Temporal variations in micropollutant inlet concentrations matter when planning the design and compliance assessment of stormwater control measures.

Stormwater Control Measures (SCMs) contribute to reducing micropollutant emissions from separate sewer systems. SCM planning and design are often performed by looking at the hydrological performance. Assessment of pollutant removal and the ability to comply with discharge concentration limits is often simplified due to a lack of data and limited monitoring resources. This study analyses the impact of using different time resolutions of input stormwater concentrations when assessing the compliance of SCMs against water quality standards. The behaviour of three indicator micropollutants (MP - Copper, Diuron, Benzo[a]pyrene) was assessed in four SCM archetypes, which were defined to represent typical SCM removal processes. High resolution MP data were extrapolated by using high resolution (2 min) measurements of TSS over a long period (343 events). The compliance assessment showed that high resolution input concentrations can result in a different level of compliance with water quality standards, especially when discharged concentrations are close to the limit values. This study underlines the importance of considering the high temporal variability of stormwater micropollutants when planning and designing SCMs to identify the most effective solutions for stormwater pollution management and to ensure a thorough consideration of all the environmental implications.

Inhaled immunoantimicrobials for the treatment of chronic obstructive pulmonary disease.

Effective therapeutic modalities and drug administration strategies for the treatment of chronic obstructive pulmonary disease (COPD) exacerbations are lacking. Here, mucus and biofilm dual-penetrating immunoantimicrobials (IMAMs) are developed for bridging antibacterial therapy and pro-resolving immunotherapy of COPD. IMAMs are constructed from ceftazidime (CAZ)-encapsulated hollow mesoporous silica nanoparticles (HMSNs) gated with a charge/conformation-transformable polypeptide. The polypeptide adopts a negatively charged, random-coiled conformation, masking the pores of HMSNs to prevent antibiotic leakage and allowing the nebulized IMAMs to efficiently penetrate the bronchial mucus and biofilm. Inside the acidic biofilm, the polypeptide transforms into a cationic and rigid α helix, enhancing biofilm retention and unmasking the pores to release CAZ. Meanwhile, the polypeptide is conditionally activated to disrupt bacterial membranes and scavenge bacterial DNA, functioning as an adjuvant of CAZ to eradicate lung-colonizing bacteria and inhibiting Toll-like receptor 9 activation to foster inflammation resolution. This immunoantibacterial strategy may shift the current paradigm of COPD management.

Viral Communities Contribute More to the Lysis of Antibiotic-Resistant Bacteria than the Transduction of Antibiotic Resistance Genes in Anaerobic Digestion Revealed by Metagenomics.

Ecological role of the viral community on the fate of antibiotic resistance genes (ARGs) (reduction vs proliferation) remains unclear in anaerobic digestion (AD). Metagenomics revealed a dominance of Siphoviridae and Podoviridae among 13,895 identified viral operational taxonomic units (vOTUs) within AD, and only 21 of the vOTUs carried ARGs, which only accounted for 0.57 ± 0.43% of AD antibiotic resistome. Conversely, ARGs locating on plasmids and integrative and conjugative elements accounted for above 61.0%, indicating a substantial potential for conjugation in driving horizontal gene transfer of ARGs within AD. Virus-host prediction based on CRISPR spacer, tRNA, and homology matches indicated that most viruses (80.2%) could not infect across genera. Among 480 high-quality metagenome assembly genomes, 95 carried ARGs and were considered as putative antibiotic-resistant bacteria (pARB). Furthermore, lytic phages of 66 pARBs were identified and devoid of ARGs, and virus/host abundance ratios with an average value of 71.7 indicated extensive viral activity and lysis. The infectivity of lytic phage was also elucidated through laboratory experiments concerning changes of the phage-to-host ratio, pH, and temperature. Although metagenomic evidence for dissemination of ARGs by phage transduction was found, the higher proportion of lytic phages infecting pARBs suggested that the viral community played a greater role in reducing ARB numbers than spreading ARGs in AD.

Making waves: Magneto-responsive membranes with special and switchable wettability: new opportunities for membrane distillation.

