UBE2C-induced crosstalk between mono- and polyubiquitination of SNAT2 promotes lymphatic metastasis in bladder cancer.

Ubiquitination plays an essential role in protein stability, subcellular localization, and interactions. Crosstalk between different types of ubiquitination results in distinct biological outcomes for proteins. However, the role of ubiquitination-related crosstalk in lymph node (LN) metastasis and the key regulatory factors controlling this process have not been determined. Using high-throughput sequencing, we found that ubiquitin-conjugating enzyme E2 C (UBE2C) was overexpressed in bladder cancer (BCa) and was strongly associated with an unfavorable prognosis. Overexpression of UBE2C increased BCa lymphangiogenesis and promoted LN metastasis both in vitro and in vivo. Mechanistically, UBE2C mediated sodium-coupled neutral amino acid transporter 2 (SNAT2) monoubiquitination at lysine 59 to inhibit K63-linked polyubiquitination at lysine 33 of SNAT2. Crosstalk between monoubiquitination and K63-linked polyubiquitination increased SNAT2 membrane protein levels by suppressing epsin 1-mediated (EPN1-mediated) endocytosis. SNAT2 facilitated glutamine uptake and metabolism to promote VEGFC secretion, ultimately leading to lymphangiogenesis and LN metastasis in patients with BCa. Importantly, inhibition of UBE2C significantly attenuated BCa lymphangiogenesis in a patient-derived xenograft model. Our results reveal the mechanism by which UBE2C mediates crosstalk between the monoubiquitination and K63-linked polyubiquitination of SNAT2 to promote BCa metastasis and identify UBE2C as a promising target for treating LN-metastatic BCa.

Improvement of PbSn Solder Reliability with Ge Microalloying-Induced Optimization of Intermetallic Compounds Growth.

PbSn solders are used in semiconductor devices for aerospace or military purposes with high levels of reliability requirements. Microalloying has been widely adopted to improve the reliability for Pb-free solders, but its application in PbSn solders is scarce. In this article, the optimization of PbSn solder reliability with Ge microalloying was investigated using both experimental and calculation methods. Intermetallic compounds (IMC) growth and morphologies evolution during reliability tests were considered to be the main factors of device failure. Through first-principle calculation, the growth mechanism of interfacial Ni3Sn4 was discussed, including the formation of vacancies, the Ni-vacancies exchange diffusion and the dominant Ni diffusion along the [1 0 0] direction. The doping of Ge in the cell increased the exchange energy barrier and thus inhibited the IMC development and coarsening trend. In three reliability tests, only 0.013 wt% Ge microalloying in Pb60Sn40 was able to reduce IMC thickness by an increment of 22.6~38.7%. The proposed Ge microalloying method in traditional PbSn solder could yield a prospective candidate for highly reliable applications.

PDGFRα+ITGA11+ fibroblasts foster early-stage cancer lymphovascular invasion and lymphatic metastasis via ITGA11-SELE interplay.

Cancer-associated fibroblasts (CAFs) exhibit considerable heterogeneity in advanced cancers; however, the functional annotation and mechanism of CAFs in early-stage cancers remain elusive. Utilizing single-cell RNA sequencing and spatial transcriptomic, we identify a previously unknown PDGFRα+ITGA11+ CAF subset in early-stage bladder cancer (BCa). Multicenter clinical analysis of a 910-case cohort confirms that PDGFRα+ITGA11+ CAFs are associated with lymphovascular invasion (LVI) and poor prognosis in early-stage BCa. These CAFs facilitate LVI and lymph node (LN) metastasis in early-stage BCa, as evidenced in a PDGFRα+ITGA11+ CAFs-specific deficient mouse model. Mechanistically, PDGFRα+ITGA11+ CAFs promote lymphangiogenesis via recognizing ITGA11 surface receptor SELE on lymphatic endothelial cells to activate SRC-p-VEGFR3-MAPK pathway. Further, CHI3L1 from PDGFRα+ITGA11+ CAFs aligns the surrounding matrix to assist cancer cell intravasation, fostering early-stage BCa LVI and LN metastasis. Collectively, our study reveals the crucial role of PDGFRα+ITGA11+ CAFs in shaping metastatic landscape, informing the treatment of early-stage BCa LVI.

