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Objective To investigate the key physical and chemical properties of nintedanib liposomes prepared by 4 different methods in order to screen out the best preparation method of nintedanib liposomes. Methods Firstly, nintedanib liposomes were prepared by thin film dispersion, reverse evaporation, ethanol injection and modified ethanol injection, respectively. The entrapment efficiency of nintedanib liposomes was then determined by dialysis and characterized for particle size, dispersibility, surface potential, and morphology. Their stability was evaluated after being placed at room temperature for 7 d. Results Circular nintedanib liposomes were respectively prepared by thin film dispersion, reverse evaporation, ethanol injection and modified ethanol injection, with a particle size of (285.1±12.3), (271.4±5.9), (226.3±14.8) and (197.2±11.2) nm, an encapsulation rate of (15.82±1.26)%, (16.71±1.35)%, (25.12±3.21)% and (32.5±3.61)%, respectively. The nintedanib liposomes prepared by modified ethanol injection had significantly smallest particle size and highest encapsulation efficiency than the liposomes by the other 3 methods (P < 0.05). In 7 d after being placed at room temperature, the particle sizes of the liposomes prepared by film dispersion and reverse evaporation were increased notably (P < 0.01), but no such change was observed in the liposomes prepared by ethanol injection and modified ethanol injection (P>0.05). Conclusion Nintedanib liposomes prepared by modified ethanol injection have excellent key physical and chemical properties, and this method is an optical one for preparing nintedanib liposomes.

The 2019-nCoV is officially called SARS-CoV-2 and the disease is named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002-2003 and MERS in 2012. While human strains of Coronavirus are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Extreme quarantine measures, including sealing off large cities, closing borders and confining people to their homes, were instituted in January 2020 to prevent spread of the virus, but by that time much of the damage had been done, as human-human transmission became evident. While these quarantine measures are necessary and have prevented a historical disaster along the lines of the Spanish flu, earlier recognition and earlier implementation of quarantine measures may have been even more effective. Lessons learned from SARS resulted in faster determination of the nucleic acid sequence and a more robust quarantine strategy. However, it is clear that finding an effective antiviral and developing a vaccine are still significant challenges. The costs of the epidemic are not limited to medical aspects, as the virus has led to significant sociological, psychological and economic effects globally. Unfortunately, emergence of SARS-CoV-2 has led to numerous reports of Asians being subjected to racist behavior and hate crimes across the world.

The mechanisms underlying protective immunity in mild Mycoplasma pneumoniae pneumonia (MPP) and the pathogenesis of severe MPP, characterized by dysregulated immune responses, remain unclear. Here, we performed single‐cell RNA sequencing (scRNA‐seq) to profile bronchoalveolar lavage fluid (BALF) samples from 13 healthy donors and 24 hospitalized pediatric patients with MPP, covering both mild and severe cases. Severe MPP patients exhibited high levels of exhausted T cells and M1‐like macrophages, with the exhaustion of T cells attributed to persistent type I interferon signaling and inadequate assistance from CD4+ T cells. Significant cell‐cell interactions between exhausted T cells and programmed death‐ligand 1+ (PD‐L1+) macrophages were detected in severe patients, potentially mediated through inhibitor molecules (e.g., PD1) and their receptors (e.g., PD‐L1), as well as human leukocyte antigen class I molecules and their receptors (e.g., KLRC1/D2), resulting in the dysfunction of anti‐MP immune responses. Mild MPP patients were featured by an increased abundance of neutrophils, coupled with enhanced activation, contributing to protective immunity. Together, our study provides a detailed characterization of the BALF immune landscape in MPP patients, revealing distinct immune characteristics between mild and severe cases, which offers a valuable resource for understanding MPP immunopathogenesis and formulating effective therapeutic strategies. [ABSTRACT FROM AUTHOR]

Designing and making sustainable plastics is especially urgent to reduce their ecological and environmental impacts. However, it remains challenging to construct plastics with simultaneous high sustainability and outstanding comprehensive performance. Here, a composite strategy of in situ polymerizing a petroleum‐based monomer with the presence of an industrialized bio‐derived polymer in a quasi‐solvent‐free system is introduced, affording the plastic with excellent mechanical robustness, impressive thermal and solvent stability, as well as low energy, consumes during production, processing, and recycling. Particularly, the plastic can be easily processed into diverse shapes through 3D printing, injection molding, etc. during polymerization and further reprocessed into other complex structures via eco‐friendly hydrosetting. In addition, the plastic is mechanically robust with Young's modulus of up to 3.7 GPa and tensile breaking strength of up to 150.2 MPa, superior to many commercially available plastics and other sustainable plastics. It is revealed that hierarchical hydrogen bonds in plastic predominate the well‐balanced sustainability and performance. This work provides a new path for fabricating high‐performance sustainable plastic toward practical applications, contributing to the circular economy. [ABSTRACT FROM AUTHOR]

Reduced kidney AMPK activity is associated with nutrient stress–induced chronic kidney disease (CKD) in male mice. In contrast, female mice resist nutrient stress–induced CKD. The role of kidney AMPK in sex-related organ protection against nutrient stress and metabolite changes was evaluated in diabetic kidney tubule–specific AMPKγ2KO (KTAMPKγ2ΚΟ) male and female mice. In wild-type (WT) males, diabetes increased albuminuria, urinary kidney injury molecule-1, hypertension, kidney p70S6K phosphorylation, and kidney matrix accumulation; these features were not exacerbated with KTAMPKγ2ΚΟ. Whereas WT females had protection against diabetes-induced kidney injury, KTAMPKγ2ΚΟ led to loss of female protection against kidney disease. The hormone 17β-estradiol ameliorated high glucose–induced AMPK inactivation, p70S6K phosphorylation, and matrix protein accumulation in kidney tubule cells. The mechanism for female protection against diabetes-induced kidney injury is likely via an estrogen-AMPK pathway, as inhibition of AMPK led to loss of estrogen protection to glucose-induced mTORC1 activation and matrix production. RNA sequencing and metabolomic analysis identified a decrease in the degradation pathway of phenylalanine and tyrosine resulting in increased urinary phenylalanine and tyrosine levels in females. The metabolite levels correlated with loss of female protection. The findings provide new insights to explain evolutionary advantages to females during states of nutrient challenges. Article Highlights: The basis for protection against kidney disease injury associated with obesity and diabetes in females is not known. In the present studies, genetic deletion of kidney tubule–specific gamma subunit of AMPK led to loss of female protection against diabetic kidney injury along with dysregulation of phenylalanine and tyrosine degradation. These new data indicate that AMPK in the kidney is critical for diabetic kidney disease. Importantly, differential regulation of kidney AMPK contributes to sex disparities. Our results provide a previously unrecognized mechanism for the development of precision treatments in sex dependence. [ABSTRACT FROM AUTHOR]