Evaluation of a Three-Dimensional Printed Guide and a Polyoxymethylene Thermoplastic Regulator for Percutaneous Pedicle Screw Fixation in Patients with Thoracolumbar Fracture.

BACKGROUND This study aimed to evaluate the efficacy of a porous polyoxymethylene thermoplastic regulator combined with a three-dimensional (3D) printed template to guide pedicle needle insertion in patients undergoing percutaneous pedicle screw fixation (PPSF) for thoracolumbar fracture. MATERIAL AND METHODS Forty patients were randomly divided into group A, treated using a porous polyoxymethylene thermoplastic regulator combined with a 3D printed template, and group B, who underwent conventional PPSF. Data recorded included the number of pedicle screws successfully inserted on the first attempt, the number of attempts, the time to successful needle insertion, the total time of fluoroscopy, and the duration of surgery. The Visual Analogue Scale (VAS) and the Oswestry Disability Index (ODI) scores one day before surgery, and at day 1, day 7, month 1, and month 3 after surgery were recorded. The postoperative vertebral posterior kyphotic angle (KA) and the rate of change of KA were recorded. RESULTS Group A had a significantly increased total number of successful first insertions compared with group BV (P<0.05). Postoperative VAS and ODI scores of patients in both groups were significantly lower than before surgery (P<0.05), with no significant difference between the two groups at postoperative month 1 and month 3 (P>0.05). The postoperative vertebral posterior KA decreased significantly in both groups after surgery, with no significant difference between the two groups (P>0.05). CONCLUSIONS The use of a porous polyoxymethylene thermoplastic regulator combined with a 3D printed template may improve the success of pedicle insertion in patients undergoing PPSF.

Global analysis of the adverse effects of micro- and nanoplastics on intestinal health and microbiota of fish.

The wide occurrence of micro- and nanoplastics (MPs/NPs) within aquatic ecosystems has raised increasing concerns regarding their potential effects on aquatic organisms. However, the effects of MPs/NPs on intestinal health and microbiota of fish remain controversial, and there is a lack of comprehensive understanding regarding how the impact of MPs/NPs is influenced by MPs/NPs characteristics and experimental designs. Here, we conducted a global analysis to synthesize the effects of MPs/NPs on 47 variables associated with fish intestinal health and microbiota from 118 studies. We found that MPs/NPs generally exerted obvious adverse effects on intestinal histological structure, permeability, digestive function, immune and oxidative-antioxidative systems. By contrast, MPs/NPs showed slight effects on intestinal microbial variables. Further, we observed that the responses of intestinal variables to MPs/NPs were significantly regulated by MPs/NPs characteristics and experimental designs. For instance, polyvinyl chloride plastics showed higher toxicity to fish gut than polyethylene and polystyrene did. Additionally, larval fish appeared to be more sensitive to MPs/NPs than juvenile fish. Collectively, this study highlights the potential impacts of MPs/NPs on intestinal health and microbiota of fish, and underscores the determinant role of MPs/NPs characteristics and experimental designs in MPs/NPs toxicity.

Discovery of the novel and potent histamine H1 receptor antagonists for treatment of allergic diseases.

Desloratadine, a second-generation histamine H1 receptor antagonist, has established itself as a first-line drug for the treatment of allergic diseases. Despite its effectiveness, desloratadine exhibits an antagonistic effect on muscarinic M3 receptor, which can cause side effects such as dry mouth and urinary retention, ultimately limiting its clinical application. Herein, we describe the discovery of compound Ⅲ-4, a novel H1 receptor antagonist with significant H1 receptor antagonistic activity (IC50 = 24.12 nM) and enhanced selectivity towards peripheral H1 receptor. In particular, Ⅲ-4 exhibits reduced M3 receptor inhibitory potency (IC50 > 10,000 nM) and acceptable hERG inhibitory activity (17.6 ± 2.1 µM) compare with desloratadine. Additionally, Ⅲ-4 exhibits favorable pharmacokinetic properties, as well as in vivo efficacy and safety profiles. All of these reveal that Ⅲ-4 has potential to emerge as a novel H1 receptor antagonist for the treatment of allergic diseases. More importantly, the compound Ⅲ-4 (HY-078020) has recently been granted clinical approval.

Anthracene-containing wide-band-gap conjugated polymers for high-open-circuit-voltage polymer solar cells.

The synthesis, characterization, and photophysical and photovoltaic properties of two anthracene-containing wide-band-gap donor and acceptor (D-A) alternating conjugated polymers (P1 and P2) are described. These two polymers absorb in the range of 300-600 nm with a band gap of about 2.12 eV. Polymer solar cells with P1:PC71 BM as the active layer demonstrate a power conversion efficiency (PCE) of 2.23% with a high Voc of 0.96 V, a Jsc of 4.4 mA cm(-2) , and a comparable fill factor (FF) of 0.53 under simulated solar illumination of AM 1.5 G (100 mW cm(-2) ). In addition, P2:PC71 BM blend-based solar cells exhibit a PCE of 1.42% with a comparable Voc of 0.89 V, a Jsc of 3.0 mA cm(-2) , and an FF of 0.53.

