The mitochondrial RNA polymerase POLRMT promotes skin squamous cell carcinoma cell growth.

RNA polymerase mitochondrial (POLRMT) expression and the potential biological functions in skin squamous cell carcinoma (SCC) were explored. We showed that POLRMT is significantly elevated in skin SCC. Genetic depletion of POLRMT, using shRNA-induced knockdown or CRISPR/Cas9-mediated knockout (KO), resulted in profound anti-skin SCC cell activity. In patient-derived primary skin SCC cells or immortalized lines (A431 and SCC-9), POLRMT shRNA or KO potently suppressed mitochondrial DNA (mtDNA) transcription and suppressed cell viability, proliferation and migration. POLRMT shRNA or KO impaired mitochondrial functions in different skin SCC cells, leading to production of ROS (reactive oxygen species), depolarization of mitochondria and depletion of ATP. Moreover, mitochondrial apoptosis cascade was induced in POLRMT-depleted skin SCC cells. IMT1, a POLRMT inhibitor, largely inhibited proliferation and migration, while inducing depolarization of mitochondria and apoptosis in primary skin SCC cells. Contrarily, ectopic overexpression of POLRMT increased mtDNA transcription and augmented skin SCC cell growth. Importantly, POLRMT shRNA adeno-associated virus injection robustly hindered growth of the subcutaneous A431 xenografts in mice. In the POLRMT shRNA virus-treated A431 xenograft tissues, POLRMT depletion, mtDNA transcription inhibition, cell apoptosis, lipid peroxidation and ATP depletion were detected. Together, overexpressed POLRMT increases mtDNA transcription and promotes skin SCC growth.

Iminyl radical-triggered relay annulation for the construction of bridged aza-tetracycles bearing four contiguous stereogenic centers.

Bridged tetracyclic nitrogen scaffolds are found in numerous biologically active molecules and medicinally relevant structures. Traditional methods usually require tedious reaction steps, and/or the use of structurally specific starting materials. We report an unprecedented, iminyl radical-triggered relay annulation from oxime-derived peresters and azadienes, which shows good substrate scope and functional group compatibility, and can deliver various bridged aza-tetracyclic compounds with complex molecular topology and four contiguous stereogenic centers (dr > 19 : 1) in a single operation. This transformation represents the first example of trifunctionalization of iminyl radicals through simultaneous formation of one C-N and two C-C bonds. DFT calculation studies were conducted to obtain an in-depth insight into the reaction pathways, which revealed that the reactions involved an interesting 1,6-hydrogen atom transfer process.

Deconstructive Insertion of Oximes into Coumarins: Modular Synthesis of Dihydrobenzofuran-Fused Pyridones.

In the presence of a copper catalyst, a series of oximes undergo deconstructive insertion into coumarins to afford structurally interesting dihydrobenzofuran-fused pyridones in moderate to good yields with good functional group compatibility. The reaction likely involves a radical relay annulation, leading to the ring opening of the lactone moiety of the coumarins, and simultaneous formation of three new bonds. The investigation of photoluminescent properties reveals that several obtained compounds may have potential as fluorescent materials.

Plant contribution to the remediation of PAH-contaminated soil of Dagang Oilfield by Fire Phoenix.

Pot experiments were conducted to evaluate plant contribution during remediation of the polycyclic aromatic hydrocarbons (PAH)-contaminated soil of Dagang Oilfield by Fire Phoenix (a mixture of Festuca L.). The results showed that Fire Phoenix could grow in soil contaminated by high and low concentrations of PAHs. After being planted for 150 days, the total removal rate of six PAHs in the high and low PAH concentrations was 80.36% and 79.79%, significantly higher than the 58.79% and 53.29% of the unplanted control group, respectively. Thus, Fire Phoenix can effectively repair the soil contaminated by different concentrations of PAHs. In high concentrations of PAHs, the results indicated a positive linear relationship between PAH absorption in tissues of Fire Phoenix and the growth time in the early stage. In contrast, the contents of PAHs were just slightly increased in the late period of plant growth. The main factor for the dissipation of PAHs was plant-promoted biodegradation (99.04%-99.93%), suggesting a low contribution of PAH uptake and transformation (0.07%-0.96%). The results revealed that Fire Phoenix did not remove the PAHs in the soil by accumulation but promoted PAH dissipation in the soil by stimulating the microbial metabolism in the rhizosphere.

[Combined remediation of polycyclic aromatic hydrocarbons (PAHs) by plant and immobilized bacteria in contaminated soil]. / 植物-固定化菌剂联合修复多环芳烃污染土壤.

