Advanced modification of drug nanocrystals by using novel fabrication and downstream approaches for tailor-made drug delivery

Drug nanosuspensions/nanocrystals have been recognized as one useful and successful approach for drug delivery. Drug nanocrystals could be further decorated to possess extended functions (such as controlled release) and designed for special in vivo applications (such as drug tracking), which make best use of the advantages of drug nanocrystals. A lot of novel and advanced size reduction methods have been invented recently for special drug deliveries. In addition, some novel downstream processes have been combined with nanosuspensions, which have highly broadened its application areas (such as targeting) besides traditional routes. A large number of recent research publication regarding as nanocrystals focuses on above mentioned aspects, which have widely attracted attention. This review will focus on the recent development of nanocrystals and give an overview of regarding modification of nanocrystal by some new approaches for tailor-made drug delivery

Strong aftershocks traffic light system: A case study of the 8 January 2022 MS6.9 Menyuan earthquake, Qinghai Province, China

Strong aftershocks, especially the disaster-causing M≥5.0 kind, are a key concern for mitigation of seismic risks because they often lead to superimposed earthquake damage. However, the real-time forecasting results of the traditional probability prediction models based on statistics are usually far from accurate and therefore unsatisfactory. Borrowing an idea from the foreshock traffic light system (FTLS), which is based on observations of decreasing b-values or increasing differential stress just before a strong aftershock, we constructed a strong aftershock traffic light system (SATLS) that uses data-driven technology to improve the reliability of time sequence b-value calculations, and analyzed the b-value variations of strong aftershocks in the China continent. We applied this system to the MS6.9 Menyuan earthquake occurred on 8 January 2022. The earthquake occurrence rates before the largest aftershock (MS5.2) forecast by the Omi-R-J model were too low, although the model could accurately forecast aftershock rates for each magnitude interval in most time-periods. However, reliable b-values can be calculated using the time-sequence b-value data-driven (TbDD) method, and the results showed that the b-values continued declining from 1.3 days before the MS5.2 aftershock and gradually recovered afterward. This would suggest that the stress evolution in the focal area can provide data for deciding when to post risk alerts of strong aftershocks. In the process of building the SATLS, we studied thirty-four M≥6.0 intraplate earthquake sequences in the China continent and concluded that the differences between the b-values of the aftershock sequences and of the background events, △b = bafter - bbg = ±0.1, could be used as thresholds to determine whether M≥5.0 aftershocks would occur. The △b value obtained using the events before the MS5.2 aftershock of the MS6.9 Menyuan sequence was about -0.04, which would have caused the SATLS to declare a yellow alert, but there would have been some gap expected before a red alert was triggered by the b-value difference derived from the events associated with this strong aftershock. To accurately forecast a strong aftershock of M≥5.0, a deeper understanding of the true b-value and a detailed description of the stress evolution state in the source area is necessary

A high-energy liquid-jet hammer with specially designed backward stroke end buffer structure

A high-energy liquid-jet hammer with specially designed backward stroke end buffer structure was investigated computationally. Computational Fluid Dynamics (CFD) with the technique of dynamic and sliding meshes method was employed in this study. Results indicated that each of the geometric parameter of the buffer structure had a significant effect on the backward impacting energy of the impact body and brought a maximum of 49.8 % of backward impacting energy reduction. Experimental tests based on the non-contact measuring method were conducted to verify the simulation results, by which the accuracy and reliability of this CFD simulation method was proved. In addition, the high-energy liquid-jet hammer worked well with the optimal parameters of the buffer structure in bench testing and reached high penetration rate in a drilled borehole

Impact of Phenolic Constituents and Antioxidant Activities of Acer truncatum Leaves and Flowers upon Different Thermal Treatments

