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Due to the trend of continuous pharmaceutical manufacturing, twin screw wet granulation (TSWG), a continuous process, has gained increased research interest as a potential substitution of traditional batch granulation processes. Despite the complex nature of TSWG, its mechanisms have been gradually unveiled with the aid of innovative research strategies. This review synthesizes these recent findings to provide a comprehensive and mechanistic understanding of TSWG. We explain the impact of screw profiles (i.e. conveying, kneading, turbine mixing, and screw mixing elements) and process conditions (i.e. screw speed, feed rate, and liquid-to-solid ratio) on TSWG mixing performance and granule growth along the barrel, both of which ultimately affect critical granule attributes such as content uniformity, size distribution, strength, and compaction properties.Introduction It is now accepted that Parkinson's disease (PD) is not simply due to dopaminergic dysfunction, and there is interest in developing non-dopaminergic approaches to disease management. Adenosine A2A receptor antagonists represent a new way forward in the symptomatic treatment of PD.Areas covered In this narrative review, we summarize the literature supporting the utility of adenosine A2A antagonists in PD with a specific focus on istradefylline, the most studied and only adenosine A2A antagonist currently in clinical use.Expert opinion At this time, the use of istradefylline in the treatment of PD is limited to the management of motor fluctuations as supported by the results of randomized clinical trials and evaluation by Japanese and USA regulatory authorities. The relatively complicated clinical development of istradefylline was based on classically designed studies conducted in PD patients with motor fluctuations on an optimized regimen of levodopa plus adjunctive dopaminergic medications. In animal models, there is consensus that a more robust effect of istradefylline in improving motor function is produced when combined with low or threshold doses of levodopa rather than with high doses that produce maximal dopaminergic improvement. Exploration of istradefylline as a 'levodopa sparing' strategy in earlier PD would seem warranted.Injectable hydrogels attract more attention to hard tissue engineering for the fulfilment of the defects with irregular shapes. Therefore, the researchers investigated the biocompatibility and immune response to the injectable PCL-PEG-PCL-Col/nHA hydrogels in a mouse model. The histological examination was done via H&E. The activation of the immune cells was evaluated by using antibodies against the CD68, CD4, and CD8 markers. The expression of CCL-2, BCL-2, IL-10, and CD31 genes was measured. Moreover, serum levels of the ALT, ALP, AST, and Urea were detected. The results of the chemical analysis showed that the collagen and Nano-hydroxyapatite were successfully integrated into the PCL-PEG-PCL hydrogels. The histological examination revealed a delayed biodegradation rate after the addition of the collagen and Nano-hydroxyapatite. No prominent pro-inflammatory response was found at the site of the injection. There are no significant differences in the levels of the CD68 and CD8/CD4 lymphocyte ratio among groups (p > .05). The expression of the CD31, IL-10 was significantly increased in the PCL-PEG-PCL-Col/nHA hydrogel (p  .05). These in vivo results demonstrated that the injectable PCL-PEG-PCL-Col/nHA hydrogels are biocompatible and suitable for further research in hard tissue regeneration.Aim To investigate the expression profiles of circRNAs after intracerebral hemorrhage (ICH). Materials & methods RNA sequencing and qRT-PCR were used to investigate and validate circRNA expression levels. Bioinformatics analysis was performed to explore potential functions of the circRNAs. Results Expression levels of 15 circRNAs were consistently altered in patients with ICH compared with their expression levels in hypertension. Three circRNAs, hsa_circ_0001240, hsa_circ_0001947 and hsa_circ_0001386, individually or combined, were confirmed as promising biomarkers for predicting and diagnosing ICH. Bomedemstat cost The circRNAs were involved mainly in lysine degradation and the immune system. Conclusion This is the first study to report expression profiles of circRNAs after ICH and to propose that three circRNAs are potential biomarkers for ICH.Huanglongbing (HLB) incidence is increasing and threatening citrus production in São Paulo State, Brazil, despite multiple efforts to control the disease and its vector, the Asian citrus psyllid (ACP) (Diaphorina citri). The objective of this research was to study the temporal dynamics of HLB epidemics, under intensive disease management, in 177 individual commercial citrus blocks on a single property in São Paulo State. The effect of internal and external sources of HLB-associated bacteria and its vector were explored based on the disease epidemics and vector dynamics in the studied area. To manage HLB, the property owner used healthy nursery plants, eradicated symptomatic trees, and insecticides to control ACP. Logistic and Gompertz models were fitted to the data to describe dynamics of HLB incidence for all blocks. The average ACP per yellow sticky trap was determined for the same blocks for a period of four consecutive years. Both logistic and Gompertz models described the HLB epidemics well, although the Gompertz model provided a slightly better fit. Disease progress rates, HLB incidences and average ACP per trap in the 177 blocks were low compared with reports in the literature. HLB incidence and number of ACP per trap were higher (p-value ≤0.05) in part of citrus blocks located around the edge of the property. A large number of non-commercial trees was found near the property and are a potential primary inoculum source of HLB-associated bacteria, accounting for the higher incidence of HLB and ACP per trap in blocks located closest to the property´s edge. These results support the recommended preventive measures to HLB management and the necessity of external actions, to include trees in commercial orchards, and non-commercial trees located near commercial citrus properties, in an attempt to maximize the effectiveness of these preventive measures.

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