Anti-inflammatory acetylenic meroterpenoids from the ascidian-derived fungus Amphichorda felina SYSU-MS7908.

A combination strategy of 13C NMR and bioinformatics was established to expedite the discovery of acetylenic meroterpenoids from the ascidian-derived fungus Amphichorda felina SYSU-MS7908. This approach led to the identification of 13 acetylenic meroterpenoids (1-13) and four biogenic analogs (14-17), including five new ones named felinoids A-E (1-4 and 15). Their structures and absolute configurations were elucidated using extensive spectroscopy, ECD quantum chemical calculations, and single-crystal X-ray diffraction analysis. Compound 1 possessed a rare cyclic carbonate in natural acetylenic meroterpenoids. The plausible shikimate-terpenoid biosynthetic pathways of 1-4 were also postulated. Five of these isolates exhibited anti-inflammatory activity by inhibiting NO production in LPS-induced RAW264.7 cells (IC50 = 11.6-19.5 µM). Moreover, oxirapentyn E diacetate showed a dose-dependent inhibition of pro-inflammatory cytokines IL-6 and TNF-α. Structural modification of oxirapentyn B yielded 29 new derivatives, among which seven showed improved activity (IC50 < 3 µM) and higher selectivity index (SI > 22). The structure-activity relationship study indicated that 7, 8-epoxy, and 6-acylation were crucial for the activity. These findings may provide a powerful tool to accelerate the discovery of new fungal acetylenic meroterpenoids for future anti-inflammatory drug development.

hUC-MSCs exosomal miR-451 alleviated acute lung injury by modulating macrophage M2 polarization via regulating MIF-PI3K-AKT signaling pathway.

In the previous study, we have proved that exosomal miR-451 from human umbilical cord mesenchymal stem cells (hUC-MSCs) attenuated burn-induced acute lung injury (ALI). However, the mechanism of exosomal miR-451 in ALI remains unclear. Therefore, this study aimed to study the molecular mechanism of hUC-MSCs-derived exosomal miR-451 on ALI by regulating macrophage polarization. Exosomes were isolated and identified by transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA). The expression of miR-451, macrophage migration inhibitory factor (MIF) and PI3K/AKT signaling pathway proteins were detected by qRT-PCR and western blot. Flow cytometry was used to detect the CD80 and CD206 positive cells. Severe burn rat model was established and HE was used to detect the inflammatory cell infiltration and inflammatory injury. Dual luciferase reporter system was used to detect the regulation of miR-451 to MIF. The contents of cytokines were detected by ELISA. The results showed that hUC-MSCs exosomes promoted macrophage M1 to M2 polarization. Furthermore, hUC-MSCs-derived exosomal miR-451 alleviated ALI development and promoted macrophage M1 to M2 polarization. Moreover, MIF was a direct target of miR-451. Downregulation of MIF regulated by miR-451 alleviated ALI development promoted macrophage M1 to M2 polarization. In addition, we found that MIF and hUC-MSCs-derived exosomal miR-451 participated in ALI by regulating PI3K/AKT signaling pathway. In conclusion, we indicated that hUC-MSCs-derived exosomal miR-451 alleviated ALI by modulating macrophage M2 polarization via regulating MIF-PI3K-AKT signaling pathway, which provided great scientific significance and clinical application value for the treatment of burn-induced ALI.

The combination of multiple linear regression and adaptive neuro-fuzzy inference system can accurately predict trihalomethane levels in tap water with fewer water quality parameters.

Artificial Neural Network (ANN) models are accurate in predicting the levels of disinfection by-products (DBPs) in drinking water. However, these models are not yet practical due to the large number of parameters involved, which should take a significant amount of time and cost to detect. Developing accurate and reliable prediction models of DBPs with fewest parameters is essential in the management of drinking water safety. This study used the adaptive neuro-fuzzy inference system (ANFIS) and radial basis function artificial neural network (RBF-ANN) to predict the levels of trihalomethanes (THMs), the most abundant DBPs in drinking water. Two water quality parameters identified by multiple linear regression (MLR) models were used as model inputs, and the quality of the models was assessed based on criteria such as correlation coefficient (r), mean absolute relative error (MARE), and the percentage of predictions with absolute relative error less than 25% (NE<25%) and over than 40% (NE>40%), etc. The results showed that the ANFIS models had higher correlation coefficients (r = 0.853-0.898) and prediction accuracy (NE<25% = 91%-94%) compared to RBF-ANN models (r = 0.553-0.819; NE<25% = 77%-86%) and traditional MLR models (r = 0.389-0.619; NE<25% = 67%-77%). Conversely, the prediction error, as indicated by MARE and NE>40%, showed the opposite trend: ANFIS models (MARE = 8%-11%; NE>40% = 0-5%) < RBF-ANN models (MARE = 15%-18%; NE>40% = 5%-11%) < MLR models (MARE = 19%-21%; NE>40% = 11%-17%). The present study provided a novel approach for constructing high-quality prediction models of THMs in water supply systems using only two parameters. This method holds promise as a viable alternative for monitoring THMs concentrations in tap water, thereby contributing to the improvement of water quality management strategies.

