Ultrafast universal fabrication of configurable porous silicone-based elastomers by Joule heating chemistry.

Silicone-based elastomers (SEs) have been extensively applied in numerous cutting-edge areas, including flexible electronics, biomedicine, 5G smart devices, mechanics, optics, soft robotics, etc. However, traditional strategies for the synthesis of polymer elastomers, such as bulk polymerization, suspension polymerization, solution polymerization, and emulsion polymerization, are inevitably restricted by long-time usage, organic solvent additives, high energy consumption, and environmental pollution. Here, we propose a Joule heating chemistry method for ultrafast universal fabrication of SEs with configurable porous structures and tunable components (e.g., graphene, Ag, graphene oxide, TiO2, ZnO, Fe3O4, V2O5, MoS2, BN, g-C3N4, BaCO3, CuI, BaTiO3, polyvinylidene fluoride, cellulose, styrene-butadiene rubber, montmorillonite, and EuDySrAlSiOx) within seconds by only employing H2O as the solvent. The intrinsic dynamics of the in situ polymerization and porosity creation of these SEs have been widely investigated. Notably, a flexible capacitive sensor made from as-fabricated silicone-based elastomers exhibits a wide pressure range, fast responses, long-term durability, extreme operating temperatures, and outstanding applicability in various media, and a wireless human-machine interaction system used for rescue activities in extreme conditions is established, which paves the way for more polymer-based material synthesis and wider applications.

CD4+ T-Cell Legumain Deficiency Attenuates Hypertensive Damage via Preservation of TRAF6.

BACKGROUND: T cells are central to the immune responses contributing to hypertension. LGMN (legumain) is highly expressed in T cells; however, its role in the pathogenesis of hypertension remains unclear. METHODS: Peripheral blood samples were collected from patients with hypertension, and cluster of differentiation (CD)4+ T cells were sorted for gene expression and Western blotting analysis. TLGMNKO (T cell-specific LGMN-knockout) mice (Lgmnf/f/CD4Cre), regulatory T cell (Treg)-specific LGMN-knockout mice (Lgmnf/f/Foxp3YFP Cre), and RR-11a (LGMN inhibitor)-treated C57BL/6 mice were infused with Ang II (angiotensin II) or deoxycorticosterone acetate/salt to establish hypertensive animal models. Flow cytometry, 4-dimensional label-free proteomics, coimmunoprecipitation, Treg suppression, and in vivo Treg depletion or adoptive transfer were used to delineate the functional importance of T-cell LGMN in hypertension development. RESULTS: LGMN mRNA expression was increased in CD4+ T cells isolated from hypertensive patients and mice, was positively correlated with both systolic and diastolic blood pressure, and was negatively correlated with serum IL (interleukin)-10 levels. TLGMNKO mice exhibited reduced Ang II-induced or deoxycorticosterone acetate/salt-induced hypertension and target organ damage relative to wild-type (WT) mice. Genetic and pharmacological inhibition of LGMN blocked Ang II-induced or deoxycorticosterone acetate/salt-induced immunoinhibitory Treg reduction in the kidneys and blood. Anti-CD25 antibody depletion of Tregs abolished the protective effects against Ang II-induced hypertension in TLGMNKO mice, and LGMN deletion in Tregs prevented Ang II-induced hypertension in mice. Mechanistically, endogenous LGMN impaired Treg differentiation and function by directly interacting with and facilitating the degradation of TRAF6 (tumor necrosis factor receptor-associated factor 6) via chaperone-mediated autophagy, thereby inhibiting NF-κB (nuclear factor kappa B) activation. Adoptive transfer of LGMN-deficient Tregs reversed Ang II-induced hypertension, whereas depletion of TRAF6 in LGMN-deficient Tregs blocked the protective effects. CONCLUSIONS: LGMN deficiency in T cells prevents hypertension and its complications by promoting Treg differentiation and function. Specifically targeting LGMN in Tregs may be an innovative approach for hypertension treatment.