SUMOylation-Driven mRNA Circularization Enhances Translation and Promotes Lymphatic Metastasis of Bladder Cancer.

Aberrant gene expression is a prominent feature of metastatic cancer. Translational initiation is a vital step in fine-tuning gene expression. Thus, exploring translation initiation regulators may identify therapeutic targets for preventing and treating metastasis. Herein, we identified that DHCR24 was overexpressed in lymph node (LN) metastatic bladder cancer and correlated with poor prognosis of patients. DHCR24 promoted lymphangiogenesis and LN metastasis of bladder cancer in vitro and in vivo. Mechanistically, DHCR24 mediated and recognized the SUMO2 modification at lysine 108 of hnRNPA2B1 to foster TBK1 mRNA circularization and eIF4F initiation complex assembly by enhancing hnRNPA2B1-eIF4G1 interaction. Moreover, DHCR24 directly anchored to TBK1 mRNA 3'-untranslated region to increase its stability, thus forming a feed forward loop to elevate TBK1 expression. TBK1 activated PI3K/Akt signaling to promote VEGFC secretion, resulting in lymphangiogenesis and LN metastasis. DHCR24 silencing significantly impeded bladder cancer lymphangiogenesis and lymphatic metastasis in a patient-derived xenograft model. Collectively, these findings elucidate DHCR24-mediated translation machinery that promotes lymphatic metastasis of bladder cancer and supports the potential application of DHCR24-targeted therapy for LN-metastatic bladder cancer. SIGNIFICANCE: DHCR24 is a SUMOylation regulator that controls translation initiation complex assembly and orchestrates TBK1 mRNA circularization to activate Akt/VEGFC signaling, which stimulates lymphangiogenesis and promotes lymph node metastasis in bladder cancer.

An unsupervised real-time spike sorting system based on optimized OSort.

Objective. The OSort algorithm, a pivotal unsupervised spike sorting method, has been implemented in dedicated hardware devices for real-time spike sorting. However, due to the inherent complexity of neural recording environments, OSort still grapples with numerous transient cluster occurrences during the practical sorting process. This leads to substantial memory usage, heavy computational load, and complex hardware architectures, especially in noisy recordings and multi-channel systems.Approach. This study introduces an optimized OSort algorithm (opt-OSort) which utilizes correlation coefficient (CC), instead of Euclidean distance as classification criterion. TheCCmethod not only bolsters the robustness of spike classification amidst the diverse and ever-changing conditions of physiological and recording noise environments, but also can finish the entire sorting procedure within a fixed number of cluster slots, thus preventing a large number of transient clusters. Moreover, the opt-OSort incorporates two configurable validation loops to efficiently reject cluster outliers and track recording variations caused by electrode drifting in real-time.Main results. The opt-OSort significantly reduces transient cluster occurrences by two orders of magnitude and decreases memory usage by 2.5-80 times in the number of pre-allocated transient clusters compared with other hardware implementations of OSort. The opt-OSort maintains an accuracy comparable to offline OSort and other commonly-used algorithms, with a sorting time of 0.68µs as measured by the hardware-implemented system in both simulated datasets and experimental data. The opt-OSort's ability to handle variations in neural activity caused by electrode drifting is also demonstrated.Significance. These results present a rapid, precise, and robust spike sorting solution suitable for integration into low-power, portable, closed-loop neural control systems and brain-computer interfaces.

SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer.

Lymph node (LN) metastasis is one of the predominant metastatic routes of non-small cell lung cancer (NSCLC) and is considered as a leading cause for the unsatisfactory prognosis of patients. Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis, the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear. In this study, we employed high-throughput sequencing to identify a novel circular RNA (circRNA), circTLCD4-RWDD3, which was significantly upregulated in extracellular vesicles (EVs) from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort. Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo. Mechanically, circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9. Subsequently, circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif (SIM) of ALIX and activated ALIX to recruit ESCRT-III, thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs. Moreover, EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1, resulting in the lymphangiogenesis and LN metastasis of NSCLC. Importantly, blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo. Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC, suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC.