In order to promote the development and application of Acer truncatum leaves and flowers in the food area, in this study, the dynamic changes of their phenolic composition and antioxidant activity were investigated under steam, microwave, and baking treatments, meanwhile, three time periods were further selected to determine the contents of total phenols and major phenolic compounds, together with the variations of antioxidant abilities of samples before and after the three treatments, and those data were finally analyzed through principal components and correlation analyses. The results showed that baking significantly increased the total phenol content from 75.80±3.54 mg GAE/g to 82.55±2.54~87.78±1.53 mg GAE/g in Acer truncatum leaves (P<0.05), while there was no significant difference of the total phenol content among untreated leaves and flowers and those samples under other treatments. Among phenolic compounds in leaves, gallates including gallic acid, ethyl gallate, and 1,2,3,4,6-penta-O-galloyl-β-d-glucose increased in varying degrees under all three treatments, and 1,2,3,4,6-penta-O-galloyl-β-d-glucose increased 1.88-fold under 15 min baking. Nevertheless, prolong microwave or baking treatment led to the reduction of increasing rate of gallates content. The above change pattern of gallates also existed in flowers, but in a relatively gentle mode. The result of antioxidant assays demonstrated that the oxygen radical absorbance capacity values significantly increased in Acer truncatum leaves and flowers after most treatments, and the highest increase in leaves and flowers were 1.49 and 1.21 times, respectively. Principal components and correlation analysis revealed that the variation of the gallates was significantly correlated with the change of the total phenol content, and different phenolic compounds in leaves and flowers had different degrees of contribution to the overall antioxidant activity. The above results indicated that thermal treatment method and time period all significantly affected the phenolic composition and antioxidant activities of Acer truncatum leaves and flowers (P<0.05). Therefore, a proper selection of treatment condition was vital for the improvement of their biological activity and commodity value. Among which, FM10 (microwave treatment for 10 min) led to the enhancement of antioxidant activity of both leaves and flowers. Above all, the present research provided a theoretical basis for the processing and further study of Acer truncatum leaves and flowers as food resources

A mechanism of glucose tolerance and stimulation of GH1 β-glucosidases

β-Glucosidases are enzymes that hydrolyze β-glycosidic bonds to release non-reducing terminal glucosyl residues from glycosides and oligosaccharides, and thus have significant application potential in industries. However, most β-glucosidases are feedback inhibited by the glucose product, which restricts their application. Remarkably, some β-glucosidases of the glycoside hydrolase (GH) 1 family are tolerant to or even stimulated by glucose. Elucidation of the mechanisms of glucose tolerance and stimulation of the GH1 β-glucosidases will be crucial to improve their application through enzyme engineering. In this study, by comparing the primary and tertiary structures of two GH1 β-glucosidases with distinct glucose dependence, some putative glucose-dependence relevant sites were mutated to investigate their exact roles. Both biochemical and structural characterization of the mutants suggested that some sites at the entrance and middle of the substrate channel regulate the effects of glucose, and the relative binding affinity/preference of these sites to glucose modulates the glucose dependence. A mechanism was therefore proposed to interpret the glucose dependence of GH1 β-glucosidases. This research provides fresh insight into our current understanding of the properties and mechanisms of GH1 β-glycosidases and related enzymes that modulate their activity via feedback control mechanism

Habitat Elevation Shapes Microbial Community Composition and Alter the Metabolic Functions in Wild Sable (Martes zibellina) Guts

In recent decades, wild sable (Carnivora Mustelidae Martes zibellina) habitats, which are often natural forests, have been squeezed by anthropogenic disturbances such as clear-cutting, tilling and grazing. Sables tend to live in sloped areas with relatively harsh conditions. Here, we determine effects of environmental factors on wild sable gut microbial communities between high and low altitude habitats using Illumina Miseq sequencing of bacterial 16S rRNA genes. Our results showed that despite wild sable gut microbial community diversity being resilient to many environmental factors, community composition was sensitive to altitude. Wild sable gut microbial communities were dominated by Firmicutes (relative abundance 38.23%), followed by Actinobacteria (30.29%), and Proteobacteria (28.15%). Altitude was negatively correlated with the abundance of Firmicutes, suggesting sable likely consume more vegetarian food in lower habitats where plant diversity, temperature and vegetation coverage were greater. In addition, our functional genes prediction and qPCR results demonstrated that energy/fat processing microorganisms and functional genes are enriched with increasing altitude, which likely enhanced metabolic functions and supported wild sables to survive in elevated habitats. Overall, our results improve the knowledge of the ecological impact of habitat change, providing insights into wild animal protection at the mountain area with hash climate conditions

