Coalescence-Induced Self-Propelled Particle Transport with Asymmetry Arrangement.

We experimentally investigated the coalescence-induced droplet-particle jumping phenomenon on a submillimeter scale in symmetric and asymmetric particle arrangements with poly(methyl methacrylate) (PMMA) particles and stainless steel (SS) particles. Coalescence-induced droplet-particle jumping exhibited excellent capability and interesting behavior for both droplet jumping enhancement and particle transport. The particle increased the normalized droplet jumping velocity from 0.250 for no particle case to 0.315 and 0.320 for symmetric and asymmetric particle cases. Compared with similar-sized macrostructures fixed between droplets, better jumping performance with particles may be attributed to avoiding the work of adhesion during droplet-macrostructure separation. Besides, all particles always sunk at the bottom in the symmetric cases, while the stick mode for PMMA particles and sink, wander, and jet modes for SS particles appeared in the asymmetry cases. We revealed that the asymmetric particle arrangement induces an unbalanced surface tension force, which may provide a driving force in the vertical direction. Additionally, a small enough resistive force caused by hydrophobic particles is another necessary condition for the wonder and jet mode. Finally, we realized a significantly superior particle transport in the asymmetric SS particle cases with maximum particle height reaching ∼2.1 mm, ∼12.4 times the particle radius, the most significant vertical self-propelled transport distance currently.

The hepatotoxicity of hexafluoropropylene oxide trimer acid caused by apoptosis via endoplasmic reticulum-mitochondrial crosstalk.

As a ubiquitous pollutant in the environment, hexafluoropropylene oxide trimer acid (HFPO-TA) has been proven to have strong hepatotoxicity. However, the underlying mechanism is still unclear. Consequently, in vivo and in vitro models of HFPO-TA exposure were established to investigate the detrimental effects of HFPO-TA on the liver. In vivo, we discovered that HFPO-TA enhanced endoplasmic reticulum (ER)-mitochondrial association, caused mitochondrial oxidative damage, activated ER stress, and induced apoptosis in mouse livers. In vitro experiments confirmed that IP3R overexpression on ER structure increased mitochondrial calcium levels, which led to mitochondrial damage and mitochondria-dependent apoptosis in HepG2 cells exposed to HFPO-TA. Subsequently, damaged mitochondria released a large amount of mitochondrial ROS, which activated ER stress and ER stress-dependent apoptosis. In conclusion, this study demonstrates that HFPO-TA can induce apoptosis by regulating the crosstalk between ER and mitochondria, ultimately leading to liver damage. These findings reveal the significant hepatotoxicity of HFPO-TA and its potential mechanisms.

Impact of preoperative [18F]FDG PET/CT vs. contrast-enhanced CT in the staging and survival of patients with clinical stage I and II non-small cell lung cancer: a 10-year follow-up study.

OBJECTIVES: To elucidate the impact of [18F]FDG positron emission tomography/computed tomography (PET/CT) vs. CT workup on staging and prognostic evaluation of clinical stage (c) I-II NSCLC. METHODS: We retrospectively identified 659 cI-II NSCLC who underwent CT (267 patients) or preoperative CT followed by PET/CT (392 patients), followed by curative-intended complete resection in our hospital from January 2008 to December 2013. Differences were assessed between preoperative and postoperative stage. Five-year disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier approach and compared with log-rank test. Impact of preoperative PET/CT on survival was assessed by Cox regression analysis. RESULTS: The study included 659 patients [mean age, 59.5 years ± 10.8 (standard deviation); 379 men]. The PET/CT group was superior over CT group in DFS [12.6 vs. 6.9 years, HR 0.67 (95% CI 0.53-0.84), p < 0.001] and OS [13.9 vs. 10.5 years, HR 0.64 (95% CI 0.50-0.81), p < 0.001]. In CT group, more patients thought to have cN0 migrated to pN1/2 disease as compared with PET/CT group [26.4% (66/250) vs. 19.2% (67/349), p < 0.001], resulting in more stage cI cases being upstaged to pII-IV [24.7% (49/198) vs. 16.1% (47/292), p = 0.02], yet this was not found in cII NSCLC [27.5% (19/69) vs. 27.0% (27/100), p = 0.94]. Cox regression analysis identified preoperative PET/CT as an independent prognostic factor of OS and DFS (p = 0.002, HR = 0.69, 95% CI 0.54-0.88; p = 0.004, HR = 0.72, 95% CI 0.58-0.90). CONCLUSION: Addition of preoperative [18F]FDG PET/CT was associated with superior DFS and OS in resectable cI-II NSCLC, which may result from accurate staging and stage-appropriate therapy.