Excessive Daytime Sleepiness and Insomnia Symptoms in Adolescents With Major Depressive Disorder: Prevalence, Clinical Correlates, and the Relationship With Psychiatric Medications Use.

OBJECTIVE: Excessive daytime sleepiness (EDS) and insomnia symptoms are common in patients with major depressive disorder (MDD), which might lead to a poor prognosis and an increased risk of depression relapse. The current study aimed to investigate the prevalence, and sociodemographic and clinical correlates of EDS and insomnia symptoms among adolescents with MDD. METHODS: The sample of this cross-sectional study included 297 adolescents (mean age=15.26 years; range=12-18 years; 218 females) with MDD recruited from three general and four psychiatric hospitals in five cities (Hefei, Bengbu, Fuyang, Suzhou, and Ma'anshan) in Anhui Province, China between January and August, 2021. EDS and insomnia symptoms, and clinical severity of depressive symptoms were assessed using Epworth sleepiness scale, Insomnia Severity Index, and Clinical Global Impression-Severity. RESULTS: The prevalence of EDS and insomnia symptoms in adolescents with MDD was 39.7% and 38.0%, respectively. Binary logistic regression analyses showed that EDS symptoms were significantly associated with higher body mass index (odds ratio [OR]=1.097, 95% confidence interval [CI]=1.027-1.172), more severe depressive symptoms (OR=1.313, 95% CI=1.028-1.679), and selective serotonin reuptake inhibitors use (OR=2.078, 95% CI=1.199-3.601). And insomnia symptoms were positively associated with female sex (OR=1.955, 95% CI=1.052-3.633), suicide attempts (OR=1.765, 95% CI=1.037-3.005), more severe depressive symptoms (OR=2.031, 95% CI=1.523-2.709), and negatively associated with antipsychotics use (OR=0.433, 95% CI=0.196-0.952). CONCLUSION: EDS and insomnia symptoms are common among adolescents with MDD. Considering their negative effects on the clinical prognosis, regular screening and clinical managements should be developed for this patient population.

Deep Learning for Visual Localization and Mapping: A Survey.

Deep-learning-based localization and mapping approaches have recently emerged as a new research direction and receive significant attention from both industry and academia. Instead of creating hand-designed algorithms based on physical models or geometric theories, deep learning solutions provide an alternative to solve the problem in a data-driven way. Benefiting from the ever-increasing volumes of data and computational power on devices, these learning methods are fast evolving into a new area that shows potential to track self-motion and estimate environmental models accurately and robustly for mobile agents. In this work, we provide a comprehensive survey and propose a taxonomy for the localization and mapping methods using deep learning. This survey aims to discuss two basic questions: whether deep learning is promising for localization and mapping, and how deep learning should be applied to solve this problem. To this end, a series of localization and mapping topics are investigated, from the learning-based visual odometry and global relocalization to mapping, and simultaneous localization and mapping (SLAM). It is our hope that this survey organically weaves together the recent works in this vein from robotics, computer vision, and machine learning communities and serves as a guideline for future researchers to apply deep learning to tackle the problem of visual localization and mapping.

ZEB1-mediated biogenesis of circNIPBL sustains the metastasis of bladder cancer via Wnt/ß-catenin pathway.