Robust Ionics Reinforced Fiber As Implantable Sensor for Early Operando Monitoring Cell Thermal Safety of Commercial Lithium-Ion Batteries.

Commercial batteries have been largely applied in mobile electronics, electric vehicles, and scalable energy storage systems. However, thermal runaway of batteries still obstructs the reliability of electric equipment. Considering this, building upon recent investigations of energy thermal safety, commercially available organogel fiber-based implantable sensors have been developed through 3D printing technology for first operando implantable monitoring of cell temperature. The printed fibers present excellent reliability and superelasticity because of internal supramolecular cross-linking. High temperature sensitivity (-39.84% °C-1/-1.557% °C-1) within a wide range (-15 to 80 °C) is achieved, and the corresponding mechanism is clarified based on in situ temperature-dependent Raman technology. Furthermore, taking the pouch cell as an example, combined with finite element analysis, the real-time observation system of cell temperature is successfully demonstrated through an implanted sensor with wireless Bluetooth transmission. This enlightening approach paves the way for achieving safety monitoring and smart warnings for various electric equipment.

Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.

Loneliness status transitions and risk of cardiovascular disease among middle-aged and older adults.

BACKGROUND AND AIMS: Loneliness is a risk factor for cardiovascular disease (CVD), and the levels at which individuals experience it can transition over time. However, the impact of increased loneliness or decreased loneliness on later CVD risk remains unexplored. We aimed to identify the age-specific association between loneliness status transitions and subsequent CVD incidences in middle-aged and older adults. METHODS AND RESULTS: Data was extracted from the China Health and Retirement Longitudinal Study (CHARLS) on 8463 adults to evaluate how loneliness status transitions across two data collection points were associated with the subsequent CVD incidence at a five-year follow-up. Loneliness status transitions were divided into four categories: stable low loneliness, decreased loneliness, increased loneliness, and stable high loneliness. Data were analyzed using a Cox-proportional hazards model with age subgroups, accounting for covariates at baseline. During follow-up, the incidence rate of CVD per 1000 person-years was lower for the stable low loneliness group and decreased loneliness group compared to the increased loneliness and stable high loneliness group. Increased loneliness is associated with the highest risk of overall CVD and heart disease (HR 2.44, P < 0.001; HR 2.34, P < 0.001), while stable high loneliness is associated with the highest risk of stroke among the four loneliness categories (HR 4.29, P < 0.05). The age-specific analyses revealed no statistically significant interaction in terms of loneliness status transitions and age group. CONCLUSION: Increased loneliness and stable high loneliness are associated with higher CVD risk. In clinical practice, it is important to monitor patients' loneliness status transitions to reduce CVD incidences.

Disparity of serum uric acid threshold for CKD among hypertensive and non-hypertensive individuals.

INTRODUCTION: Hypertension and rising serum uric acid (sUA) played a pivotal role in the development of Chronic Kidney Disease (CKD). This study investigates the interactive effect of sUA and hypertension on CKD and identifies the optimal threshold of sUA among individuals with and without hypertension in the Chinese community population. MATERIALS AND METHODS: The study included 4180 individuals aged 45-85 years, derived from the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2015. Additionally, a hospital-based study enrolled subjects in the Department of Nephrology at Zhongshan Hospital, China from January 1, 2019, to December 31, 2021. The interaction effect analysis were used to assess the impact of sUA and hypertension on CKD. We also compared the distribution of sUA and the CKD risk in community populations, distinguishing between those with and without hypertension. For the hospital-based population, kidney injury was marked by a KIM-1 positive area. RESULTS: Our results indicate a higher prevalence of CKD in the community population with hypertension (10.2% vs. 3.9%, p < .001). A significant additive synergistic effects of the sUA and hypertension on the CKD risk were found. When the sUA level was < 4.55 mg/dL in the hypertensive population and < 5.58 mg/dL in the non-hypertensive population, the risk of CKD was comparable (p = .809). In the propensity score matched (PSM) population, the result remained roughly constant. CONCLUSION: Therefore, even moderate levels of sUA was associated with a higher risk of CKD in middle-aged hypertensive patients, who warrant stricter sUA control.

