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BackgroundPrevious studies indicated the calcium-binding protein S100A12 to be involved in the pathophysiology of pulmonary inflammatory diseases. However, the role of S100A12 has remained elusive in patients with community-acquired pneumonia (CAP). Therefore, the purpose of this prospective cohort study was to evaluate the association between serum S100A12 with severity and prognosis in CAP patients.MethodsTwo groups with either 239 CAP patients or 239 healthy controls were enrolled in our study. Fasting blood and clinical characteristics were collected. On admission, serum S100A12 was measured using enzyme-linked immunosorbent assay (ELISA).ResultsSerum S100A12 was increased in CAP patients compared to control subjects. Furthermore, serum S100A12 was elevated according to the severity of CAP. Correlative analysis suggested that the level of serum S100A12 was associated with blood routine indices, renal function markers, inflammatory cytokines and other clinical parameters among CAP patients. Additionally, linear and logistical regression analyses indicated that serum S100A12 was positively associated with CAP severity scores in CAP patients. In addition, the association of high serum S100A12 and prognosis was accessed using a follow-up research. Elevated serum S100A12 on admission increased the risk of death and hospital stay in CAP patients during hospitalization.ConclusionsElevated serum S100A12 on admission is positively associated with the severity and adverse prognosis in CAP patients, suggesting that S100A12 may involve in the pathophysiological process of CAP. The titre of serum S100A12 may be used as a biomarker for diagnosis and prognosis among CAP patients.

The eastern Tianshan Terrane is a highly prospective zone that contains several porphyry Cu–Mo, VMS Cu–Zn, magmatic Cu–Ni, epithermal and orogenic Au deposits. However, few attention has been paid to tungsten deposits. Of these, the source and evolution of the mineralising fluids related to the skarn W deposits are poorly understood. The Heiyanshan W deposit is hosted by metamorphosed clastic and carbonate beds in the Mesoproterozoic Jianshanzi Formation deposited on a continental margin tectonic setting. The Jianshanzi Formation is intruded by biotite monzogranite that yield weighted 206Pb/238U age of 326.9 ± 1.6 Ma, which suggest that the Heiyanshan W deposit was formed in the Carboniferous. The mineralisation is hosted by a prograde hydrothermal altered zone represented by a garnet (–pyroxene) skarn, and retrograde skarn characterised by fine-grained scheelite. The paragenesis of the Heiyanshan mineralisation can be subdivided into prograde skarn stage, retrograde skarn stage, quartz-sulphide stage and quartz-calcite vein stage. The types of fluid inclusions recognised in the various minerals in the deposits are liquid-rich aqueous, vapour-rich aqueous, and daughter mineral-bearing. The homogenisation temperatures of fluid inclusions from the Heiyanshan deposit decrease from 290 ± 28°C in garnet, through 232 ± 31°C in scheelite, to 232 ± 36°C in quartz and 158 ± 15°C in non-mineralised calcite, which is typical of W-bearing skarn deposits worldwide. The δ18Owater values from the Heiyanshan deposit range from +4.7 to +6.6‰ in garnet, +1.3 to +1.9‰ in quartz and −6.1 to −4.4‰ in calcite. We have measured δD in fluid inclusions from different minerals, although these bulk analyses are just a mixture of the different FIA’s present in the sample. The δD values of fluid inclusions in garnet, quartz, and calcite are from −121 to −71‰, −84 to −75‰ and −101 to −82‰, respectively, also indicative of deep-sourced magmatic fluids mixed with meteoric water. The decrease in the homogenisation temperatures for the fluid inclusions at the Heiyanshan deposit is accompanied by a drop in salinity indicating that tungsten-bearing minerals precipitated during fluid mixing between magmatic fluids and meteoric water. We conclude that eastern Tianshan Terrane contains two pulse of tungsten metallogenic events of Late Carboniferous and Early Triassic.

Bicarbonate (HCO3–) transport mechanisms play an essential role in the acid-base homeostasis of aquatic animals, and anion exchange protein 3 (AE3) is a membrane transport protein that exchanges Cl–/HCO3– across the cell membrane to regulate the intracellular pH. In this study, the full-length cDNA of AE3 (Lv-AE3) was obtained from the Pacific white shrimp (Litopenaeus vannamei). The Lv-AE3 cDNA is 4,943 bp in length, contains an open reading frame of 2,850 bp, coding for a protein of 949 amino acids with 12 transmembrane domains. Lv-AE3 shows high sequence homology with other AE3 at the protein level. Lv-AE3 mRNA was ubiquitously detected in all tissues selected, with the highest expression level in the gill, followed by the ovary, eyestalk and brain. By in situ hybridization, Lv-AE3-positive cells were shown predominant localization in the secondary gill filaments. The expression levels of Lv-AE3 were further investigated during the essential life processes of shrimp, including ontogeny, molting, and ovarian development. In this case, the spatiotemporal expression profiles of Lv-AE3 in L. vannamei were highly correlated with the activities of water and ion absorption; for example, increased mRNA levels were present after hatching, during embryonic development, after ecdysis during the molt cycle, and in the stage IV ovary during gonadal development. After low/high pH and low/high salinity challenges, the transcript levels of Lv-AE3 were reduced in the gill, while the cell apoptosis rate increased. In addition, knockdown of Lv-AE3 mRNA expression induced cell apoptosis in the gill, indicating a potential link between Lv-AE3 and gill damage. Altogether, this study thoroughly investigated the relationship between the mRNA expression profiles of Lv-AE3 and multiple developmental and physiological processes in L. vannamei, and it may benefit the protection of crustaceans from fluctuated aquatic environments.

Function brain network (FBN) analysis has shown great potential in identifying brain diseases, such as Alzheimer's disease (AD) and its prodromal stage, namely mild cognitive impairment (MCI). It is essential to identify discriminative and interpretable features from function brain networks, so as to improve classification performance and help us understand the pathological mechanism of AD-related brain disorders. Previous studies usually extract node statistics or edge weights from FBNs to represent each subject. However, these methods generally ignore the topological structure (such as modularity) of FBNs. To address this issue, we propose a modular-LASSO feature selection (MLFS) framework that can explicitly model the modularity information to identify discriminative and interpretable features from FBNs for automated AD/MCI classification. Specifically, the proposed MLFS method first searches the modular structure of FBNs through a signed spectral clustering algorithm, and then selects discriminative features via a modularity-induced group LASSO method, followed by a support vector machine (SVM) for classification. To evaluate the effectiveness of the proposed method, extensive experiments are performed on 563 resting-state functional MRI scans from the public ADNI database to identify subjects with AD/MCI from normal controls and predict the future progress of MCI subjects. Experimental results demonstrate that our method is superior to previous methods in both tasks of AD/MCI identification and MCI conversion prediction, and also helps discover discriminative brain regions and functional connectivities associated with AD.

