Optimized rAAV8 targeting acinar KLF4 ameliorates fibrosis in chronic pancreatitis via exosomes-enriched let-7s suppressing pancreatic stellate cells activation.

Chronic pancreatitis (CP) is marked by progressive fibrosis and the activation of pancreatic stellate cells (PSCs), accompanied by the destruction of pancreatic parenchyma, leading to the loss of acinar cells (ACs). Few research studies have explored the mechanism by which damaged ACs (DACs) contribute to PSCs activation and pancreatic fibrosis. Currently, there are no effective drugs for curing CP or limiting the progression of pancreatic fibrosis. In this research, co-culture with intact acinar cells (IACs) suppressed PSC activation, while co-culture with DACs did the opposite. Krüppel-like factor 4 (KLF4) was significantly upregulated in DACs and was established as the key molecule that switches ACs from PSCs-suppressor to PSCs-activator. We revealed the exosomes of IACs contributed to the anti-activated function of IACs-CS on PSCs. MiRNome profiling showed that let-7 family is significantly enriched in IAC-derived exosomes (>30% miRNome), which partially mediates IACs' suppressive impacts on PSCs. Furthermore, it has been observed that the enrichment of let-7 in exosomes was influenced by the expression level of KLF4. Mechanistic studies demonstrated that KLF4 in ACs upregulated Lin28A, thereby decreasing let-7 levels in AC-derived exosomes, and thus promoting PSCs activation. We utilized an adeno-associated virus specifically targeting KLF4 in ACs (shKLF4-pAAV) to suppress PSCs activation in CP, resulting in reduced pancreatic fibrosis. IAC-derived exosomes hold potential as potent weapons against PSCs activation via let-7s, while activated KLF4/Lin28A signaling in DACs diminished such functions. ShKLF4-pAAV holds promise as a novel therapeutic approach for CP.

A comparative investigation between particle oxidation catalyst (POC) and diesel particulate filter (DPF) coupling aftertreatment system on emission reduction of a non-road diesel engine.

Non-road emission regulations are becoming increasingly rigorous, which makes it necessary for non-road engines to adopt aftertreatment systems. The commonly used aftertreatments mainly include diesel oxidation catalytic (DOC), diesel particulate filter (DPF), particle oxidation catalyst (POC), selective catalytic reduction (SCR) and ammonia purification catalyst (ASC). The purpose of this study is to investigate the effects of using an integrated system (DOC + DPF/POC + SCR + ASC) on non-road diesel engine emissions under steady-state and transient operating conditions, respectively. The major works are the comparison between POC and DPF from the viewpoint of emission reduction. The results show that both POC and DPF can effectively reduce particulate matter (PM) and nitrogen oxide (NOX) emissions under steady-state conditions, and DPF has better purification effect than POC, especially for PM. The PM conversion rate of DPF is up to 87%, while that of POC is only 60% under the non-road steady-state test cycle (NRSC). Both NOX and hydrocarbon (HC) conversion rates are high, exceeding 95%. The conversions of PM, NOX, HC, and carbon monoxide (CO) of DPF in the non-road transient test cycle (NRTC) are 92.83%, 96.99%, 96.86% and 81.45%, respectively, while those of POC are 60.12%, 95.45%, 92.82% and 79.51%, respectively. Both the POC and DPF systems can meet the emission regulation limits. As a result, POC has the potential to substitute DPF in non-road engines due to its lower product and maintenance costs. We hope that the comparison study will provide useful guidance for improving the emissions performance of non-road diesel engines.

Mechanical properties analysis of medical endodontic instruments based on parameterization.

To study the relationship between structural parameters and mechanical properties of endodontic instruments, the T02004B25 nickel-titanium endodontic instrument was selected for bending and torsion tests and finite element simulation analysis, which demonstrated the feasibility of simulation analysis method. Then based on the idea of parametric design, the models of the endodontic instruments with different structural parameters (cross-section, pitch, taper) were established, and the bending-torsion performance simulation analysis was completed. The results showed that the mechanical properties of endodontic instruments with different structural parameters are different. It is necessary to find the optimal parameters for different structure parameters of endodontic instruments to maximize their service life.