Feasibility of using Nakagami distribution in evaluating the formation of ultrasound-induced thermal lesions.

The acoustic posterior shadowing effects of bubbles influence the accuracy for defining the location and range of ablated thermal lesions during focused ultrasound surgery when using ultrasonic monitoring imaging. This paper explored the feasibility of using Nakagami distribution to evaluate the ablated region induced by focused ultrasound exposures at different acoustic power levels in transparent tissue-mimicking phantoms. The mean value of the Nakagami parameter m was about 0.5 in the cavitation region and increased to around 1 in the ablated region. Nakagami images were not subject to significant shadowing effects of bubbles. Ultrasound-induced thermal lesions observed in the photos and Nakagami images were overshadowed by bubbles in the B-mode images. The lesion size predicted in the Nakagami images was smaller than that predicted in the photos due to the sub resolvable effect of Nakagami imaging at the interface. This preliminary study on tissue-mimicking phantom suggested that the Nakagami parameter m may have the potential use in evaluating the formation of ultrasound-induced thermal lesion when the shadowing effect of bubbles is strong while the thermal lesion was small. Further studies in vivo and in vitro will be needed to evaluate the potential application.

Compare ultrasound-mediated heating and cavitation between flowing polymer- and lipid-shelled microbubbles during focused ultrasound exposures.

This paper compares the efficiency of flowing polymer- and lipid-shelled microbubbles (MBs) in the heating and cavitation during focused ultrasound exposures. Temperature and cavitation activity were simultaneously measured as the two types of shelled MBs and saline flowing through a 3 mm diameter vessel in the phantom with varying flow velocities (0-20 cm/s) at different acoustic power levels (0.6-20 W) with each exposure for 5 s. Temperature and cavitation for the lipid-shelled MBs were higher than those for the polymer-shelled MBs. Temperature rise decreased with increasing flow velocities for the two types of shelled MBs and saline at acoustic power 1.5 W. At acoustic power 11.1 W, temperature rise increased with increasing flow velocities for the lipid-shelled MBs. For the polymer-shelled MBs, the temperature rise increased with increasing flow velocities from 3-15 cm/s and decreased at 20 cm/s. Cavitation increased with increasing flow velocity for the two shelled MBs and there were no significant changes of cavitation with increasing flow velocities for saline. These results suggested that lipid-shelled MBs may have a greater efficiency than polymer-shelled MBs in heating and cavitation during focused ultrasound exposures.

Ultrasound line-by-line scanning method of spatial-temporal active cavitation mapping for high-intensity focused ultrasound.

This paper presented an ultrasound line-by-line scanning method of spatial-temporal active cavitation mapping applicable in a liquid or liquid filled tissue cavities exposed by high-intensity focused ultrasound (HIFU). Scattered signals from cavitation bubbles were obtained in a scan line immediately after one HIFU exposure, and then there was a waiting time of 2 s long enough to make the liquid back to the original state. As this pattern extended, an image was built up by sequentially measuring a series of such lines. The acquisition of the beamformed radiofrequency (RF) signals for a scan line was synchronized with HIFU exposure. The duration of HIFU exposure, as well as the delay of the interrogating pulse relative to the moment while HIFU was turned off, could vary from microseconds to seconds. The feasibility of this method was demonstrated in tap-water and a tap-water filled cavity in the tissue-mimicking gelatin-agar phantom as capable of observing temporal evolutions of cavitation bubble cloud with temporal resolution of several microseconds, lateral and axial resolution of 0.50 mm and 0.29 mm respectively. The dissolution process of cavitation bubble cloud and spatial distribution affected by cavitation previously generated were also investigated. Although the application is limited by the requirement for a gassy fluid (e.g. tap water, etc.) that allows replenishment of nuclei between HIFU exposures, the technique may be a useful tool in spatial-temporal cavitation mapping for HIFU with high precision and resolution, providing a reference for clinical therapy.