Polyethyleneimine-mediated assembly of DNA nanotubes for KRAS siRNA delivery in lung adenocarcinoma therapy.

Self-assembled DNA nanostructures hold great promise in biosensing, drug delivery and nanomedicine. Nevertheless, challenges like instability and inefficiency in cellular uptake of DNA nanostructures under physiological conditions limit their practical use. To tackle these obstacles, this study proposes a novel approach that integrates the cationic polymer polyethyleneimine (PEI) with DNA self-assembly. The hypothesis is that the positively charged linear PEI can facilitate the self-assembly of DNA nanostructures, safeguard them against harsh conditions and impart them with the cellular penetration characteristic of PEI. As a demonstration, a DNA nanotube (PNT) was successfully synthesized through PEI mediation, and it exhibited significantly enhanced stability and cellular uptake efficiency compared to conventional Mg2+-assembled DNA nanotubes. The internalization mechanism was further found to be both clathrin-mediated and caveolin-mediated endocytosis, influenced by both PEI and DNA. To showcase the applicability of this hybrid nanostructure for biomedical settings, the KRAS siRNA-loaded PNT was efficiently delivered into lung adenocarcinoma cells, leading to excellent anticancer effects in vitro. These findings suggest that the PEI-mediated DNA assembly could become a valuable tool for future biomedical applications.

OTUB1/NDUFS2 axis promotes pancreatic tumorigenesis through protecting against mitochondrial cell death.

Pancreatic cancer is one of the most fatal cancers in the world. A growing number of studies have begun to demonstrate that mitochondria play a key role in tumorigenesis. Our previous study reveals that NDUFS2 (NADH: ubiquinone oxidoreductase core subunit S2), a core subunit of the mitochondrial respiratory chain complex I, is upregulated in Pancreatic adenocarcinoma (PAAD). However, its role in the development of PAAD remains unknown. Here, we showed that NDUFS2 played a critical role in the survival, proliferation and migration of pancreatic cancer cells by inhibiting mitochondrial cell death. Additionally, protein mass spectrometry indicated that the NDUFS2 was interacted with a deubiquitinase, OTUB1. Overexpression of OTUB1 increased NDUFS2 expression at the protein level, while knockdown of OTUB1 restored the effects in vitro. Accordingly, overexpression and knockdown of OTUB1 phenocopied those of NDUFS2 in pancreatic cancer cells, respectively. Mechanically, NDUFS2 was deubiquitinated by OTUB1 via K48-linked polyubiquitin chains, resulted in an elevated protein stability of NDUFS2. Moreover, the growth of OTUB1-overexpressed pancreatic cancer xenograft tumor was promoted in vivo, while the OTUB1-silenced pancreatic cancer xenograft tumor was inhibited in vivo. In conclusion, we revealed that OTUB1 increased the stability of NDUFS2 in PAAD by deubiquitylation and this axis plays a pivotal role in pancreatic cancer tumorigenesis and development.

New Quality Evaluation of Qizhi Xiangfu Pills Based on Fingerprint with Chemometric Analysis and Quantitative Analysis of Multi-Components by Single Marker.

Qizhi Xiangfu Pills (QZXFPs) is one of the most commonly used traditional Chinese medicine preparations for the treatment of dysmenorrhea, but the existing quality evaluation standards have certain shortcomings and deficiencies. An effective and scientific quality evaluation method plays a vital role in medication safety. In this study, fingerprint combined with chemometric analysis and quantitative analysis of multi-components by a single marker (QAMS) method was used to comprehensively evaluate the quality of QZXFPs. The fingerprints of 28 batches samples were established and 23 common peaks were distinguished, of which 7 peaks were identified as albiflorin, paeoniflorin, baicalin, ligustilide, cyperotundone, nootkatone and α-cyperone. The content of these seven active ingredients was determined simultaneously by the QAMS method and there was no significantly different between QAMS and the external standard method. Additionally, similarity analysis, hierarchical cluster analysis, principal component analysis and orthogonal partial least squares discrimination analysis were applied for classifying the 28 batches of samples, and to find the main components causing the quality differences between different batches. In conclusion, the established method can comprehensively evaluate the consistency of quality between different batches and provide a reference for formulation quality evaluation to ensure safe and effective application of QZXFPs.

