Loss of NLRP6 expression increases the severity of intestinal injury after syngeneic hematopoietic stem cell transplantation.

NLRP6 plays a crucial role in maintaining intestinal homeostasis by regulating the interaction between the intestinal mucosa and the microbiota. However, the impact of NLRP6 deficiency on intestinal damage following hematopoietic stem cell transplantation (HSCT) remains poorly understood. In this study, we established a syngeneic HSCT mouse model using C57BL/6 mice as donors and NLRP6-/- or C57BL/6 mice as recipients. Our findings revealed that NLRP6 deficiency had minimal influence on peripheral blood cell counts and splenic immune cell proportions in transplanted mice. However, it exacerbated pathological changes in the small intestine on day 14 post-transplantation, accompanied by increased proportions of macrophages, dendritic cells, and neutrophils. Furthermore, the NLRP6 deficiency resulted in elevated expression of MPO and CD11b, while reducing the levels mature caspase-1 and mature IL-1ß in the intestine. Moreover, the NLRP6 deficiency disturbed the expression of apoptosis-related molecules and decreased the tight junction protein occludin. Notably, recipient mice with NLRP6 deficiency exhibited lower mRNA expression levels of antimicrobial genes, such as Reg3γ and Pla2g2a. The short-term increase in inflammatory cell infiltration caused by NLRP6 deficiency was associated with intestinal damage, increased apoptosis, reduced expression of antimicrobial peptides, and impaired intestinal repair. Taken together, our findings demonstrate that the loss of NLRP6 exacerbates post-transplantation intestinal damage in recipient mice.

Assessment of intestinal status in MPLW515L mutant myeloproliferative neoplasms mice model.

The MPLW515L mutation is a prevalent genetic mutation in patients with myeloproliferative neoplasms (MPN), and utilizing this mutation in mice model can provide important insights into the disease. However, the relationship between intestinal homeostasis and MPN mice model remains elusive. In this study, we utilized a retroviral vector to transfect hematopoietic stem cells with the MPLW515L mutation, creating mutated MPN mice model to investigate their intestinal status. Our results revealed that the MPLW515L in MPN mice model aggravated inflammation in the intestines, decreased the levels of tight junction proteins and receptors for bacteria metabolites. Additionally, there was increased activation of the caspase1/IL-1ß signaling pathway and a significant reduction in phos-p38 levels in the intestinal tissue in MPN mice. The MPLW515L mutation also led to up-expression of anti-microbial genes in the intestinal tract. Though the mutation had no impact on the alpha diversity and dominant bacterial taxa, it did influence the rare bacterial taxa/sub-communities and consequently impacted intestinal homeostasis. Our findings demonstrate the significance of MPLW515L mice model for studying MPN disease and highlight the mutation's influence on intestinal homeostasis, including inflammation, activation of the IL-1ß signaling pathway, and the composition of gut microbial communities.

Shear Adhesion of Ice on Large-Sized Grooved Aluminum Surfaces.

Ice adhesion is important when designing aircraft anti-icing/de-icing systems. Major and minor grooves are common in the skin of aircraft. However, the effects of millimeter-scale grooves on ice adhesive strength have not been given due attention. Specimens with varying depths, widths, and numbers of grooves were fabricated by machining to investigate the ice adhesive characteristics of large-sized grooved aluminum surfaces. After the ice cube was frozen on the surface using a silicon mold, the adhesive force was measured using a self-assembled shear adhesive force setup. A correlation between groove size and apparent adhesive strength in the perpendicular loading direction was established based on the experimental results. Every 1% increase in the groove width ratio was associated with an 18.7 kPa increase in apparent adhesive strength. The increasing speed of the adhesion rapidly decayed as the groove depth increased. The increase in adhesion reached 99% of the maximum increase when the groove depth reached 0.8 times the width. The number of grooves had little effect on the adhesion when the total width of the grooves was kept constant. Stress distribution analysis was conducted using the finite element method, and the results were in accordance with the cracking phenomena in the experiments. The adhesive strength in the parallel loading direction was 30% lower than that in the perpendicular loading direction for all six chosen surfaces. This study is the first to propose a quantitative relationship between the surface textures of millimeter-sized grooves and ice adhesive strength. The loading orientation also had a substantial influence on adhesion. The results will serve as a valuable reference for future studies on ice adhesion on textured surfaces and for improving the performance of anti-icing/de-icing systems.

Effect of lower extremity amputation on cardiovascular hemodynamic environment: An in vitro study.

Lower extremity amputation (LEA) was associated with a greater risk of cardiovascular disease, but its hemodynamic mechanisms have not been fully studied. Therefore, to clarify the interrelationship between them, and figure out the potential pathogenesis, the exploration of the hemodynamic environment change of patients after LEA was premeditatedly executed. A near-physiological mock circulatory system (MCS) was employed in the present work to replicate the cardiovascular circulation after LEA in a short time and the unsteady-state numerical simulation was utilized as an auxiliary method to observe the changes of the hemodynamic environment inside the blood vessel. Higher severity of LEA leads to higher peripheral vascular impedance, higher blood pressure, and more obvious redistribution of blood perfusion volume. In addition, higher severity of LEA leads to lower wall shear stress (WSS), higher oscillatory shear index (OSI), and higher relative residence time (RRT) appeared in the infrarenal abdominal aorta and the iliac artery, while these changes are closely related to the higher probability of cardiovascular diseases. Results showed that different degrees of LEA (varying heights, unilateral/bilateral) have diverse effects on the patient's hemodynamic environment. This study explained the potential pathogenesis of cardiovascular diseases after LEA from a hemodynamic perspective and provided a certain reference value for the improvement of the cardiovascular hemodynamic environment and the prevention of cardiovascular diseases in lower extremity amputees.

Reallocation of cutaneous and global blood circulation during sauna bathing through a closed-loop model.

OBJECTIVE: Sauna bathing (SB) is an important strategy in cardiovascular protection, but there is no mathematical explanation for the reallocation of blood circulation during heat-induced superficial vasodilation. We sought to reveal such reallocation via a simulated hemodynamic model. METHODS: A closed-loop cardiovascular model with a series of electrical parameters was constructed. The body surface was divided into seven blocks and each block was modeled by a lumped resistance. These resistances were adjusted to increase skin blood flow (SBF), with the aim of reflecting heat-induced vasodilation during SB. Finally, the blood pressure was compared before and after SB, and the blood flow inside the aorta and visceral arteries were also analyzed. RESULTS: With increasing SBF in this model, the systolic, diastolic, and mean blood pressure in the arterial trunk decreased by 13-29, 18-36, and 19-37 mmHg, respectively. Despite the increase in the peak and mean blood flow in the arterial trunk, the diastolic blood flow reversal in the thoracic and abdominal aortas increased significantly. Nevertheless, the blood supply to the heart, liver, stomach, spleen, kidney, and intestine decreased by at least 25%. Moreover, the pulmonary blood flow increased significantly. CONCLUSION: Simulated heat-induced cutaneous vasodilation in this model lowers blood pressure, induces visceral ischemia, and promotes pulmonary circulation, suggesting that the present closed-loop model may be able to describe the effect of sauna bathing on blood circulation. However, the increase of retrograde flow in the aortas found in this model deserves further examination.