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Improving the drug loading and delivery efficiency of biodegradable nanomaterials used for targeting prostate cancer (PCa) remains a challenging task. To accomplish this task, herein, a new surface molecularly imprinted polymer (ZIF-8/DOX-HA@MIP) was designed and constructed with a hyaluronic acid (HA)-modified zeolitic imidazolate framework-8 (ZIF-8) metal–organic framework loaded with doxorubicin (DOX) as a substrate and a responsive molecularly imprinted polymer film as a shell. Owing to the large surface area of ZIF-8, DOX was successfully loaded into the ZIF-8/DOX-HA@MIP with a high drug loading efficiency (more than 88%). In vitro cell experiments have shown that the strengthened targeting ability of ZIF-8/DOX-HA@MIP to PCa cells was realized through the synergistic effect of HA and the molecularly imprinted membrane. Under the condition of simulated tumor microenvironment solution, Zn species were released and the particle size of ZIF-8/DOX-HA@MIP decreased gradually by the synergistic effect of hyaluronidase, pH, and glutathione, showing excellent biodegradability. In vivo antitumor research indicated the excellent antitumor activity and biocompatibility of ZIF-8/DOX-HA@MIP. The multifunctional ZIF-8/DOX-HA@MIP constructed herein provides a novel impetus for the development of targeted drug delivery in PCa treatment and a new strategy for treating other tumors.

Eradication of biofilms that may harbor pathogens in water distribution systems is an elusive goal due to limited penetration of residual disinfectants. Here, we explore the use of engineered filamentous coliphage M13 for enhanced biofilm affinity and precise delivery of lytic polyvalent phages (i.e., broad-host-range phages lysing multiple host strains after infection). To promote biofilm attachment, we modified the M13 major coat protein (pVIII) by inserting a peptide sequence with high affinity for Pseudomonas aeruginosa(P. aeruginosa) extracellular polysaccharides (commonly present on the surface of biofilms in natural and engineered systems). Additionally, we engineered the M13 tail fiber protein (pIII) to contain a peptide sequence capable of binding a specific polyvalent lytic phage. The modified M13 had 102- and 5-fold higher affinity for P. aeruginosa-dominated mixed-species biofilms than wildtype M13 and unconjugated polyvalent phage, respectively. When applied to a simulated water distribution system, the resulting phage conjugates achieved targeted phage delivery to the biofilm and were more effective than polyvalent phages alone in reducing live bacterial biomass (84 vs 34%) and biofilm surface coverage (81 vs 22%). Biofilm regrowth was also mitigated as high phage concentrations induced residual bacteria to downregulate genes associated with quorum sensing and extracellular polymeric substance secretion. Overall, we demonstrate that engineered M13 can enable more accurate delivery of polyvalent phages to biofilms in flow-through systems for enhanced biofilm control.

Wild birds are known to harbor and discharge antibiotic-resistant bacteria (ARB) and their associated antibiotic resistance genes (ARGs). However, assessments of their contribution to the dissemination of antibiotic resistance in the environment are limited to culture-dependent bacterial snapshots. Here, we present a high-throughput sequencing study that corroborates extensive ARG exchange between wild bird feces and their habitats and implies the need to scrutinize high-mobility birds as potential vectors for global propagation of ARGs. We characterized the resistome (281 ARGs) and microbiome of seven wild bird species and their terrestrial and aquatic habitats. The resistomes of bird feces were influenced by the microbial community structure, mobile genetic elements (MGEs), and residual antibiotics. We designated 33 ARGs found in more than 90% of the bird fecal samples as core ARGs of wild bird feces, among which 16 ARGs were shared as core ARGs in both wild bird feces and their habitats; these genes represent a large proportion of both the bird feces (35.0 ± 15.9%) and the environmental resistome (29.9 ± 21.4%). One of the most detected β-lactam resistance genes (blaTEM, commonly harbored by multidrug resistant “superbugs”) was used as molecular marker to demonstrate the high interconnectivity of ARGs between the microbiomes of wild birds and their habitats. Overall, this work provides a comprehensive analysis of the wild bird resistome and underscores the importance to consider genetic exchange between animals and the environment in the One Health approach.

