To explore in vitro release rules of isoniazid (INH) when Isoniazid Super paramagnetic Iron Oxide Microspheres (ISPIOM) are subject to no external magnetic field, applied mechanical magnetic field and scillating magnetic field. ISPIOM was prepared by using the spray drying method; Isoniazid contented in the microspheres was determined, the drug loading capacity and encapsulation efficiency were calculated. Release of isoniazid in the microspheres was determined respectively under the effect of no external magnetic field, applied mechanical magnetic field and oscillating magnetic field, to explore the release rules. In solution with pH=7.4 PBS, microspheres featured 8-hour sustained release under the effect of magnetic field, the released rate of the microspheres is accelerated,. In solution with pH=3 PBS, microspheres release faster and could realize the fastest completion of release in 2 hours under the effect of oscillating magnetic field. To join the external magnetic field in different point time to can't affect the release, under pH=3 of medium, ISPIOM release faster; under the effect of magnetic field, the released rate of the microspheres is accelerated, and the longer effect of magnetic field, the faster release. Oscillating magnetic field can make ISPIOM within a certain period of time, get ideal release curve, so as to achieve good control release effect.
HIV risk behaviors and psychological well-being among men who have sex with men (MSM) in Kuala Lumpur, Malaysia (n = 140), were quantitatively described in relation to demographic and psychosocial factors. Most participants were tested for HIV and 41.4% reported living with HIV. Malay participants had significantly higher levels of depression (p < .05), homophobia (p < .01), and needs for social support (p < .01) than Chinese. More Chinese participants reported suicidal thoughts than Malaysians (p < .05). A multivariate analysis revealed that participants with gay/MSM-identified or had lower levels of self-esteem showed significantly higher levels of depression. Future intervention projects should address depression and mental health issues among MSM and strengthen self-esteem and social support through culturally competent support and individual counseling programs (e.g., addressing MSM's conflicts with religious beliefs and norms). Structural changes must be made incrementally to reduce homophobia against MSM in Malaysia while advocating human rights.
Porcine reproductive and respiratory syndrome virus (PRRSV) poses widespread epidemics in swine herds, yet the drivers underlying lineage replacements/fitness dynamics remain unclear. To delineate the evolutionary trajectories of PRRSV-2 lineages prevalent in China, we performed a comprehensive longitudinal phylodynamic analysis of 822 viral sequences spanning 1991-2022. The objectives encompassed evaluating lineage dynamics, genetic diversity, recombination patterns and glycosylation profiles. A significant shift in the dominance of PRRSV-2 sub-lineages has been observed over the past 3 decades, transitioning from sub-lineage 8.7 to sub-lineage 1.8, followed by extensive diversification. The analysis revealed discordant recombination patterns between the two dominant viral sub-lineages 1.8 and 8.7, underscoring that modular genetic exchanges contribute significantly to their evolutionary shaping. Additionally, a strong association was found between recombination breakpoint locations and transcriptional regulatory sequences (TRSs). Glycosylation patterns also demonstrated considerable variability across sub-lineages and temporally, providing evidence for immune-driven viral evolution. Furthermore, we quantified different evolutionary rates across sub-lineages, with sub-lineage 1.8 uniquely displaying the highest nucleotide substitution rates. Taken together, these findings provide refined insight into the evolutionary mechanisms underpinning cyclic shifts in dominance among regionally circulating PRRSV sub-lineages.
Aflatoxin is one of the most toxic biotoxins found in contaminated agricultural products. It has strong mutagenicity, carcinogenesis and teratogenicity to humans and animals. In this study, instant catapult steam explosion combined with ammonia water was examined for its potential to degrade aflatoxin B1 in peanut cake in order to improve its utilization as a toxic-free animal feed. Incubation of AFB1-containing peanut cake followed by processing with Instant Catapult Steam Explosion (ICSE) led to approximately 79.03 % degradation of AFB1, while the degradation of AFB1 was up to 91.48 % under the treatment of ICSE combined with 4 % NH₃·H₂O at 1.2 MPa in 200 s of process time. After treatment, nutrients in peanut cake were not significantly changed. The toxicity of AFB1 degradation products was evaluated and the results showed that the toxicity of these products were found to be substantially less than that possessed by AFB1. A low chemical pollution, efficient and toxic-free technology system of AFB1 degradation was established, which detoxify aflatoxin-contaminated biomass for sustainable and safe utilization of agricultural biomass as animal feed.
Overactivation of the rat sarcoma virus (RAS) signaling is responsible for 30% of all human malignancies. Son of sevenless 1 (SOS1), a crucial node in the RAS signaling pathway, could modulate RAS activation, offering a promising therapeutic strategy for RAS-driven cancers. Applying machine learning (ML)-based virtual screening (VS) on small-molecule databases, we selected a random forest (RF) regressor for its robustness and performance. Screening was performed with the L-series and EGFR-related datasets, and was extended to the Chinese National Compound Library (CNCL) with more than 1.4 million compounds. In addition to a series of documented SOS1-related molecules, we uncovered nine compounds that have an unexplored chemical framework and displayed inhibitory activity, with the most potent achieving more than 50% inhibition rate in the KRAS G12C/SOS1 PPI assay and an IC50 value in the proximity of 20 μg mL-1. Compared with the manner that known inhibitory agents bind to the target, hit compounds represented by CL01545365 occupy a unique pocket in molecular docking. An in silico drug-likeness assessment suggested that the compound has moderately favorable drug-like properties and pharmacokinetic characteristics. Altogether, our findings strongly support that, characterized by the distinctive binding modes, the recognition of novel skeletons from the carboxylic acid series could be candidates for developing promising SOS1 inhibitors.