Parkin-mediated mitophagy protects against aluminum trichloride-induced hippocampal apoptosis in mice via the mtROS-NLRP3 pathway.

Aluminum is a neurotoxic food contaminant. Aluminum trichloride (AlCl3) causes hippocampal mitochondrial damage, leading to hippocampal injury. Damaged mitochondria can release mitochondrial reactive oxygen species (mtROS) and activate nucleotide-binding oligomerization domain-like receptor-containing 3 (NLRP3) inflammasomes and apoptosis. E3 ubiquitin ligase PARK2 (Parkin)-mediated mitophagy can attenuate mitochondrial damage. However, the role of mitophagy in AlCl3-induced mice hippocampal damage and its regulatory mechanism remain elusive. First, C57BL/6 N mice were treated with 0, 44.825, 89.65, and 179.3 mg/kg body weight AlCl3 drinking water for 90 d. Apoptosis, NLRP3-inflammasome activation and mitochondrial damage were increased in AlCl3-induced hippocampal damage. In addition, Parkin-mediated mitophagy peaked in the middle-dose group and was slightly attenuated in the high-dose group. Subsequently, we used wild-type and Parkin knockout (Parkin-/-) mice to investigate the AlCl3-induced hippocampal damage. The results showed that Parkin-/- inhibited mitophagy, and aggravated AlCl3-induced mitochondrial damage, NLRP3-inflammasome activation, apoptosis and hippocampal damage. Finally, we administered MitoQ (mtROS inhibitor) and MCC950 (NLRP3 inhibitor) to AlCl3-treated Parkin-/- mice to investigate the mechanism of Parkin-mediated mitophagy. The results showed that inhibition of mtROS and NLRP3 attenuated hippocampal NLRP3-inflammasome activation, apoptosis, and damage in AlCl3-treated Parkin-/- mice. These findings indicate that Parkin-mediated mitophagy protects against AlCl3-induced hippocampal apoptosis in mice via the mtROS-NLRP3 pathway.

Hexafluoropropylene oxide trimer acid exposure triggers necroptosis and inflammation through the Wnt/ß-catenin/NF-κB axis in the liver.

Hexafluoropropylene oxide trimer acid (HFPO-TA), an emerging alternative to perfluorooctanoic acid (PFOA), has recently been identified as a significant environmental pollutant. Nevertheless, there is a scarcity of studies regarding the hepatotoxic effects of HFPO-TA. Here, we investigated the types and potential mechanisms of liver damage caused by HFPO-TA. Initially, we validated that the introduction of HFPO-TA resulted in the Wnt/ß-catenin signaling (W/ß signaling) activation, as well as the induction of necroptosis and inflammation, both in the liver of mice and in HepG2 cells. Subsequently, we established that the W/ß signaling mediated the necroptosis and inflammation observed in the liver and HepG2 cells exposed to HFPO-TA. Finally, we demonstrated that the phosphorylated form of NF-κB p65 (p-NF-κB p65) played a role in mediating the necroptosis and inflammation, and its activity could be regulated by the W/ß signaling pathway in the liver of mice and HepG2 cells exposed to HFPO-TA. In conclusion, our investigation elucidates the role of HFPO-TA in inducing necroptosis and inflammation in the liver, which is facilitated through the activation of the W/ß/NF-κB axis.