BACKGROUND: Circular RNAs (circRNAs) circularized by back-splicing of pre-mRNA are widely expressed and affected the proliferation, invasion and metastasis of bladder cancer (BCa). However, the mechanism underlying circRNA biogenesis in mediating the distant metastasis of BCa still unexplored. METHODS: RNA sequencing data between BCa and normal adjacent tissues was applied to identify the differentially expressed circRNAs. The functions of circNIPBL in BCa were investigated via a series of biochemical experiments. The Clinical significance of circNIPBL was examined in a cohort of larger BCa tissues. RESULTS: In the present study, we identified a novel circRNA (hsa_circ_0001472), circNIPBL, which was significantly upregulated and had great influence on the poor prognosis of patients with BCa. Functionally, circNIPBL promotes BCa metastasis in vitro and in vivo. Mechanistically, circNIPBL upregulate the expression of Wnt5a and activated the Wnt/ß-catenin signaling pathway via directly sponged miR-16-2-3p, leading to the upregulation of ZEB1, which triggers the EMT of BCa. Moreover, we revealed that ZEB1 interacted with the flanking introns of exons 2-9 on NIPBL pre-mRNA to trigger circNIPBL biogenesis, thus forming a positive feedback loop. Importantly, circNIPBL overexpression significantly facilitated the distant metastasis of BCa in the orthotopic bladder cancer model, while silencing ZEB1 remarkably blocked the effects of metastasis induced by circNIPBL overexpression. CONCLUSIONS: Our study highlights that circNIPBL-induced Wnt signaling pathway activation triggers ZEB1-mediated circNIPBL biogenesis, which forms a positive feedback loop via the circNIPBL/miR-16-2-3p/Wnt5a/ZEB1 axis, supporting circNIPBL as a novel therapeutic target and potential biomarker for BCa patients.

An HGF-dependent positive feedback loop between bladder cancer cells and fibroblasts mediates lymphangiogenesis and lymphatic metastasis.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play a vital role in facilitating tumor progression through extensive reciprocal interplay with cancer cells. Tumor-derived extracellular vesicles (EVs) are the critical mediators involved in the crosstalk between cancer cells and stromal cells, contributing to the metastasis of cancers. Yet, the biological mechanisms of tumor-derived EVs in triggering CAFs phenotype to stimulate the lymph node (LN) metastasis of bladder cancer (BCa) are largely unknown. Here, we aimed to explore the effects and molecular mechanisms of tumor-derived EV-mediated CAFs phenotype in regulating BCa LN metastasis. METHODS: The high-throughput sequencing was utilized to identify the crucial long non-coding RNA (lncRNA) associated with CAF enrichment in BCa. The functional role of the transition of fibroblasts to CAFs induced by LINC00665-mediated EVs was investigated through the in vitro and in vivo assays. Chromatin isolation by RNA purification assays, fluorescence resonance energy transfer assays, cytokine profiling and patient-derived xenograft (PDX) model were performed to explore the underlying mechanism of LINC00665 in the LN metastasis of BCa. RESULTS: We found that CAFs are widely enriched in the tumor microenvironment of BCa, which correlated with BCa lymphangiogenesis and LN metastasis. We then identified a CAF-associated long non-coding RNA, LINC00665, which acted as a crucial mediator of CAF infiltration in BCa. Clinically, LINC00665 was associated with LN metastasis and poor prognosis in patients with BCa. Mechanistically, LINC00665 transcriptionally upregulated RAB27B expression and induced H3K4me3 modification on the promoter of RAB27B through the recruitment of hnRNPL. Moreover, RAB27B-induced EVs secretion endowed fibroblasts with the CAF phenotype, which reciprocally induced LINC00665 overexpression to form a RAB27B-HGF-c-Myc positive feedback loop, enhancing the lymphangiogenesis and LN metastasis of BCa. Importantly, we demonstrated that blocking EV-transmitted LINC00665 or HGF broke this loop and impaired BCa lymphangiogenesis in a PDX model. CONCLUSION: Our study uncovers a precise mechanism that LINC00665 sustains BCa LN metastasis by inducing a RAB27B-HGF-c-Myc positive feedback loop between BCa cells and fibroblasts, suggesting that LINC00665 could be a promising therapeutic target for patients with LN metastatic BCa.

Self-Driven Droplet Motions Below their Icing Points.