Role of polystyrene microplastics in sunlight-mediated transformation of silver in aquatic environments: Mechanisms, kinetics and toxicity.

Sunlight-oxidative ageing is a common and critical process for microplastics (MPs) in aquatic environments. O2•-, 1O2, and •OH generation has been widely proven in this process, which can alter metal speciation based on its reduction and oxidation potential. Herein, chemical speciation of Ag mediated by polystyrene (PS) MPs was determined under simulated sunlight irradiation. The O2•- generation on the PS MPs surfaces is the vital factor for Ag+ reduction, regardless of acid or base conditions. The 1O2 and •OH are dominant factors, and 1O2 played a more important role than •OH for its higher formation amount, causing oxidative dissolution of newly formed Ag0 nanoparticles (NPs). The Ag NPs can hetero-aggregate with PS MPs through electrostatic interactions with O-containing groups (C-O, C-OH and CO), and co-precipitate from the water phase. This hetero-aggregation can stabilize Ag NPs by inhibiting Ag NPs surface photooxidation and suppressing Ag+ release. Transformation of Ag species (from Ag+ to Ag0 NPs) mediated by sunlight with PS MPs significantly suppressed acute toxicity of Ag+ to Escherichia coli, Selenastrum capricornutum, Daphnia magna and zebrafish. This study emphasized that PS MPs play an important role in the speciation, migration and toxicity of Ag+ in freshwater environments.

[Indicator Function of Ragworm (Nereididae) on Sediment Microplastic in Haizhou Bay Intertidal Zone].

Sediment samples were collected from nine sites of three sections, in the intertidal zone of Haizhou bay in July 2018. The abundance and characteristics of microplastics in the sediments (and ragworms within the sediments) were then determined to identify the source of microplastics in ragworms, and to explore the effects of ragworms on microplastics in sediment. The average abundance of microplastics in tidal flat sediments was (0.49±0.17) n·g-1, which was at a high level in domestic offshore environmental studies. Among all the microplastics detected, the most common form and color were fiber and black-gray, respectively, and the materials were mainly polyethylene (PE), polyester (PET), and polystyrene (PS). The detection rate of microplastics in ragworm was 77.78%-86.67%, with an average abundance of (6.68±2.21) n·ind-1; the abundance was significantly correlated with individual mass (r=0.42, P=0.002). The microplastic abundance was significantly higher in ragworms with individual mass over 1.5 g than in those with a mass of<0.5 g or 0.5-1 g (F3=141.029, P=0.000). In ragworms, microplastics were dominated by small black or blue fibers, and the main materials were PE and PET. By analyzing the various characteristics of microplastics with a particle size of 0-3 mm, it was found that the abundance of microplastics in sediments was strongly correlated with that in ragworms (r=0.79,P=0.01); the main form (r=0.90, P=0.035) and the material composition (r=0.73, P=0.024) also showed significant correlation between sediments and ragworms. This indicates that ragworms ingest microplastics in the sedimentary environment and exchange the microplastics with the sediments. Therefore, ragworms can be used as an indicator species of microplastic pollution in sediments.

Reprogramming axial ligands facilitates the self-assembly of a platinum(iv) prodrug: overcoming drug resistance and safer in vivo delivery of cisplatin.

We herein reprogrammed axial ligands of platinum(iv) prodrugs, conferring the constructed prodrug entities with the ability to self-assemble in aqueous solution. Further cloaking of the PEG chain with Pluronic surfactant makes this nanoassembly (termed Pt(iv)-NP) suitable for systemic injection. Notably, Pt(iv)-NP significantly alleviated the toxicity of the parent cisplatin drug in vivo while preserving the pharmacological activity.

Precise Engineering of Prodrug Cocktails into Single Polymeric Nanoparticles for Combination Cancer Therapy: Extended and Sequentially Controllable Drug Release.

The synergistic combination of two or more chemotherapeutics frequently requires packaging in single delivery vehicles for the sequential release of each substance in a predictable manner. Here, we demonstrate for the first time that the rational engineering of a prodrug cocktail into single polymeric nanoparticles (NPs) can enable the sequential release of chemotherapeutics in a controllable manner. Exploiting combretastatin-A4 (CA4, 1) as a model antiangiogenesis agent, two ester derivatives, 2 and 3, tethered with saturated fatty acids (butanoic and heptanoic acid for 2 and 3, respectively) were synthesized. 7-Ethyl-10-hydroxycamptothecin (SN38) derivative 4, esterified with α-linolenic acid, was used as a cytotoxic drug. Because of their augmented lipophilicity and miscibility, all constructed prodrugs readily assembled with clinically approved polymeric matrices. Results showed that altering the aliphatic chains of modifiers for CA4 chemical derivatization enabled the drug retention capacity within particle systems to be adjusted, leading to the identification of the prodrug cocktail of 2 and 4 as an optimal combination for subsequent preclinical studies. Furthermore, in vivo assessements indicated that the resulting NPs simultaneously formulating 2 and 4 exhibited synergistic activities and outperformed NPs loaded with individual prodrugs 2 or 4 in terms of therapeutic efficacy. These findings highlight a novel and versatile strategy for tailoring chemically disparate prodrug cocktails for adaptation within a single nanoplatform as a potential modality for synergistic cancer therapy.

