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Abstract Background Our study aims to investigate the mechanisms through which Fc receptor‐like A (FCRLA) promotes renal cell carcinoma (RCC) and to examine its significance in relation to tumor immune infiltration. Materials and Methods The correlation between FCRLA and data clinically related to RCC was explored using The Cancer Genome Atlas (TCGA), then validated using Gene Expression Omnibus (GEO) gene chip data. Enrichment and protein–protein interaction (PPI) network analyses were performed for FCRLA and its co‐expressed genes. FCRLA was knocked down in RCC cell lines to evaluate its impact on biological behavior. Then the potential downstream regulators of FCRLA were determined by western blotting, and rescue experiments were performed for verification. The relevance between FCRLA and various immune cells was analyzed through GSEA, TIMER, and GEPIA tools. TIDE and ESTIMATE algorithms were used to predict the effect of FCRLA in immunotherapy. Results Fc receptor‐like A was associated with clinical and T stages and could predict the M stage (AUC = 0.692) and 1–3‐ and 5‐year survival rates (AUC = 0.823, 0.834, and 0.862) of RCC patients. Higher expression of FCLRA predicted an unfavorable overall survival (OS) in TCGA‐RCC and GSE167573 datasets (p = 0.03, p = 0.04). FCRLA promoted the malignant biological behavior of RCC cells through the pERK1/2/‐MMP2 pathway and was associated with tumor immune microenvironment in RCC. Conclusion Fc receptor‐like A is positively correlated with poor outcomes in RCC patients and plays an oncogenic role in RCC through the pERK1/2‐MMP2 pathway. Patients with RCC might benefit from immunotherapy targeting FCRLA.

Abstract Background The innovative combination of all‐trans retinoic acid (ATRA) and arsenic trioxide (ATO) has established a new chapter of curative approach in acute promyelocytic leukemia (APL). The disease characteristics and prognostic influence of additional cytogenetic abnormalities (ACA) in APL with modern therapeutic strategy need to be elucidated. Methods In the present study, we retrospectively investigated disease features and prognostic power of ACA in 171 APL patients treated with ATRA‐ATO‐containing regimens. Results Patients with ACA had markedly decreased hemoglobin levels than that without ACA (p = 0.021). Risk stratification in the ACA group was significantly worse than that in the non‐ACA group (p = 0.032). With a median follow‐up period of 62.0 months, worse event‐free survival (EFS) was demonstrated in patients harboring ACA. Multivariate analysis showed that ACA was an independent adverse factor for EFS (p = 0.033). By further subgroup analysis, in CD34 and CD56 negative APL, patients harboring ACA had inferior EFS (p = 0.017; p = 0.037). Conclusions To sum up, ACA remains the independent prognostic value for EFS, we should build risk‐adapted therapeutic strategies in the long‐term management of APL when such abnormalities are detected.

Abstract The solar‐driven interfacial evaporation (SIE) technology shows great prospects in seawater desalination and sewage treatment, but it is unable to obtain highly efficient and high‐quality clean nontoxic water at low cost. Here, a novel biodegradable hydrogel‐based solar evaporator (BBH‐L) with a bionic coral structure taking Chinese ink as the solar absorber was developed. This evaporator consists of chitosan/polyvinyl alcohol hydrogel and a loofah substrate. The average evaporation rate and efficiency of BBH‐L reach 4.37 kg/(m2·h) and 98.2%, respectively, under one sun illumination (1 kW/m2), which are attributed to its excellent thermal localization and water transporting abilities. Meanwhile, high salt resistance enables BBH‐L to achieve efficient desalination and purification of other unconventional water. Heavy metal ions in seawater can be effectively removed by chelation and forming hydrogen bonds in hydrogels. This study is anticipated to provide new possibilities to enhance evaporation performance and reduce the costs of water treatment systems.

Abstract Despite the impressive progress of stimuli‐responsive fluorescent materials, little is known about the influence of confinement created by crystalline polymer over the fluorescence properties of fluorescent molecules. The effects of confinement on the fluorescence of an aggregation‐induced emission luminogen (AIEgen) are investigated using computational simulations, which reveal that the confined space induces the AIEgens to take a more planar conformation, resulting in a red‐shifted emission spectrum. With this property, the study is extended to explore the confinement generated by various polymer crystalline forms, and it is shown that different fluorescence colors are activated. This confinement fluorescence effect is attributed to the different spatial dimensions of the polymer amorphous layer between lamellar crystals where the AIEgens are located. These results indicate the immediate association between crystalline structure and fluorescence signals, activating unprecedented photophysical properties of luminescent materials, and also providing the possibility for crystalline structure visualization, it is important for the many polymer crystallization processes occurring in the materials processing.