Liquid fluidity is a most key prerequisite for a broad range of technologies, from energy, fluid machineries, microfluidic devices, water, and oil transportation to bio-deliveries. While from thermodynamics, the liquid fluidity gradually diminishes as temperature decreases until completely solidified below icing points. Here, self-driven droplet motions are discovered and demonstrated occurring in icing environments and accelerating with both moving distances and droplet volumes. The self-driven motions, including self-depinning and continuous wriggling, require no surface pre-preparation or energy input but are triggered by the overpressure spontaneously established during icing and then continuously accelerated by capillary pulling of frosts. Such self-driven motions are generic to a broad class of liquid types, volumes, and numbers on various micro-nanostructured surfaces and can be facilely manipulated by introducing pressure gradients spontaneously or externally. The discovery and control of self-driven motions below icing points can greatly broaden liquid-related applications in icing environments.

Epidemiology, treatments, and related biomarkers of locally advanced or metastatic urothelial carcinoma in Chinese population: A scoping review.

OBJECTIVE: Bladder cancer is the 13th most common cancer in China with the predominant histologic type being urothelial carcinoma (UC). Locally advanced and metastatic (la/m) UC accounts for 12% of UC and the five-year survival rate is only 39.4%, imposing a significant disease and economic burden on the patients. The aim of this scoping review is to synthesize existing evidence of epidemiology, the landscape of treatment options and associated efficacy and safety profiles, as well as treatment-related biomarkers among Chinese la/mUC patients. METHODS: A systematic search was conducted on five databases (PubMed, Web of Science, Embase, Wanfang, and CNKI) from January 2011 to March 2022 based on the scoping review criteria in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews. RESULTS: A total of 6211 records were identified, and further review resulted in 41 relevant studies that met all criteria. Additional searches were conducted on epidemiology and treatment-related biomarkers of bladder cancer to supplement the evidence. Among 41 studies, 24 reported on platinum-based chemotherapy, eight on non-platinum-based chemotherapy, six on immunotherapy, two on targeted therapy, and one on surgery. Efficacy outcomes were summarized by line of therapy. Treatment-related biomarkers including PD-L1, HER2, and FGFR3 alterations were identified, and the alteration rate of FGFR3 of Chinese UC patients was lower than that of the western patients. CONCLUSIONS: Despite chemotherapy has been the main treatment choice for decades, appealing new therapeutic strategies including ICIs, targeted therapies and ADCs were applied in clinical practice. Further research on epidemiology and treatment-related biomarkers of la/mUC patients is needed given only a limited number of studies have been identified thus far. High genomic heterogeneity and complexity of molecular features were observed among la/mUC patients; thus, further studies are required to identify critical drivers and promote potential precise therapies.

Mutant KRAS Mediates circARFGEF2 Biogenesis to Promote Lymphatic Metastasis of Pancreatic Ductal Adenocarcinoma.

Circular RNAs (circRNA) contribute to cancer stemness, proliferation, and metastasis. The biogenesis of circRNAs can be impacted by the genetic landscape of tumors. Herein, we identified a novel circRNA, circARFGEF2 (hsa_circ_0060665), which was upregulated in KRASG12D pancreatic ductal adenocarcinoma (PDAC) and positively associated with KRASG12D PDAC lymph node (LN) metastasis. CircARFGEF2 overexpression significantly facilitated KRASG12D PDAC LN metastasis in vitro and in vivo. Mechanistically, circARFGEF2 biogenesis in KRASG12D PDAC was significantly activated by the alternative splicing factor QKI-5, which recruited U2AF35 to facilitate spliceosome assembly. QKI-5 bound the QKI binding motifs and neighboring reverse complement sequence in intron 3 and 6 of ARFGEF2 pre-mRNA to facilitate circARFGEF2 biogenesis. CircARFGEF2 sponged miR-1205 and promoted the activation of JAK2, which phosphorylated STAT3 to trigger KRASG12D PDAC lymphangiogenesis and LN metastasis. Importantly, circARFGEF2 silencing significantly inhibited LN metastasis in the KrasG12D/+Trp53R172H/+Pdx-1-Cre (KPC) mouse PDAC model. These findings provide insight into the mechanism and metastasis-promoting function of mutant KRAS-mediated circRNA biogenesis. SIGNIFICANCE: Increased splicing-mediated biogenesis of circARFGEF2 in KRAS-mutant pancreatic ductal adenocarcinoma activates JAK2-STAT3 signaling and triggers lymph node metastasis, suggesting circARFGEF2 could be a therapeutic target to inhibit pancreatic cancer progression.