Liver fibrosis develops from the excessive deposition of extracellular matrix in the liver caused by chronic liver inflammation or various chronic injuries, and it eventually develops into liver cirrhosis. The process of liver fibrosis is closely related to the immune response, and increasing evidence reveals the role of T lymphocytes, including Th1, Th2, Th17, regulatory T cells, and mucosa‐associated invariant T cells, in liver fibrosis. These immune cells play antifibrotic or profibrotic roles during fibrosis, and the reversal of fibrosis by targeting immune cells has attracted widespread attention. Activation of hepatic stellate cells, which form the core of fibrosis, is regulated by various immune mediators, including various immune cells and their associated cytokines. Therefore, the mechanism of action elicited by each cell type must be further elucidated to provide a basis for the design of new therapeutic targets. The purpose of this review is to summarize the roles and mechanisms of T lymphocytes and their subsets in liver fibrosis and highlight the biomarkers and potential therapeutic targets associated with these cells. Continuous stimulation by multiple factors leads to chronic hepatocyte injury, during which immune cells, including Kupffer cells and T cells, are recruited into the Disse space and interact with hepatic stellate cells to activate hepatic stellate cells to produce extracellular matrix and participate in the process of hepatic fibrosis. ECM, extracellular matrix; HSC, hepatic stellate cell. The liver's specific immunological milieu is critical for liver fibrosis.A variety of immune cells have different effects on liver fibrosis.Regulation of T lymphocytes can provide a new direction for liver fibrosis reversal. The liver's specific immunological milieu is critical for liver fibrosis. A variety of immune cells have different effects on liver fibrosis. Regulation of T lymphocytes can provide a new direction for liver fibrosis reversal.

p-Cresol is a harmful phenolic substance that can cause serious effects on human health even at a low concentration in water. Therefore, the detection of p-cresol in a water environment is particularly important. In this paper, a novel zeolite imidazolate framework-67 (ZIF-67) material with regular morphology was prepared on the surface of graphene oxide doped with silver nanoparticles. The composite was modified on the glassy carbon electrode surface to increase the specific surface area, accelerate the electron transfer rate, enhance the current response and improve the performance of electrochemical sensors. Furthermore, a layer of p-cresol-molecularly imprinted polymer was prepared on the surface of the modified electrode by electropolymerization for the selective, rapid and sensitive detection of p-cresol, which greatly improved the specific recognition of p-cresol. Under optimal conditions, the prepared sensor had a good linear range of 1.0 × 10−10M to 1.0 × 10−5M with a detection limit as low as 5.4 × 10−11M, and it presented excellent reproducibility, stability and selectivity. Moreover, the sensor was successfully applied for the detection of trace p-cresol in a real water environment, providing a reliable assay for sensitive, rapid and selective detection of p-cresol in complex samples.

LncRNAs play essential roles in tumorigenesis and tumor progression. Pseudogene UBE2CP3 is an antisense intronic lncRNA. However, the biological function of UBE2CP3 in gastric cancer (GC) remains unknown. In this study, we revealed that lncRNA UBE2CP3 was aberrantly upregulated in multiple independent gastric cancer cohorts, and its overexpression was clinically associated with poor prognosis in GC. UBE2CP3 was mainly located in cytoplasm and promoted migratory and invasive capacities of GC cells in vitro and in vivo. Mechanismly, a novel dysregulated ceRNA network UB2CP3/miR-138-5p/ITGA2 was identified in GC by transcriptome sequencing. Furthermore, rescue assay further confirmed that UBE2CP3 mainly promoted GC progression through miR-138-5p/ITGA2 axis. More importantly, our data proved that UBE2CP3/IGFBP7 could form an RNA duplex, thereby directly interacting with the ILF3 protein. In turn, this RNA-RNA interaction between IGFBP7 mRNA and UBE2CP3 mediated by ILF3 protein plays an essential role in protecting the mRNA stability of UBE2CP3. In addition, transcription factor ELF3 was identified to be a direct repressor of lncRNA UBE2CP3 in GC. Taken together, overexpression of UBE2CP3 promotes tumor progression via cascade amplification of ITGA2 upregulation in GC. Our finding has revealed that the dysregulation of UBE2CP3 is probably due to the downregulation of ELF3 and/or the overexpression of IGFBP7 mRNA in GC. Our findings reveal, for the first time, that UBE2CP3 plays crucial a role in GC progression by modulating miR-138-5p/ITGA2 axis, suggesting that UBE2CP3 may serve as a potential therapeutic target in GC.

Metal oxide catalysts with different cerium and manganese ratios were synthesized by a co-precipitation method to remove HCN and NO from exhaust gas. Ce1Mn2exhibited the highest HCN conversion and NO removal effect with a maximum N2selectivity of 72%. The existence of NO can promote the conversion of HCN at low temperatures, which may be due to the reaction between the two substances forming formyl and nitrogen. CO was not detected as a product over the entire reaction temperature range. However, high concentrations of CO2, NH3, and a small amount of NOxwere detected. Results indicate that HCN was first oxidized to isocyanate followed by isocyanate further reacting with H2O to generate NH3and CO2. Part of NO was removed by the selective catalytic reduction (SCR) and oxidation reaction. Catalyst characterization showed that Ce1Mn2exhibited a higher specific surface area, with manganese oxide mainly existing in an amorphous state, potentially forming a solid solution structure with cerium oxide. The introduction of a suitable amount of cerium was beneficial, increasing the concentration of chemisorbed oxygen on the catalyst surface. The catalyst also exhibited the properties of adsorbing H2O, which was helpful for the isocyanic acid hydrolysis reaction.

