Mechanochemical Formation of Poly(melamine-formaldehyde) Microplastic Fibers During Abrasion of Cleaning Sponges.

The abrasion of synthetic textile fibers is a significant factor in the generation of environmental microplastic fibers (MPFs). The extent to which polymer sponges designed specifically for surface cleaning have a tendency to release MPFs during normal use remains unknown. Here, the tribological behaviors of melamine cleaning sponges (also known as "magic erasers") with different strut densities against metal surfaces of different roughness were investigated using a reciprocating abrader. The MPFs formed by sponge wear under various conditions were characterized in terms of their morphology, composition, and quantity. They were mainly composed of poly(melamine-formaldehyde) polymer with linear or branched fiber morphologies (10-405 µm in length), which were formed through deformation and fracture of the struts within open cells of the sponges, facilitated by friction-induced polymer decomposition. The rate and capability of MPF production generally increased with increasing roughness of the metal surface and density of the struts, respectively. The sponge wear could release 6.5 million MPFs/g, which could suggest a global overall emission of 4.9 trillion MPFs due to sponge consumption. Our study reveals a hitherto unrecognized source of the environmental MPF contamination and highlights the need to evaluate exposure risks associated with these new forms of MPFs.

Lensless shadow microscopy-based shortcut analysis strategy for fast quantification of microplastic fibers released to water.

Fast quantification is the primary challenge in monitoring microplastic fiber (MPF) pollution in water. The process of quantifying the number of MPFs in water typically involves filtration, imaging on a filter membrane, and manual counting. However, this routine workflow has limitations in terms of speed and accuracy. Here, we present an alternative analysis strategy based on our high-resolution lensless shadow microscope (LSM) for rapid imaging of MPFs on a chip and modified deep learning algorithms for automatic counting. Our LSM system was equipped with wide field-of-view submicron-pixel imaging sensors (>1 cm2; ∼500 nm/pixel) and could simultaneously capture the projection image of >3-µm microplastic spheres within 90 s. The algorithms enabled accurate classification and detection of the number and length of >10-µm linear and branched MPFs derived from melamine cleaning sponges in each image (∼0.4 gigapixels) within 60 s. Importantly, neither MPF morphology (dispersed or aggregated) nor environmental matrix had a notable impact on the automatic recognition of the MPFs by the algorithms. This new strategy had a detection limit of 10 particles/mL and significantly reduced the time of MPF imaging and counting from several hours with membrane-based methods to just a few minutes per sample. The strategy could be employed to monitor water pollution caused by microplastics if an efficient sample separation and a comprehensive sample image database were available.

Design, Synthesis, Antitumour Evaluation, and In Silico Studies of Pyrazolo-[1,5-c]quinazolinone Derivatives Targeting Potential Cyclin-Dependent Kinases.

An efficient, straightforward, and metal-free methodology to rapidly access functionalised pyrazolo-[1,5-c]quinazolinones via a [3 + 2] dipolar cycloaddition and regioselective ring expansion process was developed. The synthesised compounds were characterised by methods such as NMR, HRMS, and HPLC. The in vitro antiproliferative activity against A549 cells (non-small cell lung cancer) was significant for compounds 4i, 4m, and 4n with IC50 values of 17.0, 14.2, and 18.1 µM, respectively. In particular, compounds 4t and 4n showed inhibitory activity against CDK9/2. Predicted biological target and molecular modelling studies suggest that the compound 4t may target CDKs for antitumour effects. The synthesised derivatives were considered to have moderate drug-likeness and sufficient safety in silico. In summary, a series of pyrazolo-[1,5-c]quinazolinone derivatives with antitumour activity is reported for the first time. We provide not only a simple and efficient synthetic method but also helpful lead compounds for the further development of novel cyclin-dependent kinase (CDK) inhibitors.

Cardioprotective Effects of n-3 Polyunsaturated Fatty Acids: Orchestration of mRNA Expression, Protein Phosphorylation, and Lipid Metabolism in Pressure Overload Hearts.