Membrane distillation (MD) has promising potential in the water purification and wastewater treatment industries; however, fouling and wetting are the main obstacles to its commercialization, and higher fluxes and energy efficiencies are essential. Magneto-responsive membranes (MagMem) with integrated magnetic nanoparticles (MNPs) enable in situ fouling mitigation and switchable separation by nano-mixing or nano-heating, triggered by external magnetic fields, in a range of membrane processes, but not yet been demonstrated in MD. This perspective discussed the potential paths of MagMem utilization in MD based on the research status and dilemmas of MD. It can be envisioned that MagMem will lead to a paradigm shift in MD, especially by in situ fouling/wetting mitigation and enhancing energy efficiency via in-place actuation and localized heating by MNPs. Moreover, remotely controllable pore tuning and specific or switchable wettability can also be anticipated. Overall, MagMem provides attractive opportunities for advanced robust and efficient MD.

Mixed scaling patterns and mechanisms of high-pressure nanofiltration in hypersaline wastewater desalination.

Nanofiltration (NF) will play a crucial role in salt fractionation and recovery, but the complicated and severe mixed scaling is not yet fully understood. In this work, the mixed scaling patterns and mechanisms of high-pressure NF in zero-liquid discharge (ZLD) scenarios were investigated by disclosing the role of key foulants. The bulk crystallization of CaSO4 and Mg-Si complexes and the resultant pore blocking and cake formation under high pressure were the main scaling mechanisms in hypersaline desalination. The incipient scalants were Mg-Si hydrates, CaF2, CaCO3, and CaMg(CO3)2. Si deposited by adsorption and polymerization prior to and impeded Ca scaling when Mg was not added, thus pore blocking was the main mechanism. The amorphous Mg-Si hydrates contribute to dense cake formation under high hydraulic pressure and permeate drag force, causing rapid flux decline as Mg was added. Humic acid has a high affinity to Ca2+by complexation, which enhances incipient scaling by adsorption or lowers the energy barrier of nucleation but improves the interconnectivity of the foulants layer and inhibits bulk crystallization due to the chelation and directional adsorption. Bovine serum albumin promotes cake formation due to the low electrostatic repulsion and acts as a cement to particles by adsorption and bridging in bulk. This work fills the research gaps in mixed scaling of NF, which is believed to support the application of ZLD and shed light on scaling in hypersaline/ultra-hypersaline wastewater desalination applications.

[Effects of Nitrogen Speciation Transformation on Microbial Community Succession in Input Rivers of Miyun Reservoir].

The Miyun Reservoir is the major source of surface drinking water in Beijing. However, the total nitrogen (TN) concentrations in the Miyun Reservoir and inflowing rivers have recently been increasing. In this study, the Mangniu River, a typical inflow river in the upper reaches of the Miyun Reservoir, was selected as the study area to investigate the spatial distribution and transformation of various nitrogen forms from the perspective of microbial community composition and predicting function, aimimg at providing a scientific reference for nitrogen pollution control of the Miyun Reservoir. The results indicated that except for TN, all the other physical and chemical water quality indicators in the upper reaches of the Miyun Reservoir met the Class II criteria of the environmental quality standards for surface water in China (GB 3838-2002). Additionally, NO3--N was the primary constituent of TN, ranging from 77.7% to 92.9%. Banchengzi Reservoir has a certain self-purification ability because its high C/N ratio promotes denitrification. Significant differences in microbial community structure were observed between the water and sediments of Mangniu River along with spatial distribution. High NO3--N concentration was the major environmental factor affecting the succession of microbial community structure. Many nitrification and denitrification microorganisms existed in Mengniu River, and the relative abundance of denitrification bacteria (DNB) was higher than that of nitrification bacteria, and that in the sediments was slightly higher than that in the water. Nitrosopumilus and Pseudomonas were the dominant nitrification and denitrification bacteria in Mengniuhe River, respectively. The results of phylogenetic investigation of communities by the reconstruction of unobserved states (PICRUSt2) showed that NO3--N reduction module was the major nitrogen metabolism module, which primarily occurred in water. The abundance of the functional genes for nitrification (i.e., narGH) was the highest in water, and the major functional gene involved in NO3--N reduction was nirBD of DNRA, which was primarily present in the sediments; however, the main functional gene involved in denitrification was nirK.