Boosting water evaporation via continuous formation of a 3D thin film through triple-level super-wicking routes.

Capillary-fed thin-film evaporation via micro/nanoscale structures has attracted increasing attention for its high evaporation flux and pumpless liquid replenishment. However, maximizing thin-film evaporation has been hindered by the intrinsic trade-off between the heat flux and liquid transport. Here, we designed and fabricated nanostructured micro-steam volcanoes on copper surfaces featuring triple-level super-wicking routes to overcome this trade-off and boost water evaporation. The triple-level super-wicking routes enable the continuous formation of a 3D thin film for highly efficient evaporation by continuous self-driven liquid replenishment and extending the thin-film region. The micro-steam volcanoes increased the surface area by 225%, improving the evaporation rate by 141%, with a rapid self-pumping water transport speed up to 80 mm s-1. A remarkable solar-driven water evaporation rate of 3.33 kg m-2 h-1 under one sun vertical incidence was achieved, which is among the highest reported values for metal-based evaporators. When attached to electric-heating plates, the evaporator realized an electrothermal evaporation rate of 12.13 kg m-2 h-1. Moreover, it can also be used for evaporative cooling with enhanced convective heat transfer, reaching a 36.2 °C temperature reduction on a heat source with a heat flux of 6 W cm-2. This study promises a general strategy for designing thin-film evaporators with high efficiencies, low costs, and multi-functional compatibilities.

Passive Anti-Icing Performances of the Same Superhydrophobic Surfaces under Static Freezing, Dynamic Supercooled-Droplet Impinging, and Icing Wind Tunnel Tests.

Overcoming ice accretion on external aircraft wing surfaces plays a crucial role in aviation, and developing environmentally friendly passive anti-icing surfaces is considered to be a promising strategy. Superhydrophobic surfaces (SHSs) have attracted increasing attention due to their potential advantages of keeping the airframe dry without causing additional aerodynamic losses. However, the passive anti-icing performances of SHSs reported to date varied a lot under different icing test conditions. Therefore, a systematic investigation is necessary to elucidate the icing conditions where SHSs can remain effective and pave the way for SHSs toward practical anti-icing applications. Herein, we designed and fabricated a typical type of SHS featuring dual-scale hierarchical structures with arrayed micromountains (with both spacings and heights of tens of micrometers) covered by single-scale sandy-corrugation-like periodic structures (with both spacings and heights of only several micrometers) (termed SS1). Its anti-icing performances under three representative icing conditions, including static water freezing, dynamic supercooled-droplet impinging, and icing wind tunnel conditions, were comparatively investigated. The SS1 SHS maintained a lower static ice-adhesion strength (<60 kPa even after 50 deicing cycles at temperatures as low as -25 °C), which was attributed to a cumulative cracking effect facilitating the ice detachment. Within the laboratory dynamic icing tests, the SS1 SHSs with micromountain heights of 20-30 µm performed optimally in the antiadhesion of supercooled droplets (at an impinging velocity of 3.4 m/s and temperatures of -5 to -25 °C). In spite of the significant anti-icing performances of the SS1 SHSs in both static and dynamic laboratory tests, they could hardly sustain reliable passive anti-icing performances in harsher icing wind tunnel tests with supercooled droplets impinging their surfaces at velocities of up to 50 m/s at a temperature of -5 °C for 10 min. This study can inspire the development of improved SHSs for achieving satisfactory anti-icing performances in real-aviation conditions.

CoQ10 alleviates hepatic ischemia reperfusion injury via inhibiting NLRP3 activity and promoting Tregs infiltration.