Upland cotton is the most widely planted for natural fiber around the world, and either lint percentage (LP) or fiber length (FL) is the crucial component tremendously affecting cotton yield and fiber quality, respectively. In this study, two lines MBZ70-053 and MBZ70-236 derived from G. hirsutum CCRI70 recombinant inbred line (RIL) population presenting different phenotypes in LP and FL traits were chosen to conduct RNA sequencing on ovule and fiber samples, aiming at exploring the differences of molecular and genetic mechanisms during cotton fiber initiation and elongation stages. As a result, 249/128, 369/206, 4296/1198 and 3547/2129 up-/down- regulated differentially expressed genes (DGEs) in L2 were obtained at −3, 0, 5 and 10 days post-anthesis (DPA), respectively. Seven gene expression profiles were discriminated using Short Time-series Expression Miner (STEM) analysis; seven modules and hub genes were identified using weighted gene co-expression network analysis. The DEGs were mainly enriched into energetic metabolism and accumulating as well as auxin signaling pathway in initiation and elongation stages, respectively. Meanwhile, 29 hub genes were identified as 14-3-3ω, TBL35, GhACS, PME3, GAMMA-TIP, PUM-7, etc., where the DEGs and hub genes revealed the genetic and molecular mechanisms and differences during cotton fiber development.

Abstract Background High rates of recurrence and metastasis are the major cause of the poor outcomes for patients with lung cancer. In previous research, we have demonstrated that Tac2-N promotes tumor growth by suppressing p53 signaling in lung cancer. Beyond that, other biological functions and clinical significance of Tac2-N in lung cancer progression are still unknown. Methods Tissue microarrays of 272 lung cancer patients were constructed to assess the association of Tac2-N expression and prognosis of lung cancer patients with different clinical stages. The protein expression of Tac2-N in metastatic and non-metastatic specimens were detected by IHC. In vitro migration and invasion and in vivo nude mice metastasis model were used to evaluate the effect of Tac2-N ectopic expression on metastasis capability of lung cancer cells. The downstream signaling pathway of Tac2-N was explored using luciferase reporter assays and WB. Results The expression of Tac2-N was associated with advanced stages, but not with early stages (P = 0.513). Tac2-N expression is sharply overexpressed in metastatic tumors compared with non-metastatic tumors. In vitro and in vivo assays suggested that Tac2-N facilitated migration and invasion of lung cancer cells in vitro and promoted tumor metastasis in vivo. Mechanistically, Tac2-N increased the degradation of IκB by promoting its phosphorylation, and subsequently activated NF-κB activity by facilitating the nuclear translocation of NF-κB and stimulating the transcription of targets, MMP7 and MMP9. Notably, the C2B domain of Tac2-N was crucial for Tac2-N to activate NF-κB signal. Blockage of NF-κB by shRNA or inhibitor attenuates the function of Tac2-N in the promotion of metastasis. Conclusions Our study provided proof of principle to show that Tac2-N serves as a novel oncogene gene and plays an important role in the progression and metastasis of lung cancer.

Abstract Background MAPK/ERK kinases transmit signals from many growth factors/kinase receptors during normal cell growth/differentiation, and their dysregulation is a hallmark of diverse types of cancers. A plethora of drugs were developed to block this kinase pathway for clinical application. With the exception of a recently identified agent, EQW, most of these inhibitors target upstream factors but not ERK1/2; no activator of ERK1/2 is currently available. Method A library of compounds isolated from medicinal plants of China was screened for anti-cancer activities. Three limonoid compounds, termed A1541–43, originally isolated from the plant Melia azedarach, exhibiting strong anti-leukemic activity. The anti-neoplastic activity and the biological target of these compounds were explored using various methods, including western blotting, flow cytometry, molecular docking and animal model for leukemia. Results Compounds A1541–43, exhibiting potent anti-leukemic activity, was shown to induce ERK1/2 phosphorylation. In contrast, the natural product Cedrelone, which shares structural similarities with A1541–43, functions as a potent inhibitor of ERK1/2. We provided evidence that A1541–43 and Cedrelone specifically target ERK1/2, but not the upstream MAPK/ERK pathway. Computational docking analysis predicts that compounds A1541–43 bind a region in ERK1/2 that is distinct from that to which Cedrelone and EQW bind. Interestingly, both A1541–43, which act as ERK1/2 agonists, and Cedrelone, which inhibit these kinases, exerted strong anti-proliferative activity against multiple leukemic cell lines, and induced robust apoptosis as well as erythroid and megakaryocytic differentiation in erythroleukemic cell lines. These compounds also suppressed tumor progression in a mouse model of erythroleukemia. Conclusions This study identifies for the first time activators of ERK1/2 with therapeutic potential for the treatment of cancers driven by dysregulation of the MAPK/ERK pathway and possibly for other disorders.