Abstract Tissue regeneration is regulated by morphological clues of implants in bone defect repair. Engineered morphology can boost regenerative biocascades that conquer challenges such as material bioinertness and pathological microenvironments. Herein, a correlation between the liver extracellular skeleton morphology and the regenerative signaling, namely hepatocyte growth factor receptor (MET), is found to explain the mystery of rapid liver regeneration. Inspired by this unique structure, a biomimetic morphology is prepared on polyetherketoneketone (PEKK) via femtosecond laser etching and sulfonation. The morphology reproduces MET signaling in macrophages, causing positive immunoregulation and optimized osteogenesis. Moreover, the morphological clue activates an anti‐inflammatory reserve (arginase‐2) to translocate retrogradely from mitochondria to the cytoplasm due to the difference in spatial binding of heat shock protein 70. This translocation enhances oxidative respiration and complex II activity, reprogramming the metabolism of energy and arginine. The importance of MET signaling and arginase‐2 in the anti‐inflammatory repair of biomimetic scaffolds is also verified via chemical inhibition and gene knockout. Altogether, this study not only provides a novel biomimetic scaffold for osteoporotic bone defect repair that can simulate regenerative signals, but also reveals the significance and feasibility of strategies to mobilize anti‐inflammatory reserves in bone regeneration.

Abstract Objective To compare and analyze the pass rate and screening strategy of hearing rescreening for newborns with high risk factors. Methods Retrospective chart review of high‐risk newborns who failed their initial newborn hearing screen and subsequently underwent secondary hearing tests from June 2011 to June 2018 in Guangzhou Women and Children's Medical Center were performed. Results Eight hundred and sixty‐eight newborns with high risk factors were included in the study. The 57‐70 days (83.5%) and 71‐84 days (83.4%) group had the highest pass rate compared with 42‐56 days (75.8%) and < 42 days (68.3%) group. As for different screening strategies, the pass rate of OAE(otoacoustic emissions), AABR (auto auditory brainstem response) and OAE + AABR was the highest in 57–70 days group and 71‐84 days group, respectively. The OAE + AABR had the lowest pass rate compared to the other two modalities. When the pass rate was compared as different risk factors, the 57–70 days and 71–84 days group also had the highest pass rate compared with 42–56 days and < 42 days group and the pass rate had no significant differences among various risk factors group. Conclusion Our results showed that all the pass rate of OAE, AABR and OAE + AABR was the highest in 57–70 days group and 71–84 days group with significant difference, suggesting that the delayed screening time (>57 days) may increase the re‐screening pass rate and reduce anxiety of parents, which is of great significance for clinical work.

Abstract Conductive hydrogels as promising material candidates for soft electronics have been rapidly developed in recent years. However, the low ionic conductivity, limited mechanical properties, and insufficient freeze‐resistance greatly limit their applications for flexible and wearable electronics. Herein, aramid nanofiber (ANF)‐reinforced poly(vinyl alcohol) (PVA) organohydrogels containing dimethyl sulfoxide (DMSO)/H2O mixed solvents with outstanding freeze‐resistance are fabricated through solution casting and 3D printing methods. The organohydrogels show both high tensile strength and toughness due to the synergistic effect of ANFs and DMSO in the system, which promotes PVA crystallization and intermolecular hydrogen bonding interactions between PVA molecules as well as ANFs and PVA, confirmed by a suite of characterization and molecular dynamics simulations. The organohydrogels also exhibit ultrahigh ionic conductivity, ranging from 1.1 to 34.3 S m−1 at −50 to 60 °C. Building on these excellent material properties, the organohydrogel‐based strain sensors and solid‐state zinc–air batteries (ZABs) are fabricated, which have a broad working temperature range. Particularly, the ZABs not only exhibit high specific capacity (262 mAh g−1) with ultra‐long cycling life (355 cycles, 118 h) even at −30 °C, but also can work properly under various deformation states, manifesting their great potential applications in soft robotics and wearable electronics.