Effective enrichment of anaerobic ammonia oxidation sludge with feast-starvation strategy: activity, sedimentation, growth kinetics, and microbial community.

To address the issue of floating and loss of floc sludge caused by gas production in anaerobic ammonia oxidation (anammox) reactors, this study proposes a limited nitrite supply strategy to regulate gas production during the settling and enhance sludge retention. Results indicate that the effluent suspended solids in the anammox reactor can be reduced to as low as 0.11 g/L under specific feast-starvation conditions. Even under long-term intermittent nitrite-starvation stress, the maximum growth rate of Candidatus_Kuenenia can still reach 0.085d-1, with its abundance increasing from 0.47% to 8.83% within 69 days. Although the combined effects of starvation and sedimentation would lead to a temporary decrease in anammox activity, this reversible inhibition can be fully restored through substrate intervention. The limited nitrite supply strategy promotes the sedimentation of anammox sludge without significantly affecting its growth rate, and effective sludge retention is crucial for enriching anammox sludge during initial cultivation.

Microbial community structure and functional prediction in five full-scale industrial park wastewater treatment plants.

The development of industrial parks has become an important global trend contributing significantly to economic and industrial growth. However, this growth comes at a cost, as the treatment of multisource industrial wastewater generated in these parks can be difficult owing to its complex composition. Microorganisms play a critical role in pollutant removal during industrial park wastewater treatment. Therefore, our study focused on the microbial communities in five full-scale industrial park wastewater treatment plants (WWTPs) with similar treatment processes and capacities. The results showed that denitrifying bacteria were dominant in almost every process section of all the plants, with heterotrophic denitrification being the main pathway. Moreover, autotrophic sulfur denitrification and methane oxidation denitrification may contribute to total nitrogen (TN) removal. In plants where the influent had low levels of COD and TN, dominant bacteria included oligotrophic microorganisms like Prosthecobacter (2.88 % ~ 10.02 %) and hgcI_clade (2.05 % ~ 9.49 %). Heavy metal metabolizing microorganisms, such as Norank_f__PHOS-HE36 (3.96 % ~ 5.36 %) and Sediminibacterium (1.86 % ~ 5.34 %), were prevalent in oxidation ditch and secondary settling tanks in certain plants. Functional Annotation of Prokaryotic Taxa (FAPROTAX) revealed that microbial communities in the regulation and hydrolysis tanks exhibited higher potential activity in the nitrogen (N) and sulfur (S) cycles than those in the oxidation ditch. Sulfate/sulfite reduction was common in most plants, whereas the potential occurrence of sulfide compounds and thiosulfate oxidation tended to be higher in plants with a relatively high sulfate concentration and low COD content in their influent. Our study provides a new understanding of the microbial community in full-scale industrial park WWTPs and highlights the critical role of microorganisms in the treatment of industrial wastewater.

Swine-manure composts induce the enrichment of antibiotic-resistant bacteria but not antibiotic resistance genes in soils.

Composting is a common and effective strategy for reducing antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) from animal manure. However, it is unclear whether the advantages of composting for the control of ARGs and ARB can be further increased in land application. This study investigated the fate of ARB and ARGs after land application of swine-manure composts (SMCs) to three different soil types (red soil, loess and black soil). The results showed that although the SMCs caused an increase in the abundance of total ARGs in the soil in the short period, they significantly reduced (p < 0.01) the abundance of total ARGs after 82 days compared to the control. The decay rate of ARGs reflected by the half-life times (t1/2) varied by soil type, with red soil being the longest. The SMCs mainly introduced ermF, tetG and tetX into the soils, while these ARGs quickly declined to the control level. Notably, SMCs increased the number of ARB in the soils, especially for cefotaxime-resistant bacteria. Although SMCs only affected the microbiome significantly during the early stage (p < 0.05), it took a much longer time for the microbiome to recover compared to the control. Statistical analysis indicated that changes in the microbial community contributed more to the fate of ARGs during SMCs land application than other factors. Overall, it is proposed that the advantages of ARGs control in the composting process for swine manure can be further increased in land application, but it can still bring some risks in regard to ARB.

