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In recent years, light-guided robotic soft actuators have attracted intense scientific attention and rapidly developed, although it still remains challenging to precisely and reversibly modulate the moving directions and shape morphing modes of soft actuators with ease of stimulating operation. Here we report a strategy of building a multi-stimuli-responsive liquid crystal elastomer soft actuator system capable of performing not only multi-directional movement, but also different shape morphing modes. This strategy is based on the selective stimulation of specific domains of the hierarchical structured actuator through the modulation of three wavelength bands (520, 808, 980 nm) of light stimulus, which release the actuation system from light scanning position/direction restriction. Three near-infrared dual-wavelength modulated actuators and one visible/infrared tri-wavelength modulated multi-directional walker robot are demonstrated in this work. These devices have broad application prospects in robotic and biomimetic technology. Light-guided robotic soft actuators have attracted intense scientific attention but it remains challenging to modulate the moving directions and shape morphing modes. Here the authors report a stimuli-responsive soft actuator system which is capable of performing multi-directional movement as well as different shape morphing modes.

The Brother of Regulator of Imprinted Sites (BORIS, gene symbol CTCFL) has previously been shown to promote colorectal cancer cell proliferation, inhibit cancer cell apoptosis, and resist chemotherapy. However, it is unknown whether Boris plays a role in the progression of in situ colorectal cancer. Here Boris knockout (KO) mice were constructed. The function loss of the cloned Boris mutation that was retained in KO mice was verified by testing its activities in colorectal cell lines compared with the Boris wild‐type gene. Boris knockout reduced the incidence and severity of azoxymethane/dextran sulfate‐sodium (AOM/DSS)‐induced colon cancer. The importance of Boris is emphasized in the progression of in situ colorectal cancer. Boris knockout significantly promoted the phosphorylation of γH2AX and the DNA damage in colorectal cancer tissues and suppressed Wnt and MAPK pathways that are responsible for the callback of DNA damage repair. This indicates the strong inhibition of colorectal cancer in Boris KO mice. By considering that the DSS‐promoted inflammation contributes to tumorigenesis, Boris KO mice were also studied in DSS‐induced colitis. Our data showed that Boris knockout alleviated DSS‐induced colitis and that Boris knockdown inhibited the NF‐κB signaling pathway in RAW264.7 cells. Therefore Boris knockout eliminates colorectal cancer generation by inhibiting DNA damage repair in cancer cells and relieving inflammation in macrophages. Our findings demonstrate the importance of Boris in the development of in situ colorectal cancer and provide evidence for the feasibility of colorectal cancer therapy on Boris. Our study demonstrated that BORIS knockout eliminates colorectal cancer generation by inhibiting the MAPK pathway and promoting DNA damage and provided the feasibility for the targeted therapy of colorectal cancer on BORIS.

Twisted toroidal ribbons such as the one-sided Möbius strip have inspired scientists, engineers and artists for many centuries. A physical Möbius strip exhibits interesting mechanical properties deriving from a tendency to redistribute the torsional strain away from the twist region. This leads to the interesting possibility of building topological actuators with continuous deformations. Here we report on a series of corresponding bi-layered stripe actuators using a photothermally responsive liquid crystal elastomer as the fundamental polymeric material. Employing a special procedure, even Möbius strips with an odd number of twists can be fabricated exhibiting a seamless homeotropic and homogeneous morphology. Imposing a suitable contraction gradient under near-infrared light irradiation, these ribbons can realize continuous anticlockwise/clockwise in-situ rotation. Our work could pave the way for developing actuators and shape morphing materials that need not rely on switching between distinct states. Shape morphing materials are usually difficult to operate in a continuous fashion. Nie et al. fabricate stripes with liquid crystalline elastomers that can be given a Möbius-like morphology with seamless material composition, and perpetually driven under photothermally induced actuation.

Neat1 is widely expressed in many tissues and cells and exerts pro-proliferation effects on many cancer cells. However, little is known about the function of Neat1 in myogenesis. Here we characterized the roles of Neat1 in muscle cell formation and muscle regeneration. Gain- or loss-of-function studies in C2C12 cells demonstrated that Neat1 accelerates myoblast proliferation but suppresses myoblast differentiation and fusion. Further, knockdown of Neat1 in vivo increased the cross-sectional area of muscle fibers but impaired muscle regeneration. Mechanically, Neat1 physically interacted with Ezh2 mainly through the core binding region (1001–1540 bp) and recruited Ezh2 to target gene promoters. Neat1 promoted myoblast proliferation mainly by decreasing the expression of the cyclin-dependent kinase inhibitor P21 gene but inhibited myoblast differentiation by suppressing the transcription of myogenic marker genes, such as Myog , Myh4 , and Tnni2 . Altogether, we uncover a previously unknown function of Neat1 in muscle development and the molecular mechanism by which Neat1 regulates myogenesis.

Myogenesis is a complex biological process, and understanding the regulatory network of skeletal myogenesis will contribute to the treatment of human muscle related diseases and improvement of agricultural animal meat production. Long noncoding RNAs (lncRNAs) serve as regulators in gene expression networks, and participate in various biological processes. Recent studies have identified functional lncRNAs involved in skeletal muscle development and disease. These lncRNAs regulate the proliferation, differentiation, and fusion of myoblasts through multiple mechanisms, such as chromatin modification, transcription regulation, and microRNA sponge activity. In this review, we presented the latest advances regarding the functions and regulatory activities of lncRNAs involved in muscle development, muscle disease, and meat production. Moreover, challenges and future perspectives related to the identification of functional lncRNAs were also discussed.