Dynamic wetting of Newtonian and viscoelastic fluids on microstructured surfaces.

Hypothesis Although extensive research has been conducted on the dynamic wetting of Newtonian fluids, limited insights have been gained for viscoelastic fluids, particularly on engineered surfaces. We hypothesize that differences in dynamic wetting on microstructured surfaces exist between such fluids, which may be attributed to variations in viscosity and elasticity as well as changes in the microscopic morphology of the moving contact line. Experiments To systematically investigate the wetting differences between Newtonian and viscoelastic fluids on microstructured surfaces, we conducted forced wetting experiments of glycerol-water and carboxymethyl cellulose aqueous solutions on microstructured polytetrafluoroethylene surfaces through a modified Wilhelmy plate method. Findings Results demonstrated an apparent difference in the relationship between the dynamic contact angle and moving velocity with different microstructured surfaces for Newtonian and viscoelastic fluids. The power-law exponent between the capillary number and cubic of the dynamic contact angle increases with the strengthening of shear thinning and elastic effects. In contrast, this exponent is rarely influenced by the scale of microstructured surfaces, particularly in highly viscous regions where viscous force dominates. In addition, viscosity affects the viscous bending and distance that liquid molecules jump at the contact line. These findings have potential applications in coating complex fluids on engineered surfaces.

Inhibiting the Leidenfrost Effect by Superhydrophilic Nickel Foams with Ultrafast Droplet Permeation.

Inhibiting the Leidenfrost effect has drawn extensive attention due to its detrimental impact on heat dissipation in high-temperature industrial applications. Although hierarchical structures have improved the Leidenfrost point to over 1000 °C, the current performance of single-scale structures remains inadequate. Herein, we present a facile high-temperature treatment method to fabricate superhydrophilic nickel foams that demonstrate ultrafast droplet permeation within tens of milliseconds, elevating the Leidenfrost point above 500 °C. Theoretical analysis based on the pressure balance suggests that these remarkable features arise from the superhydrophilic property, high porosity, and large pore diameter of nickel foams that promote capillary wicking and vapor evacuation. Compared to solid nickel surfaces with a Leidenfrost temperature of approximately 235 °C, nickel foams nucleate boiling at high superheat, triggering an order of magnitude higher heat flux. The effects of the pore diameter and surface temperature on droplet permeation behaviors and heat transfer characteristics are also elucidated. The results indicate that droplet permeation is dominated by inertial and capillary forces at low and high superheat, respectively, and moderate pore diameters are more conducive to facilitating droplet permeation. Furthermore, our heat transfer model reveals that pore diameter plays a negligible role in the heat flux at high surface temperatures due to the trade-off between effective thermal conductivity and specific surface area. This work provides a new strategy to address the Leidenfrost effect by metal foams, which may promise great potential in steel forging and nuclear reactor safety.

Necroptosis and NLPR3 inflammasome activation mediated by ROS/JNK pathway participate in AlCl3-induced kidney damage.

Aluminum (Al) is a common environmental pollutant that can induce kidney damage. However, the mechanism is not clear. In the present study, to explored the exact mechanism of AlCl3-induced nephrotoxicity, C57BL/6 N male mice and HK-2 cells were used as experimental subjects. Our results showed that Al induced reactive oxygen species (ROS) overproduction, c-Jun N-terminal kinase (JNK) signaling activation, RIPK3-dependent necroptosis, NLRP3 inflammasome activation, and kidney damage. In addition, inhibiting JNK signaling could downregulate the protein expressions of necroptosis and NLRP3 inflammasome, thereby alleviating kidney damage. Meanwhile, clearing ROS effectively inhibited JNK signaling activation, which in turn inhibited necroptosis and NLRP3 inflammasome activation, ultimately alleviating kidney damage. In conclusion, these findings suggest that necroptosis and NLPR3 inflammasome activation mediated by ROS/JNK pathway participate in AlCl3-induced kidney damage.