Constructing Carbon Nanotube Hybrid Fiber Electrodes with Unique Hierarchical Microcrack Structure for High-Voltage, Ultrahigh-Rate, and Ultralong-Life Flexible Aqueous Zinc Batteries.

Flexible aqueous zinc batteries are promising candidates as safe power sources for fast-growing portable and wearable electronics. However, the low working voltage, poor rate capability, and cycling stability have greatly restricted their development and applications. Here, a new family of flexible bimetallic phosphide/carbon nanotube hybrid fiber electrodes with unique macroscopic microcrack structure and microscopic porous nanoflower structure is reported. The hierarchical microcrack structure not only facilitates the penetration of electrolyte for effective exposure of active sites, but also can serve as buffers to relieve the stress concentrations of the fiber electrode under deformations, enabling impressive electrochemical performance and mechanical flexibility. Particularly, the fabricated flexible aqueous zinc batteries demonstrate high working voltage plateau and specific capacity (≈1.7 V, 258.9 mAh g-1 at 2 A g-1 ), ultrahigh rate capability (135.8 mAh g-1 at 50 A g-1 , fully charged in only 9.8 s) and impressive power density of 79 000 W kg-1 . Moreover, the flexible batteries show ultralong cycling life with 74.6% capacity retention after 20 000 cycles. The fiber batteries are also highly flexible and can be easily knitted into soft electronic textiles to power a smartphone, which are particularly promising for the next-generation of flexible and wearable electronics.

Risk factor mining and prediction of urine protein progression in chronic kidney disease: a machine learning- based study.

BACKGROUND: Chronic kidney disease (CKD) is a global public health concern. Therefore, to provide timely intervention for non-hospitalized high-risk patients and rationally allocate limited clinical resources is important to mine the key factors when designing a CKD prediction model. METHODS: This study included data from 1,358 patients with CKD pathologically confirmed during the period from December 2017 to September 2020 at Zhongshan Hospital. A CKD prediction interpretation framework based on machine learning was proposed. From among 100 variables, 17 were selected for the model construction through a recursive feature elimination with logistic regression feature screening. Several machine learning classifiers, including extreme gradient boosting, gaussian-based naive bayes, a neural network, ridge regression, and linear model logistic regression (LR), were trained, and an ensemble model was developed to predict 24-hour urine protein. The detailed relationship between the risk of CKD progression and these predictors was determined using a global interpretation. A patient-specific analysis was conducted using a local interpretation. RESULTS: The results showed that LR achieved the best performance, with an area under the curve (AUC) of 0.850 in a single machine learning model. The ensemble model constructed using the voting integration method further improved the AUC to 0.856. The major predictors of moderate-to-severe severity included lower levels of 25-OH-vitamin, albumin, transferrin in males, and higher levels of cystatin C. CONCLUSIONS: Compared with the clinical single kidney function evaluation indicators (eGFR, Scr), the machine learning model proposed in this study improved the prediction accuracy of CKD progression by 17.6% and 24.6%, respectively, and the AUC was improved by 0.250 and 0.236, respectively. Our framework can achieve a good predictive interpretation and provide effective clinical decision support.

Intelligent upgrade of waste-activated sludge dewatering process based on artificial neural network model: Core influential factor identification and non-experimental prediction of sludge dewatering performance.

