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Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, Pmeta = 8.36 × 10−8, OR = 1.29; rs7259428, 19q12, ZNF536, Pmeta = 7.58 × 10−8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, Pmeta = 1.95 × 10−8; rs2414487, 15q21.3, LOC145783, Pmeta = 4.53 × 10−9; rs2106525, 7q31.1, MDFIC, Pmeta = 6.24 × 10−9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.

Background IL13, IL4, IL4RA, FCER1B and ADRB2 are susceptible genes of asthma and atopy. Our previous study has found gene–gene interactions on asthma between these genes in Chinese Han children. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and then cause subsequent allergic diseases have yet to be determined. This study aimed to determine whether there are gene–gene and gene-environment interactions on CBIgE elevation among the aforementioned five genes and prenatal environmental factors in Chinese Han population. Methods 989 cord blood samples from a Chinese birth cohort were genotyped for nine single-nucleotide polymorphisms (SNPs) in the five genes, and measured for CBIgE levels. Prenatal environmental factors were collected using a questionnaire. Gene–gene and gene-environment interactions were analyzed with generalized multifactor dimensionality methods. Results A four-way gene–gene interaction model (IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805, P = 9.03 × 10–4). Among the four SNPs, only IL13 rs20541 was identified to have an independent effect on elevated CBIgE (odds ratio (OR) = 1.36, P = 3.57 × 10–3), while the other three had small but synergistic effects. Carriers of IL13 rs20541 TT, IL13 rs1800925 CT/TT, IL4 rs2243250 TT and ADRB2 rs1042713 AA were estimated to be at more than fourfold higher risk for CBIgE elevation (OR = 4.14, P = 2.69 × 10–2). Gene-environment interaction on elevated CBIgE was found between IL4 rs2243250 and maternal atopy (OR = 1.41, P = 2.65 × 10–2). Conclusions Gene–gene interaction between IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713, and gene-environment interaction between IL4 rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.

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.

It is widely believed in the medical community that the pathological and anatomical basis for the occurrence of external abdominal hernia is the fascia defect, and how to correctly deal with this kind of fascia defect is the key point in the treatment of external abdominal hernia. Theodore Billorth famously said that if we could artificially create dense and tough tissues like fascia and tendons, the secret to the complete healing of hernia would be solved. These similar theories largely guide the research and practice in the treatment of external abdominal hernia. along with the breakthrough progress in the mesh treatment of external abdominal hernia, According to the chemical composition and biological characteristics, the patch materials can be divided into non-absorbable materials, absorbable materials, composite repair materials and biological materials. Methods In this paper, Pubmed database and Chinese journal full-text database literatures were searched,and all mesh materials used in inguinal hernia repair were comprehensively studied, summarized and analyzed in clinical application. Keywords: external abdominal hernia; patch material; conclusion; application

Remote ischemic postconditioning (RIPostC) could reduce myocardial ischemia/reperfusion injury markedly. However, the mechanism of the protective signal transfer of RIPostC to the heart remains unclear. In this study, we hypothesize that macrophage migration inhibitory factor (MIF) plays an important role in the cardioprotection conferred by RIPostC.RIPostC was induced by 4 cycles of 5 min ischemia/5 min reperfusion on the lower limbs of rats immediately after myocardial reperfusion. The plasma level of MIF was compared between the RIPostC and reperfusion injury groups. (S,R)-3-(4-hydroxy -phenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester (ISO-1) was used as a potent inhibitor of MIF. 2-methoxyestradiol (2ME2), an inhibitor of HIF-1α (hypoxia-inducible factor-1α)，was used as a tool to inhibit the role of HIF-1α.We found that a significant elevation in the level of plasma MIF occurred when RIPostC was carried out; this elevation could be blocked by femoral occlusion. The cardiac MIF level decreased significantly after RIPostC stimulus compared with the ischemia/reperfusion (IR) group (P0.01). In addition, inhibition of MIF by ISO-1 could induce the loss of cardioprotection and aggravate the apoptosis of the heart in RIPostC. RIPostC confers protection against myocardial IR injury via the MIF-AMPK signaling pathway. Finally, inhibition of HIF-1α may result in the reduction of plasma MIF in RIPostC.MIF plays an important role in RIPostC through the humoral pathway in a HIF-1α-dependent manner, which could activate the cardiac AMP-activated protein kinase (AMPK) pathway to confer powerful cardioprotection.

Recently, immunotherapy has become the fourth pillar of cancer treatment in addition to surgery therapy, chemotherapy, and radiation therapy. The inhibitors of programed cell death protein 1 (PD-1) and its ligand PD-L1 are the new stars in immunotherapy, as they can overcome tumor immunosuppression. However, the efficacy of PD-1 inhibitors still needs to be further developed for clinical treatment. Therefore, research into treatment with anti-PD-1 drugs has emerged as a new development field. This review provides novel insights into the role and mechanism of PD-1 combination anti-tumor therapy, thereby promoting its clinical application in anti-tumor immunotherapy.