Dibutyl phthalate induces liver fibrosis via p38MAPK/NF-κB/NLRP3-mediated pyroptosis.

Dibutyl phthalate (DBP) is one of the most employed plasticizers pervading the environment. DBP is a newly identified global organic pollutant that can activate NLRP3 inflammasomes and induce inflammatory liver injury. However, its hepatotoxicity remains poorly understood. The objective of this investigation was to investigate the probable pathways underlying DBP-induced liver injury. First, C57BL/6N mice were orally administered DBP at 10 and 50 mg/kg B.W. doses for 28 days. The observed results indicated a significant increase in liver collagen deposition and upregulated protein expression of fibrosis markers in mice. In addition, the p38MAPK/NF-κB signaling pathway and pyroptosis-related protein expression were upregulated. To establish a correlation between these changes, we conducted a conditioned medium co-culture of human hepatocellular carcinoma (HepG2) and human hepatic stellate (LX-2) cells. We performed inhibitor interventions to validate the mechanism of DBP-induced liver fibrosis in vitro. After treatment with p38MAPK (SB203580), NF-κB (PDTC), and NLRP3 (MCC950) inhibitors, the activation of LX-2 cells, the p38MAPK/NF-κB signaling pathway and pyroptosis due to DBP were alleviated. Therefore, DBP exposure leads to NLRP3-mediated pyroptosis of hepatocytes via the p38MAPK/NF-κB signaling pathway, activating LX-2 cells and causing liver fibrosis. Our findings offer a conceptual framework to understand the pathological underpinnings of DBP-induced liver injury while proposing novel ideas to prevent and treat DBP hepatotoxicity. Thus, targeting p38MAPK, NF-κB, and NLRP3 may prevent DBP-induced liver fibrosis.

Dibutyl phthalate causes heart damage by disrupting Ca2+ transfer from endoplasmic reticulum to mitochondria and triggering subsequent pyroptosis.

Dibutyl phthalate (DBP) is a typical plasticizer and is widely used in industrial manufacturing. DBP has been reported to be cardiotoxic, manifested by oxidative stress and inflammatory damage. However, the potential mechanism of heart damage caused by DBP remains unclear. By in vivo and in vitro experiments, first, this study demonstrated that DBP induced endoplasmic reticulum (ER) stress, mitochondrial damage, and pyroptosis in cardiomyocytes; second, it was confirmed that the ER stress increased mitochondrial-associated ER membrane (MAM), which led to mitochondrial damage by abnormalizing Ca2+ transfer within MAMs; finally, it was confirmed that mitochondrial reactive oxygen species (mtROS) production was increased after mitochondrial damage, which activated NLRP3 inflammasome and pyroptosis in cardiomyocytes. In summary, ER stress is the initiation of DBP cardiotoxicity, which leads to mitochondrial damage by disrupting Ca2+ transfer from ER to mitochondria. Subsequently, released mtROS promotes the activation of NLRP3 inflammasome and pyroptosis, eventually leading to heart damage.

Hexafluoropropylene oxide trimer acid causes fibrosis in mice liver via mitochondrial ROS/cGAS-STING/NLRP3-mediated pyroptosis.

Hexafluoropropylene oxide trimer acid (HFPO-TA) causes hepatotoxicity, however, its underlying mechanisms have not been conclusively determined. We investigated the effects of HFPO-TA on mice liver after 28 days of orally administered 0 or 0.5 mg/kg/d HFPO-TA. Administration of HFPO-TA induced mitochondrial ROS (mtROS) overexpression, cGAS-STING signaling activation, pyroptosis and fibrosis in mice liver. To determine the HFPO-TA-associated hepatotoxic mechanisms, mtROS, cGAS-STING signaling and pyroptosis intervention assays were performed in HFPO-TA-exposed mice liver. First, mtROS was found to be an upstream regulatory target of cGAS-STING signaling, pyroptosis and fibrosis. Second, cGAS-STING signaling was established to be an upstream regulatory mechanism of pyroptosis and fibrosis. Finally, pyroptosis was shown to regulate fibrosis. The above results confirm that HFPO-TA causes mice liver fibrosis via mtROS/cGAS-STING/NLRP3-mediated pyroptosis.