Maleic anhydride promotes humus formation via inducing functional enzymes response in composting.

The purpose of this paper was to explore the promotion of maleic anhydride on the polymerization of precursors into humus in composting, and analyze the changes of key functional enzymes. The results showed that the content of humus in the treatment group added maleic anhydride (MAH) was higher than that in the control check (CK). The decrease rate of humus precursor concentration of MAH was also higher than that of CK. In MAH, the activities of laccase and tyrosinase were improved, thus enhanced the catalytic conversion of humus precursors. The analysis of bacterial community showed that maleic anhydride optimized the community structure of humification functional enzymes producing bacteria, with the most obvious increase of Firmicutes. In conclusion, this study provided theoretical supports for the introduction of maleic anhydride into the compost system to promote the polymerization of precursors to form humus.

Competition and interaction between DNRA and denitrification in composting ecosystems: Insights from metagenomic analysis.

This study investigated denitrification and dissimilatory nitrate reduction to ammonium (DNRA) competition for nitrite in composting of sugarcane pith and cow manure. Metagenomic analysis showed that Actinobacteria was the main DNRA microorganism. During heating phase and thermophilic phase, the abundances of denitrification functional genes (nirK and nirS decreased by 40.22% and 98.60%, respectively) and DNRA functional genes (nirB, nirD increased by 195.24% and 176.61%, and nrfA decreased by 45%, respectively) showed different trends. Interestingly, the abundance of nrfA increased by 250% during cooling and maturity phases. Mantel test revealed that competition between denitrification and DNRA microorganisms for NO2--N limited the succession of their respective communities (P < 0.01). Network analysis showed that unclassified Solirubrobacterales, Altererythrobacter and Microbacterium were the key microorganisms in DNRA microbial communities. The results provided new insights into the key microorganisms and their driving factors affecting DNRA and nitrogen management in the composting ecosystems.

Comprehensive Quality Evaluation of Qizhi Xiangfu Pills Based on Quantitative Analysis of Multi-Components by a Single Marker Combined with GC Fingerprints and Chemometrics.

BACKGROUND: Qizhi Xiangfu Pills (QXPs) are a traditional Chinese medicine (TCM) used clinically for qi stagnation and blood stasis. The current quality control of QXPs in the ministry standards and the reported literature is minimal, and requires improvement. OBJECTIVE: This study aimed to analyze and determine the active ingredients in QXPs for its overall evaluation. METHODS: In this study, a quantitative analysis of multi-components by a single marker (QAMS) method was established to simultaneously determine caryophyllene oxide, cyperotundone, ligustilide, and α-cyperone in QXPs by GC. Moreover, the GC fingerprints of 22 batches of samples were also established, and the common peaks were initially identified by GC-MS, then classified in various dimensions using chemometric methods, and the main markers causing the discrepancies between groups were analyzed by orthogonal partial least-squares discrimination analysis (OPLS-DA). RESULTS: Compared with an internal standard method (ISM), the determination results obtained by QAMS had no significant difference. Twenty-two common peaks were distinguished in the fingerprint of 22 batches of QXPs, 17 of which were identified, and the similarity of the fingerprints was greater than 0.898. The 22 batches of QXPs were roughly divided into 3 categories, and 12 main markers causing the discrepancies were discovered. CONCLUSION: The established QAMS method combined with the GC fingerprint and chemometrics is convenient and feasible, which helps to improve the quality evaluation of QXPs and provides a demonstration for the related study of compound preparations and single herbs. HIGHLIGHTS: QAMS combined with a GC fingerprint and chemometrics method was established to evaluate the quality of QXPs for the first time.

Diversity of lignocellulolytic functional genes and heterogeneity of thermophilic microbes during different wastes composting.