Background The diagnosis and treatment of acute myocardial infarction (AMI) patients with chronic kidney disease (CKD) is still a challenging problem. The high sensitivity C-reactive protein (hs-CRP) to albumin ratio (HCAR) was proved to be a sensitive biomarker in predicting the prognosis of many diseases. The purpose of this study was to investigate the prognostic value of HCAR in postoperative 2-year mortality of AMI patients with CKD undergoing coronary angiography(CAG). Methods A total of 11933 patients underging CAG were collected in this retrospective study. Finally, 466 AMI patients with CKD undergoing CAG were enrolled. HCAR was calculated by dividing hs-CRP by albumin obtained from blood biochemical examination. Patients were divided into two groups according to the HCAR cutoff value in predicting 2-year mortality by Receiver operating characteristic (ROC) curve analysis. The primary endpoint was all-cause mortality at a 2-year follow-up. The Kaplan-Meier method and Cox regression analyses were used to analyze the survival of patients. Results A significant correlation was found between HCAR and NT-proBNP, LVEF, CK-MB, TnI and eGFR (P

To investigate the correlation between FOXP3, CD11c protein expression and the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).This study included 48 patients with DLBCL who were admitted to Jiujiang No.1 People's Hospital and TCM-Integrated Hospital of Southern Medical University from January 2015 to January 2019. The DLBCL tissues removed during the operation were collected as test specimens. The expression of FOXP3 and CD11c protein were detected by immunohistochemistry. The deadline for postoperative follow-up was December 31, 2019, and the patient's short-term efficacy (complete remission, partial remission) and progression-free survival were recorded.FOXP3 protein was positively expressed in the nucleus, mostly focally or diffusely distributed, the FOXP3In some patients with DLBCL, FOXP3 and CD11c expresse positively, and the positive expression rate is related to the clinical stage and international prognostic index score. The positive expression of FOXP3 and CD11c indicate a good prognosis.FOXP3、CD11c蛋白表达与弥漫性大B细胞淋巴瘤患者预后的相关性.探讨FOXP3、CD11c蛋白表达与弥漫性大B细胞淋巴瘤（DLBCL）患者预后的相关性.本研究纳入2015年1月至2019年1月九江市第一人民医院和南方医科大学中西医结合医院收治的48例DLBCL患者，收集患者术中切除的DLBCL组织作为检测标本，采用免疫组织化学法检测组织中FOXP3、CD11c蛋白的表达，术后随访截止日期为2019年12月31日，记录患者的近期疗效（完全缓解、部分缓解）和无进展生存期.FOXP3蛋白为核阳性表达，多以局灶性或弥漫性分布，FOXP3阳性率为54.17%（26/48）；CD11c蛋白为细胞膜阳性表达，多以弥漫性分布，CD11c阳性率为60.47%（29/48）。FOXP3、CD11c蛋白表达与DLBCL患者的年龄、性别、累及部位及乳酸脱氢酶水平无明显相关性，但与临床分期和国际预后指数评分存在明显相关性，差异有统计学意义（P0.05），即DLBCL患者临床分期越低、国际预后指数评分越低，则FOXP3、CD11c蛋白阳性表达率越高（r=0.637，r=0.709）。术后1年，FOXP3阳性表达或CD11c阳性表达的DLBCL患者的总有效率明显高于FOXP3阴性表达或CD11c阴性表达患者（P0.05）；至随访结束，FOXP3阳性表达或CD11c阳性表达的DLBCL患者的中位无进展生存期也明显长于FOXP3阴性表达或CD11c阴性表达患者（P0.05）.在部分DLBCL患者组织中FOXP3、CD11c阳性表达，且阳性表达率与临床分期及国际预后指数评分相关，FOXP3和CD11c蛋白阳性表达提示预后良好.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a master regulator of adipogenesis and lipogenesis. To understand its roles in fiber formation and fat deposition in skeletal muscle, we successfully generated muscle-specific overexpression of PPARγ in two pig models by random insertion and CRISPR/Cas9 transgenic cloning procedures. The content of intramuscular fat was significantly increased in PPARγ pigs while had no changes on lean meat ratio. PPARγ could promote adipocyte differentiation by activating adipocyte differentiating regulators such as FABP4 and CCAAT/enhancer-binding protein (C/EBP), along with enhanced expression of LPL, FABP4, and PLIN1 to proceed fat deposition. Proteomics analyses demonstrated that oxidative metabolism of fatty acids and respiratory chain were activated in PPARγ pigs, thus, gathered more Ca2+ in PPARγ pigs. Raising of Ca2+ could result in increased phosphorylation of CAMKII and p38 MAPK in PPARγ pigs, which can stimulate MEF2 and PGC1α to affect fiber type and oxidative capacity. These results support that skeletal muscle-specific overexpression of PPARγ can promote oxidative fiber formation and intramuscular fat deposition in pigs.