Role of ROS/JAK2/STAT3 signaling pathway in di-n-butyl phthalate-induced testosterone synthesis inhibition and antagonism of lycopene.

Di-n-butyl phthalate (DBP) causes adverse effects on male reproduction, especially testosterone synthesis inhibition. However, the specific mechanism of DBP-induced testosterone synthesis inhibition and its effective intervention measures of prevention and treatment are scarce presently. Lycopene (LYC) plays beneficial roles in male infertility because of its antioxidant activity. Nevertheless, it is unclear whether LYC could prevent DBP-induced male reproductive toxicity. By in vitro and in vivo investigations, this study demonstrated that DBP activated ROS/JAK2/STAT3 signaling pathway, promoted mitophagy and apoptosis, which in turn inhibited testosterone synthesis. Additionally, another major finding was that LYC supplement could reverse the above change, presenting as the restraint of ROS/JAK2/STAT3 signaling pathway, reduction of mitophagy and apoptosis, and improvement of testosterone synthesis. Our study facilitates deeper understandings of the mechanism in DBP-induced testosterone synthesis inhibition, and identifies LYC as the effective prevention and control strategies for DBP poisoning.

Spreading dynamics of microdroplets on nanostructured surfaces.

HYPOTHESIS: Droplet spreading governs various daily phenomena and industrial processes. Insights about microdroplet spreading are limited due to experimental difficulties arising from microdroplet manipulation and substrate wettability control. For droplet sizes approaching the capillary length scale, the gravitational force plays an important role in spreading. In contrast, capillary and viscous forces dominate as the droplet size reduces to smaller length scales. We hypothesize that the dynamic spreading behavior of microdroplets whose radius is far lower than the capillary length differs substantially from established and well understood dynamics. EXPERIMENTS: To systematically investigate the spreading dynamics of microdroplets, we develop contact-initiated wetting techniques combined with structuring-independent wettability control to achieve microdroplet (<500 µm) spreading on arbitrary surfaces while eliminating parasitic pinning effects (pining force âˆ¼ 0) and initial impact momentum effects (Weber number âˆ¼ 0). FINDINGS: Our experiments reveal that the capillary-driven initial spreading of microdroplets is shorter, with significantly reduced oscillation dampening, when compared to millimeter-scale droplets. Furthermore, spreading along with capillary wave propagation results in coupling between the spreading velocity and dynamic contact angle at the contact line. These findings, along with our proposed microdroplet manipulation platform, may find application in microscale heat transfer, advanced manufacturing, and aerosol transmission studies.

Steerable directional bouncing and contact time reduction of impacting droplets on superhydrophobic stepped surfaces.

HYPOTHESIS: The unbalanced capillary force provided by wettability patterns, non-uniform/asymmetric microtextures enables directional droplet transport, while macrotextures have shown potentials in reducing the contact time. Inspired by these findings, we design millimeter superhydrophobic stepped surfaces to simultaneously achieve highly steerable directional bouncing and contact time reduction of impacting droplets. EXPERIMENTS: The stepped surfaces are fabricated by computerized numerical control, chemical oxidation, hydrophobic treatment. Systematic impact experiments are conducted under Weber number ranging from 10.5 to 20.5, two step heights (0.5 mm and 1.0 mm) and extensive impact positions. FINDINGS: Compared with known microtextured surfaces, the stepped surfaces exhibit excellent performance with the maximum lateral movement distance about 8 times of droplet radius, controllable rebound angle ranging from âˆ¼ 32° to âˆ¼ 90° and up to âˆ¼ 30 % reduction in contact time. Particularly, we divide the directional bouncing characteristics into six regimes and attribute the variation of rebound velocity by the synergistic effects of viscous dissipation, excess surface energy, excess kinetic energy. It is demonstrated that the contact time is reduced by liquid mass redistribution and asymmetry enhancement. Predictive models of contact time that incorporate the coupling effects of impact position, impact velocity and step height are also established.