Imperative assessment on the current status of rubber wastewater treatment: Research development and future perspectives.

The environment has been significantly impacted by the rubber industry through the release of large quantities of wastewater during various industrial processes. Therefore, it is crucial to treat the wastewater from the rubber industry before discharging it into natural water bodies. With the understanding that alarmingly depleting freshwater sources need to be preserved for future generations, this paper reviews the status of the rubber industry and the pollution caused by them, focusing mainly on water pollution. The review pays special attention to the recent advancements in wastewater treatment techniques for rubber industry wastewater categorizing them into pre-treatment, secondary, and tertiary treatment processes while discussing the advantages and disadvantages. Through a comprehensive analysis of existing literature, it was determined that organic content and NH4+ are the most frequently focused water quality parameters, and despite some treatment methods demonstrating superior performance, many of the methods still face limitations and require further research to improve systems to handle high organic loading on the treatment systems and to implement them in industrial scale. The paper also explores the potential of utilizing untreated or treated wastewater and byproducts of wastewater treatment in contributing towards achieving several United Nations sustainable development goals (UN-SDGs); SDG 6, SDG 7, SDG 9, and SDG 12.

Anaerobic membrane bioreactor for hygiene wastewater treatment in controlled ecological life support systems: Degradation of surfactants and microbial community succession.

The treatment and reuse of hygiene wastewater is crucial to "close the loop" in the controlled ecological life support system (CELSS), and to guarantee longer space missions or planetary habitation. In this work, anaerobic membrane bioreactor (AnMBR) was applied for hygiene wastewater treatment, focused on surfactant degradation and microbial community succession. The removal efficiency of COD and surfactants was 90%∼97% and 80% with a urine source-separation strategy. The microbial community gradually shifted from methanogens to sulfur-metabolizing and surfactant-degradation bacteria, such as Aeromonas. Sulfate was a surfactant degradation product, which triggered sulfate reduction and methane inhibition. The activated carbohydrate and sulfur metabolism were the key mechanism of the microbial process for the excellent performance of AnMBR. This study analyzed the degradation mechanism from the perspective of microbial mechanism, offers a solution for CELSS hygiene wastewater treatment, and supports the future improvement and refinement of AnMBR technology.

Mixed scaling deconstruction in vacuum membrane distillation for desulfurization wastewater treatment by a cascade strategy.

Mineral scaling is one key obstacle to membrane distillation in hypersaline wastewater desalination, but the scaling or fouling mechanism is poorly understood. Addressing this challenge required revealing the foulants layer formation process. In this work, the scaling process was deconstructed with a cascade strategy by stepwise changing the composition of the synthetic desulfurization wastewater. The flux decline curves presented a 3-stage mode in vacuum membrane distillation (VMD). Heterogeneous nucleation of CaMg(CO3)2, CaF2, and CaCO3 was the main incipient scaling mechanism. Mg-Si complex was the leading foulant in 2nd-stage, during which the scaling mechanism shifted from surface to bulk crystallization. The flux decreased sharply for the formation of a thick and compacted scaling layer by the bricklaying of CaSO4 and Mg-Si-BSA complexes in the 3rd-stage. Bulk crystallization was identified as the key scaling mechanism in VMD for the high salinity and concentration multiple. The organic matter had an anti-scaling effect by changing the bulk crystallization. Humic acids (HA) and colloidal silica also contributed to incipient scaling for the high affinity to membrane, bovine serum albumin (BSA) acting as the cement of Mg-Si complexes. Mg altered the Si scaling from polymerization to Mg-Si complex formation, which significantly influence the mixed scaling mechanism. This work deconstructed the mixed scaling process and illuminated the role of main foulants, filling in the knowledge gap on the mixed scaling mechanism in VMD for hypersaline wastewater treatment and recovery.

Rational Construction of Protein-Mimetic Nano-Switch Systems Based on Secondary Structure Transitions of Synthetic Polypeptides.

