-0.96, p = 0.03), complications related to prosthesis (RR 0.39, 95% CI 0.23-0.68, p = 0.0008), residual pain (RR 0.66, 95% CI 0.52-0.83, p = 0.0004), and operation time (MD 8.22, 95% CI 6.30-10.14, p < 0.00001). There were no significant between-group differences with respect to local and general complications, duration of hospital stay, hip function, and mortality. CONCLUSIONS: This meta-analysis showed cemented hemiarthroplasty might be an optimum choice for treating unstable femoral neck fractures in older patients. However, the results of this meta-analysis should be interpreted cautiously owing to some limitations. Further studies are required to provide more robust evidence.

Quantitation of large, middle and small hepatitis B surface proteins in HBeAg-positive patients treated with peginterferon alfa-2a.

BACKGROUND & AIMS: Hepatitis B virus (HBV) contains three viral surface proteins, large, middle and small hepatitis B surface protein (LHBs, MHBs, SHBs). Proportions of LHBs and MHBs are lower in patients with inactive vs active chronic infection. Interferon alfa may convert hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) to an inactive carrier state, but prediction of sustained response is unsatisfactory. The aim of this study was to test the hypothesis that quantification of MHBs and LHBs may allow for a better prognosis of therapeutic response than total hepatitis B surface antigen (HBsAg) concentration. METHODS: Hepatitis B surface proteins were measured before and during peginterferon alfa-2a therapy in serum from 127 Asian patients with HBeAg-positive CHB. Sustained response was defined as HBeAg seroconversion 24 weeks post-treatment. RESULTS: Mean total HBs levels were significantly lower in responders vs nonresponders at all time points (P < .05) and decreased steadily during the initial 24 weeks treatment (by 1.16 vs 0.86 ng/mL in responders/nonresponders respectively) with unchanged relative proportions. Genotype B had a two-fold higher proportion of LHBs than genotype C (13% vs 6%). HBV DNA, HBeAg, HBsAg and HBs protein levels predicted response equally well but not optimally (area under the receiver operating characteristic curve values >0.70). CONCLUSIONS: Hepatitis B surface protein levels differ by HBV genotype. However, quantification of HBs proteins has no advantage over the already established HBsAg assays to predict response to peginterferon alfa-2a therapy in HBeAg-positive patients.

Desirable PEGylation for improving tumor selectivity of hyaluronic acid-based nanoparticles via low hepatic captured, long circulation times and CD44 receptor-mediated tumor targeting.

PEG coating was regarded as one effective method to improve the tumor-targeting efficiency of hyaluronic acid-based nanoparticles (HBN). However, the research of interaction between PEG coating and different receptors such as stabilin-2 and CD44 was limited. Herein, we synthesized a series of PEGylated hyaluronic acid with Curcumin (PHCs) to evaluate the role of PEG coating density in the interaction between HA and its receptors, which influenced tissues targeting activity, pharmacokinetic profiles and therapeutic efficacy of HBN. Compared with other counterparts, PHC HBN with about 5% PEG coating density preferably accumulated in the tumor mass, rather than in the liver, and hold desirable anti-cancer effect. These results indicated that to obtain optimized anticancer effect of HBN, the cellular uptake efficiency between different types of the cells should be carefully balanced by different PEG densities.

[Autosomal dominant intellectual disability-40 caused by a de novo mutation of the CHAMP1 gene: a case report].

A boy, aged 6 months, had the manifestations of intellectual and motor developmental delay, head instability, general weakness, unawareness of grasping objects by hands, and unusual facies (slightly wide eye distance, epicanthus, esotropia, mouth-opening appearance, short philtrum, and low-set ears). Gene detection results showed a de novo heterozygous frameshift mutation of the CHAMP1 gene at the chromosomal location of chr13:115089847, and nuclear acid was changed to c.530delCinsTTT, resulting in a change in amino acid to p.S177Ffs*2. Therefore, the boy was diagnosed with autosomal dominant intellectual disability-40 caused by the mutation in the CHAMP1 gene. This case report suggests that for children with unexplained intellectual disability, especially those with generalized hypotonia and severe language disorder, the possibility of CHAMP1 gene mutation should be considered, and genetic testing should be performed as early as possible.