Abstract Background To determine the effects of age and the serum anti-Müllerian hormone (AMH) level on in vitro fertilization (IVF) outcomes, especially among young women with low serum AMH levels and older women with high AMH levels. Methods This study was a cohort study in which a total of 9431 women aged 20–51 years who were undergoing their first IVF cycles were recruited. Ovarian response parameters included the number of retrieved oocytes, the number of 2 pronuclear zygotes (2PN), and the frequency of good-quality embryos (GQE). Pregnancy outcomes included the clinical pregnancy rate (CPR), live birth rate (LBR), miscarriage rate (MR), and cumulative CPR and LBR (CCPR and CLBR). Results Among women under 35 years of age, the ovarian response, CPR, CCPR, LBR and CLBR (p

Abstract Background Prehydrolyzate, which is from the prehydrolysis process in dissolving pulps industry, contains various sugar-derived and lignin compounds such as xylooligosaccharides (XOS), gluco-oligosaccharides, xylose, glucose, and soluble lignin (S-L). The XOS has several beneficial effects on human physiology. XOS and S-L in prehydrolyzate are difficult to efficiently fractionate due to their similar molecular weights and water solubility. In this work, we proposed a sustainable and green process using polystyrene divinylbenzene (PS-DVB) resin to simultaneously separate and recover XOS and S-L. Enzymatic hydrolysis with endo-1,4-β-xylanase and fermentation with P. stipites were sequentially applied to purify XOS to minimize xylose content as well as amplify contents of xylobiose and xylotriose. In addition, 2D-HSQC NMR was used to analyze the structural characteristics of XOS and S-L. Furthermore, the biological abilities of antioxidants and prebiotics of these fractions were investigated by scavenging radicals and cultivating intestinally beneficial bacterias, respectively. Results Results showed that PS-DVB resin could simultaneously separate XOS and solubilized lignin with excellent yields of 93.2% and 85.3%, respectively. The obtained XOS after being purified by enzymatic hydrolysis and fermentation contained 57.7% of xylobiose and xylotriose. 10.4% amount of inherent xylan was found in the S-L fraction obtained by PS-DVB resin separation. 2D-HSQC NMR revealed that lignin carbohydrate complexes existed in both XOS and S-L as covalent linkages between lignin and 4-O-methylglucuronoarabinoxylan. The biological application results showed that the antioxidant capacity of S-L was stronger than XOS, while XOS was superior in promoting growth of intestinal Bifidobacteria adolescentis and stimulating production of short-chain fatty acids by Lactobacillus acidophilus. Conclusions The proposed strategy of sequentially combining hydrophobic resin separation, enzymatic hydrolysis, and fermentation was successfully demonstrated and resulted in simultaneous production of high-quality XOS and solubilized lignin. These biomass-derived products in prehydrolyzate can be regarded as value-adding prebiotics and antioxidants.

Abstract Background Stevens-Johnson Syndrome (SJS) is an acute mucocutaneous eruption with blisters of the skin and haemorrhagic erosions of mucous membranes. This report describes air-leak syndrome and obstructive uropathy occurring simultaneously in a teenage patient affected by SJS. Case presentation A 17-year-old Malay female with SJS suffered from bilateral pneumothoraces, pneumomediastinum, and obstructive uropathy as early complications of her disease. She required intubation, chest tube insertion, and bilateral ureteric stenting as part of her intensive care management. These extra-cutaneous complications of renal and pulmonary systems were likely secondary to widespread epithelial detachment. Conclusion Despite paucity of cases in adult literature, post-renal causes for acute kidney injury must be considered in SJS, especially in the setting of gross haematuria. Bedside point-of-care ultrasonography may be a useful tool for excluding obstructive uropathy. Pneumothorax is a rare but documented complication of SJS in paediatric cases and, to a lesser extent, adult patients. Extra care should be exercised when caring for mechanically ventilated patients suffering from SJS.

By $(\mathbb{Z}^+)^{\infty}$ we denote the set of all theinfinite sequences $\mathcal{S}=\{s_i\}_{i=1}^{\infty}$ of positiveintegers (note that all the $s_i$ are not necessarily distinct and notnecessarily monotonic). Let $f(x)$ be a polynomial of nonnegativeinteger coefficients. For any integer $n\ge 1$, one lets$\mathcal{S}_n:=\{s_1, ..., s_n\}$ and$H_f(\mathcal{S}_n):=\sum_{k=1}^{n}\frac{1}{f(k)^{s_{k}}}$.In this paper, we use a result of Kakeya to show thatif $\frac{1}{f(k)}\le\sum_{i=1}^\infty\frac{1}{f(k+i)}$holds for all positive integers $k$, then the union set$\bigcup\limits_{\mathcal{S}\in (\mathbb{Z}^+)^{\infty}}\{ H_f(\mathcal{S}_n) | n\in \mathbb{Z}^+ \}$ is densein the interval $(0,\alpha_f)$ with$\alpha_f:=\sum_{k=1}^{\infty}\frac{1}{f(k)}$.It is well known that $\alpha_{x^2+1}=\frac{1}{2}\big(\pi\frac{e^{2\pi}+1}{e^{2\pi}-1}-1\big)\approx 1.076674$.Our dense result infers that for any sufficiently small$\varepsilon >0$, there are positive integers $n_1$ and$n_2$ and infinite sequences $\mathcal{S}^{(1)}$ and$\mathcal{S}^{(2)}$ of positive integers such that$1-\varepsilon

Mobile edge computing (MEC) is envisioned as a new paradigm by integrating the mobile computing functionality into 5G wireless networks, aiming at empowering communication networks with low-latency services. In general, mobile devices have finite battery lifetime (e.g., machine-type devices) and the energy harvesting is advocated to provide perpetual energy supply for achieving sustainable operation, which is very important for facilitating sustainable computing in future applications. In this paper, we propose a wireless powered MEC network architecture that employs device-to-device (D2D) communications underlaying heterogeneous networks (HetNets) to enable the computational tasks offloading to resource-rich edge servers. A dynamic offloading decision is made to execute the computation tasks. Then, we focus on the energy-efficient offloading scheme, and joint offloading and user association scheme. From the illustrative results, we provide insights for the design of this new network architecture. Furthermore, several open research topics are discussed.

Abstract Background Verticillium wilt (VW), also known as “cotton cancer,” is one of the most destructive diseases in global cotton production that seriously impacts fiber yield and quality. Despite numerous attempts, little significant progress has been made in improving the VW resistance of upland cotton. The development of chromosome segment substitution lines (CSSLs) from Gossypium hirsutum × G. barbadense has emerged as a means of simultaneously developing new cotton varieties with high-yield, superior fiber, and resistance to VW. Results In this study, VW-resistant investigations were first conducted in an artificial greenhouse, a natural field, and diseased nursery conditions, resulting in the identification of one stably VW-resistant CSSL, MBI8255, and one VW-susceptible G. hirsutum, CCRI36, which were subsequently subjected to biochemical tests and transcriptome sequencing during V991 infection (0, 1, and 2 days after inoculation). Eighteen root samples with three replications were collected to perform multiple comparisons of enzyme activity and biochemical substance contents. The findings indicated that VW resistance was positively correlated with peroxidase and polyphenol oxidase activity, but negatively correlated with malondialdehyde content. Additionally, RNA sequencing was used for the same root samples, resulting in a total of 77,412 genes, of which 23,180 differentially expressed genes were identified from multiple comparisons between samples. After Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis on the expression profiles identified using Short Time-series Expression Miner, we found that the metabolic process in the biological process, as well as the pathways of phenylpropanoid biosynthesis and plant hormone signal transduction, participated significantly in the response to VW. Gene functional annotation and expression quantity analysis indicated the important roles of the phenylpropanoid metabolic pathway and oxidation-reduction process in response to VW, which also provided plenty of candidate genes related to plant resistance. Conclusions This study concentrates on the preliminary response to V991 infection by comparing the VW-resistant CSSL and its VW-susceptible recurrent parent. Not only do our findings facilitate the culturing of new resistant varieties with high yield and superior performance, but they also broaden our understanding of the mechanisms of cotton resistance to VW.