The manipulation of the flexibility/rigidity of polymeric chains to control their function is commonly observed in natural macromolecules but largely unexplored in synthetic systems. Herein, we construct a series of protein-mimetic nano-switches consisting of a gold nanoparticle (GNP) core, a synthetic polypeptide linker, and an optically functional molecule (OFM), whose biological function can be dynamically regulated by the flexibility of the polypeptide linker. At the dormant state, the polypeptide adopts a flexible, random-coiled conformation, bringing GNP and OFM in close proximity that leads to the "turn-off" of the OFM. Once treated with alkaline phosphatase (ALP), the nano-switches are activated due to the increased separation distance between GNP and OFM driven by the coil-to-helix and flexible-to-rigid transition of the polypeptide linker. The nano-switches therefore enable selective fluorescence imaging or photodynamic therapy in response to ALP overproduced by tumor cells. The control over polymer flexibility represents an effective strategy to manipulate the optical activity of nano-switches, which mimics the delicate structure-property relationship of natural proteins.

An extensive assessment of seasonal rainfall on intracellular and extracellular antibiotic resistance genes in Urban River systems.

Rainfall events are responsible for the accelerated transfer of antibiotic-resistant contaminants to receiving environments. However, the specific profiles of various ARG types, including intra- and extracellular ARGs (iARGs and eARGs) responding to season rainfall needed more comprehensive assessments. Particularly, the key factors driving the distribution and transport of iARGs and eARGs have not been well characterized. Results revealed that the absolute abundance of eARGs was observed to be more than one order of magnitude greater than that of iARGs during the dry season in the reservoir. However, the absolute abundance of iARGs significantly increased after rainfall (p < 0.01). Meanwhile, seasonal rainfall significantly decreased the diversity of eARGs and the number of shared genes between iARGs and eARGs (p < 0.01). Results of structural equation models (SEM) and network analysis showed the rank and co-occurrence of influencing factors (e.g., microbial community, MGEs, environmental variables, and dissolved organic matter (DOM)) concerning the changes in iARGs and eARGs. DOM contributed majorly to eARGs in the reservoir and pathogens was responsible for eARGs in the river during the wet season. Network analysis revealed that the tnp-04 and IS613 genes-related MGEs co-occurred with eARGs in the dry and wet seasons, which were regarded as potential molecular indicators to shape eARGs profiles in urban rivers. Besides, the results demonstrated close relationships between DOM fluorescence signatures and two-typed ARGs. Specifically, humic acid was significantly and positively correlated with the eARGs in the reservoir during the wet season, while fulvic acid-like substances exhibited strong correlations of iARGs and eARGs in the river during the dry season (p < 0.01). This work provides extensive insights into the potential effect of seasonal rainfall on the dynamic distribution of iARGs and eARGs and the dominance of DOM in driving the fate of two-typed ARGs in urban river systems.

Response of prokaryotic, eukaryotic and algal communities to heavy rainfall in a reservoir supplied with reclaimed water.

The global climate change made the heavy rainfall happen more frequently, and the non-point source pollution caused by it would exacerbate the risk to the water ecological environment. In this study, we took a reservoir (Shahe reservoir, Beijing, China) supplied with reclaimed water as an exapmle to investigate how spatiotemporal changes in the quantity and diversity of prokaryotic, eukaryotic, and algal communities respond to heavy rainfall. Results showed that heavy rainfall could directly impact the composition of the prokaryotic community by introducing amounts of runoff closely associated bacterium especially for the human potential pathogens such as Aliarcobacter, Aeromonas and Pseudomonas in the Shahe reservoir area. While the eukaryotic community was rather stable, and the development and changes in algal communities occurred in the last few days after heavy rainfall. The microbial source tracking through FEAST indicated that Nansha river (S) was the major contributor to the development of all the three concerned communities in the reservoir. The co-occurrence analysis showed that the modules with the highest cumulative abundance in each community were all strongly and positively connected with Chl-a, pH, turbidity, COD and TOC, but negatively correlated with NO3-N (p < 0.01). The network analysis showed that the eukaryotes played a key role in the interaction network among the three communities, and were more likely to interact with algae and prokaryotes. It was suggested that the controlling of human potential pathogens associated with prokaryotic community should be emphasized at the beginning of the heavy rainfall, but the prevention of the eutrophication bloom should be another focus after the heavy rainfall. This study provided valuable information concerning the role of heavy rainfall on the water ecological environment from the perspective of microbial community.