The goal of this study was to investigate the heterogeneity of thermophilic microorganisms and their lignocellulose-degrading gene diversity during composting. In this study, bagasse pith/dairy manure (BAG) and sawdust/dairy manure (SAW) were used as experimental subjects. The pour plate method indicated that thermophilic bacteria and thermophilic actinobacteria were more culturable than thermophilic fungi. Metagenomics analysis showed that the Actinobacteria, Firmicutes and Proteobacteria were the dominant phyla during composting. In addition, auxiliary activity and glycoside hydrolase families were critical for lignocellulosic degradation, which were found to be more abundant in BAG. As a result, the degradation rates of cellulose, hemicellulose and lignin in BAG (7.36%, 13.99% and 5.68%) were observably higher than those in SAW (6.13%, 12.09% and 2.62%). These findings contribute to understanding how thermophilic microbial communities play a role in the deconstruction of different lignocelluloses and provide a potential strategy to comprehensively utilize the resources of lignocellulosic biomass.

A novel sensor for visual and selective detection of Hg2+ based on functionalized doped quantum dots.

In this paper, a novel analytical platform for the visual, sensitive and reliable analysis of mercury ions (Hg2+) is fabricated based on functionalized doped quantum dots. We synthesized a new specific nano-material, zinc dithiothreitol combined with graphene quantum dots (ZnNCs-NGQDs), by a simple and convenient method which, as an efficient luminophore, was then applied to construct an electrochemiluminescence (ECL) system for the first time. Under optimized conditions, the ECL sensor showed an excellent response for Hg2+ in the linear range of 1.0 mM to 10 pM, with a low detection limit of 3 pM. Moreover, the proposed method demonstrated satisfactory selectivity, stability and acceptable reproducibility for the detection of Hg2+. The recovery of tap water and lake water samples ranged from 96% to 105%, indicating the potential applicability of the proposed method for monitoring environmental water samples. Meanwhile, visual attempts for mercury ion detection by using doped quantum dots have also obtained satisfactory results. Importantly, our research revealed a viable method for improving the sensitivity and convenience of target studies in sensing fields derived from functional material design.

Lignocellulosic depolymerization induced by ionic liquids regulating composting habitats based on metagenomics analysis.

The application of ionic liquids with sawdust and fresh dairy manure was studied in composting. The degradation of organic matter (OM), dissolved organic matter (DOM), and lignocellulose was analyzed. The DOM decreased by 14.25 mg/g and 11.11 mg/g in experimental group (ILs) and control group (CK), respectively. OM decreased by 7.32% (CK) and 8.91% (ILs), respectively. The degradation rates of hemicellulose, lignin, and cellulose in ILs (56.62%, 42.01%, and 23.97%) were higher than in CK (38.39%, 39.82%, and 16.04%). Microbial community and carbohydrate-active enzymes (CAZymes) were analyzed based on metagenomics. Metagenomic analysis results showed that ionic liquids enriched Actinobacteria and Proteobacteria in composting. Compared with CK, the total abundance values of GH11, GH6, AA6, and AA3_2 in ILs increased by 13.98%, 10.12%, 11.21%, and 13.68%, respectively. Ionic liquids can improve the lignocellulosic degradation by regulating the environmental physicochemical parameters (temperature, pH, C/N) to promote the growth of Actinobacteria and Proteobacteria and carbohydrate-active enzymes (CAZymes) abundance. Therefore, ionic liquids are a promising additive in lignocellulosic waste composting.

Exploring the effects of heavy metal passivation under Fenton-like reaction on the removal of antibiotic resistance genes during composting.

This study aims to explore the succession of microbes carrying antibiotic resistance genes (ARGs), the relationship between heavy metal speciation and ARGs via Fenton-like reaction during composting. The results indicated that the passivation of Cu and Ni was more prominent, and the Fenton-like reaction promoted exceptionally the passivation of Zn, Ni and Mn. The removals of macrolides-lincosamids-streptogramins (MLS), aminoglycoside and tetracycline resistance genes were induced with the composting process, but the relative abundance of bacitracin resistance genes increased. Additionally, Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes were main carriers and disseminators of ARGs, and the Fenton-like reaction improved the contribution degree of Proteobacteria to bacitracin, tetracycline and aminoglycoside resistance genes. Redundancy analysis revealed the passivation of heavy metal contributed to the removal of tetracycline, MLS and aminoglycoside resistance genes. Conclusively, the Fenton-like reaction promoted the passivation of Zn, Ni and Mn, and controlled the abundance of bacitracin resistance genes in composting.