Owing to the extremely complex compositions and origins of waste-activated sludge (WAS), the multiple physiochemical properties of WAS have impacts on its dewaterability, and there is a complex interaction relationship among the multiple physiochemical properties, which makes it difficult to identify the controlling factors on WAS dewaterability. Accordingly, there is still no unified certainty in the appropriate ranges of physiochemical properties for the optimal dewaterability of sludge from different sources, resulting in a lack of clear theoretical basis for technical selection and optimization of sludge dewatering processes. The large consumption of conditioning chemicals and low process efficiency stand for the major deficiency of existing sludge conditioning technologies. This study proposed to use a non-linear, adaptive and self-organizing artificial neural network (ANN) model to integrate the multiple physiochemical properties of WAS affecting its dewaterability, and WAS dewatering performance under certain conditioning schemes could be predicated by ANN model with the multiple physiochemical properties and conditioning operation parameters as the input arguments. Thus, the laborious filtration experiments for screening conditioning chemicals could be replaced by the input adjustment of ANN model. Rooted mean squared error (RMSE) of 6.51 and coefficient of determination (R2) of 0.73 confirmed the satisfied stability and accuracy of established ANN model. Furthermore, the predictor-exclusive method revealed that the exclusion of polar interface free energy decreased most, which reflected the importance of surface hydrophilicity reduction in sludge dewaterability improvement. All the contributions presented here were believed to provide an intelligent insight to improve the experience operation status of WAS dewatering process.

Clinical and radiological evaluation of cage subsidence following oblique lumbar interbody fusion combined with anterolateral fixation.

BACKGROUND: Cage subsidence (CS) was previously reported as one of the most common complications following oblique lumbar interbody fusion (OLIF). We aimed to assess the impacts of CS on surgical results following OLIF combined with anterolateral fixation, and determine its radiological characteristics as well as related risk factors. METHODS: Two hundred and forty-two patients who underwent OLIF at L4-5 and with a minimum 12 months follow-up were reviewed. Patients were divided into three groups according to the extent of disk height (DH) decrease during follow-up: no CS (DH decrease ≤ 2 mm), mild CS (2 mm < DH decrease ≤ 4 mm) and severe CS (DH decrease > 4 mm). The clinical and radiological results were compared between groups to evaluate radiological features, clinical effects and risk factors of CS. RESULTS: CS was identified in 79 (32.6%) patients, including 48 (19.8%) with mild CS and 31 (11.8%) with severe CS. CS was mainly identified within 1 month postoperatively, it did not progress after 3 months postoperatively, and more noted in the caudal endplate (44, 55.7%). In terms of clinical results, patients in the mild CS group were significantly worse than those in the no CS group, and patients in the severe CS group were significantly worse than those in the mild CS group. There was no significant difference in fusion rate between no CS (92.6%, 151/163) and mild CS (83.3%, 40/48) groups. However, significant lower fusion rate was observed in severe CS group (64.5%, 20/31) compared to no CS group. CS related risk factors included osteoporosis (OR = 5.976), DH overdistraction (OR = 1.175), flat disk space (OR = 3.309) and endplate injury (OR = 6.135). CONCLUSION: CS following OLIF was an early postoperative complication. Higher magnitudes of CS were associated with worse clinical improvements and lower intervertebral fusion. Osteoporosis and endplate injury were significant risk factors for CS. Additionally, flat disk space and DH over-distraction were also correlated with an increased probability of CS.

Influence of coronal-morphology of endplate and intervertebral space to cage subsidence and fusion following oblique lumbar interbody fusion.