Eutrophication caused by excessive total nitrogen (TN) and total phosphorus (TP) emissions is of wide concern for society at large. Studies have revealed certain relationships among land use, TN, and TP. However, the relationships among land use compound topographic position, TP, and TN have seldom been studied. Therefore, the objectives of this paper are to construct optimal zoning of land use and reduce the nutrient load of lakes. Spearman correlation and redundancy analyses were used to reveal the relationship between land use comprehensive topographic position and TN and TP in the lakes of Guizhou Plateau. The results show that the nutritional state of the research area is medium. The trophic level index (TLI) value and TN concentration were high during flood periods, while TP concentration was high in dry periods. The TN concentration in the tributaries was higher than that in the reservoir area. Construction land and valley were the sources of the pollution, whereas forest land and gentle slope were the sink. According to the ”source–sink” effect, once the optimal zoning of land use is completed, the governance of urban land pollution governed areas should be strengthened next. This paper can provide decision support for water environment management and sustainable development decision-making.

Abstract Background Different histological subtypes of non-small cell lung cancer (NSCLC) show different molecular characteristics and responses to therapeutic strategy. Identification of specific gene, clarification of its special roles and molecular mechanisms are crucial for developing new therapeutic approach for particular subtype patients. Methods Surgical specimens of 540 NSCLC patients were recruited. Immunohistochemistry was used to detect SOX30 expression, and correlations with clinical parameters were analyzed. Functional experiments and gene ontology analysis were performed to investigate roles of SOX30. Network analysis, TOP/FOP-Flash assays, luciferase reporter assays and ChIP-PCR assays were performed to determine the mechanism. Survival analyses were calculated by Kaplan-Meier and Cox regression. Recovery experiment was investigated the importance of the target of SOX30. Results SOX30 expression is closely associated with histological types of NSCLC, and metastasis of adenocarcinoma (ADC) patients but not of squamous cell carcinoma (SCC) patients. SOX30 strongly inhibits cancer cell migration and invasion in ADC cell lines, whrereas not affects cell migration and invasion in SCC cell lines. The genes associated with SOX30 preferentially enrich in metastasis process and Wnt-signaling in only ADC patients. Consistently, SOX30 is negatively associated with the expression of Wnt-signaling and metastasis-related gene CTNNB1 (β-catenin) in ADC, but not in SCC. At the molecular level, SOX30 represses Wnt-signaling by directly transcriptional inhibition of CTNNB1 in ADC, and also not in SCC. In the clinical, SOX30 is a favorable and independent prognostic factor in ADC patients, whereas is an unfavorable and independent prognostic factor in SCC patients. Moreover, SOX30 expression is a double face early-stage prognostic biomarker in ADC and SCC patients. In addition, forcible restoration of CTNNB1 indeed can inhibit the anti-metastatic role of SOX30 in ADC patients. Conclusions In early-stage ADC patients, elevated SOX30 expression inhibits tumor-metastasis by directly binding to CTNNB1 promoter resulting in a favorable prognosis of these patients. However, in early-stage SCC patients, SOX30 has no inhibitory role on tumor-metastasis due to not binding to CTNNB1 promoter leading to an unfavorable prognosis of the patients. This study highlights a special role and prognostic value of SOX30 in ADC, providing a novel therapeutic target for particular subtype NSCLC patients.

Angiogenesis is an essential process during development. Abnormal angiogenesis also contributes to many disease conditions such as tumor and retinal diseases. Previous studies have established the Hippo signaling pathway effector Yes-associated protein (YAP) as a crucial regulator of angiogenesis. In ECs, activated YAP promotes endothelial cell proliferation, migration and sprouting. YAP activity is regulated by vascular endothelial growth factor (VEGF) and mechanical cues such as extracellular matrix (ECM) stiffness. However, it is unclear how VEGF or ECM stiffness signal to YAP, especially how dephosphorylation of YAP occurs in response to VEGF stimulus or ECM stiffening. Here, we show that protein phosphatase 2A (PP2A) is required for this process. Blocking PP2A activity abolishes VEGF or ECM stiffening mediated YAP activation. Systemic administration of a PP2A inhibitor suppresses YAP activity in blood vessels in developmental and pathological angiogenesis mouse models. Consistently, PP2A inhibitor also inhibits sprouting angiogenesis. Mechanistically, PP2A directly interacts with YAP, and this interaction requires proper cytoskeleton dynamics. These findings identify PP2A as a crucial mediator of YAP activation in ECs and hence as an important regulator of angiogenesis.

Background: Triglyceride-glucose (TyG) index is a recently proposed surrogate indicator of insulin resistance. Previous studies evaluating the association between TyG index and hypertension risk in general adult population showed inconsistent results. We performed a meta-analysis to systematically evaluate this association.Methods: Observational studies, which evaluated the independent association between TyG index and hypertension in the general adult population, were identified by systematic search of PubMed, Embase, Web of Science, Wanfang data, and Chinese National Knowledge Infrastructure databases. A random-effect model, which incorporated the potential intra-study heterogeneity, was used for the meta-analysis.Results: Eight observational studies including 200,044 participants were included. Results showed that compared with those with the lowest category of TyG index, subjects with the highest category of TyG index were associated with higher odds of hypertension [adjusted risk ratio (RR): 1.53, 95% confidence interval (CI): 1.26–1.85, I2 = 54%, P < 0.001]. Sensitivity analysis by excluding one dataset at a time showed consistent result (adjusted RR: 1.44–1.62, P all < 0.001). Results of univariate meta-regression analysis showed that differences in sample size, mean age, male proportion, mean body mass index, and study quality score among the included studies did not have significant influence on the association between TyG index and hypertension (P values all > 0.10), suggesting that differences in these characteristics may not be the major source of heterogeneity. Subgroup analyses showed that study characteristics such as study design, participant ethnicity, age, or sex of the participants did not significantly affect the association (P for subgroup difference all >0.05).Conclusions: Higher TyG index may be associated with higher odds of hypertension in general adult population. Large-scale prospective cohort studies are needed to validate these findings, and further studies are needed to elucidate the potential pathophysiological mechanisms underlying the association between TyG index and hypertension.