Efficacy and Safety of Peginterferon Alfa-2a (40KD) in Children With Chronic Hepatitis B: The PEG-B-ACTIVE Study.

Children with chronic hepatitis B (CHB) represent an area of unmet medical need, attributed to increased lifetime risk of CHB sequelae and limited therapeutic options compared with adult CHB patients. The PEG-B-ACTIVE (NCT01519960) phase III study evaluated peginterferon (PegIFN) alfa-2a treatment in children aged 3 to <18 years with CHB. A total of 161 hepatitis B e antigen (HBeAg)-positive immune-active patients without advanced fibrosis (AF)/cirrhosis were randomized (2:1) to PegIFN alfa-2a (Group A, n = 101) or no treatment (Group B, n = 50); patients with AF were assigned to PegIFN alfa-2a (Group C, n = 10). PegIFN alfa-2a was administered for 48 weeks by body surface area (BSA) category, based on 180 µg/1.73 m2 . HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in Group A (25.7% vs. 6%; P = 0.0043), as were the rates of hepatitis B surface antigen (HBsAg) clearance (8.9% vs. 0%; P = 0.03), hepatitis B virus (HBV) DNA <2,000 IU/mL (28.7% vs. 2.0%; P < 0.001) or undetectable (16.8% vs. 2.0%; P = 0.0069), and alanine aminotransferase (ALT) normalization (51.5% vs. 12%; P < 0.001). Safety, including incidence of ALT flares and neutropenia, was comparable to the established PegIFN alfa-2a profile in HBV-infected adults or hepatitis C virus-infected children. Changes in growth parameters were minimal during treatment and comparable to those in untreated patients. Safety and efficacy outcomes in Group C were in line with Group A. Conclusion: PegIFN alfa-2a treatment of children in the immune-active phase of CHB was efficacious and well tolerated, and associated with higher incidence of HBsAg clearance than in adults. This represents an important advance to the treatment options for children with CHB.

In Vivo Antibacterial Efficacy of Nitric Oxide-Releasing Hyperbranched Polymers against Porphyromonas gingivalis.

The in vivo antibacterial activity of NO-releasing hyperbranched polymers was evaluated against Porphyromonas gingivalis, a key oral pathogen associated with periodontitis, using a murine subcutaneous chamber model. Escalating doses of NO-releasing polymers (1.5, 7.5, and 37.5 mg/kg) were administered into a P. gingivalis-infected chamber once a day for 3 days. Chamber fluids were collected on day 4, with microbiological evaluation indicating a dose-dependent bactericidal action. In particular, NO-releasing polymers at 37.5 mg/kg (1170 µg of NO/kg) achieved complete bacterial eradication (>6-log reduction in bacterial viability), demonstrating greater efficacy than amoxicillin (∼4-log reduction in bacterial viability), a commonly used antibiotic. Time-kill assays further revealed that largest dose (37.5 mg/kg; 1170 µg of NO/kg) resulted in ∼3-log killing of P. gingivalis after only a single dose. Based on these results, the potential clinical utility of NO-releasing hyperbranched polymers appears promising, particularly for oral health applications.

Local administration of aspirin with ß-tricalcium phosphate/poly-lactic-co-glycolic acid (ß-TCP/PLGA) could enhance osteoporotic bone regeneration.

Composite materials ß-tricalcium phosphate (ß-TCP) and poly-lactic-co-glycolic acid (PLGA) have achieved stable bone regeneration without cell transplantation in previous studies. Recent research shows that aspirin (ASP) has great potential in promoting bone regeneration. The objective of the present study was to incorporate PLGA into ß-TCP combined with a lower single-dose local administration of ASP to enhance its in vivo biodegradation and bone tissue growth. After the creation of a rodent critical-sized femoral metaphyseal bone defect, PLGA -modified ß-TCP (TP) was prepared by mixing sieved granules of ß-TCP and PLGA (50:50, v/v) for medical use, then TP with dripped 50 µg/0.1 ml and 100 µg/0.1 ml aspirin solution was implanted into the defect of OVX rats until death at 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, biomechanics and real time RT-PCR. The results of our study show that a single-dose local administration of ASP combined with the local usage of TP can increase the healing of defects in OVX rats. Single-dose local administration of aspirin can improve the transcription of genes involved in the regulation of bone formation and vascularization in the defect area, and inhibits osteoclast activity. Furthermore, treatments with a higher single-dose local administration of ASP and TP showed a stronger effect on accelerating the local bone formation than while using a lower dose of ASP. The results from our study demonstrate that the combination of a single-dose local administration of ASP and ß-TCP/PLGA had an additive effect on local bone formation in osteoporosis rats, and bone regeneration by PLGA/ß-TCP/ASP occured in a dose-dependent manner.