BACKGROUND: Endplate morphology is considered to be one of the influencing factors of cage subsidence after lumbar interbody fusion (LIF). Previous radiographic evaluations on the endplate mostly used sagittal X-ray or MRI. However, there are few studies on the CT evaluation of the endplate and intervertebral space (IVS), especially the evaluation of coronal morphology and its influence on subsidence and fusion after LIF. We aimed to measure and classify the shapes of the endplate and IVS using coronal CT imaging and evaluate the radiographic and clinical outcomes of different shapes of the endplate/IVS following oblique lateral lumbar interbody fusion (OLIF). METHODS: A total of 137 patients (average age 59.1 years, including 75 males and 62 females) who underwent L4-5 OLIF combined with anterolateral fixation from June 2018 to June 2020 were included. The endplate concavity depth (ECD) was measured on the preoperative coronal CT image. According to ECD, the endplate was classified as flat (< 2 mm), shallow (2-4 mm), or deep (> 4 mm). The L4-5 IVS was further classified according to endplate type. The disc height (DH), DH changes, subsidence rate, fusion rate, and Oswestry Disability Index (ODI) in different endplate/IVS shapes were evaluated during 1-year follow up. RESULTS: The ECD of L4 inferior endplate (IEP) was significantly deeper than that of L5 superior endplate (SEP) (4.2 ± 1.1 vs 1.6 ± 0.8, P < 0.01). Four types of L4-5 IVS were identified: shallow-shallow (16, 11.7%), shallow-flat (45, 32.9%), deep-shallow (32, 23.4%), and deep-flat (44, 32.1%). A total of 45 (32.9%) cases of cage subsidence were observed. Only one (6.3%) subsidence event occurred in the shallow-shallow group, which was significantly lower than in the other three groups (19 shallow-flat, 6 deep-shallow, and 19 deep-flat) (P < 0.05). Meanwhile, the shallow-shallow group had the highest fusion rate (15, 93.8%) and the highest rate of reach minimal clinically important difference (MCID) ODI among the four types. For a single endplate, the shape of L4 IEP is the main influencing factor of the final interbody fusion rate, and the shallow shape L4 IEP facilitates fusion ( OR = 2.85, p = 0.03). On the other hand, the flat shape L5 SEP was the main risk factor to cage subsidence (OR = 4.36, p < 0.01). CONCLUSION: The L4-5 IVS is asymmetrical on coronal CT view and tends to be fornix-above and flat-down. The shallow-shallow IVS has the lowest subsidence rate and best fusion result, which is possibly because it has a relatively good degree in matching either the upper or lower interface of the cage and endplates. These findings provide a basis for the further improvements in the design of OLIF cages.

Diurnal transcriptomics analysis reveals the regulatory role of the circadian rhythm in super-hybrid rice LY2186.

Heterosis, an important biological phenomenon wherein F1 hybrids exhibit better performance than any of their parents, has been widely applied; however, its underlying mechanism remains largely unknown. Here, we studied and compared the dynamic transcriptional profiles of super-hybrid rice LY2186 and its parents at 17 time points during 2 day/night cycles and identified 1552 rhythmic differentially expressed genes (RDGs). Cluster and functional enrichment analyses revealed that the day- and night-phased RDGs were mainly enriched in the photosynthesis and stress response categories, respectively. Regulatory network analysis indicated that circadian-related RDGs are core components in both the day and night phases and extensively regulate downstream genes involved in photosynthesis, starch synthesis, plant hormone signal transduction, and other pathways. Furthermore, among the 282 RDGs mapped onto the quantitative tract loci of small intervals (≤100 genes), 72.3% were significantly enriched in the yield, vigor, and anatomy categories. These findings provide valuable information for exploring heterosis mechanisms further and guiding breeding practices.

Electrolyte Dynamics Engineering for Flexible Fiber-Shaped Aqueous Zinc-Ion Battery with Ultralong Stability.

Flexible aqueous zinc-ion batteries (ZIBs) are considered as promising energy storage devices for wearable electronics due to their cost-effectiveness, environmental friendliness, and high theoretical energy density. Herein, a flexible fiber-shaped aqueous ZIB is demonstrated by using a self-assembled Co3O4 nanosheet array on a carbon nanotube fiber as the cathode and Zn nanosheets deposited on a carbon nanotube fiber as the anode. The cycle life span of the fiber-shaped battery is largely enhanced by a simple electrolyte dynamics engineering strategy of preadding a trace amount of Co2+ cations in the mild aqueous electrolyte. The assembled fiber-shaped ZIB shows a high specific capacity (158.70 mAh g-1 at 1 A g-1), superior rate capacity, and excellent cycling life span (97.27% capacity retention after 10,000 cycles). Additionally, the fiber-shaped ZIB also shows superior flexibility, which can charge a smart watch under deformed states. This work provides new opportunities for the development of flexible, safe, and high-performance energy storage devices for wearable electronics.

Long non-coding RNA LINC00337 induces autophagy and chemoresistance to cisplatin in esophageal squamous cell carcinoma cells via upregulation of TPX2 by recruiting E2F4.