Background: Nitrous oxide (N2O), commonly known as laughing gas, is inhaled recreationally because it produces the feelings of euphoria and freedom from pain. The risk of neurological dysfunction secondary to N2O abuse and its clinical diagnosis are, however, not yet sufficiently recognized, especially in China. Here, we have summarized the key clinical characteristics of N2O-induced neurological disorders.Materials and Methods: We recruited 20 patients with N2O-induced neurological disorders and analyzed their clinical features, laboratory data, magnetic resonance imaging and electromyography. We also carried out a literature review and compared 99 previously reported patients with our case series to confirm our results. Subgroup analysis was performed to explore the difference in demographical and clinical characteristics of N2O abuse between Asian and non-Asian patients.Results: The most common initial symptoms of N2O-induced neurological disorders were weakness and/or paresthesia. Most patients presented with myelopathy and/or peripheral neuropathy. The most commonly involved segment of the spinal cord was the cervical spinal cord, extending over 4–6 vertebral levels, but more than half of the patients with myelopathy had no sensory change at the corresponding spinal level. Homocysteine was found to be the most sensitive and practical indicator for diagnosis. Subgroup analysis showed that the Asian patients (median: 22.0 years old, Q1–Q3:19.0–26.0 years old) with N2O abuse were younger than non-Asian patients [26.0 (22.3–31.0) years old, P = 2.8 × 10−4]. The incidence of myelopathy combined with peripheral neuropathy was significantly higher in Asian patients than in non-Asian patients, who had myelopathy or peripheral neuropathy (P = 2 × 10−5).Conclusions: Key clinical characteristics of N2O abuse are longitudinally extensive cervical myelopathy and peripheral neuropathy. Recognition of these traits in young people in the age group of 20–30 years will provide important guidance for accurate diagnosis of neurological disease associated with N2O abuse. The clinical manifestations differ in Asian patients and non-Asian patients.

68Ga labeled FAPI is the current standard for FAPI-PET, but its batch activity is limited. [18F]AlF-NOTA-FAPI-04 is a promising alternative combining the advantages of a chelator-based radiolabeling method with the unique properties of fluorine-18. The objective of this study was to develop a quick automatic method for synthesis of [18F]AlF-NOTA-FAPI-04 using a AllinOne synthesis system, and perform PET imaging with [18F]AlF-NOTA-FAPI-04 on patients. [18F]AlF-NOTA-FAPI-04 was produced, and its quality control was conducted by HPLC equipped with a radioactive detector. [18F]AlF-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice (n = 3) and 4T1 breast cancer models (n = 3) to determine its biodistribution. Then [18F]AlF-NOTA-FAPI-04 and 18F-fluorodeoxyglucose (FDG) PET/CT imaging were performed in an invasive ductal carcinoma patient (female, 54 years old). The synthesis time of [18F]AlF-NOTA-FAPI-04 was about 25 min, and the radiochemical yield was 26.4 ± 1.5% (attenuation correction, n = 10). The radiochemical purity was above 99.0% and was above 98.0% after 6 h. The product was colorless transparent solution with pH value of 7.0–7.5, and the specific activity was 49.41 ± 3.19 GBq/μmol. PET/CT imaging in mice showed that physiological uptake of [18F]AlF-NOTA-FAPI-04 was mainly in the biliary system and bladder, and [18F]AlF-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that [18F]AlF-NOTA-FAPI-04 obtained high tumor background ratio (TBR) value of 8.44 in segment V and VI, while TBR value was 2.55 by 18F-FDG. [18F]AlF-NOTA-FAPI-04 could be synthesized with high radiochemical yield and batch production by AllinOne module and show excellent diagnosis performance in cancer patients.

Purpose18F labelled PSMA-1007 presents promising results in detecting prostate cancer (PC), while some pitfalls exists meanwhile. An intra-individual comparison of 18F-FDG and 18F-PSMA-1007 in patients with prostate cancer were aimed to be performed in the present study. Then, the pitfalls of 18F-PSMA-1007 PET/CT in imaging of patients with prostate cancer were analyzed.Methods and Material21 prostate cancer patients underwent 18F-PSMA-1007 PET/CT as well as 18F-FDG PET/CT before treatment. All positive lesions were noticed in both 18F-PSMA-1007 PET/CT and 18F-FDG PET/CT, then differentiated PC metastasis from benign lesions. the SUVmax, SUVmean and TBR of lesions, up to 10 metastases and 10 benign lesions per patients were recorded (5 for bone, 5 for soft tissue metastasis ). The distribution of positive lesions were analyzed for two imaging. Detection rates, SUVmax, SUVmean and TBR in 18F-PSMA-1007 PET/CT and 18F-FDG PET/CT were compared, respectively. The optimal cut-off values of SUVmax, SUVmean for metastases vs. benign lesions was found through areas under ROC in 18F-PSMA-1007.ResultsThe detection rates of primary lesions in 18F-PSMA-1007 PET/CT was higher than that of 18F-FDG PET/CT(100% (21/21) vs. 67%(14/21)). For extra- prostatic lesions, 18F-PSMA-1007 PET/CT revealed 124 positive lesions, 49(49/124, 40%) attributed to a benign origin; 18F-FDG PET/CT revealed 68 positive lesions, 14(14/68, 21%) attributed to a benign origin. The SUVmax, SUVmean, TBR of primary tumor in 18F-PSMA-1007 PET/CT was higher than that in 18F-FDG PET/CT (15.20 vs. 4.20 for SUVmax; 8.70 vs. 2.80 for SUVmean; 24.92 vs. 4.82 for TBR, respectively); The SUVmax, SUVmean, TBR of metastases in 18F-PSMA-1007 PET/CT was higher than that in 18F-FDG PET/CT (10.72 vs. 4.42 for SUVmax; 6.67 vs. 2.59 for SUVmean; The TBR of metastases was 13.3 vs. 7.91). For 18F-FDG PET/CT, the SUVmax, SUVmean in metastases was higher than that in benign lesions (4.42 vs. 3.04 for SUVmax, 2.59 vs. 1.75 for SUVmean, respectively). Similarly, for 18F-PSMA-1007 PET/CT, the SUVmax, SUVmean in metastases was significantly higher than that in benign lesions(10.72 vs. 3.14 for SUVmax, 6.67 vs. 1.91 for SUVmean, respectively), ROC suggested that SUVmax=7.71, SUVmean=5.35 might be the optimal cut-off values for metastases vs. benign lesions.ConclusionThe pilot study suggested that 18F-PSMA-1007 showed superiority over 18F-FDG because its high detecting rate of PC lesions and excellent tumor uptake. While non-tumor uptake in 18F-PSMA-1007 may lead to misdiagnosis, recognizing these pitfalls and careful analysis can improve the accuracy of diagnosis.

