Synthesis and NLRP3-Inflammasome Inhibitory Activity of the Naturally Occurring Velutone F and of Its Non-Natural Regioisomeric Chalconoids

Plant-derived remedies rich in chalcone-based compounds have been known for centuries in the treatment of specific diseases, and nowadays, the fascinating chalcone framework is considered a useful and, above all, abundant natural chemotype. Velutone F, a new chalconoid from Millettia velutina, exhibits a potent effect as an NLRP3-inflammasome inhibitor; the search for new natural/non-natural lead compounds as NLRP3 inhibitors is a current topical subject in medicinal chemistry. The details of our work toward the synthesis of velutone F and the unknown non-natural regioisomers are herein reported. We used different synthetic strategies both for the construction of the distinctive benzofuran nucleus (BF) and for the key phenylpropenone system (PhP). Importantly, we have disclosed a facile entry to the velutone F via synthetic routes that can also be useful for preparing non-natural analogs, a prerequisite for extensive SAR studies on the new flavonoid class of NLRP3-inhibitors

Deciphering transcriptional regulation mechanisms underlining fruit development and ripening in Vitis vinifera

BACKGROUND: Grapes (Vitis vinifera ) are an important woody crop cultivated in a broad range of environmental conditions. Grapefruit development is a physiological process whose molecular regulatory networks are still not sufficiently investigated. OBJECTIVE: The primary aim of the work was to identify which key genes, molecular mechanisms and networks were involved in fruit ripening and development through a comparison of available transcriptomic data at different stages during grape development and ripening. Secondly, we aimed at identifying among these fruit-related genes, which genes play also a functional role in other developmental and physiological processes in reproductive tissues (bud and flower). METHODS: The two objectives were obtained through a meta-analysis on 9 RNA-Sequencing (RNA-Seq) studies. Raw data was downloaded from publicly available resource and re-analyzed to find out the significant differentially expressed genes (DEGs) (p -value <0.05). Gene enrichment and functional analysis were done using MapMan and PageMan. DAVID web server was used to identify gene ontology. NetworkAnalyst was used for finding out the protein-protein interaction. RESULTS: 721 (178 were up-regulated and 534 were down-regulated) differentially regulated genes in fruit development were in common between all the four fruit studies. The gene set enrichment analysis performed on these commonly regulated genes showed that the following biological processes were significantly affected during the fruit development: induction of major CHO metabolism, starch and lactoylglutathione lyase and repression of cell wall-related pathways, photosynthesis and cytokinin synthesis. Some of the key genes involved in ethylene, brassinosteroid and cytokinin were down-regulated in the late stage of fruit ripening, while two key abscisic acid-related genes were up-regulated. Fruit ripening up-regulated some key genes encoding Homeobox (HB17), AP2EREBP (RAP2), C2C2-CO-like, WRKY (WRKY9), MYB (MYB62) while repressing several key genes encoding bHLH, MYBs, WRKYs and C2H2. CONCLUSION: This comprehensive meta-analysis allowed identifying which genes should be the main targets of a grape breeding strategy to improve physiological processes linked to fruit development and ripening. These data will be used for future sustainable biotechnologies strategies based on small-molecule treatments and genome editing

Micro Gasturbine Integrated Design. Part 1: Thermodynamic Cycle, Combustor, Recuperator and Bearings

In the last years micro gasturbines for cogeneration power plants have been proved to be a promising technical solution for the distributed production of electricity and heat. In order to enhance the machine efficiency and make it competitive with internal combustion engines, it is necessary to improve the efficiency of each component of the GT: in the first part of the paper the focus will be put on the combustor, the recuperator and the bearings. Combustor and bearings are cutting edge technology and for them a brief description of the design procedure has been reported. The recuperator plays a key role in the cycle efficiency, since the reduction of the pinch point temperature difference can strongly enhance the overall efficiency

Gaining Insight into Exclusive and Common Transcriptomic Features Linked to Drought and Salinity Responses across Fruit Tree Crops

The present study aimed at identifying and mapping key genes expressed in root tissues involved in drought and salinity tolerance/resistance conserved among different fruit tree species. Twenty-six RNA-Seq samples were analyzed from six published studies in five plant species (Olea europaea, Vitis riparia Michx, Prunus mahaleb, Prunus persica, Phoenix dactylifera). This meta-analysis used a bioinformatic pipeline identifying 750 genes that were commonly modulated in three salinity studies and 683 genes that were commonly regulated among three drought studies, implying their conserved role in resistance/tolerance/response to these environmental stresses. A comparison was done on the genes that were in common among both salinity and drought resulted in 82 genes, of which 39 were commonly regulated with the same trend of expression (23 were upregulated and 16 were downregulated). Gene set enrichment and pathway analysis pointed out that pathways encoding regulation of defense response, drug transmembrane transport, and metal ion binding are general key molecular responses to these two abiotic stress responses. Furthermore, hormonal molecular crosstalk plays an essential role in the fine-tuning of plant responses to drought and salinity. Drought and salinity induced a different molecular “hormonal fingerprint”. Dehydration stress specifically enhanced multiple genes responsive to abscisic acid, gibberellin, brassinosteroids, and the ethylene-activated signaling pathway. Salt stress mostly repressed genes encoding for key enzymes in signaling proteins in auxin-, gibberellin-(gibberellin 2 oxidase 8), and abscisic acid-related pathways (aldehyde oxidase 4, abscisic acid-responsive element-binding protein 3). Abiotic stress-related genes were mapped into the chromosome to identify molecular markers usable for the improvement of these complex quantitative traits. This meta-analysis identified genes that serve as potential targets to develop cultivars with enhanced drought and salinity resistance and/or tolerance across different fruit tree crops in a biotechnological sustainable way

Bronchoscopic lung volume reduction with one way valves in patients with heterogeneous emphysema.

BACKGROUND: We evaluated the feasibility and short-term functional outcome after bronchoscopic lung-volume reduction performed with one-way valves in patients with severe heterogeneous emphysema. METHODS: Thirteen patients entered this pilot study. Endobronchial one-way valves were placed in the segmental bronchi supplying the most hyperinflated parts of the emphysematous lungs to allow lung deflation, reduce lung volume, and alleviate symptoms. The valves and delivery catheter were inserted under intravenous anesthesia and spontaneous assisted ventilation, with visual control through a flexible bronchoscope. We performed unilateral bronchoscopic lung-volume reduction in 11 patients and staged bilateral procedures in 2. Preoperative median forced expiratory volume in 1 second (FEV1) was 0.75 L/s (22%), residual volume was 5.3 L (233%), total lung capacity, 7.9 L (123%); intrathoracic gas volume, 6.5 L (176%); and 6-minute walk test, 223 meters. All patients required supplemental oxygen at rest (1.4 L/min). The median preoperative Medical Research Council (MRC) scale dyspnea score was 4. RESULTS: Six complications occurred in 3 patients: two bilateral and one contralateral pneumothorax, one pneumonia, and two episodes of bronchospasm. Functional results at 1 and 3 months showed a significant improvement in FEV1, residual volume, and 6-minute walk test; 43% of the patients were able to completely stop supplemental oxygen. The posttreatment MRC median dyspnea score at 1 and 3 months was 2. Bronchoscopic follow up at 1 and 3 months showed that the valves were correctly in place with no granulation. CONCLUSIONS: Bronchoscopic lung-volume reduction with one-way valves can be performed with acceptable short-term safety and worthwhile functional benefits