Hepatic ischemia-reperfusion injury (IRI) has been concerned as a main complication of liver surgery and transplantation. Previous studies show that reactive oxygen species (ROS) associated inflammation response and contribute to the liver damage during IRI. Coenzyme Q10 (CoQ10) has shown many beneficial effects on abrogating ROS production and ameliorating liver injury. This study found lower CoQ10 level in the process of liver IRI in a mouse model of hepatic IRI. Meanwhile, our results showed that CoQ10 administration significantly attenuate hepatic IRI proved by HE staining, serum ALT/AST. The NOD-like receptor protein 3 (NLRP3) inflammasome is activated by ROS which triggers the activation of inflammatory caspases. In this study, NLRP3 was significantly suppressed by CoQ10 while Foxp3 exhibited increased expression in liver. Furthermore, Kupffer cells (KCs) pretreated with CoQ10 under the condition of hypoxia and reoxygenation contributed to improved CD4+CD25+Foxp3+ regulatory T cells (Tregs) ratio in co-culture system. Furthermore, NLRP3 inflammasome activator treatment in vivo resulted in higher expression of caspase-1 and NLRP3 and reduction of Tregs in liver, which reversed the protection of CoQ10 in the liver injury. Taken together, our study discovered that CoQ10 can suppress NLRP3 activity in KCs and improves Foxp3+ Tregs differentiation depending on M2 macrophage polarization of KCs to ameliorate hepatic IRI.

Crack-Initiated Durable Low-Adhesion Trilayer Icephobic Surfaces with Microcone-Array Anchored Porous Sponges and Polydimethylsiloxane Cover.

Reducing unfavorable ice accretion on surfaces exposed in cold environment requires effective passive anti-icing/deicing techniques. Icephobic surfaces are widely applied on various infrastructures due to their low ice adhesion strength and flexibility, whereas their poor mechanical durability, common liquid infusion, weak resistance to contamination, and low bonding strength to substrates are the major remaining challenges. According to the fracture mechanics of ice layer, initiating cracks at the ice-solid interfaces via the proper design of internal structures of icephobic materials is a promising way to icephobicity. Herein, a crack initiating icephobic surface with porous PDMS sponges sandwiched between a protective, dense PDMS layer and a textured metal microstructure was proposed and fabricated. The combination of high- and low- stiffness PDMS layers anchored by the structured metal surface give the sandwich-like structure excellent icephobicity with both high durability and low ice adhesion (5.3 kPa in the icing-deicing cycles). The porosity and the elastic modulus of the PDMS sponges and the periodicity of the metal surface structures can both be tailored to realize enhanced icephobicity. The sandwich-like icephobic surface remained insignificantly changed under solid particle impacting and the durability characterized via linear abrasion tests was elevated compared with PDMS coating on flat metal surfaces. Additionally, the trilayer icephobic surface possesses durability, low ice adhesion strength, and improved resistance to contamination and is applicable on various surfaces.

Superhydrophobic microstructures for better anti-icing performances: open-cell or closed-cell?

Based on geometrical characteristics, all surface microstructures are categorized into two types: closed-cell and open-cell structures. Closed-cell structures are well-known to have more stable and durable superhydrophobicity at room temperatures. However, in low-temperature environments where massive environmentally induced physical changes emerge, whether closed-cell surfaces can maintain good anti-icing performances has not yet been confirmed, and thus how to design optimal superhydrophobic anti-icing microstructures is rarely reported. Here, we apply an ultrafast laser to fabricate superhydrophobic surfaces with tunable patterned micro-nanostructures from a complete closed-cell to different ratios and to a complete open-cell. We discover that droplets on closed-cell structures completely degrade to the high-adhesion Wenzel state after icing and melting cycles while those on the open-cell structures well recover to the original Cassie-Baxter state. We propose an improved ideal gas model to clarify the mechanisms that the decreased air pocket pressure and the air dissolution on closed-cell structures induce easy impalement during icing and the difficult recovery during melting, paving the way for optimizing the anti-icing structure design. The optimized open-cell surfaces exhibit over 33 times lower ice adhesion strengths (1.4 kPa) and long-term icephobic durability (<20 kPa after 33 deicing cycles) owing to the increased air pocket pressure at low temperatures. Significant dewetting processes during condensation endow the open-cell structures with more remarkable high-humidity resistance and anti-frosting properties. Our study reveals the general design principle of superhydrophobic anti-icing structures, which might guide the design of superhydrophobic anti-icing surfaces in practical harsh environments.