Esophageal cancer represents the eighth most frequently occurring cancer, as well as the sixth most widespread cause of cancer-related deaths. In recent years, accumulating evidence has implicated long non-coding RNAs in the progression of esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the potential involvement and underlying mechanisms of LINC00337 in ESCC. Expression patterns of LINC00337 and targeting protein for Xenopus kinesin-like protein 2 (TPX2) in ESCC tissues and cells were detected using RT-qPCR and immunohistochemical staining. Next, the interactions among LINC00337, E2F4, and TPX2 were identified using chromatin immunoprecipitation, dual-luciferase reporter, and RNA-binding protein immunoprecipitation assays, suggesting that LINC00337 could recruit E2F4 to enhance the transcription of TPX2. Thereafter, the regulatory roles of LINC00337 and TPX2 in ESCC were analyzed by altering the expression of LINC00337 or TPX2 in ESCC cells following treatment with cisplatin (DDP). The levels of autophagy-related proteins Beclin1 and LC3II/LC3I, viability, autophagy, apoptosis, and chemoresistance of ESCC cells to DDP were measured following transfection treatment with different plasmids. Additionally, the role of the LINC00337/E2F4/TPX2 axis was assessed in vivo by measuring tumor formation in nude mice. The results demonstrated that LINC00337 upregulated TPX2, consequently leading to elevated levels of Beclin1 and LC3II/LC3I, promoted cell viability and autophagy, while inhibiting apoptosis and chemosensitivity to DDP in ESCC. In sum, the current study evidenced that the overexpression of LINC00337 could potentially enhance ESCC cell autophagy and chemoresistance to DDP via the upregulation of TPX2 by recruiting E2F4. Thus, LINC00337 may serve as a potential candidate for the treatment of ESCC.

Metallic Sandwiched-Aerogel Hybrids Enabling Flexible and Stretchable Intelligent Sensor.

Flexible strain sensors have been widely investigated with their rapid development in human-machine interfaces, soft robots, and medical care monitoring. Here, we report a new in situ catalytic strategy toward the fabrication of metallic aerogel hybrids, which are composed of vanadium nitride (VN) nanosheets decorated with well-defined vertically aligned carbon nanotube arrays (VN/CNTs) for the first time. In this architecture, the two-dimensional VN nanosheets as the main bone structure are favorable for the flexible devices due to their excellent structural compatibility during the repetitive deforming process. In addition, the sandwiched aerogel hybrids form highly conductive 3D network, affording outstanding sensitivity for the strain-responsive behaviors. Further, the VN/CNTs-based flexible strain sensors are successfully fabricated, showing a high gauge factor of 386 within a small strain of 10%, fast response, and extraordinary durability. The monitoring of physical signals and an actual real-time human-machine controlling system based on the sensors are also presented.

Osteoprotegerin promotes intimal hyperplasia and contributes to in-stent restenosis: Role of an αVß3/FAK dependent YAP pathway.

OBJECTIVE: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are related to in-stent-restenosis (ISR) following percutaneous coronary intervention (PCI). Osteoprotegerin (OPG) has been implicated in various vascular diseases. However, the effects of OPG on ISR and the underlying mechanism remained elusive. We here investigated the association between OPG and ISR, and to demonstrate the role and potential mechanisms of OPG in neointimal hyperplasia. APPROACH AND RESULTS: From 2962 patients who received coronary angiography and follow-up coronary angiography at approximately one year, 291 patients were diagnosed with ISR, and another 291 gender- and age- matched patients without ISR were selected as controls. Serum OPG levels were significantly increased in patients with ISR. Multivariable logistic regression analysis indicated that OPG level was independently associated with the increased risk of ISR. In a mouse femoral artery wire injury model, upregulated OPG was evidenced in vascular tissue after injury. OPG deletion attenuated the vascular injury-induced neointimal hyperplasia and related gene expression in mice. OPG promoted neointimal hyperplasia and human aortic smooth muscle cell (hASMC) proliferation and migration through activation of yes-associated protein (YAP), a major downstream effector of the Hippo signaling pathway, whereas knockdown or inhibition of YAP in hASMCs blunted OPG-induced above effects. Moreover, we found that OPG, as a ligand for integrin αVß3, mediated phosphorylation of focal adhesion kinase (FAK) and actin cytoskeleton reorganization, resulting in YAP dephosphorylation in hASMCs. OPG-dependent YAP and VSMC activation was prevented by treatment with αVß3-blocking antibodies and inhibitors of FAK and actin stress fibers. CONCLUSIONS: Increased serum OPG levels are associated with increased risk of ISR following PCI and OPG could promote neointimal hyperplasia in response to injury through integrin αVß3 mediated FAK and YAP activation, indicating OPG/YAP inhibition might serve as an attractive novel target for the prevention of ISR after PCI.