Mannose-mediated nanodelivery of methotrexate to macrophages augments rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that gravely jeopardizes the quality of life of numerous people. Methotrexate (MTX) is a disease-modifying anti-rheumatic drug commonly used in clinics; however, it suffers from slow onset, moderate efficacy, and adverse reactions such as renal dysfunction, myelosuppression, and bone erosion after long-term treatment. Here, we explored macrophage targeted delivery of MTX using mannose-installed chimaeric polymersomes (Man-PMTX) as an advanced treatment for RA. Man-PMTX exhibited high (∼18 wt%) and robust loading of MTX, uniform size of 51-55 nm, minimal hemolytic activity, and glutathione-actuated drug release property. Man-PMTX showed better uptake by activated macrophages than PMTX, and more repolarization of bone marrow-derived macrophages (BMDMs) to anti-inflammatory M2 type macrophages and less secretion of TNF-α and IL-1ß compared with free MTX and PMTX. In vivo studies revealed that Man-PMTX showed significantly higher accumulation in inflammatory joints than in healthy joints and effectively treated RA by relieving inflammation, repolarizing macrophages from M1 type to M2 type, and mitigating proinflammatory cytokines. Accordingly, Man-PMTX effectively protected the synovium and bone from damage. Mannose-mediated nanodelivery of methotrexate to macrophages appears to be an attractive strategy to augment rheumatoid arthritis therapy.

Resilience of anammox application from sidestream to mainstream: A combined system coupling denitrification, partial nitritation and partial denitrification with anammox.

Anaerobic ammonium oxidation (anammox) is a potential process to achieve the neutralization of energy and carbon. Due to the low temperature and variation of municipal sewage, the application of mainstream anammox is hard to be implemented. For spreading mainstream anammox in practice, several key issues and bottlenecks including the start-up, stable NO2--N supply, maintenance and dominance of AnAOB with high activity, prevention of NO3--N buildup, reduction of sludge loss, adaption to the seasonal temperature and alleviation of COD impacts on AnAOB are discussed and summarized in this review in order to improve its startup, stable operation and resilience of mainstream anammox. Hence a combined biological nitrogen removal (CBNR) system based on conventional denitrification, shortcut nitrification-denitrification, Partial Nitritation and partial Denitrification combined Anammox (PANDA) process through the management of organic matter and nitrate is proposed correspondingly aiming at adaptation to the variations of seasonal temperature and pollutants in influent.

Comprehensive understanding of DOM reactivity in anaerobic fermentation of persulfate-pretreated sewage sludge via FT-ICR mass spectrometry and reactomics analysis.

Understanding the composition and reactivity of dissolved organic matter (DOM) at molecular level is vital for deciphering potential regulators or indicators relating to anaerobic process performance, though it was hardly achieved by traditional analyses. Here, the DOM composition, molecular reactivity and transformation in the enhanced sludge fermentation process were comprehensively elucidated using high-resolution mass spectrometry measurement, and data mining with machine learning and paired mass distance (PMD)-based reactomics. In the fermentation process for dewatered sludge, persulfate (PDS) pretreatment presented its highest performance in improving volatile fatty acids (VFAs) production with the increase from 2,711 mg/L to 3,869 mg/L, whereas its activation in the presence of Fe (as well as the hybrid of Fe and activated carbon) led to the decreased VFAs production performance. In addition to the conventional view of improved decomposition and solubilization of N-containing structures from sludge under the sole PDS pretreatment, the improved VFAs production was associated with the alternation of DOM molecular compositions such as humification generating molecules with high O/C, N/C, S/C and aromatic index (AImod). Machine learning was capable of predicting the DOM reactivity classes with 74-76 % accuracy and found that these molecular parameters in addition to nominal oxidation state of carbon (NOSC) were among the most important variables determining the generation or disappearance of bio-resistant molecules in the PDS pretreatment. The constructed PMD-based network suggested that highly connected molecular network with long path length and high diameter was in favor of VFAs production. Especially, -NH related transformation was found to be active under the enhanced fermentation process. Moreover, network topology analysis revealed that CHONS compounds (e.g., C13H27O8N1S1) can be the keystone molecules, suggesting that the presence of sulfur related molecules (e.g., cysteine-like compounds) should be paid more attention as potential regulators or indicators for controlling sludge fermentation performance. This study also proposed the non-targeted DOM molecular analysis and downstream data mining for extending our understanding of DOM transformation at molecular level.

