Divergent synthesis of difluoromethylated indole-3-carbinols, bisindolylmethanes and indole-3-methanamines.

Indole-3-carbinol, bisindolylmethanes (BIMs) and indole-3-methanamines exhibit diverse therapeutic activities. Fluorinated molecules are widely used in pharmaceuticals. Herein we report a facile and straightforward method for the successful synthesis of difluoromethylated indole-3-carbinols, bisindolylmethanes and indole-3-methanamines by a Friedel-Crafts reaction. The reaction involves the in situ generation of difluoroacetaldehyde from difluoroacetaldehyde ethyl hemiacetal in the presence of a base or an acid. This protocol is distinguished by its good to excellent yields, broad substrate compatibility, good functional group tolerance and scalability.

Isolation, Behavioral Identification, and Pathogenicity Assessment of Entomopathogenic Fungi from a Forest Wood Borer.

Forest wood borers (FWB) cause severe tree damage and economic losses worldwide. The release of entomopathogenic fungi (EPF) during the FWB emergence period is considered an acceptable alternative to chemical control. However, EPF resources have been significantly less explored for FWBs, in contrast to agricultural insect pests. This paper presents a protocol for exploring EPF resources from FWBs using wild Monochamus alternatus populations as an example. In this protocol, the assignment of traps baited with M. alternatus attractants to different populations guaranteed the collection of adequate samples with natural infection symptoms, during the emergence periods of the beetle. Following finely dissecting integuments and placing them onto a selective medium, fungal species were isolated from each part of beetle bodies and identified based on both molecular and morphological traits. Several fungal species were certified as parasitic EPFs via re-infection of healthy M. alternatus with spore suspensions. Their behavioral phenotypes on M. alternatus were observed using scanning electron microscopy and further compared with those on the Coleopteran model insect Tribolium castaneum. For EPFs that present consistent parasitism phenotypes on both beetle species, evaluation of their activities on T. castaneum provided valuable information on lethality for future study on M. alternatus. This protocol helped the discovery of EPF newly reported on M. alternatus populations in China, which could be applied as an efficient approach to explore more EPF resources from other FWBs.

Hemodynamic investigation and in vitro evaluation of a novel mixed-flow blood pump.

INTRODUCTION: Ventricular assist devices (VADs) are considered an effective treatment for patients with advanced heart failure, while complications associated with blood damage remain a burden. Structure design innovation has the potential to reduce hemolysis and improve hemocompatibility. METHODS: In this research, a novel mixed-flow blood pump that integrates structural features of the axial and centrifugal VADs was proposed. The pump consists of an inducer, a mixed impeller supported by two ceramic pivot bearings, and a volute. The flow field and laminar viscous shear stress were analyzed by the in silico simulation. The hydraulic and hemolytic performance were evaluated in vitro by using a 3D printed pump. RESULTS: The flow field distribution showed that streamlines in the connection area were smoothly transitioned through structural integration and no irregular flow occurred in the entire flow channel. The axial blades work as a fluid accelerator (generating 18.56% of the energy), and the centrifugal blades provide the main pressure head. The proportion of fluid inside the pump exposed to low laminar viscous shear stress (<50 Pa) and high laminar viscous shear stress (>150 Pa) was 99.02% and 0.03%, respectively. The in vitro hemolysis test results showed that the NIH (Normalized Index of Hemolysis) value of the mixed pump is 0.0079 ± 0.0039 g/100 L (n = 6). CONCLUSION: It can be concluded that the mixed flow structure is effective at improving hydraulic performance, eliminating flow disturbance, and minimizing shear stresses. This novel pump design is expected to provide a new direction for the development of next-generation VADs.

Fabrication and Hemocompatibility Evaluation of a Robust Honeycomb Nanostructure on Medical Pure Titanium Surface.

Thrombosis induced by blood-contacting medical devices is still a major clinical problem, resulting in some serious complications such as infarction, irreversible tissue damage, and even death. Therefore, seeking an effective and safe surface modification approach to improve the hemocompatibility of the material is still urgent. In this research, a novel and facile approach was proposed to fabricate a robust honeycomb nanostructure on medical pure titanium surface by two-step anodic oxidation, which effectively enhanced the physicochemical performance and hemocompatibility of the material. Especially, the honeycomb nanostructure that underwent annealing treatment at 500 °C (HN-Ti-500 °C) presented significant performance to suppress the coagulation cascade in the in vitro tests, the reason mainly ascribed to an overall repulsive interaction between the protein molecule related to thrombosis and material surface based on an extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory analysis. Furthermore, a vessel stent fabricated by HN-Ti-500 °C was implanted into the left carotid artery of rabbits for 1 month. The antithrombotic mechanism and biocompatibility of the modified surface were further verified. The results presented that no thrombus generated and adhered onto the inner surface of the modified stent, and no obvious disorder hyperplasia and inflammation were observed in the intima tissue of the vessel at the implantation site, which indicated that the modified surface could effectively decrease the risk of in-stent restenosis and thrombosis. This work offers a promising strategy for surface modification of blood-contacting medical titanium material to address the clinical complications associated with restenosis and thrombosis.

Discovery of entomopathogenic fungi across geographical regions in southern China on pine sawyer beetle Monochamus alternatus and implication for multi-pathogen vectoring potential of this beetle.

Entomopathogen-based biocontrol is crucial for blocking the transmission of vector-borne diseases; however, few cross-latitudinal investigations of entomopathogens have been reported for vectors transmitting woody plant diseases in forest ecosystems. The pine sawyer beetle Monochamus alternatus is an important wood borer and a major vector transmitting pine wilt disease, facilitating invasion of the pinewood nematode Bursaphelenchus xylophilus (PWN) in China. Due to the limited geographical breadth of sampling regions, species diversity of fungal associates (especially entomopathogenic fungi) on M. alternatus adults and their potential ecological functions have been markedly underestimated. In this study, through traditional fungal isolation with morphological and molecular identification, 640 fungal strains (affiliated with 15 genera and 39 species) were isolated from 81 beetle cadavers covered by mycelia or those symptomatically alive across five regional populations of this pest in southern China. Multivariate analyses revealed significant differences in the fungal community composition among geographical populations of M. alternatus, presenting regionalized characteristics, whereas no significant differences were found in fungal composition between beetle genders or among body positions. Four region-representative fungi, namely, Lecanicillium attenuatum (Zhejiang), Aspergillus austwickii (Sichuan), Scopulariopsis alboflavescens (Fujian), and A. ruber (Guangxi), as well as the three fungal species Beauveria bassiana, Penicillium citrinum, and Trichoderma dorotheae, showed significantly stronger entomopathogenic activities than other fungi. Additionally, insect-parasitic entomopathogenic fungi (A. austwickii, B. bassiana, L. attenuatum, and S. alboflavescens) exhibited less to no obvious phytopathogenic activities on the host pine Pinus massoniana, whereas P. citrinum, Purpureocillium lilacinum, and certain species of Fusarium spp.-isolated from M. alternatus body surfaces-exhibited remarkably higher phytopathogenicity. Our results provide a broader view of the entomopathogenic fungal community on the vector beetle M. alternatus, some of which are reported for the first time on Monochamus spp. in China. Moreover, this beetle might be more highly-risk in pine forests than previously considered, as a potential multi-pathogen vector of both PWN and phytopathogenic fungi.