Search

Therapeutics based on messenger RNA (mRNA) have become a promising class of methods for various diseases' treatments in recent years. The safe and effective delivery of mRNA into target cells is the premise of the clinical translation of mRNA. Due to the protonation of ionizable lipids in acidic conditions, the ionizable lipid nanoparticles (iLNPs) have lower toxicity and higher endosomal escape efficiency than permanent cationic lipid nanoparticles (cLNPs). They not only exhibit excellent delivery ability in commercial COVID-19 mRNA vaccines but also are highly potential carriers for delivering mRNA drugs. This review summarizes the composition, preparation, stability of mRNA iLNPs, and the recent progress in the mRNA delivery by iLNPs. According to the structure characteristics of ionizable heads, the ionizable lipids are classified into tertiary amine, quaternary amine, imidazole core, piperidine core, piperazine core, and diketopiperazine core-based head lipids. Their design, optimization, and applications on mRNA delivery are discussed. The current status of representative clinical trials based on mRNA iLNPs delivery is also analyzed. The challenges and prospects of mRNA iLNPs delivery in clinical applications are proposed at the end. [ABSTRACT FROM AUTHOR]

The use of nanocrystal technology to manufacture drug delivery systems intended to enhance therapeutic efficacy has attracted the attention of the pharmaceutical industry. However, the clinical application of nanocrystal drugs for injection is restricted by Ostwald ripening and the large-scale use of stabilizers such as polysorbate and lecithin, which have potential toxicity risks including hemolysis and allergies. Here, we designed an amorphous nanocrystal drug complex (IHNC), which is stabilizer-free and composed of indocyanine green (ICG) framework loading with a chemotherapeutic agent of 10-hydroxycamptothecin (HCPT). Considering the possibility of industrial manufacturing, IHNC was simply prepared with the assistance of ferric ion (III) via supramolecular assembly strategy. The theoretical result of Materials Studio simulation indicated that the prepared ICG-Fe(III) framework showed a stable spherical structure with the appropriate cavity for encapsulating the two drugs of HCPT and ICG with equal mass ratio. The IHNC was stable at physiological pH, with excellent PTT/PDT efficacy, and in vivo probing characteristics. The nanoscale size and reductive stimuli-responsiveness can be conducive to drug accumulation into the tumor site and rapid unloading of cargo. Moreover, such combination therapy showed synergistic photo/chemotherapy effect against 4T1 breast cancer and its tumor inhibition rate even up to 79.4%. These findings demonstrated that the nanocrystal drug delivery strategy could avoid the use of stabilizers and provide a new strategy for drug delivery for combination therapy. [ABSTRACT FROM AUTHOR]

Objective: Ischemia and hemorrhage of pituitary adenomas (PA) caused important clinical syndrome. However, the differences on clinical characteristics and surgical outcomes between these two kinds apoplexy were less reported. Methods: A retrospective analysis was made of patients with pituitary apoplexy between January 2013 and June 2018. Baseline and clinical characteristics before surgery were reviewed. All patients underwent transsphenoidal surgery and were followed up at least 1 year. Results: Total 67 cases (5.8%) among 1147 pituitary tumor patients were enrolled, which consisted of 28 (~2.4%) ischemic PA and 39 (~3.4%) hemorrhagic PA. There were more male patients in the ischemic group compared with hemorrhagic group (78.6% vs 53.8%, p=0.043). However, the mean age, tumor size and functional tumor ratio were significant higher in the hemorrhagic group. Headache was more common in ischemic PA (82.1%) than that of hemorrhagic PA (51.3%, p=0.011). Magnetic resonance imaging findings found that mucosal thickening and enhancement of the sphenoid sinus was observed in 15 ischemic PA patients (n=27, 55.6%), but none in patients with hemorrhagic PA (n=38, p<0.0001). It was worth noting that the rate of pre-surgical hypopituitarism in ischemic PA patients were seemed higher than that in hemorrhagic PA patients, but not significant. The two groups got a total tumor resection rate at 94.1% and 92.9%, independently. No significant difference on the operative time, blood loss in operation and complications in perioperative period was observed in two groups. After operation, cranial nerve symptoms recovered to normal at 81.8% of ischemic PA patients and 82.6% of hemorrhagic PA patients. Importantly, the incidence of postoperative hypopituitarism partially decreased in both groups, among which the rate of hypothyroidism in ischemic PA patients significantly decreased from 46.4% to 18.5% (p=0.044). Conclusion: Patients with ischemic PA presented different clinical characteristics to the hemorrhagic ones. Transsphenoidal surgery should be considered for the patients with neuro-ophthalmic deficits and might benefit for pituitary function recovery of the apoplectic adenoma patients, especially pituitary thyroid axis in ischemic PA patients. [ABSTRACT FROM AUTHOR]

The high-temperature deformation process and dynamic recrystallization (DRX) process of 21-4N were investigated under the conditions of the deformation temperature range of 1273~1453K, the strain rate range of 0.01~10s-1 and the deformation degree of 60% (the total deformation is 0.916) by using Gleeble-1500D thermal simulated test machine. The curves of stress-strain (σ – ε) were obtained, and the curves of work hardening rate (θ) and strain (ε) were obtained by taking derivative of σ - ε. The DRX cri tical strains under different conditions were determined by the curves of work hardening rate (θ - ε), and the DRX critical strain model was established. The peak strains of 21-4N were obtained by the curves of σ - ε, the relationship between peak stress (sp) and critical strain (ec) was determined, and the peak strain model was established. The DRX volume fraction models of 21-4N were established by using Avrami equation. The DRX grain size of 21-4N was calculated by Image Pro Plus 6.0, and its DRX grain size models were established. [ABSTRACT FROM AUTHOR]

In this paper, a controlmethod for a hydraulic loading systemof an electromechanical platform based on a fractional-order PID (Proportion-Integration-Differentiation) controller is proposed, which is used to drive the loading system of a mechatronic journal test rig. The mathematical model of the control system is established according to the principle of the electro-hydraulic system. Considering the indetermination of model parameters, the method of parameter identification was used to verify the rationality of the theoretical model. In order to improve the control precision of the hydraulic loading system, the traditional PID controller and fractional-order PID controller are designed by selecting appropriate tuning parameters. Their control performances are analyzed in frequency domain and time domain, respectively. The results show that the fractional-order PID controller has better control effect. By observing the actual control effect of the fractional-order PID controller on the journal test rig, the effectiveness of this control algorithm is verified. [ABSTRACT FROM AUTHOR]