In-situ generation of H2O2 by zero valent iron to control depolymerization of lignocellulose in composting niche.

Lignocellulosic degradation is a bottleneck of bioconversion during the composting process. In-situ generation of H2O2 in the composting system was an ideal method for efficiently promoting lignocellulase degradation, and zero valent iron (ZVI) was concerned because it can generate H2O2 by reducing dissolved oxygen. This study focused on the effects of ZVI treatment on lignocellulose degradation, microbial communities, and carbohydrate-active enzymes (CAZymes) genes during composting. Its results indicated that ZVI increased H2O2 content during composting, accompanied by the formation of •OH. The degradation rates of lignin, cellulose and hemicellulose in ZVI group (20.77%, 30.35% and 44.7%) were significantly higher than in CK group (17.01%, 26.12% and 38.5%). Metagenomic analysis showed that ZVI induced microbial growth that favored lignocellulose degradation, which increased the abundance of Actinobacteria and Firmicutes but reduced Proteobacteria. At the genus level, the abundance of Thermomonospora, Streptomyces, and Bacillus significantly increased. In addition, glycoside hydrolases and auxiliary activities were important CAZymes families of lignocellulose degradation, and their abundance was higher in the ZVI group. Redundancy analysis showed that the increased H2O2 and •OH content was a critical factor in improving lignocellulose degradation. Overall, H2O2 as a co-substrate enhanced the enzymatic efficiency, •OH unspecifically attacked lignocellulose, and the increase in functional microbial abundance was the main reason for promoting lignocellulose degradation in composting.

Signature of dissolved organic matter and microbial communities based on different oxygen levels response during distillers dried grains with solubles plus sugarcane pith co-fermentations.

The objective of this study was to investigate the relationship between dissolved organic matter (DOM) and microbial communities during the co-fermentation of distillers dried grains with solubles (DDGS) and sugarcane pith at different oxygen levels. In aerobic fermentation (AF), the content of DOM decreased from 32.61 mg/g to 14.14 mg/g, and decreased from 32.61 mg/g to 30.83 mg/g in anaerobic fermentation (ANF). Phenols and alcohols were consumed first in AF, while lipids and proteins were consumed first in ANF. Degradation rates of cellulose, hemicellulose and lignin in AF (6.67%, 39.93%, 36.50%) were higher than those in ANF (0.69%, 18.36%, 9.12%). Firmicutes, Actinobacteriota and Ascomycota were the main phyla in community. Distance-based redundancy analysis showed that pH, organic matter (OM) and DOM were the main driving factors of microbial community succession.

Red mud conserved compost nitrogen by enhancing nitrogen fixation and inhibiting denitrification revealed via metagenomic analysis.

The objective of this study was to investigate the effects of adding red mud (RM) on denitrification and nitrogen fixation in composting. The results revealed that the retentions of NH4+-N and NO3--N in experimental group (T) with RM were 16.20% and 7.27% higher than that in control group (CK) at the mature stage, respectively. The composition and structure of RM can effectively inhibit denitrification and enhance nitrogen fixation. Moreover, metagenomic analysis revealed that Actinobacteria and Proteobacteria were the main microorganisms in denitrification process, while Firmicutes were the main microorganisms in nitrogen fixation process. In T, denitrifying genes nirK and nosZ were 11% and 18% lower than those in CK, respectively, while nitrogen-fixing genes nifK and nifD were 18% and 34% higher than those in control group, respectively. Therefore, adding RM could reduce nitrogen loss and improve the quality of compost via enhancing nitrogen fixation and inhibiting denitrification process.

Humification process and mechanisms investigated by Fenton-like reaction and laccase functional expression during composting.

This study aims to explore the impacts of the Fenton-like reaction on hydrogen peroxide, hydroxyl radicals, humic substance (HS) formation, laccase activity and microbial communities during composting to optimize composting performances. The results indicated that the activity of laccase in the presence of the Fenton-like reaction (HC) (35.92 U/g) was significantly higher than that in the control (CP) (29.56 U/g). The content of HS in HC (151.91 g/kg) was higher than that in CP (131.73 g/kg), and amides, quinones, aliphatic compounds and aromatic compounds were promoted to form HS in HC by 2D-FTIR-COS analysis. Proteobacteria contributed most greatly to AA1 at phylum level, Pseudomonas and Sphingomonas abundances increased in HC. Redundancy analysis indicated that there was a strong positive correlation among the Fenton-like reaction, laccase and HS. Conclusively, the Fenton-like reaction improved the activity of laccase, promoted the formation of HS and enhanced the quality of compost.