The supported ultra-small Fe2O3 nanoparticles, as conventional functional materials for versatile applications, are scarcely investigated for their catalytic properties in peroxymonosulfate-activated reactions to deal with the ever-growing environment issues. In this work, highly dispersed ultrafine Fe2O3 nanoparticles are successfully generated in framework of mesoporous silicas (such as Fe/Si-3, with 3.01 wt% of Fe content) through an in-situ approach with iron phthalocyanine as Fe source. The formation of Fe-N or Fe-C bonds exerted remarkable isolation effect on the generation of the nanoparticles. Fe/Si-3 gave superior activity to other Fe catalysts analogues including bulk Fe2O3 in peroxymonosulfate-triggered degradation of tetracycline. Fe/Si-3 has a wide working pH window of 3–11. It can be recycled for 3 times without significant loss of the degradation activity. The radicals of S O 4 ⋅ − , ⋅ O H , O 2 ⋅ − and 1O2 all contributed to the degradation reaction. The factors for high degradation efficiency and broad working pH range of Fe/Si-3, the mechanism for formation of various radicals, as well as the transformation pathway of tetracycline molecules were proposed.

PPARγ is a master regulator of adipogenesis and lipogenesis. To understand its roles in fat deposition and fiber formation in skeletal muscle, we successfully generated muscle-specific overexpression of PPARγ by pig cloning procedures. The content of intramuscular fat was significantly increased in PPARγ transgenic pigs while the muscle mass as lean percentage of body weight was not changed. The proteomics analysis demonstrated oxidative metabolism of fatty acids and respiratory chain were increased in PPARγ pigs. Furthermore, expressions of oxidative muscle fiber-related genes such as MyHC1 and TNNT1 were enhanced. CAMK2, MEF2 and PGC1α were also significantly increased in skeletal muscle of PPARγ pigs, indicating that Ca2+-sensitive phosphatases and kinases may play an important role in the switch of muscle fiber types when PPARγ activity is elevated in skeletal muscle. The results support skeletal muscle-specific overexpression of PPARγ can promote oxidative fiber formation and intramuscular fat deposition in pigs.

A snake-mimic soft actuator composed of a bilayered liquid crystal elastomer ribbon and two serrated feet is reported in this work. Under repeated on/off near-infrared light irradiation, this actuator can move forward relying on a reversible shape morphing between S-curve structure and reverse S-curve structure, which is similar to the serpentine locomotion of snakes.

Somatic cloning has had a significant impact on the life sciences and is important in a variety of processes, including medical research and animal production. However, the application of somatic cloning has been limited due to its low success rate. Therefore, potential epigenetic variations between cloned and donor animals are still unclear. DNA methylation, one of the factors which is responsible for phenotypic differences in animals, is a commonly researched topic in epigenetic studies of mammals. To investigate the epigenetic variations between cloned and donor animals, we selected blood and ear fibroblasts of a donor pig and a cloned pig to perform whole-genome bisulfite sequencing (WGBS). A total of 215 and 707 differential methylation genes (DMGs) were identified in blood and ear fibroblasts, respectively. Functional annotation revealed that DMGs are enriched in many pathways, including T/B or natural killer (NK) cell differentiation, oocyte maturation, embryonic development, and reproductive hormone secretion. Moreover, 22 DMGs in the blood and 75 in the ear were associated with immune responses (e.g., CD244, CDK6, CD5, CD2, CD83, and CDC7). We also found that 18 DMGs in blood and 53 in ear fibroblasts were involved in reproduction. Understanding the expression patterns of DMGs, especially in relation to immune responses and reproduction, will reveal insights that will aid the advancement of future somatic cloning techniques in swine.

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.

In nature, many flowers can open their petals into blooming flowers or furl them into buds and simultaneously alter the petal colors under the precise control of light, temperature, pH, humidity, o...

Doxorubicin is a widely used anthracycline-based anti-tumor agent for both solid and liquid tumors. Mounting evidence has demonstrated that microRNAs (miRNAs) are involved in chemoresistance and tumorigenesis. However, the roles of microRNA-501-5p (miR-501) in doxorubicin resistance and gastric cancer cell proliferation and invasion are still not fully understood. In this study, we identified that BLID (BH3-like motif-containing protein, cell death inducer) was directly regulated by miR-501 at the post-transcriptional level in multiple gastric cancer cell lines. Endogenous miR-501 was higher, whereas BLID was lower, in doxorubicin-resistant gastric cancer SGC7901/ADR cells compared with their parental SGC7901 cells. miR-501 suppressed gastric cancer cell apoptosis, induced resistance to doxorubicin, and enhanced cell proliferation, migration, and invasion. Subcutaneous injection of miR-501 lentivirus-infected SGC7901 cells resulted in rapid growth of xenograft tumors and resistance to doxorubicin treatment, unlike injection of negative miRNA lentivirus-infected SGC7901 cells. This is achieved at least partially by directly targeting BLID and subsequent inactivation of caspase-9 and caspase-3 and phosphorylation of Akt. Taken together, miR-501 induces doxorubicin resistance and enhances the tumorigenesis of gastric cancer cells by suppressing BLID. miR-501 might be a potential target for doxorubicin resistance and gastric cancer therapy. Keywords: microRNA-501-5p, chemoresistance, doxorubicin, BLID, gastric cancer

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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.

Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus that causes encephalitis and reproductive disorders in mammalian species. However, key host genes involved in the JEV life cycle and cell death are poorly understood. Here, we designed 85,674 single guide RNAs (sgRNAs) targeting 17,743 protein-coding genes, 11,053 long ncRNAs (lncRNAs), and 551 microRNAs (miRNAs) in the porcine genome, and subsequently developed a porcine sgRNA library and genome-scale CRISPR/Cas9 knockout (PigGeCKO) system. These sgRNAs were delivered into porcine kidney-15 (PK-15) cells that constitutively express Cas9, positive selection screening of the resulting PigGeCKO cell collection for resistance to JEV-induced cell death led to the identification of several previously unreported genes required for JEV infection. We conducted follow-up studies to verify the dependency of JEV on these genes, and identified functional contributions for six of the many candidate JEV-related host genes, including an endoplasmic reticulum membrane protein complex subunit 3 (EMC3) and calreticulin (CALR). Additionally, we identified that four genes associated with heparan sulfate proteoglycans (HSPGs) metabolism, specifically those responsible for HSPG sulfurylation, facilitated JEV entry into PK-15 cells. Thus, beyond our development of the largest CRISPR-based functional genomic screening platform for pig research to date, this work deepens our basic understanding of flavivirus infection and identifies multiple potentially vulnerable targets for the development of medical and breeding technologies to prevent and treat diseases caused by Japanese encephalitis virus.

The Kafubu Emerald Area in Zambia is an important producer of gemstone-quality emeralds. The country rocks include carbonatization altered rock and emerald-hosting biotite chlorite schist from the Anzan emerald deposit in the Kafubu area, Zambia. The technique of LA-MC-ICP-MS is used to perform chronology measurements of the country rock and emerald-hosting rock which belong to Muva Supergroup, yielding zircon U-Pb concordia ages of 1966 ± 12 Ma in carbonatization altered rock and 1853 ± 58 Ma and 1344 ± 30 Ma in biotite chlorite schist. Meanwhile, dating of biotite chlorite schist using the biotite 40 Ar– 39 Ar method has obtained the plateau age of t = 578.3 ± 2.6 Ma, isochron age of 577.5 ± 3.0 Ma and reverse isochron age of 577.4 ± 3.0 Ma. Thus, we have redefined the age of Muva Supergroup in the Copperbelt Province in Zambia to be older than or equal to 1966 ± 12 Ma, and found that the ore bodies in the Anzan emerald deposit underwent three phases of metamorphism at 1853 ± 58 Ma, 1344 Ma ± 30 and 578.3 ± 2.6 Ma and finally accomplished the emerald mineralization. The age of the Anzan emerald deposit is earlier than the Kagem (452.1 ± 16 Ma) and the Kamakanga emerald deposits (447 ± 8.6 Ma).

Male sterile lines play an important role in the utilization of heterosis. To explore and exploit the heterosis of polyploid hybrid rice, two photoperiod- and thermo-sensitive genic male sterile lines of polyploid rice, PS006 and PS012, were bred via chromosome doubling, complex hybridization and self-breeding. The characteristics of these two lines, including the agronomic traits, growth, development, fertility transformation and combining ability, were investigated. Both lines had good agronomic characteristics and flowering habits, a high outcrossing rate, obvious fertility alterations and good combining abilities. Their hybrids showed strong heterosis and great potential for increasing rice productivity and quality. The new polyploid rice photoperiod- and thermo-sensitive genic male sterile lines will provide material for further research into polyploidy and hybrid vigour in rice and promote the exploitation of polyploid hybrid rice.

N-Myc downstream-regulated gene 4 (NDRG4) plays an important role in biological processes and pathogenesis, but its function in muscle development is unclear. In this study, we investigated the function of the NDRG4 gene in the regulation of myogenic differentiation. NDRG4 expression is upregulated during muscle regeneration and C2C12 myoblast differentiation. Gain and loss of function studies revealed that NDRG4 dramatically promotes expression of myogenic differentiation factor (MyoD), myogenin (MyoG), and myosin heavy chain (MyHC) genes and myotube formation. Mechanistically, the binding of NDRG4 to carboxyl-terminal modulator protein (CTMP) abates the interaction of CTMP and protein kinase B (Akt) and increases the phosphorylation of Akt and cAMP response element binding protein (CREB), which leads to increased expression of myogenic genes. Our results reveal that NDRG4 promotes myogenic differentiation via Akt/CREB activation.

Muscle fiber formation is a complex process and subject to fine regulation of a variety of protein-coding genes and non-coding RNA. In this study, we identified a nuclear protein-coding gene ANKRD23 which was highly expressed in muscle. Quantitative real-time PCR, western blotting and immunofluorescence were used to detect the expression change of myoblast differentiation marker genes after knockdown and overexpression of ANKRD23. The results showed that the expression of myoblast differentiation marker genes were increased by interference and reduced by ANKRD23 overexpression, indicating that ANKRD23 played a negative role in the myoblast differentiation. Interestingly, we discovered a long non-coding RNA-AK004293 which was overlapped with the 3'UTR of ANKRD23 gene. Then we detected the effect of AK004293 on the expression of ANKRD23 and myoblast differentiation marker genes in C2C12 myoblasts. The results showed that AK004293 had no significant effect on the expression of myoblast differentiation maker genes and ANKRD23. In conclusion, our results established the foundation for further studies about the regulation mechanism of ANKRD23 in muscle development.