Given that thermal stability is of considerable importance in the field of photovoltaics, inorganic perovskites have attracted numerous attempts to overcome instability caused by volatile cations in organic–inorganic hybrid perovskites. As always, crystallization optimization is a paramount strategy to enhance the performance of inorganic perovskite‐based solar cells. Recently, nanoconfined crystallization is regarded as a novel and effective strategy due to the absence of chemical reactions. Herein, 1D ordered mesoporous silica is introduced into inorganic perovskite precursors to facilely induce the nanoconfined crystallization. Both theoretical and experimental analyses verify that the nanoconfined crystallization is successfully triggered by the ordered mesoporous silica, fostering the formation of 1D perovskite monocrystal. In addition, the crystallization and morphology of inorganic perovskite are effectively facilitated. As a result, the nonradiative recombination is suppressed along with the distinctly reduced trap‐state density and remarkably enhanced charge transport in perovskite. Finally, the power conversion efficiencies of CsPbIBr2‐ and CsPbI3‐based solar cells are boosted from 8.67% to 10.04% and from 14.10% to 14.69%, respectively. Meanwhile, stability tests of solar cells also show enhancement using the nanoconfined crystallization. This work provides a facile, effective, and flexible crystallization modulating strategy for fabricating efficient and stable inorganic perovskite solar cells.

UDP-glucose dehydrogenase (UGD; EC1.1.1.22) is a NAD+-dependent enzyme that catalyzes the two-fold oxidation of UDP-glucose (UDP-Glc) to produce UDP-glucuronic acid and plays an important role in plant cell wall synthesis. A total of 42 UGD genes from four Gossypium genomes including G. hirsutum, G. arboretum, G. barbadense, and G. raimondii were identified and found that the UGD gene family has conservative evolution patterns in gene structure and protein domain. The growth of fibers can be effectively promoted after adding the UDP-Glc to the medium, and the GhUGD gene expression enhanced. In addition, the transgenic Arabidopsis lines over-expressing GH_D12G1806 had longer root lengths and higher gene expression level than the wild-type plants of Columbia-0. These results indicated that UGD may play important roles in cotton fiber development and has a guiding significance for dissecting fiber development mechanism.

In various leading-edge ultracold atom experiments in fields such as quantum simulation, quantum computing, and quantum precision measurement, precise and fast control of the magnetic field is important and a current source with a low noise level and high control bandwidth is required. Conventional commercial current sources, even the expensive ones, may not meet the requirements. Here, we present a battery-powered current source (BPCS) solution that has a maximum output of 100 A with a root-mean-square noise of about only 0.35 mA (integrated from 1 Hz to 3 MHz) and a control bandwidth of about 10 kHz. The large output current is sourced from a lead-acid battery, a fluxgate current sensor is used to detect the output current, and fast feedback regulation is done by using an insulated-gate bipolar transistor under the control of an analog proportional-integral controller. The battery power method eliminates the switching noise. A prepulse method is applied to shorten the settling time when the current steps down from a high level to a low level that is close to zero. These features make the BPCS a suitable analog-controlled floating current source for cold-atom experiments such as the preparation of a single 2D quantum gas and optical lattice atomic clocks.

While the COVID-19 pandemic continues, the world is on high alert regarding the second public health threat of a global monkeypox outbreak. Monkeypox, a relative of smallpox, is a zoonotic disease that was initially restricted to Africa. However, a novel outbreak has occurred in Europe, a non-endemic region, starting in May 2022. In the face of this unprecedented event, people should be aware of several crucial facts regarding monkeypox to support global public health prevention and control of the outbreak, including pathogenetic epidemiological and diagnostic aspects. As the cases outside Africa rapidly increase, including in a large proportion of men who have sex with men, thinking about the potential effects on global public health, as well as the shifting epidemiological trends of monkeypox and the insights from this novel outbreak, will be crucial.

The Buddhist ideas and practices of hell were bureaucratized in medieval China. The cult of Dizang and the Ten Kings of Hell was popular from the late Tang Dynasty onward. However, the concept of the Three Kings of Hell (King Yama 閻羅王, the Magistrate of Mount Tai 泰山府君, and the Great Spirit of the Five Paths 五道大神) appeared before that of the Ten Kings and has long been ignored. This article aimed to make a textual comparison of the descriptions of Dizang and the Three Kings in the literature with the bureaucratic system of the Three Departments (sansheng zhi 三省制), which was the central government system during the Tang Dynasty, where the Three Departments performed their respective functions. There are several structural and functional parallels between the underworldly afterlife and the political bureaucracies of the world. The workings of the system in hell changed in texts from different periods, showing the evolution of the Three Departments system during the Tang Dynasty. This case study demonstrated that the system of Dizang and the Three Kings of Hell were constructed based on the official system used in human society and that the underworld was reinterpreted as a bureaucratic system similar to the temporal one.