Long noncoding RNA HAGLR acts as a microRNA-143-5p sponge to regulate epithelial-mesenchymal transition and metastatic potential in esophageal cancer by regulating LAMP3.

Homeobox D gene cluster antisense growth-associated long noncoding RNA (HAGLR) functions as a crucial regulator in the progression and development of human cancers. We analyzed effects of HAGLR, microRNA (miR)-143-5p and lysosome-associated membrane glycoprotein (LAMP)3 on esophageal cancer (EC) and the related mechanisms. Microarray analysis was used to screen out EC-related genes and the regulation network among HAGLR, miR-143-5p, and LAMP3. The regulatory mechanisms of HAGLR and miR-143-5p in EC were analyzed following the treatment of miR-143-5p mimic, miR-143-5p inhibitor, HAGLR vector, or small interfering RNA against HAGLR in EC cells. The expression of N-cadherin, vimentin, Twist1, Snail1, and E-cadherin as well as the abilities of cell proliferation, invasion, and migration were measured. The effects of the HAGLR/miR-143-5p/LAMP3 axis were determined in vivo by assessing tumor formation in nude mice. The expression of HAGLR and LAMP3 was increased, whereas that of miR-143-5p was diminished in EC tissues and cells. HAGLR could competitively bind to miR-143-5p, and miR-143-5p targeted LAMP3. Down-regulated HAGLR or up-regulated miR-143-5p increased E-cadherin expression and significantly diminished expression of LAMP3, N-cadherin, vimentin, Twist1, and Snail1. Moreover, down-regulated HAGLR inhibited cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), and tumor growth. Moreover, down-regulation of HAGLR inhibited LAMP3 expression by sponging miR-143-5p, thereby suppressing the progression of EC. Taken together, our results suggest HAGLR acts as a competing endogenous RNA of miR-143-5p to increase the expression of LAMP3, thus promoting EMT, proliferation, invasion, and migration in EC cells.-Yang, C., Shen, S., Zheng, X., Ye, K., Sun, Y., Lu, Y., Ge, H. Long noncoding RNA HAGLR acts as a microRNA-143-5p sponge to regulate epithelial-mesenchymal transition and metastatic potential in esophageal cancer by regulating LAMP3.

Effects of microRNA-217 on proliferation, apoptosis, and autophagy of hepatocytes in rat models of CCL4-induced liver injury by targeting NAT2.

Liver injury is an important cause of serious liver disease. This study aims to explore the effects of miR-217 targeting NAT2 on hepatocyte proliferation, apoptosis, and autophagy following carbon tetrachloride (CCL4)-induced liver injury. Rat models of CCL4-induced liver injury were established. Healthy Wistar rats were randomized into the normal, blank, negative control (NC), microRNA-217 (miR-217) mimic, miR-217 inhibitor, small interfering RNA (siRNA)-N-acetyltransferase 2 (NAT2), and miR-217 inhibitor + siRNA-NAT2 groups. NAT2 activity was evaluated with reversed-phase high-performance liquid chromatographic method. Immunohistochemistry was used to detect NAT2 protein positive rate. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to examine expressions of miR-217, NAT2, Bcl-2, Bax, p35, LC3-II, Becline-1, and the ratio of caspase-3/cleaved caspase-3. Autophagy, proliferation, and cell cycle distribution were determined by electron microscope, CCK-8, and flow cytometry. NAT2 protein positive rate and miR-217, NAT2, Bcl-2, and p35 expressions were higher and Bax, LC3-II, and Becline-1 expressions and the ratio of caspase-3/cleaved caspase-3 lower in the normal group than the other six groups. Compared with the blank and NC groups, in the miR-217 mimic and siRNA-NAT2 groups, Bax, LC3-II, and Becline-1 expressions and the ratio of caspase-3/cleaved caspase-3, and hepatocyte apoptosis and autophagy increased, while NAT2, Bcl-2, and p35 expressions and hepatocyte proliferation decreased; opposite results were observed in the miR-217 inhibitor group. Collectively, miR-217 targeting NAT2 inhibits proliferation and promotes apoptosis and autophagy of hepatocytes in CCL4-induced liver injury.