A novel self-coated polydopamine nanoparticle for synergistic photothermal-chemotherapy.

The combination of photothermal therapy (PTT) and chemotherapy is a promising strategy to overcome the shortcomings of monotherapy. For the first time, we designed a self-coated nanoparticle formed by mesoporous polydopamine (MPDA) core and polydopamine (PDA) shell, which was used to load docetaxel and modified with hyaluronic acid (HA). The obtained nanoparticle can achieve targeted drug delivery and further exert the synergistic effect of PTT and chemotherapy. The MPDA core has high drug loading due to mesopores, and the PDA shell can prevent the drug from releasing in the non-target-site because of the pH-sensitivity of the PDA. Compared with other PDA coated nanoparticle, self-coated nanoparticle has a simpler composition and can avoid the potential toxicity caused by the introduction of other materials. Experimental results showed that it had good photothermal conversion ability both in vivo and in vitro, and could be actively targeted into tumor cells through HA-mediated targeting. Under laser irradiation, it ablated the tumors. Simple ingredient and preparation, good compatibility and obvious therapeutic effect make it have a broad application prospect in tumor therapy.

Facile preparation of hyaluronic acid-based quercetin nanoformulation for targeted tumor therapy.

In this study, a novel hyaluronic acid-based quercetin nanoformulation (QUT/HA-NF) was constructed for targeted tumor therapy. QUT/HA-NFs have the advantages of simple operation steps, low production cost and good industrialization prospects. Moreover, surfactants, solvents and chemicals are not involved in the preparation process, which avoid the cumbersome extraction of surfactants and the side effects caused by residual solvents or chemicals. The QUT/HA-NFs we prepared have small particle size and high drug loading. In vitro studies have shown that QUT/HA-NFs can significantly enhance tumor cell uptake and tumor cell killing through CD44 receptor mediation. In a xenograft mouse model of 4T1 tumor, QUT/HA-NFs showed stronger inhibition of tumor growth compared with quercetin alone. The QUT/HA-NFs proposed in this study are expected to provide a potential candidate for the treatment of tumors.

MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents.

Molecular targeted agents, such as sorafenib, remain the only choice of an antitumor drug for the treatment of advanced hepatocellular carcinoma (HCC). The Notch signaling pathway plays central roles in regulating the cellular injury/stress response, anti-apoptosis, or epithelial-mesenchymal transition process in HCC cells, and is a promising target for enhancing the sensitivity of HCC cells to antitumor agents. The ADAM metalloprotease domain-17 (ADAM-17) mediates the cleavage and activation of Notch protein. In the present study, microRNA-3163 (miR-3163), which binds to the 3'-untranslated region of ADAM-17, was screened using online methods. miRDB and pre-miR-3163 sequences were prepared into lentivirus particles to infect HCC cells. miR-3163 targeted ADAM-17 and inhibited the activation of the Notch signaling pathway. Infection of HCC cells with miR-3163 enhanced their sensitivity to molecular targeted agents, such as sorafenib. Therefore, miR-3163 may contribute to the development of more effective strategies for the treatment of advanced HCC.

Hyaluronic acid and polydopamine functionalized phase change nanoparticles for ultrasound imaging-guided photothermal-chemotherapy.

