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International Journal of Nanomedicine 2024Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods...
BACKGROUND
Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods and their effectiveness in stimulating anti-tumor immune responses require further enhancement. Tumor cell lysates containing tumor-specific antigens and biomarkers can trigger a stronger immune response to tumors. In addition, strategies involving multiple gene therapies offer potential optimization paths for tumor gene treatments.
METHODS
Based on the previously developed ideal mRNA delivery system called DOTAP-mPEG-PCL (DMP), which was formed through the self-assembly of 1.2-dioleoyl-3-trimethylammonium-propane (DOTAP) and methoxypoly (ethylene glycol)-b-poly (ε-caprolactone) (mPEG-PCL), we introduced a fused cell-penetrating peptide (fCPP) into the framework and encapsulated tumor cell lysates to form a novel nanovector, termed CLSV system (CLS: CT26 tumor cell lysate, V: nanovector). This system served a dual purpose of facilitating the delivery of two mRNAs and enhancing tumor immunogene therapy through tumor cell lysates.
RESULTS
The synthesized CLSV system had an average size of 241.17 nm and a potential of 39.53 mV. The CLSV system could not only encapsulate tumor cell lysates, but also deliver two mRNAs to tumor cells simultaneously, with a transfection efficiency of up to 60%. The CLSV system effectively activated the immune system such as dendritic cells to mature and activate, leading to an anti-tumor immune response. By loading Bim-encoded mRNA and IL-23A-encoded mRNA, CLSV/Bim and CLSV/IL-23A complexes were formed, respectively, to further induce apoptosis and anti-tumor immunity. The prepared CLSV/dual-mRNA complex showed significant anti-cancer effects in multiple CT26 mouse models.
CONCLUSION
Our results suggest that the prepared CLSV system is an ideal delivery system for dual-mRNA immunogene therapy.
Topics: Animals; RNA, Messenger; Cell Line, Tumor; Colonic Neoplasms; Genetic Therapy; Immunotherapy; Nanoparticles; Mice; Mice, Inbred BALB C; Cell-Penetrating Peptides; Polyethylene Glycols; Humans; Polyesters; Female; Quaternary Ammonium Compounds; Fatty Acids, Monounsaturated
PubMed: 38828196
DOI: 10.2147/IJN.S452548 -
The Journal of Organic Chemistry Jun 2024The short and first total synthesis of (+)-colletotryptins B-D, -colletotryptin A, and diastereomer of mucronatin B, which are a group of natural...
The short and first total synthesis of (+)-colletotryptins B-D, -colletotryptin A, and diastereomer of mucronatin B, which are a group of natural 3-(indol-2-yl)-3-(indol-3-yl)-1,2-propanediol (IIPDO) analogues containing two stereogenic centers at the C8' and C9' positions, isolated from endophytic fungus sp. SC1355 and , respectively, has been successfully accomplished in two and three steps with overall yields ranging from 28 to 54%. Key features of this synthesis include an innovative Bi(OTf)-catalyzed stereoselective transindolylation of ()-3,3'-di(1-indol-3-yl)propane-1,2-diol. The operational simplicity, environmentally friendly catalyst, and broad functional group tolerance of this modular strategy render it suitable for adoption in both academic and industrial settings.
Topics: Stereoisomerism; Molecular Structure; Indoles; Catalysis; Colletotrichum
PubMed: 38809696
DOI: 10.1021/acs.joc.4c00552 -
Journal of Inorganic Biochemistry May 2024Four Pt(II) bis(pyrrole-imine) Schiff base chelates (1-4) were synthesised by previously reported methods, through a condensation reaction, and the novel crystal...
Four Pt(II) bis(pyrrole-imine) Schiff base chelates (1-4) were synthesised by previously reported methods, through a condensation reaction, and the novel crystal structure of 2,2'-{propane-1,3-diylbis[nitrilo(E)methylylidene]}bis(pyrrol-1-ido)platinum(II) (1) was obtained. Pt(II) complexes 1-4 exhibited phosphorescence, with increased luminescence in anaerobic solvents or when bound to human serum albumin (HSA). One of the complexes shows a 15.6-fold increase in quantum yield when bound to HSA and could be used to detect HSA concentrations as low as 5 nM. Pt(II) complexes 1-3 was investigated as potential theranostic agents in MCF-7 breast cancer cells, but only complex 3 exhibited cytotoxicity when irradiated with UV light (λ). Interestingly, the cytotoxicity of complex 1 was unresponsive to UV light irradiation. This indicates that only complex 3 can be considered a potential photosensitising agent.
PubMed: 38805758
DOI: 10.1016/j.jinorgbio.2024.112617 -
Scientific Reports May 2024Different from the Qaidam basin with about 320 billion m microbial gas, only limited microbial gases were found from the Junggar basin with similarly abundant type III...