PD1+ tumor associated macrophages predict poor prognosis of locally advanced esophageal squamous cell carcinoma.

Aim: Tumor associated macrophages are the most abundant cancer immune cells. However, little was known about the identity of CD68+PD1+ macrophages as well as the contributions in the prognosis of esophageal squamous cell carcinoma (ESCC). Methods & methods: Immunofluorescence, flowcytometry and RT-PCR were used to analysis PD1+ macrophages in ESCC. Results: CD68+PD1+ macrophages which can express higher M2 markers in cancer tissues, increased about 4.2-times compared with para-cancer tissues. Additionally, PD1high macrophages were significantly correlated with more malignant phenotypes and poor prognosis. PD1 treatment can enhance phagocytosis of cultured macrophages and redirect this macrophage to M1-like phenotype. Conclusion: Thus, our findings overall indicate that CD68+PD1+ macrophages are tumor associated macrophagess in ESCC, which can forecast the prognosis of ESCC.

MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1.

BACKGROUNDS/AIMS: MicroRNAs (miRs) often contribute to the progression of non-small cell lung cancer (NSCLC) via regulation of mRNAs that are involved in lung homeostasis. We conducted a study aimed at exploring the roles of miR-183 in the proliferation, epithelial-mesenchymal transition (EMT), invasion and migration of human NSCLC cells via targeting MTA1. METHODS: NSCLC and adjacent normal tissues were collected from 194 patients with NSCLC. Positive expression of MTA1 protein was detected by immunohistochemistry. The highest levels of expression of miR-183 were detected using RT-qPCR in SPC-A-1 cells, which were selected and assigned to the following groups: blank, negative control (NC), miR-183 mimic, miR-183 inhibitor, siRNA-MTA1, and miR-183 inhibitor + siRNA-MTA1. The expression of miR-183 and the mRNA and protein expression of MTA1, E-cadherin, Vimentin, Snail, PCNA, Bax and Bcl-2 in tissues and transfected cells were measured using RT-qPCR and western blot analysis. Cell proliferation, apoptosis, migration and invasion were evaluated by CCK-8, flow cytometry, scratch tests and Transwell assays. Tumor xenografts were conducted in nude mice to determine tumor growth. RESULTS: SPC-A-1 cells with the highest levels of miR-183 expression were selected. Compared with adjacent normal tissues, the expression of miR-183 and the mRNA and protein expression of E-cadherin and Bax were decreased in NSCLC tissues, while mRNA and protein expression of MTA1, Vimentin, snail, PCNA and Bcl-2 were increased. MiR-183 was over-expressed in the miR-183 mimic group and under-expressed in the miR-183 inhibitor and miR-183 inhibitor + siRNA-MTA1 groups. In the miR-183 mimic and siRNA-MTA1 groups, the mRNA and protein expression of E-cadherin and Bax, as well as cell apoptosis, were enhanced, while the expression levels of MTA1, Vimentin, snail, PCNA and Bcl-2 mRNA and protein, cell proliferation, migration, invasion and tumor growth were reduced relative to the blank and NC groups. The miR-183 inhibitor group exhibited an opposite trend. CONCLUSION: Our study indicates that miR-183 down-regulates MTA1 to inhibit the proliferation, EMT, migration and invasion of human NSCLC cells.