There is a growing need to mitigate the discharge of extracellular antibiotic resistance genes (ARGs) from municipal wastewater treatment systems. Here, molecularly-imprinted graphitic carbon nitride (MIP-C3N4) nanosheets were synthesized for selective photocatalytic degradation of a plasmid-encoded ARG (blaNDM-1, coding for multidrug resistance New Delhi metallo-β-lactamase-1) in secondary effluent. Molecular imprinting with guanine enhanced ARG adsorption, which improved the utilization of photogenerated oxidizing species to degrade blaNDM-1rather than being scavenged by background nontarget constituents. Consequently, photocatalytic removal of blaNDM-1in secondary effluent with MIP-C3N4(k= 0.111 ± 0.028 min–1) was 37 times faster than with bare graphitic carbon nitride (k= 0.003 ± 0.001 min–1) under UVA irradiation (365 nm, 3.64 × 10–6Einstein/L·s). MIP-C3N4can efficiently catalyze the fragmentation of blaNDM-1, which decreased the potential for ARG repair by transformed bacteria. Molecular imprinting also changed the primary degradation pathway; electron holes (h+) were the predominant oxidizing species responsible for blaNDM-1removal with MIP-C3N4versus free radicals (i.e., ·OH and O2–) for coated but nonimprinted C3N4. Overall, MIP-C3N4efficiently removed blaNDM-1from secondary effluent, demonstrating the potential for molecular imprinting to enhance the selectivity and efficacy of photocatalytic processes to mitigate dissemination of antibiotic resistance from sewage treatment systems.

In this study, a sialic acid (SA) and transferrin (TF) imprinted biodegradable disulfide bridging organosilicas‐based drug delivery system (SS‐DMONS/DOX‐Ce6@MIPs) for targeted cancer therapy is constructed, for the first time. Disulfide bridged dendritic mesoporous organosilicas nanoparticles (SS‐DMONs) not only enhance drug loading as the drug repository, but also provide enough specific surface area for the molecular imprinting shell to expose more degradation and imprinted sites on the surface. In addition, SS can be disturbed in a highly reducing tumor microenvironment to achieve degradation. The biodegradable imprinting film, prepared with customized 2‐amino‐N‐(3,4‐dihydroxyphenethyl)‐3‐mercaptopropanamide and 4‐mercaptophenylboronic acid as functional monomers, endows SS‐DMONs with active targeting capacity, and responsive drug release through degradation under acidic and highly reductive tumor microenvironment. SS‐DMONS/DOX‐Ce6@MIPs after binding of TF can target tumor cells actively through multiple interactions, including the affinity between antigen and antibody, and the specific recognition between molecularly imprinted polymers and template molecules. Under laser irradiation the loaded chlorin e6 (Ce6) that can produce toxic reactive oxygen, combined with the doxorubicin (DOX), achieves chemical/photodynamic synergistic anticancer effects. SS‐DMONS/DOX‐Ce6@MIPs present excellent tumor targeting and dual‐responsive drug release, which provides an effective strategy for chemical/photodynamic antitumor therapy. A double template‐imprinted polymers is successfully prepared on the surface of disulfide bridged dendritic silicon using biodegradable biomaterials as functional monomer. Biological experimental results show that this nanoparticle can actively target tumor by multiple actions and effectively inhibit the growth of cancer cells through synergistic treatment without noticeable side effects and accumulation in vivo.

Peptaibols are a large family of linear, amphipathic polypeptides consisting of 5-20 amino acid residues generated from the fungal nonribosomal peptide synthetase (NRPS) pathway. With a relatively high content of non-proteinogenic amino acids such as α-aminoisobutyrate (Aib) and isovaline (Iva) in the skeleton, peptaibols exhibit a wide range of biological activities, including anti-microbial, cytotoxic, and neuroleptic effects. With five peptaibols brought to market for use as biocontrol agents, this class of peptides has received increasing attention from both biochemists and pharmacologists. In this review, we summarized the progress made in structural characterization, elucidation of biosynthetic pathways, and investigation of biosynthesis elucidation and bioactivities, to promote further efforts to develop peptaibols as pharmaceuticals.

No relevant conflicts of interest to declare.

Background and Objectives: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for treating pediatric hematological malignancies that are refractory to other therapies. However, severe infections in neutropenic patients remain the major cause of morbidity and mortality, as well as influence the engraftment during HSCT. Multidrug-resistance (MDR) pseudomonas aeruginosa sepsis during the pre-engraftment stage has a highly prevalence of mortality, especially in patients with the primary infection site at the facial dangerous triangle. Without the efficient and time treatment, the bacterium may readily spread into the brain, causing severe intracranial infection and even death. There is an urgent need to effectively control MDR-pseudomonas aeruginosa infection and reduce the mortality of patients undergoing allo-HSCT.

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