In this study, three dominant bacteria Cellulomonas flavigena (Ⅰ), Cellulomonas flavigena (Ⅱ), Sphingomonas paucimobilis (Ⅲ) from Fire Phoenix rhizosphere soil were used to develop a multi-microbial agent system. For oil-contaminated soil in the Dagang oilfield, the immobilized test bacteria were inoculated into the Fire Phoenix rhizosphere soil to examine the effects of bacterial agents on polycyclic aromatic hydrocarbons (PAHs)-contaminated soil. The results showed that PAHs degradation was promoted under the ⅠⅢ (with an effective number of viable bacteria of 109 cfu·mL-1) and ⅠⅡⅢ (with an effective number of viable bacteria of 107 cfu·mL-1) treatments. The PAHs degradation rates were 32.2% and 41.4%, respectively, being significantly higher than that in the control treatments. The ⅠⅡⅢ treatment significantly promoted the belowground biomass of Fire Phoenix, which was 31.2% higher than that of the control treatment. Our results suggested that the multi-microbial agent constructed by the three dominant bacteria ⅠⅡⅢ could be used as a strengthening method for the remediation of PAHs-contaminated soil by Fire Phoenix, which provided a novel method for microbial enhanced phytoremediation technology.

Pressure-driven spreadable deferoxamine-laden hydrogels for vascularized skin flaps.

The development of hydrogels that support vascularization to improve the survival of skin flaps, yet establishing homogeneous angiogenic niches without compromising the ease of use in surgical settings remains a challenge. Here, pressure-driven spreadable hydrogels were developed utilizing beta-sheet rich silk nanofiber materials. These silk nanofiber-based hydrogels exhibited excellent spreading under mild pressure to form a thin coating to cover all the regions of the skin flaps. Deferoxamine (DFO) was loaded onto the silk nanofibers to support vascularization and these DFO-laden hydrogels were implanted under skin flaps in rats to fill the interface between the wound bed and the flap using the applied pressure. The thickness of the spread hydrogels was below 200 µm, minimizing the physical barrier effects from the hydrogels. The distribution of the hydrogels provided homogeneous angiogenic stimulation, accelerating rapid blood vessel network formation and significantly improving the survival of the skin flaps. The hydrogels also modulated the immune reactions, further facilitating the regeneration of the skin flaps. Considering the homogeneous distribution at the wound sites, improved vascularization, reduced barrier effects and low inflammation, these hydrogels appear to be promising candidates for use in tissue repair where a high blood supply is in demand. The pressure-driven spreading properties should simplify the use of the hydrogels in surgical settings to facilitate clinical translation.

Degradations of aroma characteristics and changes of aroma related compounds, PPO activity, and antioxidant capacity in sugarcane juice during thermal process.

Alterations of aroma properties and aroma-related attributes of sugarcane juice during thermal processing under different temperatures (90, 100, and 110 ℃) and treating time (10 s, 20 s, and 30 s) were assessed in this study. Changes in the volatility of aroma compounds were extremely complicated and respected to thermal processing conditions. Fructose, serine, and glutanic acid of sugarcane juice were increased at first and decreased at the end of treatment at high temperature. Phenolic compounds and PPO activity presented the decrease trends throughout the thermal treatment. The thermal processing of sugarcane juice could be roughly divided into three stages based on the cluster analysis of all the data in this study. Sugars, amino acids, and phenolic compounds might be important potential precursors of aroma deteriorating reactions. The comprehensive analysis of aroma relevant compounds and enzyme activities was beneficial for the investigation of degradation mechanism of aroma for sugarcane juice, and providing a theoretical basis for optimization of juice processing. PRACTICAL APPLICATION: This study demonstrated the changing process of aroma quality and associated compounds in sugarcane juice during thermal processing. This could help to find out the reasons of aroma degradations in sugarcane juice and other thermal sensitive juice. Our manuscript created a paradigm for future studies on the aroma quality control and parameter optimization during the processing of fruit and vegetable juice.

Oriented Assembly of Cell-Mimicking Nanoparticles via a Molecular Affinity Strategy for Targeted Drug Delivery.

Cell membrane cloaking is an emerging field in drug delivery in which specific functions of parent cells are conferred to newly formed biomimetic vehicles. A growing variety of delivery systems with diverse surface properties have been utilized for this strategy, but it is unclear whether the affinity of membrane-core pairs could guarantee effective and proper camouflaging. In this study, we propose a concise and effective "molecular affinity" strategy using the intracellular domain of transmembrane receptors as "grippers" during membrane coating. Red blood cell (RBC) membranes and cationic liposomes were adopted for fabrication, and a peptide ligand derived from the cytoplasmic protein P4.2 was prepared to specifically recognize the cytoplasmic domain of band 3, a key transmembrane receptor of erythrocytes. Once anchored onto the liposome surface, the P4.2-derived peptide would interact with the isolated RBC membrane, forming a "hidden peptide button", which ensures the right-side-out orientation. The membrane-coated liposomes exhibited an appropriate size distribution around 100 nm and high stability, with superior circulation durations compared with those of conventional PEGylated liposomes. Importantly, they possessed the ability to target Candida albicans by the interaction between the pathogenic fungus and host erythrocytes and to neutralize hemotoxin secreted by the pathogenic fungi. The curative effect of the model drug was thus substantially improved. In summary, the "molecular affinity" strategy may provide a powerful and universal approach for the construction of cell membrane-coated biomaterials and nanomedicines at both laboratory and industrial scales.