With the rapid development of Ultra-High Voltage (UHV) transmission lines, it is necessary to study the performance of UHV transmission towers. First, we performed full-scale tests on a transmission tower under seven loading patterns. Then, the test results were compared with the calculation results of the Chinese tower design software Transmission Tower Analysis Program (TTA), and the failure location of the tower and the stress characteristics of the key parts were studied. Finally, we discuss the influence of bolt slippage and a new joint on the tower performance, and propose some design proposals for the current Chinese code, based on the test results. The results show that a bolt slip will significantly increase the displacement of the transmission tower, but the residual displacement can correct it. The new joint design has good mechanical performance. The bracing member at the bottom of the tower leg is located at the connection of the tower leg and the foundation, and there is a significant sudden change in stiffness, which we recommend designing according to 4% of the axial force of the main members.

Apoptosis, also known as programmed cell death, is a biological process that is critical for embryonic development, organic differentiation, and tissue homeostasis of organisms. As an essential mitochondrial flavoprotein, the apoptosis-inducing factor (AIF) can directly mediate the caspase-independent mitochondrial apoptotic pathway. In this study, we identified and characterized a novel AIF-2 (HlAIF-2) from the tropical sea cucumber Holothuria leucospilota. HlAIF-2 contains a conserved Pyr_redox_2 domain and a putative C-terminal nuclear localization sequence (NLS) but lacks an N-terminal mitochondrial localization sequence (MLS). In addition, both NADH- and FAD-binding domains for oxidoreductase function are conserved in HlAIF-2. HlAIF-2 mRNA was ubiquitously detected in all tissues and increased significantly during larval development. The transcript expression of HlAIF-2 was significantly upregulated after treatment with CdCl2, but not the pathogen-associated molecular patterns (PAMPs) in primary coelomocytes. In HEK293T cells, HlAIF-2 protein was located in the cytoplasm and nucleus, and tended to transfer into the nucleus by CdCl2 incubation. Moreover, there was an overexpression of HlAIF-2-induced apoptosis in HEK293T cells. As a whole, this study provides the first evidence for heavy metal-induced apoptosis mediated by AIF-2 in sea cucumbers, and it may contribute to increasing the basic knowledge of the caspase-independent apoptotic pathway in ancient echinoderm species.

Estrogen receptor (ER) expression level of human breast cancer often reflects the stage of disease and is usually monitored by immunohistochemical staining in vitro. The preferable non-invasive and real-time diagnosis in vivo is more accessible by PET scan using 16α-[18F]FES. The objective of this study was to develop a quick automatic method for synthesis of solvent-free 16α-[18F]FES using a CFN-MPS-200 synthesis system and compare the catalytic efficiency of two phase transfer catalysts, Kryptofix 222/K2CO3 (K222/K2CO3) and tetrabutylammonium hydrogen carbonate (TBA·HCO3). In this method, phase transfer catalysts K222/K2CO3 and TBA·HCO3 were used, respectively. The intermediate products were both hydrolyzed with hydrochloric acid and neutralized with sodium bicarbonate. The crude product was purified with semi-preparative HPLC, and the solvent was removed by rotary evaporation. The effects of radiofluorination temperature and time on the synthesis were also investigated. Radiochemical purity of solvent-free product was above 99% and the decay-corrected radiochemical yield of 16α-[18F]FES was obtained in 48.7 ± 0.95% (catalyzed by K222/K2CO3, n = 4) and 46.7 ± 0.77% (catalyzed by TBA·HCO3, n = 4, respectively). The solvent-free 16α-[18F]FES was studied in clinically diagnosed breast cancer patients, and FES-PET results were compared with pathology diagnosis results to validate the diagnosis value of 16α-[18F]FES. The new method was more reliable, efficient, and time-saving. There was no significant difference in catalytic activity between K222/K2CO3 and TBA·HCO3.

Oocyte maturation and ovarian development are sequentially coordinated events critical to reproduction. In the ovaries of adult oviparous animals such as birds, bony fish, insects, and crustaceans, vitellogenin receptor (VgR) is a plasma membrane receptor that specifically mediates vitellogenin (Vg) transport into oocytes. Accumulation of Vg drives sexual maturation of the female crustaceans by acting as a pivotal regulator of nutritional accumulation within oocytes, a process known as vitellogenesis. However, the mechanisms by which VgR mediates vitellogenesis are still not fully understood. In this study, we first identified a unique VgR (Lv-VgR) and characterized its genomic organization and protein structural domains in Litopenaeus vannamei, a predominant cultured shrimp species worldwide. This newly identified Lv-VgR phylogenetically forms a group with VgRs from other crustacean species within the arthropod cluster. Duplicated LBD/EGFD regions are found exclusively among arthropod VgRs but not in paralogs from vertebrates and nematodes. In terms of expression patterns, Lv-VgR transcripts are specifically expressed in ovaries of female shrimps, which increases progressively during ovarian development, and rapidly declines toward embryonic development. The cellular and subcellular locations were For analyzed by in situ hybridization and immunofluorescence, respectively. The Lv-VgR mRNA was found to be expressed in the oocytes of ovaries, and Lv-VgR protein was found to localize in the cell membrane of maturing oocytes while accumulation of the ligand Vg protein assumed an even cytoplasmic distribution. Silencing of VgR transcript expression by RNAi was effective for stunting ovarian development. This present study has thus provided new insights into the regulatory roles of VgR in crustacean ovarian development.

In this study, the functions of Holothuria leucospilota Fas-associated death domain (HLFADD) in the innate immune-related signalling pathways were investigated. The results showed that over-expression of HLFADD in HEK293T cells could activate the transcription factors NF-κB and activator protein-1 (AP-1), and induce the secretion of downstream pro-inflammatory cytokines IL-6, IL-8 and IL-18, suggesting the involvement of the sea cucumber FADD in activating the NF-κB and c-Jun NH 2 -terminal kinase-dependent pathways. On the other hand, HLFADD could down-regulate the activations of NF-κB and AP-1 that induced by over-expression of H. leucospilota myeloid differentiation factor 88 (HLMyD88), which is supposed to be mediated through its interaction with HLMyD88 to keep the MyD88-dependent TLR signalling at a proper magnitude. The interaction of HLFADD and HLMyD88 were further supported by a co-immunoprecipitation assay. Moreover, HLFADD could activate transcription factor IFN regulatory factor-3 and induced the secretion of downstream IFN-α and IFN-β, indicating that the sea cucumber FADD may also activate the antiviral IFN signalling pathway. In summary, our study may give new insights on the functions of sea cucumber FADD in the innate immune-related signalling pathways.