Myogenic differentiation factor (MyoD) is a master transcription factor in muscle development and differentiation. Although several long non-coding RNAs (lncRNAs) linked to MyoD have been found to influence muscle development, the functions of many lncRNAs have not been explored. Here we utilized lncRNA and mRNA microarray analysis to identify potential lncRNAs regulated by MyoD in muscle cells. A total of 997 differentially expressed lncRNAs (335 up-regulated and 662 down-regulated) and 1,817 differentially expressed mRNAs (148 up-regulated and 1,669 down-regulated) were identified after MyoD knockdown in C2C12 cells. Functional predictions suggested that most lncRNAs are involved in the biological pathways related to muscle differentiation and cell cycle with co-expressed genes. To gain further insight into the MyoD-mediated lncRNA expression in muscle differentiation, tissue expression profiles and MyoD overexpression were performed, and we found one of the candidate lncRNAs-AK143003 was significantly regulated by MyoD. Further analyses showed its noncoding ability and cytoplasmic localisation. Silencing of AK143003 stimulated the accumulation of myogenic marker genes, whereas AK143003 overexpression led to their decreased synthesis. This study identified a multitude of MyoD-mediated lncRNAs for further investigation and identified a novel lncRNA, lnc-AK143003, which plays a role in controlling muscle differentiation.

Individual skeletal muscles in the animal body are heterogeneous, as each is comprised of different fiber types. Type I muscle fibers are rich with mitochondria, and have high oxidative metabolisms while type IIB fibers have few mitochondria and high glycolytic metabolic capacity. Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), a transcriptional co-activator that regulates mitochondrial biogenesis and respiratory function, is implicated in muscle fiber-type switching. Over-expression of PGC-1α in transgenic mice increased the proportion of red/oxidative type I fiber. During pig muscle growth, an increased number of type I fibers can give meat more red color. To explore the roles of PGC-1α in regulation of muscle fiber type conversion, we generated skeletal muscle-specific PGC-1α transgenic mice and pig. Ectopic over-expression of PGC-1α was detected in both fast and slow muscle fibers. The transgenic animals displayed a remarkable amount of red/oxidative muscle fibers in major skeletal muscle tissues. Skeletal muscles from transgenic mice and pigs have increased expression levels of oxidative fiber markers such as MHC1, MHC2x, myoglobin and Tnni1, and decreased expressions of glycolytic fiber genes (MHC2a, MHC2b, CASQ-1 and Tnni2). The genes responsible for the TCA cycle and oxidative phosphorylation, cytochrome coxidase 2 and 4, and citrate synthase were also increased in the transgenic mice and pigs. These results suggested that transgenic over-expressed PGC-1α significantly increased muscle mitochondrial biogenesis, resulting in qualitative changes from glycolytic to oxidative energy generation. The transgenic animals also had elevated levels of PDK4 and PPARγ proteins in muscle tissue, which can lead to increased glycogen deposition and fatty acid oxidation. Therefore, the results support a significant role of PGC-1α in conversion of fast glycolytic fibers to slow and oxidative fiber through enhanced mitochondrial respiration and fatty acid oxidation, and transgenic over-expression of PGC-1α in skeletal muscle leads to more red meat production in pigs.

A low frequency electromagnetic field was introduced into the direct chill (DC) casting process and the ingots of Al-Cu alloy were prepared to study the macrosegregation behaviour of the ingots under the influence of the electromagnetic field. The experimental results showed that there is an obvious positive segregation near to the surface and a negative segregation in the centre area of the ingot. Cu shows the highest segregation tendency among the main elements of Cu, Mg and Mn. Grain refiner element Ti shows a segregation trend opposite to that of Cu. With the application of electromagnetic field, the negative centreline segregation in the centre area of the ingot was evidently reduced although it didn’t show significant effect on the segregation near to the ingot surface. A significant grain refinement was also achieved with the application of electromagnetic field. The mechanism of the reduction of macrosegregation with electromagnetic field was also analyzed in the present work.

Background Carotid artery stenosis, mainly caused by carotid atherosclerosis, is related to ischemic stroke. This study was to investigate whether monocyte/lymphocyte ratio (MLR) was associated with increased severity of carotid stenosis in patients with ischemic stroke. Methods A total of 395 participants with ischemic stroke were retrospectively analyzed. The severity of carotid stenosis was evaluated by ultrasound examination. Patients were divided into two groups: nonsevere stenosis group and severe stenosis group. Multivariate logistic analysis was used to evaluate risk factors. Results A significant correlation was found between MLR and the severity of carotid stenosis in patients with ischemic stroke. MLR was the independent risk factor of carotid stenosis (OR: 9.74, 95% CI: 1.16–81.54). In the ROC curves analysis, a cutoff value of 0.20 for MLR predicted the severity of carotid stenosis with a sensitivity of 80.40% and specificity of 26.40% (ROC area under the curve: 0.598, 95% CI: 0.53–0.67, p = .004). Conclusion Monocyte/lymphocyte ratio plays important roles in carotid stenosis in patients with ischemic stroke and is an independent risk factor of the severity of carotid stenosis. Therefore, MLR might be considered a potential index in the diagnosis of carotid stenosis in patients with ischemic stroke., Monocyte/lymphocyte ratio (MLR) plays important roles in carotid stenosis in patients with ischemic stroke and is an independent risk factor of the severity of carotid stenosis. Therefore, MLR might be considered a potential index in the diagnosis of carotid stenosis in patients with ischemic stroke.