T-2 toxin inhibits osteoblastic differentiation and mineralization involving mutual regulation between Wnt signaling pathway and autophagy.

Mycotoxins are most frequent contaminants in environment and agricultural production globally. The T-2 toxin of Fusarium species is the most toxic type of A trichothecene mycotoxins. T-2 toxin can accumulate in bone and cause bone development disorders. Osteoblast is the functional cell responsible for bone formation. Whereas, the mechanism of T-2 toxin toxicity on osteoblast remains unknown. In present study, MC3T3-E1 cells were treated with 0, 2, 4, and 8 nM T-2 toxin for 24h to explore the effect of T-2 toxin on the differentiation and mineralization of osteoblasts. Subsequently, autophagy and Wnt intervention agents were used to explore the roles of autophagy and Wnt signaling pathway in T-2 toxin-induced osteoblastic differentiation and mineralization disorders, respectively. The results showed that 2 nM of T-2 toxin had no significant effect on cell vitality, but 4 and 8 nM of T-2 significantly inhibited cell viability. All doses of T-2 toxin inhibited both osteoblastic differentiation and mineralization, as assessed by alkaline phosphatase staining, Alizarin red S staining, and protein expressions of osteogenic proteins. In addition, the activation of Wnt signaling pathway mitigated T-2 toxin-induced osteoblast impairment, while the inhibition of autophagy exacerbated it. Our results also indicated that there was a positive feedback loop between the Wnt signaling pathway and autophagy.

Clinical study of anti-snake venom blockade in the treatment of local tissue necrosis caused by Chinese cobra (Naja atra) bites.

OBJECTIVE: This study aimed to evaluate the clinical therapeutic efficacy of anti-snake venom serum blockade in treating local tissue necrosis caused by Chinese cobra (Naja atra) bites. METHODS: Patients bitten by a Chinese cobra (Naja atra) (n = 50) that met the inclusion criteria were randomly divided into two groups: the experimental group (n = 25) and the control group (n = 25). The experimental group received regular as well as anti-snake venom serum blocking treatment, whereas regular treatment plus chymotrypsin blocking therapy was given to the control group. The necrotic volumes around snake wounds in these groups were detected on the first, third and seventh days. On the third day of treatment, some local tissues in the wounds were randomly selected for pathological biopsy, and the necrosis volume of the local tissue was observed. Furthermore, the amount of time required for wound healing was recorded. RESULTS: On the third and seventh days post-treatment, the necrotic volume of the wound of the experimental group was much smaller than that of the control group, and the experimental group's wound healing time was shorter than that of the control group (all p < 0.05). Moreover, the pathological biopsies taken from the control group showed nuclear pyknosis, fragmentation, sparse nuclear density, and blurred edges, and the degree of necrosis was much higher than that of the experimental group. CONCLUSIONS: Anti-snake venom blocking therapy is a new and improved therapy with good clinical effect on local tissue necrosis caused by Chinese cobra bites; moreover, it is superior to conventional chymotrypsin blocking therapy in the treatment of cobra bites. It can better neutralize and prevent the spread of the toxin, reduce tissue necrosis, and shorten the course of the disease by promoting healing of the wound. Furthermore, this treatment plan is also applicable to wound necrosis caused by other snake toxins, such as tissue necrosis caused by elapidae and viper families. CLINICAL TRIAL REGISTRATION: This trial is registered in the Chinese Clinical Trial Registry, a primary registry of International Clinical Trial Registry Platform, World Health Organization (Registration No. ChiCTR2200059070; trial URL:http://www.chictr.org.cn/edit.aspx?pid=134353&htm=4).