Study on mitigating membrane fouling based on precursor and flocculant Alb matching in EC/O-UF system.

One of the effective ways to remove halogenated disinfection by-products (DBPs) from drinking water is the application of ultrafiltration technology. However, membrane fouling is an important factor affecting the service life and treatment effect. In this study, the electrocoagulation/oxidation-ultrafiltration (EC/O-UF) process was used to remove the precursor substance that produced DBPs, i.e. dissolved organic matters (DOMs). Operating parameters were optimized from the matching of different flocculant morphology to low concentration DOM. The degree of membrane fouling was characterized by analyzing DOMs concentration and membrane flux. The results showed that the optimal conditions for the production of Alb were: current density 10 A/m2, hydraulic retention time 10 min, and initial pH 5.0-7.0. Under these conditions, the production of flocculant Alb could reach 58-61%, 94-97% DOMs were removed by EC/O-UF.

Serum HBV RNA as a Predictor of Peginterferon Alfa-2a Response in Patients With HBeAg-Positive Chronic Hepatitis B.

Background: Hepatitis B virus (HBV) RNA is a novel serum biomarker that has the potential to predict treatment response in patients with chronic hepatitis B. We explored whether HBV RNA serum levels can predict hepatitis B e antigen (HBeAg) seroconversion in patients treated with peginterferon alfa-2a. Methods: Serum samples from HBeAg-positive patients previously treated with peginterferon alfa-2a in 2 large randomized controlled trials were retrospectively analyzed. HBV RNA levels were measured using a real-time polymerase chain reaction assay. Ability of individual biomarkers to predict HBeAg seroconversion at 24 weeks posttreatment was evaluated using receiver operating characteristics (ROC) analyses. Results: The study included 131 subjects (70% male, 96% Asians, 35% HBV genotypes B, and 61% C), 76 treated with peginterferon alfa-2a alone and 55 in combination with lamivudine. Median HBV RNA levels were significantly lower, at all timepoints, in patients achieving HBeAg seroconversion. Levels of HBV RNA at treatment weeks 12 and 24 showed good ability to predict HBeAg seroconversion (area under ROC scores >0.75, P < .001). A HBV RNA cutoff of >5.5 log10 copies/mL identified 30% of nonresponders at week 12 (negative predictive value >90%). Conclusion: Serum HBV RNA is an early predictor of HBeAg seroconversion in patients treated with peginterferon alfa-2a. Clinical Trials Registration: NCT01705704.

Antibacterial Activity of Nitric Oxide-Releasing Hyperbranched Polyamidoamines.

Hyperbranched polyamidoamines (h-PAMAM) were prepared using a one-pot reaction to have similar molecular weight to third generation PAMAM (G3-PAMAM) dendrimers, and then functionalized with N-diazeniumdiolate nitric oxide (NO) donors. A wide range of NO storage capacities (∼1-2.50 µmol mg-1) and NO-release kinetics (t1/2 ∼30-80 min) were achieved by changing the extent of propylene oxide (PO) modification. The therapeutic potential of these materials was evaluated by studying their antibacterial activities and toxicity against common dental pathogens and human gingival fibroblast cells, respectively. Our results indicate that the combination of NO release and PO modification is necessary to yield h-PAMAM materials with efficient bactericidal action without eliciting unwarranted cytotoxicity. Of importance, NO-releasing PO-modified h-PAMAM polymers exhibited comparable biological properties (i.e., antibacterial action and cytotoxicity) to defect-free G3-PAMAM dendrimers, but at a substantially lower synthetic burden.