Isoorientin (ISO) is a naturally occurring C‑glycosyl flavone that has various pharmacological properties, such as anti‑bacterial and anti‑inflammatory effects. However, its underlying molecular mechanisms in human lung cancer cells remain unknown. In the present study, the effects of ISO on the induction of apoptosis and relative molecular mechanisms in A549 human lung cancer cells were investigated. The results of Cell Counting Kit‑8 assay (CCK‑8) indicated that ISO exerted significant cytotoxic effects on 3 lung cancer cell lines, but had no obvious side‑effects on normal cells. Moreover, flow cytometry and western blot analysis revealed that ISO induced mitochondrial‑dependent apoptosis by reducing mitochondrial membrane potential. ISO also increased the expression levels of Bax, cleaved‑caspase‑3 (cle‑cas‑3) and poly(ADP‑ribose) polymerase (PARP; cle‑PARP), and decreased the expression levels of Bcl‑2 in A549 cells. Furthermore, ISO induced G2/M cell cycle arrest by decreasing the expression levels of cyclin B1 and CDK1/2, and increasing the expression levels of p21 and p27 in A549 cells. As the duration of ISO treatment increased, intracellular reactive oxygen species (ROS) levels in A549 cells also increased. However, pre‑treatment of the cells with the ROS scavenger, N‑acetylcysteine (NAC), inhibited ISO‑induced apoptosis. In addition, ISO increased the expression levels of p‑p38, p‑JNK and IκB‑α; and decreased the expression levels of p‑extracellular signal‑regulated kinase (ERK), p‑signal transducer and activator of transcription (STAT)3, p‑nuclear factor (NF)‑κB, NF‑κB and p‑IκB; these effects were induced by mitogen‑activated protein kinase (MAPK) inhibitors and blocked by NAC. Taken together, the results of the present study indicate that ISO induces the apoptosis of A549 lung cancer cells via the ROS‑mediated MAPK/STAT3/NF‑κB signaling pathway, and thus may be a potential drug for use in the treatment of lung cancer.

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.

In order to better understand the key regulatory mechanisms of PGC1α in muscle fiber type transition, the RNA-seq was used to compare the change of gene expression in gastrocnemius muscles between wild type pigs and transgenic pigs with overexpression of PGC1α gene in muscle. 371 differentially expressed genes (P ≤ 0.05 and Ratio ≥ 2), including 184 up-regulated genes and 187 down-regulated genes, were identified. Five main signaling pathways including metabolic pathways, ECM-receptor interaction, PPAR signaling pathway, adipocytokine signaling pathway and insulin signaling pathway, were authenticated using KEGG pathway analysis. Our results indicate that the fat metabolism pathway plays an important role in the transformation of muscle fiber types regulated by PGC1α.

Calycosin is one of the main ingredients extracted from the Chinese medical herb, Radix astragali (RA). It has been shown to inhibit cell proliferation and induce apoptosis in several cancer cell lines, but the underlying mechanism remains unclear. The effects of calycosin on the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells, as well as its mechanism, were investigated in this study. Cell Counting Kit-8 assay results suggested that calycosin had anti-proliferation effects on HCC in dose- and time-dependent manners, and had less cytotoxicity in normal cells. Hoechst/PI double staining and flow cytometry results showed cellular morphological changes and apoptosis after treatment of HepG2 cells with calycosin. The western blot assay showed calycosin decreased the expression of Bcl-2 and increased the expression of Bax, caspase-3, and PARP. Calycosin induced the activation of MAPK, STAT3, NF-κB, apoptosis-related proteins, and induced cell cycle arrest in the G0/G1 phase by regulating AKT. In addition, calycosin reduced the expression of TGF-β1, SMAD2/3, SLUG, and vimentin. Furthermore, phosphorylation, apoptosis, and cell migration induced by calycosin were mediated by the production of reactive oxygen species. These events could be inhibited by pretreatment with N-acetyl-L-cysteine. Calycosin resisted HCC by activating ROS-mediated MAPK, STAT3, and NF-κB signaling pathways.

The Sino–Zambian Cooperation project provides national catchment sediment geochemical data for 58 elements including Cu and Co from 746 sediment samples at 736 sampling sites, corresponding to a sampling density of about 1 site per 1000 km2. The Cu and Co were determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) under strict quality control using field duplicates, standard reference materials and analytical replicate samples. The 95% ranges (2.5%–97.5%) of Cu and Co concentrations were from 1.8 to 57.81 × 10−6 and from 0.54 to 22.83 × 10−6, respectively, reflecting locally unevenness distributions. The median values of Cu and Co are 5.77 × 10−6 and 2.98 × 10−6, respectively. The most noticeable anomalous patterns of Cu and Co are distributed between Lusaka and Solwezi (Lufilian Arc Belt) with the trend of increasing concentrations from southeast to northwest. The all spatial distribution patterns of Cu and Co in tectonic units, drainage basins and geomorphological landscapes show good relations with parent rocks, climate, Cu (Co) deposits and smelting plants in Lufilian Arc Belt. The Cu and Co concentrations show metallogenic belts in Mkushi area, between Lusaka and Solwezi areas, and in Livingstone area.