Background Nicorandil was reported to improve microvascular dysfunction and reduce reperfusion injury when administered before primary percutaneous coronary intervention. In this multicenter, prospective, randomized, double‐blind clinical trial (CHANGE [Effects of Nicorandil Administration on Infarct Size in Patients With ST‐Segment–Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention]), we investigated the effects of nicorandil administration on infarct size in patients with ST‐segment–elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods and Results A total of 238 patients with ST‐segment–elevation myocardial infarction were randomized to receive intravenous nicorandil (n=120) or placebo (n=118) before reperfusion. Patients in the nicorandil group received a 6‐mg intravenous bolus of nicorandil followed by continuous infusion at a rate of 6 mg/h. Patients in the placebo group received the same dose of placebo. The predefined primary end point was infarct size on cardiac magnetic resonance (CMR) imaging performed at 5 to 7 days and 6 months after reperfusion. CMR imaging was performed in 201 patients (84%). Infarct size on CMR imaging at 5 to 7 days after reperfusion was significantly smaller in the nicorandil group compared with the placebo (control) group (26.5±17.1 g versus 32.4±19.3 g; P=0.022), and the effect remained significant on long‐term CMR imaging at 6 months after reperfusion (19.5±14.4 g versus 25.7±15.4 g; P=0.008). The incidence of no‐reflow/slow‐flow phenomenon during primary percutaneous coronary intervention was much lower in the nicorandil group (9.2% [11/120] versus 26.3% [31/118]; P=0.001), and thus, complete ST‐segment resolution was more frequently observed in the nicorandil group (90.8% [109/120] versus 78.0% [92/118]; P=0.006). Left ventricular ejection fraction on CMR imaging was significantly higher in the nicorandil group than in the placebo group at both 5 to 7 days (47.0±10.2% versus 43.3±10.0%; P=0.011) and 6 months (50.1±9.7% versus 46.4±8.5%; P=0.009) after reperfusion. Conclusions In the present trial, administration of nicorandil before primary percutaneous coronary intervention led to improved myocardial perfusion grade, increased left ventricular ejection fraction, and reduced myocardial infarct size in patients with ST‐segment–elevation myocardial infarction. Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03445728.

Electrohydrostatic actuator is a type of actuator that uses hydraulic energy as the energy transmission carrier, which has the advantages of small size and high power. Since it is commonly used in harsh conditions such as strong vibration, high pressure, and heavy loads, condition monitoring and fault diagnosis of its hydraulic system are particularly important. This paper proposed a novel fault feature extraction method and applied to fault diagnosis of electrohydrostatic actuator. Firstly, the pressure signal of the hydraulic system is decomposed at multiple scales to obtain the center frequency of its maximum energy intrinsic mode component, and the feature data set is constructed based on the statistical features of the time domain. Then, a fault identification model of hydraulic system based on support vector machine is established. Finally, the fault classification and identification results of the hydraulic system are outputted. After a variety of method comparisons, the method proposed in this paper has a fault time ratio accuracy of 96.7%, which provides a basis and a new way for the fault diagnosis of the hydraulic system.

Background The risk for atherosclerotic cardiovascular disease (ASCVD) events may differ by sociodemographic factors among patients meeting the definition of very high risk according to the 2018 American Heart Association/American College of Cardiology cholesterol guideline, leading to treatment disparities. We estimated the risk for recurrent ASCVD events among adults meeting the definition of very high risk by age, sex, race/ethnicity, and socioeconomic status in a US integrated healthcare system. Methods and Results The study cohort included Kaiser Permanente Southern California members aged ≥21 years with a history of clinical ASCVD on September 30, 2009. Very high risk for recurrent ASCVD was defined by a history of ≥2 major ASCVD events or a history of 1 major event along with ≥2 high‐risk conditions. Patients were followed through 2015 for a first recurrent ASCVD event. Of 77 101 patients with ASCVD, 50.8% met the definition for very high risk. Among patients meeting the definition of very high risk, recurrent ASCVD rates were higher in older (>75 years) versus younger patients (21–40 years) (sex‐adjusted hazard ratio [HR] [95% CI] 1.85; 1.23–2.79), non‐Hispanic Black patients versus non‐Hispanic White patients (age‐, sex‐adjusted HR, 1.32; 1.23–1.41), those who lived in neighborhoods with lower (

Abstract 2D metal nanomaterials offer exciting prospects in terms of their properties and functions. However, the ambient aqueous synthesis of atomically‐thin, 2D metallic nanomaterials represents a significant challenge. Herein, freestanding and atomically‐thin gold nanosheets with a thickness of only 0.47 nm (two atomic layers thick) are synthesized via a one‐step aqueous approach at 20 °C, using methyl orange as a confining agent. Owing to the high surface‐area‐to‐volume ratio, abundance of unsaturated atoms exposed on the surface and large interfacial areas arising from their ultrathin 2D nature, the as‐prepared Au nanosheets demonstrate excellent catalysis performance in the model reaction of 4‐nitrophenol reduction, and remarkable peroxidase‐mimicking activity, which enables a highly sensitive colorimetric sensing of H2O2 with a detection limit of 0.11 × 10−6 m. This work represents the first fabrication of freestanding 2D gold with a sub‐nanometer thickness, opens up an innovative pathway toward atomically‐thin metal nanomaterials that can serve as model systems for inspiring fundamental advances in materials science, and holds potential across a wide region of applications.