Different from the Qaidam basin with about 320 billion m microbial gas, only limited microbial gases were found from the Junggar basin with similarly abundant type III kerogen. To determine whether microbial gases have not yet identified, natural gas samples from the Carboniferous to Cretaceous in the Junggar basin have been analyzed for chemical and stable isotope compositions. The results reveal some of the gases from the Mahu sag, Zhongguai, Luliang and Wu-Xia areas in the basin may have mixed with microbial gas leading to straight ethane to butane trends with a "dogleg" light methane in the Chung's plot. Primary microbial gas from degradation of immature sedimentary organic matter is found to occur in the Mahu sag and secondary microbial gas from biodegradation of oils and propane occurred in the Zhongguai, Luliang and Beisantai areas where the associated oils were biodegraded to produce calcites with δC values from + 22.10‰ to + 22.16‰ or propane was biodegraded leading to its C enrichment. Microbial CH in the Mahu sag is most likely to have migrated up from the Lower Wuerhe Formation coal-bearing strata by the end of the Triassic, and secondary microbial gas in Zhongguai and Beisantan uplifts may have generated after the reservoirs were uplifted during the period of the Middle and Late Jurassic. This study suggests widespread distribution of microbial gas and shows the potential to find large microbial gas accumulation in the basin.
Topics: Methane; Natural Gas; Gases; China; Geologic Sediments; Carbon Isotopes
PubMed: 38796638
DOI: 10.1038/s41598-024-62706-8 -
Molecules (Basel, Switzerland) May 2024Noble metals have become a research hotspot for the oxidation of light alkanes due to their low ignition temperature and easy activation of C-H; however, sintering and a...
Noble metals have become a research hotspot for the oxidation of light alkanes due to their low ignition temperature and easy activation of C-H; however, sintering and a high price limit their industrial applications. The preparation of effective and low-noble-metal catalysts still presents profound challenges. Herein, we describe how a Ru@CoMnO spinel catalyst was synthesized via Ru in situ doping to promote the activity of propane oxidation. Ru@CoMnO exhibited much higher catalytic activity than CoMnO, achieving 90% propane conversion at 217 °C. H-TPR, O-TPD, and XPS were used to evaluate the catalyst adsorption/lattice oxygen activity and the adsorption and catalytic oxidation capacity of propane. It could be concluded that Ru promoted synergistic interactions between cobalt and manganese, leading to electron transfer from the highly electronegative Ru to Co and Mn. Compared with CoMnO, 0.1% Ru@CoMnO, with a higher quantity of lattice oxygen and oxygen mobility, possessed a stronger capability of reducibility, which was the main reason for the significant increase in the activity of Ru@CoMnO. In addition, intermediates of the reaction between adsorbed propane and lattice oxygen on the catalyst were monitored by in situ DRIFTS. This work highlights a new strategy for the design of a low-noble-metal catalyst for the efficient oxidation of propane.
PubMed: 38792116
DOI: 10.3390/molecules29102255 -
International Journal of Molecular... May 2024A new, eco-friendly process utilising the green solvent propylene carbonate (PC) has been developed to perform -alkylation of -, - and/or -containing heterocyclic...
A new, eco-friendly process utilising the green solvent propylene carbonate (PC) has been developed to perform -alkylation of -, - and/or -containing heterocyclic compounds. PC in these reactions served as both the reagent and solvent. Importantly, no genotoxic alkyl halides were required. No auxiliary was necessary when using anhydrous PC. Product formation includes nucleophilic substitution with the concomitant loss of water and carbon dioxide. Substrates prepared, including the newly invented PROTAC drugs, are widely used.
Topics: Alkylation; Heterocyclic Compounds; Propane; Solvents; Green Chemistry Technology
PubMed: 38791560
DOI: 10.3390/ijms25105523 -
Nature Communications May 2024By combining the porosity of crystalline metal-organic frameworks (MOFs) with the unique processability of the liquid state, melt-quenched MOF glasses offer exciting...
By combining the porosity of crystalline metal-organic frameworks (MOFs) with the unique processability of the liquid state, melt-quenched MOF glasses offer exciting opportunities for molecular separation. However, progress in this field is limited by two factors. Firstly, only very few MOFs melt at elevated temperatures and transform into stable glasses upon cooling the corresponding MOF liquid. Secondly, the MOF glasses obtained thus far feature only very small porosities and very small pore sizes. Here, we demonstrate solvent-assisted linker exchange (SALE) as a versatile method to prepare highly porous melt-quenched MOF glasses from the canonical ZIF-8. Two additional organic linkers are incorporated into the non-meltable ZIF-8, yielding high-entropy, linker-exchanged ZIF-8 derivatives undergoing crystal-to-liquid-to-glass phase transitions by thermal treatment. The ZIF-8 glasses demonstrate specific pore volumes of about 0.2 cmg, adsorb large amounts of technologically relevant C and C hydrocarbons, and feature high kinetic sorption selectivities for the separation of propylene from propane.
PubMed: 38789474
DOI: 10.1038/s41467-024-48703-5 -
Journal of Fungi (Basel, Switzerland) May 2024The enticing aroma of truffles is a key factor for their culinary value. Although all truffle species tend to be pricy, the most intensely aromatic species are the most...