A magnet is an important component of a speaker, as it makes the coil move back forth, and it is commonly used in mobile information terminals. Defects may appear on the surface of the magnet while cutting it into smaller slices, and hence, automatic detection of surface cutting defect detection becomes an important task for magnet production. In this work, an image-based detection system for magnet surface defect was constructed, a Fourier image reconstruction based on the magnet surface image processing method was proposed. The Fourier transform was used to get the spectrum image of the magnet image, and the defect was shown as a bright line in it. The Hough transform was used to detect the angle of the bright line, and this line was removed to eliminate the defect from the original gray image; then the inverse Fourier transform was applied to get the background gray image. The defect region was obtained by evaluating the gray-level differences between the original image and the background gray image. Further, the effects of several parameters in this method were studied and the optimized values were obtained. Experiment results show that the proposed method can detect surface cutting defects in a magnet automatically and efficiently.

Two novel prenylated kaempferol derivatives (1, 2), together with seven known metabolites were isolated from ethanol extract of fresh Platanus acerifolia bud’s fur by multistep chromatographic processing. Structure of compounds 1 and 2 was confirmed by 1D, 2D NMR spectra and HR-ESI-MS. In addition, compound 1 was further analysed by X-ray crystallography. Anti-proliferative activities in vitro against human breast carcinoma (MCF-7) and human hepatocellular carcinoma (Hep-G2) cell lines for compound 1, 2 and 8 were evaluated. Compound 1 exhibited cytotoxic activity towards MCF-7 and Hep-G2 cell lines with the IC50 values 38.2 and 39.5 μM, respectively. Moreover, compound 2 showed weak cytotoxic activities against the two cell lines.

Summary Rationale: IL13, IL4, IL4RA, FCER1B, and ADRB2 are important inflammatory genes associated with immunoglobulin E levels. This study attempts to determine whether there are gene–gene interactions in the five genes among asthmatic children of Chinese Han nationality. Methods: Nine single-nucleotide polymorphisms (SNPs) in the five genes were genotyped in 1,000 asthmatic children and 1,000 healthy controls using TaqMan real-time quantitative polymerase chain reaction. Multifactor–dimensionality reduction method was applied for the analysis. Results: A four-way gene–gene interaction model consisting of IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 was chosen as the optimal one for determining asthma susceptibility (testing balanced accuracy = 0.6089, cross-validation consistency = 10/10, P = 6.98E−05). Each of the four SNPs was identified to have an independent association with childhood asthma (G allele of rs20541, odds ratio (OR) = 1.24, P = 1.23E−03; T allele of rs2243250, OR = 1.25, P = 3.81E-03; A allele of rs1042713, OR = 1.29, P = 6.75E-05; G allele of rs569108, OR = 1.27, P = 3.86E−03). Individuals homozygous for the risk alleles at all the four loci (rs20541 GG, rs2243250 TT, rs1042713 AA, and rs569108 GG) had a significantly higher risk of asthma compared with those without any risk homozygotes (OR = 13.55, P = 4.28E−03), and also greater than those with less than four risk homozygotes (OR = 10.09, P = 6.51E−03). Conclusions: Our results suggest that IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108, four SNPs with significant sole effect on asthma, interact to confer a higher risk for the disease in Chinese Han children. Pediatr Pulmonol. © 2015 Wiley Periodicals, Inc.

Although many long noncoding RNAs (lncRNAs) have been identified in muscle, their physiological function and regulatory mechanisms remain largely unexplored. In this study, we systematically characterized the expression profiles of lncRNAs during C2C12 myoblast differentiation and identified an intronic lncRNA, SYISL (SYNPO2 intron sense-overlapping lncRNA), that is highly expressed in muscle. Functionally, SYISL promotes myoblast proliferation and fusion but inhibits myogenic differentiation. SYISL knockout in mice results in significantly increased muscle fiber density and muscle mass. Mechanistically, SYISL recruits the enhancer of zeste homolog 2 (EZH2) protein, the core component of polycomb repressive complex 2 (PRC2), to the promoters of the cell-cycle inhibitor gene p21 and muscle-specific genes such as myogenin (MyoG), muscle creatine kinase (MCK), and myosin heavy chain 4 (Myh4), leading to H3K27 trimethylation and epigenetic silencing of target genes. Taken together, our results reveal that SYISL is a repressor of muscle development and plays a vital role in PRC2-mediated myogenesis.