Xuejun Zhang and colleagues report results of a genome-wide association study of systemic lupus erythematosus (SLE) in a Chinese Han population. Their work identifies nine new SLE susceptibility loci and reveals overlap in the spectrum of risk alleles shared between Chinese Han and European populations. We performed a genome-wide association study (GWAS) of systemic lupus erythematosus (SLE) in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina Human610-Quad BeadChips and replicating 78 SNPs in two additional cohorts (3,152 cases and 7,050 controls). We identified nine new susceptibility loci ( ETS1 , IKZF1 , RASGRP3 , SLC15A4 , TNIP1 , 7q11.23, 10q11.22, 11q23.3 and 16p11.2; 1.77 × 10 −25 ≤ P combined ≤ 2.77 × 10 −8 ) and confirmed seven previously reported loci ( BLK , IRF5 , STAT4 , TNFAIP3 , TNFSF4 , 6q21 and 22q11.21; 5.17 × 10 −42 ≤ P combined ≤ 5.18 × 10 −12 ). Comparison with previous GWAS findings highlighted the genetic heterogeneity of SLE susceptibility between Chinese Han and European populations. This study not only advances our understanding of the genetic basis of SLE but also highlights the value of performing GWAS in diverse ancestral populations.

Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus that causes encephalitis and reproductive disorders in mammalian species. However, the host factors critical for its entry, replication, and assembly are poorly understood. Here, we design a porcine genome-scale CRISPR/Cas9 knockout (PigGeCKO) library containing 85,674 single guide RNAs targeting 17,743 protein-coding genes, 11,053 long ncRNAs, and 551 microRNAs. Subsequently, we use the PigGeCKO library to identify key host factors facilitating JEV infection in porcine cells. Several previously unreported genes required for JEV infection are highly enriched post-JEV selection. We conduct follow-up studies to verify the dependency of JEV on these genes, and identify functional contributions for six of the many candidate JEV-related host genes, including EMC3 and CALR . Additionally, we identify that four genes associated with heparan sulfate proteoglycans (HSPGs) metabolism, specifically those responsible for HSPGs sulfurylation, facilitate JEV entry into porcine cells. Thus, beyond our development of the largest CRISPR-based functional genomic screening platform for pig research to date, this study identifies multiple potentially vulnerable targets for the development of medical and breeding technologies to treat and prevent diseases caused by JEV. Here the authors report the construction of a genome-scale porcine CRISPR/Cas9 library, called PigGeCKO, for screening and analyses of host resistance genes and factors associated with Japanese encephalitis virus replication.

Long Yu and colleagues report a genome-wide association study for hepatitis B virus–related hepatocellular carcinoma (HBV-HCC). They report that genetic variants in STAT4 and HLA-DQ genes confer risk of HBV-HCC. To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4 , P meta = 2.48 × 10 −10 , odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P meta = 2.72 × 10 −17 , OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC ( P trend = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues ( P = 2.33 × 10 −14 ).

Background We aimed to explore whether monocyte to lymphocyte ratio (MLR) provides predictive value of the lesion severity in patients with coronary artery disease (CAD). Methods Five hundred forty-three patients undergoing coronary angiography were analyzed in this retrospective study. Patients with coronary stenosis were divided into three groups on the basis of Syntax score. The control group consisted of patients with normal coronary arteries. MLR was calculated by dividing monocytes count by lymphocytes count obtained from routine blood examination. Multivariate logistic analysis was used to assess risk factors of CAD. Ordinal logistic regression analysis was used to assess the relationship between MLR and the lesion severity of coronary arteries. Results MLR was found to be an independent risk factor of the presence of CAD (OR: 3.94, 95% CI: 1.20–12.95) and a predictor of the lesion severity (OR: 2.05, 95% CI: 1.15–3.66). Besides, MLR was positively correlated with Syntax score( r  = 0.437, p  < 0.001). In the receiver-operating characteristic (ROC) curve analysis, MLR, with an optimal cut-off value of 0.25, predicted the severe coronary lesion with a sensitivity of 60.26% and specificity of 78.49%. Conclusions MLR was an independent risk factor of the presence of CAD, and a predictor of the lesion severity. Compared to neutrophil to lymphocyte ratio (NLR), MLR has better performance to reflect the severity of coronary lesion.

10-Hydroxy-2-decenoic acid (10-HDA), also known as royal jelly acid, has a variety of physiological functions, and recent studies have shown that it also has anticancer effects. However, its anticancer mechanisms have not been clearly defined. In this study, we investigated the underlying mechanisms of 10-HDA in A549 human lung cancer cells. We used Cell Counting Kit-8 assay, scratch wound healing assay, flow cytometry, and western blot analysis to investigate its apoptotic effects and underlying mechanism. Our results showed that 10-HDA inhibited the proliferation of three types of human lung cancer cells and had no significant toxic effects on normal cells. Accompanying reactive oxygen species (ROS), 10-HDA induced A549 cell apoptosis by regulating mitochondrial-associated apoptosis, and caused cell cycle arrest at the G0/G1 phase in a time-dependent manner. Meanwhile, 10-HDA also regulated mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) signaling pathways by increasing the expression levels of phosphorylated c-Jun N-terminal kinase, p-p38, and I-κB, and additionally, by decreasing the expression levels of phosphorylated extracellular signal-regulated kinase, p-STAT3, and NF-κB. These effects were blocked by MAPK inhibitors and N-acetyl-L-cysteine. Furthermore, 10-HDA inhibited cell migration by regulating transforming growth factor beta 1 (TGF-β1), SNAI1, GSK-3β, E-cadherin, N-cadherin, and vimentin. Taken together, the results of this study showed that 10-HDA induced cell cycle arrest and apoptosis in A549 human lung cancer cells through ROS-mediated MAPK, STAT3, NF-κB, and TGF-β1 signaling pathways. Therefore, 10-HDA may be a potential therapy for human lung cancer.