The enticing aroma of truffles is a key factor for their culinary value. Although all truffle species tend to be pricy, the most intensely aromatic species are the most sought after. Research into the aroma of truffles encompasses various disciplines including chemistry, biology, and sensory science. This study focusses on the chemical composition of the aroma of black truffles () and the changes occurring under different storage conditions. For this, truffle samples were stored under different treatments, at different temperatures, and measured over a total storage time of 12 days. Measurements of the truffle aroma profiles were taken with SPME/GC-MS at regular intervals. To handle the ample data collected, a systematic approach utilizing multivariate data analysis techniques was taken. This approach led to a vast amount of data which we made publicly available for future exploration. Results reveal the complexity of aroma changes, with 695 compounds identified, highlighting the need for a comprehensive understanding. Principal component analyses offer initial insights into truffle composition, while individual compounds may serve as markers for age (formic acid, 1-methylpropyl ester), freshness (2-Methyl-1-propanal; 1-(methylthio)-propane), freezing (tetrahydrofuran), salt treatment (1-chloropentane), or heat exposure (4-hydroxy-3-methyl-2-butanone). This research suggests that heat treatment or salt contact significantly affects truffle aroma, while freezing and cutting have less pronounced effects in comparison. The enrichment of compounds showing significant changes during storage was investigated with a metabolomic pathway analysis. The involvement of some of the enriched compounds on the pyruvate/glycolysis and sulfur pathways was shown.
PubMed: 38786709
DOI: 10.3390/jof10050354 -
Gels (Basel, Switzerland) Apr 2024This paper proposes a new, highly effective fluorescence test for Cr(VI) detection. This method utilizes a hydrogel composed of hydroxyethyl cellulose (HEC),...
This paper proposes a new, highly effective fluorescence test for Cr(VI) detection. This method utilizes a hydrogel composed of hydroxyethyl cellulose (HEC), nitrogen-doped carbon quantum dots (N-CQDs), and poly(co-acrylamido-2-methyl-1-propane sulfonic acid) (AMPS). The N-CQDs were successfully synthesized using a simple microwave method, and then conjugated with HEC and AMPS. The higher adsorption (99.41%) and higher reduction rate in H1 likely stems from both the presence of N-CQDs (absent in HB) and their increased free functional groups (compared to H2/H3, where N-CQDs block them). This facilitates the release (desorption) of Cr(VI) from the hydrogels, making it more available for reduction to the less toxic Cr(III). The fluorescent brightness of the HEC-N-CQDs-g-poly(AMPS) hydrogel increases gradually when Cr(VI) is added in amounts ranging from 15 to 120 mg/L. The fluorescent enhancement of the HEC-N-CQDs-g-poly(AMPS) hydrogel appeared to exhibit a good linear relationship with the 15-120 mg of the Cr(VI) concentration, with a detection limit of 0.0053 mg/L, which is lower than the standard value published by WHO. Our study found that the HEC-N-CQDs-g-poly(AMPS) hydrogel served effectively as a fluorescent probe for Cr(VI) detection in aqueous solutions, demonstrating high sensitivity.
PubMed: 38786213
DOI: 10.3390/gels10050296 -
International Medical Case Reports... 2024We treated two patients with ciliary detachment due to an ab interno trabeculotomy. The ciliary detachment was improved by the use of sulfur hexafluoride (SF) gas or...
PURPOSE
We treated two patients with ciliary detachment due to an ab interno trabeculotomy. The ciliary detachment was improved by the use of sulfur hexafluoride (SF) gas or octafluoro propane (CF) tamponade.
PATIENTS AND METHODS
Patient 1 was a 52-year-old Brazilian man with primary open angle glaucoma (POAG). His preoperative intraocular pressure (IOP) was 29 mmHg. Patient 2 was a 57-year-old Japanese woman with POAG. Her preoperative IOP was 35 mmHg. Both patients underwent an ab interno trabeculotomy with a microhook. They caused ciliary detachment as a postoperative complication. We could observe their ciliary detachment with anterior segment optical coherence tomography (AS-OCT). Hypotony persisted for 2 months and the patients' ciliary detachment had not improved. They each underwent a pars plana vitrectomy (PPV) with simultaneous 20% SF filling.
RESULTS
In Patient 1, the use of the SF gas tamponade successfully attached the ciliary body. His IOP was increased to 30 mmHg after this resolution of the ciliary detachment. He underwent additional tube shunt surgery. For Patient 2, the SF gas tamponade improved the ciliary detachment but the ciliary body could not be attached. We injected 0.6 cc of 100% CF gas into the vitreous cavity, and this gas tamponade was able to attach the ciliary body.
CONCLUSION
AS-OCT is very useful to evaluate ciliary detachment. PPV+Gas tamponade can be a treatment option for ciliary detachment.
PubMed: 38774709
DOI: 10.2147/IMCRJ.S465485