Although many long noncoding RNAs (lncRNAs) have been identified in muscle, their physiological function and regulatory mechanisms remain largely unexplored. In this study, we systematically characterized the expression profiles of lncRNAs during C2C12 myoblast differentiation and identified an intronic lncRNA, SYISL (SYNPO2 intron sense-overlapping lncRNA), that is highly expressed in muscle. Functionally, SYISL promotes myoblast proliferation and fusion but inhibits myogenic differentiation. SYISL knockout in mice results in significantly increased muscle fiber density and muscle mass. Mechanistically, SYISL recruits the enhancer of zeste homolog 2 (EZH2) protein, the core component of polycomb repressive complex 2 (PRC2), to the promoters of the cell-cycle inhibitor gene p21 and muscle-specific genes such as myogenin (MyoG), muscle creatine kinase (MCK), and myosin heavy chain 4 (Myh4), leading to H3K27 trimethylation and epigenetic silencing of target genes. Taken together, our results reveal that SYISL is a repressor of muscle development and plays a vital role in PRC2-mediated myogenesis.

Background The protective effect of Neuregulin-1 (NRG-1) on heart failure is well established. In this study, we assessed whether NRG-1 could protect the heart by mimicking the cardioprotective effects of ischaemic postconditioning (IP). Methods We used a myocardial reperfusion injury rat model in vivo to compare the cardioprotective effects of NRG-1(3 μg/kg, iv. at the onset of reperfusion) and IP. In Langendorff isolated heart perfusion experiments, we used the erythroblastic leukaemia viral oncogene homolog 4 (ErbB4) inhibitor AG1478, a phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and a mitogen-activated protein/extracellular signal regulated kinase (MEK) inhibitor PD98059 to clarify whether the protective effects of NRG-1and IP depend on the NRG-1/ErbB4 signals and the reperfusion injury salvage kinase (RISK) pathway. Infarct size was detected by Evans blue and TTC. Apoptosis was detected by TUNEL assays. The expression of NRG-1/ErbB4 and downstream ERK1/2, AKT, AMPK and p70s6K were detected by western blotting. Hematoxylin/eosin (H&E) staining was used for histological analysis. Results We found that NRG-1 and IP had similar effects on reducing myocardial infarct size and apoptosis in vivo. NRG-1 heart protein levels were upregulated in the IP group. Phosphorylation of AKT, ERK1/2 and ErbB4 were also increased in both the IP and NRG-1 groups. Furthermore, in Langendorff analyses, the ErbB4 inhibitor AG1478 suppressed the phosphorylation of ErbB4 and the RISK pathway and aggravated myocardial edema and fiber fracture, thereby inhibited the cardioprotective effects in both the IP and NRG-1 groups. For assessment of downstream signals, the PI3K inhibitor LY294002 and the MEK inhibitor PD98059 suppressed the phosphorylation of AKT and ERK1/2 respectively and abolished the cardioprotective effects induced by IP and NRG-1. Conclusion In conclusion, both IP and NRG-1 could reduce infarct size and apoptosis through ErbB4-dependent activation of the RISK pathway in the same model; these results indicated the therapeutic potential of NRG-1 as a pharmacological postconditioning agent against myocardial reperfusion injury.

The monotypic lichenised genus Anamylopsora (Baeomycetaceae, Baeomycetales), with its single species A.pulcherrima, is distributed in the arid areas of the Northern Hemisphere, including China. In this paper, we introduce another species new to science, Anamylopsorapruinosa. The new species is characterised by a densely pruinose upper surface, abundantly thick and strong rhizines and terricolous habitat. It is also strongly supported by the phylogenetic and species delimitation analyses based on nrDNA ITS sequences, in which A.pruinosa forms well-supported clade separated from A.pulcherrima.

The combined electromagnetic fields were achieved by the application of an alternating magnetic field and a stationary magnetic field and were used during direct chill (DC) casting process to control the microstructure and macrosegregation of an Al-Zn-Mg-Cu alloy. Ingot microstructures were analyzed under an optical microscope (Leica DMR). The composition at different locations in the ingots was measured with inductively coupled plasma mass spectrometry (ICP) method. The results showed that the grain structure is transformed from dendrite to equiaxed structure and significantly refined with the application of combined electromagnetic fields. The uniformity of microstructure is also greatly improved. The combined electromagnetic fields show a significant effect on the distribution of elements. The negative macrosegregation in the centre area of the ingot is obviously reduced.

Hydrogen as the main cause of the gas porosity in aluminium alloys should be removed before casting. The degassing process with intensive melt shearing shows a high efficiency. In the present work, the water simulation was used to study the high shear degassing process and the effect of rotation speed on the size and distribution of inert gas bubbles. The results show that with the increase of rotation speed, the bubble size decreases and the affected region becomes larger. The proper rotation speed of the rotor for the rotor-stator high shear degassing process is 5000-6000 RPM.

Aluminum brass possesses an attractive combination of properties including high strength, high thermal and electrical conductivity, good mechanical workability, excellent corrosion resistance, low susceptibility to stress corrosion cracking. This make it a preferred choice for bimetal strips. The materials for preparing bimetal strips with cold roll bonding should have a good plasticity. In the present work, a Cu-Zn-Al-Ni alloy was proposed and the annealing process for this aluminium brass alloy was studied. The effect of annealing temperature and annealing time on the microstructure and mechanical properties was investigated. The proper annealing parameters were obtained.