An investigation into the effects of silver nanoparticles on natural microbial communities in two freshwater sediments.

The expanding production and usage of commercial silver nanoparticles (AgNPs) will inevitably increase their environmental release, with sediments as a substantial sink. However, little knowledge is available about the potential impacts of AgNPs on freshwater sediment microbial communities, as well as the interactions between microbial communities and biogeochemical factors in AgNPs polluted sediment. To address these issues, two different sediments: a eutrophic freshwater sediment and an oligotrophic freshwater sediment, were exposed to 1 mg/g of either AgNO3, uncoated AgNPs (35-nm and 75-nm), or polyvinylpyrrolidone coated AgNPs (PVP-AgNPs) (30-50 nm) for 45 days. High-throughput sequencing of 16S ribosomal ribonucleic acid (16S rRNA) genes using the Illumina MiSeq platform was conducted to evaluate the effects of Ag addition on bacterial community composition. Moreover, sediment microbial biomass and activity were assessed by counting cultivable bacterial number and determining enzyme activities. During the 45-day exposure, compared with no amendment control, some treatments had resulted in significant changes and alterations of sediment biomass or bacterial enzyme activities shortly. While the microbial components at phylum level were rarely affected by AgNPs addition, and as confirmed by the statistical analysis with two-factor analysis of similarities (ANOSIM), there were no significant differences on bacterial community structure across the amended treatments. Redundancy analysis further demonstrated that chemical parameters acid-volatile sulfide (AVS) and simultaneously extracted silver (SE-Ag) in sediment significantly structured the overall bacterial community in sediments spiked with various silver species. In summary, these findings suggested that the ecotoxicity of AgNPs may be attenuated by the transformation under complex environmental conditions and the self-adaption of sediment microbial communities.

Integrating a novel SN38 prodrug into the PEGylated liposomal system as a robust platform for efficient cancer therapy in solid tumors.

Liposomal nanoassemblies have been used extensively as carriers for the delivery of both lipophilic and hydrophilic drugs. They represent a mature, versatile technology with considerable potential for improving the pharmacokinetics of drugs. However, the formulation of many chemotherapeutics into liposome systems has posed a significant challenge due to their incompatible physicochemical properties, as was the case with camptothecin-based chemotherapeutics. Here, we present a rational paradigm of potent chemotherapeutics that were reconstructed and subsequently integrated into liposomal nanoassemblies. Using SN38 (7-ethyl-10-hydroxy camptothecin) as a model drug, a lipophilic prodrug 1 (designated as LA-SN38) was constructed by tethering the linoleic acid (LA) moiety via esterification, which was further facilitated to form liposomal nanoparticles (LipoNP) through supramolecular nanoassembly. The resulting 1-loaded LipoNP exhibited sustained drug release kinetics and decreased cellular uptake by macrophage cells. Uptake by tumor cells was enhanced relative to our previous supramolecular nanoparticles (SNP 1), which were derived from the self-assembling prodrug 1. Notably, LipoNP outperformed SNP 1 in terms of pharmacokinetics and in vivo therapeutic efficacy in both human BEL-7402 hepatocellular carcinoma (HCC) and HCT-116 colorectal cancer-derived xenograft mouse models. These results were likely due to the improved systemic circulation and preferential accumulation of nanodrugs in tumors. Hence, our results suggest that the combination of liposomal delivery platforms with rational prodrug engineering may emerge as a promising approach for the effective and safe delivery of anticancer chemotherapeutics.

Isolation of cellulose from rice straw and its conversion into cellulose acetate catalyzed by phosphotungstic acid.

Cellulose was isolated from rice straw by pretreatment with dilute alkaline and acid solutions successively, and it was further transferred into cellulose acetate in the presence of acetic anhydride and phosphotungstic acid (H3PW12O40·6H2O). The removal of hemicellulose and lignin was affected by the concentration of KOH and the immersion time in acetic acid solution, and 83wt.% content of cellulose in the treated rice straw was obtained after pretreatment with 4% KOH and immersion in acetic acid for 5h. Phosphotungstic acid was found to be an effective catalyst for the acetylation of the cellulose derived from rice straw. The degree of substitution (DS) values revealed a significant effect for the solubility of cellulose acetate, and the acetone-soluble cellulose acetate with DS values around 2.2 can be obtained by changing the amount of phosphotungstic acid and the time of acetylation. Both the structure of cellulose separated from rice straw and cellulose acetate were confirmed by FTIR and XRD.