Background: Pressure overload can result in dilated cardiomyopathy. The beneficial effects of n-3 polyunsaturated fatty acids (n-3 PUFAs) on heart disorders have been widely recognized. However, the molecular mechanisms underlying their protective effects against cardiomyopathy remain unclear. Methods: Pressure overload in mice induced by 8 weeks of transverse aortic constriction was used to induce dilated cardiomyopathy. A transgenic fat-1 mouse model carrying the n-3 fatty acid desaturase gene fat-1 gene from Caenorhabditis elegans was used to evaluate the mechanism of n-3 PUFAs in this disease. Echocardiography, transmission electron microscopy, and histopathological analyses were used to evaluate the structural integrity and function in pressure overloaded fat-1 hearts. mRNA sequencing, label-free phosphoprotein quantification, lipidomics, Western blotting, RT-qPCR, and ATP detection were performed to examine the effects of n-3 PUFAs in the heart. Results: Compared with wild-type hearts, left ventricular ejection fraction was significantly improved (C57BL/6J [32%] vs. fat-1 [53%]), while the internal diameters of the left ventricle at systole and diastole were reduced in the fat-1 pressure overload hearts. mRNA expression, protein phosphorylation and lipid metabolism were remodeled by pressure overload in wild-type and fat-1 hearts. Specifically, elevation of endogenous n-3 PUFAs maintained the phosphorylation states of proteins in the subcellular compartments of sarcomeres, cytoplasm, membranes, sarcoplasmic reticulum, and mitochondria. Moreover, transcriptomic analysis predicted that endogenous n-3 PUFAs restored mitochondrial respiratory chain function that was lost in the dilated hearts, and this was supported by reductions in detrimental oxylipins and protection of mitochondrial structure, oxidative phosphorylation, and ATP production. Conclusions: Endogenous n-3 PUFAs prevents dilated cardiomyopathy via orchestrating gene expression, protein phosphorylation, and lipid metabolism. This is the first study provides mechanistic insights into the cardioprotective effects of n-3 PUFAs in dilated cardiomyopathy through integrated multi-omics data analysis.

Combining Injectable Plasma Scaffold with Mesenchymal Stem/Stromal Cells for Repairing Infarct Cavity after Ischemic Stroke.

Stroke survivors are typically left with structural brain damage and associated functional impairment in the chronic phase of injury, for which few therapeutic options exist. We reported previously that transplantation of human embryonic stem cell (hESC)-derived neural stem cells together with Matrigel scaffolding into the brains of rats after focal ischemia reduced infarct volume and improved neurobehavioral performance. Matrigel is a gelatinous protein mixture extracted from mouse sarcoma cells, thus would not be approved for use as a scaffold clinically. In this study, we generated a gel-like scaffold from plasma that was controlled by changing the concentration of CaCl2. In vitro study confirmed that 10-20 mM CaCl2 and 10-40% plasma did not affect the viability and proliferation of human and rat bone marrow mesenchymal stem/stromal cells (BMSCs) and neural stem cells (NSCs). We transplanted plasma scaffold in combination of BMSCs into the cystic cavity after focal cerebral ischemia, and found that the atrophy volume was dramatically reduced and motor function was significantly improved in the group transplanted with scaffold/BMSCs compared with the groups treated with vehicle, scaffold or BMSCs only. Our data suggest that plasma-derived scaffold in combination of BMSCs is feasible for tissue engineering approach for the stroke treatment.

Activated regulatory T cell regulates neural stem cell proliferation in the subventricular zone of normal and ischemic mouse brain through interleukin 10.

Recent studies have demonstrated that the depletion of Regulatory T cells (Tregs) inhibits neural progenitor cell migration after brain ischemia. However, whether Tregs affect neural stem/progenitor cell proliferation is unclear. We explored the effect of Tregs on neurogenesis in the subventricular zone (SVZ) after ischemia. Tregs were isolated and activated in vitro. Adult male C57BL/6 mice underwent 60 min transient middle cerebral artery occlusion (tMCAO). Then Tregs (1 × 10(5)) were injected into the left lateral ventricle (LV) of normal and ischemic mouse brain. Neurogenesis was determined by immunostaining. The mechanism was examined by inhibiting interleukin 10 (IL-10) and transforming growth factor (TGF-ß) signaling. We found that the number of BrdU(+) cells in the SVZ was significantly increased in the activated Tregs-treated mice. Double immunostaining showed that these BrdU(+) cells expressed Mash1. Blocking IL-10 reduced the number of Mash1(+)/BrdU(+) cells, but increased the amount of GFAP(+)/BrdU(+) cells. Here, we conclude that activated Tregs enhanced neural stem cell (NSC) proliferation in the SVZ of normal and ischemic mice; blockage of IL-10 abolished Tregs-mediated NSC proliferation in vivo and in vitro. Our results suggest that activated Tregs promoted NSC proliferation via IL-10, which provides a new therapeutic approach for ischemic stroke.

Cross-talk between human neural stem/progenitor cells and peripheral blood mononuclear cells in an allogeneic co-culture model.

Transplantation of human neural stem/progenitor cells (hNSCs) as a regenerative cell replacement therapy holds great promise. However, the underlying mechanisms remain unclear. We, here, focused on the interaction between hNSCs and allogeneic peripheral blood mononuclear cells (PBMCs) in a co-culture model. We found that hNSCs significantly decrease the CD3+ and CD8+ T cells, reduce the gamma delta T cells and increase the regulatory T cells, along with reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines after co-culture. We also found that PBMCs, in turn, significantly promote the proliferation and differentiation of hNSCs. Our data suggest that hNSCs cross-talk with immune cells.