Background. Inflammation is one of the most important pathogeneses of thromboangiitis obliterans (TAO). The NLRP3 inflammasome plays a vital role in the body’s immune response and disease development. It can be activated by numerous types of pathogens or danger signals. As the core of the inflammatory response, the NLRP3 inflammasome may provide a new target for the treatment of various inflammatory diseases. Levistilide A (LA) is a phthalide dimer isolated from umbelliferous plants. Its pharmacological effect is largely unknown. This study revealed the effects of LA on endothelial cell activation, NLRP3, IL-1β, TNF-α, IL-32, and CCL-2, VCAM-1, MCP-1, and the spleen tyrosine kinase (Syk)--p38/JNK signaling axis and its effect on vasculitis in rats. Results. LA inhibited endothelial activation and the expression of IL-1β, TNF-α, IL-32, CCL-2, VCAM-1, and MCP-1. LA directly obstructed Syk phosphorylation and activity in a dose-dependent manner, inhibited the activity of p38 and JNK, and reduced the expression of NLRP3 in human umbilical vein endothelial cells and vascular tissue of rats with vasculitis. Conclusion. LA suppressed NLRP3 gene expression by blocking the Syk--p38/JNK pathway and reduced damage to the rats’ limbs in the thromboangiitis obliterans model.

Whether it is caused by viruses and bacteria infection, or low-grade chronic inflammation of atherosclerosis and cellular senescence, the transcription factor (TF) NF-κB plays a central role in the inducible expression of inflammatory genes. Accumulated evidence has indicated that the chromatin environment is the main determinant of TF binding in gene expression regulation, including the stimulus-responsive NF-κB. Dynamic changes in intra- and interchromosomes are the key regulatory mechanisms promoting the binding of TFs. When an inflammatory process is triggered, NF-κB binds to enhancers or superenhancers, triggering the transcription of enhancer RNA (eRNA), driving the chromatin of the NF-κB-binding gene locus to construct transcriptional factories, and forming intra- or interchromosomal contacts. These processes reveal a mechanism in which intrachromosomal contacts appear to be cis-control enhancer-promoter communications, whereas interchromosomal regulatory elements construct trans-form relationships with genes on other chromosomes. This article will review emerging evidence on the genome organization hierarchy underlying the inflammatory response.

We investigate the existence of S-shaped connected component in the set of positive solutions of the fourth-order boundary value problem: u′′′′x=λhxfux, x∈(0,1),u(0)=u(1)=u′′0=u′′1=0, where λ>0 is a parameter, h∈C[0,1], and f∈C[0,∞) with f0≔lims→0⁡(f(s)/s)=∞. We develop a bifurcation approach to deal with this extreme situation by constructing a sequence of functions f[n] satisfying f[n]→f and (f[n])0→∞. By studying the auxiliary problems, we get a sequence of unbounded connected components C[n], and, then, we find an unbounded connected component C in the set of positive solutions of the fourth-order boundary value problem which satisfies 0,0∈C⊂lim⁡sup⁡C[n] and is S-shaped.

Garcinia Linn. plants having rich natural xanthones and benzophenones with anti-inflammatory activity attracted a great deal of attention to discover and develop them as potential drug candidates. Through screening targeting nitric oxide accumulation in stimulated macrophage, we found that 1,3,5,7-tetrahydroxy-8-isoprenylxanthone (TIE) had potential anti-inflammatory effect. To understand how TIE elicits its anti-inflammatory activity, we uncovered that it significantly inhibits the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS/IFNγ-stimulated RAW264.7 cells. In further study, we showed that TIE reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), two key molecules responsible for the production of NO and PGE2 during inflammation progress. Additionally, TIE also suppressed the expression of inflammatory cytokines IL-6, IL-12, and TNF-α. TIE-led suppression in iNOS, COX-2, and cytokines production were probably the consequence of TIE’s capability to block ERK and p38MAPK signaling pathway. Moreover, TIE blocked activation of nuclear factor-kappa B (NF-κB) as well as NF-κB regulation of miR155 expression. Our study suggests that TIE may represent as a potential therapeutic agent for the treatment of inflammatory diseases.