In this study, we successfully prepared polydopamine (PD) and hyaluronic acid (HA) coated liquid perfluorocarbon nanoparticles, which integrated the good photothermal conversion effect of PD, the ultrasound imaging properties of the liquid fluorocarbon and active tumor-targeting of HA. Liquid perfluorocarbon nanodroplets significantly improved in terms of their physical stability after being coated with PD and HA as the shell. Photothermal and ultrasound imaging experiments showed that PD could effectively convert near-infrared (NIR) laser energy into heat for photothermal therapy, which could induce a phase change of the liquid perfluorocarbon, thereby generating microbubbles, enhancing ultrasound imaging signals and promoting drug release. In vitro cellular experiments showed that HA on the surface of the nanoparticles could actively target 4T1 breast cancer cells by CD44 receptor-mediated endocytosis. Furthermore, the novel nanosystem has shown effective inhibition of tumor growth by synergistic photothermal-chemotherapy in tumor-bearing mice. In conclusion, the novel nanosystem we prepared in this study is expected to provide a new strategy for the diagnosis and treatment of cancer.

The Accuracy Comparison of Three Simultaneous Localization and Mapping (SLAM)-Based Indoor Mapping Technologies.

The growing interest and the market for indoor Location Based Service (LBS) have been drivers for a huge demand for building data and reconstructing and updating of indoor maps in recent years. The traditional static surveying and mapping methods can't meet the requirements for accuracy, efficiency and productivity in a complicated indoor environment. Utilizing a Simultaneous Localization and Mapping (SLAM)-based mapping system with ranging and/or camera sensors providing point cloud data for the maps is an auspicious alternative to solve such challenges. There are various kinds of implementations with different sensors, for instance LiDAR, depth cameras, event cameras, etc. Due to the different budgets, the hardware investments and the accuracy requirements of indoor maps are diverse. However, limited studies on evaluation of these mapping systems are available to offer a guideline of appropriate hardware selection. In this paper we try to characterize them and provide some extensive references for SLAM or mapping system selection for different applications. Two different indoor scenes (a L shaped corridor and an open style library) were selected to review and compare three different mapping systems, namely: (1) a commercial Matterport system equipped with depth cameras; (2) SLAMMER: a high accuracy small footprint LiDAR with a fusion of hector-slam and graph-slam approaches; and (3) NAVIS: a low-cost large footprint LiDAR with Improved Maximum Likelihood Estimation (IMLE) algorithm developed by the Finnish Geospatial Research Institute (FGI). Firstly, an L shaped corridor (2nd floor of FGI) with approximately 80 m length was selected as the testing field for Matterport testing. Due to the lack of quantitative evaluation of Matterport indoor mapping performance, we attempted to characterize the pros and cons of the system by carrying out six field tests with different settings. The results showed that the mapping trajectory would influence the final mapping results and therefore, there was optimal Matterport configuration for better indoor mapping results. Secondly, a medium-size indoor environment (the FGI open library) was selected for evaluation of the mapping accuracy of these three indoor mapping technologies: SLAMMER, NAVIS and Matterport. Indoor referenced maps were collected with a small footprint Terrestrial Laser Scanner (TLS) and using spherical registration targets. The 2D indoor maps generated by these three mapping technologies were assessed by comparing them with the reference 2D map for accuracy evaluation; two feature selection methods were also utilized for the evaluation: interactive selection and minimum bounding rectangles (MBRs) selection. The mapping RMS errors of SLAMMER, NAVIS and Matterport were 2.0 cm, 3.9 cm and 4.4 cm, respectively, for the interactively selected features, and the corresponding values using MBR features were 1.7 cm, 3.2 cm and 4.7 cm. The corresponding detection rates for the feature points were 100%, 98.9%, 92.3% for the interactive selected features and 100%, 97.3% and 94.7% for the automated processing. The results indicated that the accuracy of all the evaluated systems could generate indoor map at centimeter-level, but also variation of the density and quality of collected point clouds determined the applicability of a system into a specific LBS.

A homodinuclear cobalt complex for the catalytic asymmetric Michael reaction of ß-ketoesters to nitroolefins.

A homodinuclear Co2/aminophenol sulfonamide complex has been developed for the asymmetric Michael reaction of ß-ketoesters with nitroolefins. This procedure is capable of tolerating a wide range of substrates and excellent results (up to 99% yield, >99 : 1 dr and 98% ee) can also be obtained. Moreover, the reaction could be carried out on a 50 mmol scale without any decrease in the enantioselectivity and reactivity. On the basis of the results of mechanistic studies, we proposed that the Co2/2a complex would be the active species and a possible catalytic cycle was described.