Antibacterial brush polypeptide coatings with anionic backbones.

Preventing initial colonization of bacteria on biomaterial surfaces is crucial to address the medical device-associated infection issues. Antimicrobial peptide (AMP) or cationic polymer modified surfaces have shown promising potentials to inhibit the initial colonization of bacteria by contact killing. However, their development has been impeded because of bacterial adhesion and high cytotoxicity. Herein, we report a series of brush polypeptide coatings with anionic backbones and cationic AMP mimetic side-chains that displayed superior bactericidal activity, antibacterial adhesion property, and biocompatibility. The cationic side-chain density played an important role in the bioactivities of the brush polypeptide modified surfaces. Brush polypeptide coating with low side-chain density exhibited improved bactericidal activity and antibacterial adhesion property, ascribing to the cooperative effects of adjacent side-chains and backbones/side-chains, respectively. It also showed negligible hemolysis/cytotoxicity in vitro and potent anti-infection property (≥99.9% bactericidal efficacy) in vivo. Brush polymers with anionic backbones and cationic side-chains can be used as a promising design motif to potentiate both antibacterial property and biocompatibility of coatings for combating device-associated infections. STATEMENT OF SIGNIFICANCE: Device-associated infections (DAIs) have led to increased medical cost, pain, and even mortality of patients. Antimicrobial peptide and cationic polymer coatings provide an important strategy to combat DAIs by preventing initial colonization of bacteria on biomaterial surfaces. Nevertheless, they have suffered bacterial adhesion and cytotoxicity issues. Herein, we developed a brush polypeptide coating with anionic backbones and cationic side-chains. The brush polypeptide coating showed superior bactericidal and antibacterial adhesion properties outperforming conventional antibacterial coatings based on antimicrobial peptide (i.e., melittin), lysozyme (i.e., lysostaphin), cationic polymer, anionic polymer, and the blends of cationic/anionic polymers. It also showed good biocompatibility and potent anti-infection property, making it a promising candidate to combat the DAIs.

Oral Delivery of siRNA Using Fluorinated, Small-Sized Nanocapsules toward Anti-Inflammation Treatment.

Oral delivery of small interfering RNA (siRNA) provides a promising paradigm for treating diseases that require regular injections. However, the multiple gastrointestinal (GI) and systemic barriers often lead to inefficient oral absorption and low bioavailability of siRNA. Technologies that can overcome these barriers are still lacking, which hinders the clinical potential of orally delivered siRNA. Herein, small-sized, fluorinated nanocapsules (F-NCs) are developed to mediate efficient oral delivery of tumor necrosis factor α (TNF-α) siRNA for anti-inflammation treatment. The NCs possess a disulfide-cross-linked shell structure, thus featuring robust stability in the GI tract. Because of their small size (≈30 nm) and fluorocarbon-assisted repelling of mucin adsorption, the best-performing F3 -NCs show excellent mucus penetration and intestinal transport capabilities without impairing the intestinal tight junction, conferring the oral bioavailability of 20.4% in relative to intravenous injection. The disulfide cross-linker can be cleaved inside target cells, causing NCs dissociation and siRNA release to potentiate the TNF-α silencing efficiency. In murine models of acute and chronic inflammation, orally delivered F3 -NCs provoke efficient TNF-α silencing and pronounced anti-inflammatory efficacies. This study therefore provides a transformative strategy for oral siRNA delivery, and will render promising utilities for anti-inflammation treatment.