Habitat Elevation Shapes Microbial Community Composition and Alter the Metabolic Functions in Wild Sable (Martes zibellina) Guts

In recent decades, wild sable (Carnivora Mustelidae Martes zibellina) habitats, which are often natural forests, have been squeezed by anthropogenic disturbances such as clear-cutting, tilling and grazing. Sables tend to live in sloped areas with relatively harsh conditions. Here, we determine effects of environmental factors on wild sable gut microbial communities between high and low altitude habitats using Illumina Miseq sequencing of bacterial 16S rRNA genes. Our results showed that despite wild sable gut microbial community diversity being resilient to many environmental factors, community composition was sensitive to altitude. Wild sable gut microbial communities were dominated by Firmicutes (relative abundance 38.23%), followed by Actinobacteria (30.29%), and Proteobacteria (28.15%). Altitude was negatively correlated with the abundance of Firmicutes, suggesting sable likely consume more vegetarian food in lower habitats where plant diversity, temperature and vegetation coverage were greater. In addition, our functional genes prediction and qPCR results demonstrated that energy/fat processing microorganisms and functional genes are enriched with increasing altitude, which likely enhanced metabolic functions and supported wild sables to survive in elevated habitats. Overall, our results improve the knowledge of the ecological impact of habitat change, providing insights into wild animal protection at the mountain area with hash climate conditions

Apelin protects auditory cells from cisplatin-induced toxicity in vitro by inhibiting ROS and apoptosis

Apelin, a specific endogenous ligand of the G protein-coupled receptor APJ, suppresses oxidative stress and apoptosis in vitro and in vivo. The current study explored whether Apelin protects against toxicity induced by the anticancer drug cisplatin in vitro, and the possible mechanisms that underlie this protective effect. The results showed that Apelin was expressed in the mouse auditory cell line HEI-OC1 and in cochlear hair cells (HCs) and was significantly downregulated by cisplatin, whereas pre-treatment with exogenous Apelin significantly reduced cisplatin-induced apoptosis, and thus protected HEI-OC1 cells and cochlear HCs from cisplatin-induced injury. Furthermore, Apelin reduced reactive oxygen species (ROS) generation, rescued mitochondrial membrane potential disruption, inhibited JNK signaling and attenuated the expression of pro-apoptotic factors in HEI-OC1 cells and in cochlear explants treated with cisplatin. Our findings suggest that Apelin could be used as an otoprotective agent for the prevention of cisplatin-induced ototoxicity

Expression and purification of soluble single-chain Fv against human fibroblast growth factor receptor 3 fused with Sumo tag in Escherichia coli

Background: Overexpression or mutated activation of Fibroblast growth factor receptor 3 (FGFR3) is involved in the pathogenesis of many tumors. More and more studies focus on the potential usage of therapeutic antibodies against FGFR3. Results: In this study, a novel single-chain Fv (ScFv) against FGFR3 was prepared and characterized. To achieve the soluble expression, ScFv was fused with Sumo (Small ubiquitin-related modifier) by polymerase chain reaction (PCR), and cloned into pET-20b. The recombinant bacteria were induced by 0.5 mM Isopropyl-\u3b2-D-thiogalactopyranoside (IPTG) for 16 h at 20\ub0C, and the supernatant liquid of Sumo-ScFv was harvested and purified by Ni-NTA chromatography. After being cleaved by the Sumo protease, the recombinant ScFv was released from the fusion protein, and further purified by Ni-NTA chromatography. The purity of ScFv was shown to be higher than 95% and their yield reached 4 mg per liter of bacterial culture. In vitro data showed that ScFv can significantly attenuate FGF9-induced phosphorylation of FGFR3. Conclusion: We provide a novel method to produce soluble expression and bioactive functions of ScFv in Escherichia coli