Holothuria leucospilota (Echinodermata: Holothuroidea) is a widespread tropical sea cucumber with strong value for the ecological restoration of coral reefs. Therefore, some studies regarding the artificial breeding and cultivation of H. leucospilota have been undertaken recently. However, the biological functions of the digestive system of this species have not been elucidated. In this study, a cDNA coding for α-amylase, an indicator of digestive maturity in animals, was identified from H. leucospilota and designated Hl-Amy. The full-length cDNA of the Hl-Amy gene, which is 1734 bp in length with an open reading frame (ORF) of 1578 bp, encodes a 525 amino acid (a.a.) protein with a deduced molecular weight of 59.34 kDa. According to the CaZy database annotation, Hl-Amy belongs to the class of GH-H with the official nomenclature of α-amylase (EC 3.2.1.1) or 4-α-D-glucan glucanohydrolase. The Hl-Amy protein contains a signal peptide at the N-terminal followed by a functional amylase domain, which includes the catalytic activity site. The mRNA expression of Hl-Amy was abundantly exhibited in the intestine, followed by the transverse vessel with a low level, but was hardly detected in other selected tissues. During embryonic and larval development, Hl-Amy was constitutively expressed in all stages, and the highest expression level was observed in the blastula. By in situ hybridization (ISH), positive Hl-Amy signals were observed in different parts of the three different intestinal segments (foregut, midgut and hindgut). The Hl-Amy recombinant protein was generated in an E. coli system with codon optimization, which is necessary for Hl-Amy successfully expressed in this heterogenous system. The Hl-Amy recombinant protein was purified by immobilized metal ion affinity chromatography (IMAC), and its activity of starch hydrolysis was further detected. The optimal temperatures and pH for Hl-Amy recombinant protein were 55°C and 6.0, respectively, with an activity of 62.2 U/mg. In summary, this current study has filled a knowledge gap on the biological function and expression profiles of an essential digestive enzyme in sea cucumber, which may encourage future investigation toward rationalized diets for H. leucospilota in artificial cultivation, and optimized heterogenous prokaryotic systems for producing recombinant enzymes of marine origins.

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing, as is research on the molecular mechanisms underlying cellular infection by coronaviruses, with the hope of developing therapeutic agents against this pandemic. Other important respiratory viruses such as 2009 pandemic H1N1 and H7N9 avian influenza virus (AIV), influenza A viruses, are also responsible for a possible outbreak due to their respiratory susceptibility. However, the interaction of these viruses with host cells and the regulation of post-transcriptional genes remains unclear. In this study, we detected and analyzed the comparative transcriptome profiling of SARS-CoV-2, panH1N1 (A/California/07/2009), and H7N9 (A/Shanghai/1/2013) infected cells. The results showed that the commonly upregulated genes among the three groups were mainly involved in autophagy, pertussis, and tuberculosis, which indicated that autophagy plays an important role in viral pathogenicity. There are three groups of commonly downregulated genes involved in metabolic pathways. Notably, unlike panH1N1 and H7N9, SARS-CoV-2 infection can inhibit the m-TOR pathway and activate the p53 signaling pathway, which may be responsible for unique autophagy induction and cell apoptosis. Particularly, upregulated expression of IRF1 was found in SARS-CoV-2, panH1N1, and H7N9 infection. Further analysis showed SARS-CoV-2, panH1N1, and H7N9 infection-induced upregulation of lncRNA-34087.27 could serve as a competitive endogenous RNA to stabilize IRF1 mRNA by competitively binding with miR-302b-3p. This study provides new insights into the molecular mechanisms of influenza A virus and SARS-CoV-2 infection.

The molecular mechanisms that underlie associations in GWAS, incl. chronic kidney disease (CKD), are largely unknown. Here, the authors perform an integrative analysis of genetic, transcriptomic and epigenomic data from human kidney to pinpoint plausible molecular pathways of CKD genetic associations.

Abstract Background The expression of desmosomal genes in lung adenocarcinoma and lung squamous carcinoma is different. However, the regulatory mechanism of desmosomal gene expression in lung adenocarcinoma and lung squamous carcinoma remains unknown. Methods The correlation between expression of desmosomal gene expression and SOX30 expression were analyzed by bioinformatics. The expression of SOX30, DSP, JUP and DSC3 were detected in lung cancer cell lines, lung tissues of mice and patients’ tissues by qPCR, WB, Immunofluorescence and Immunohistochemistry. A chromatin Immunoprecipitation assay was used to investigate the mechanisms of the SOX30 regulation on desmosomal gene expression. In vitro proliferation, migration and invasion assays, and an in vivo nude mice model were utilized to assess the important role of desmosomal genes on SOX30-induced tumor suppression. A WB assay and TOP/FOP flash reporter assay was used to investigate the downstream pathway regulated by the SOX30-desmosomal gene axis. A chemical carcinogenic model of SOX30-knockout mice was generated to confirm the role of the SOX30-desmosomal gene axis in tumorigenesis. Results The expression of desmosomal genes were upregulated by SOX30 in lung adenocarcinoma but not in lung squamous carcinoma. Further mechanism studies showed that SOX30 acts as a key transcriptional regulator of desmosomal genes by directly binding to the ACAAT motif of desmosomal genes promoter region and activating their transcription in lung adenocarcinoma. Knockdown of the expression of related desmosomal genes by miRNA significantly attenuated the inhibitory effect of SOX30 on cell proliferation, migration and invasion in vitro and on tumor growth and metastasis in vivo. In addition, knockout of SOX30 promotes lung tumor development and loss the inhibition of desmosomal genes on downstream Wnt and ERK signal in urethane-induced lung carcinogenesis in SOX30-knockout mice. Conclusions Overall, these findings demonstrate for the first time that SOX30 acts as a master switch of desmosomal genes, inhibits lung adenocarcinoma cell proliferation, migration and invasion by activating the transcription of desmosomal genes. This study provides novel insights on the regulatory mechanism of desmosomal genes in lung adenocarcinoma.

Although high mortality of lung cancer is greatly due to distant metastasis, the mechanism of this metastasis remains unclear. Here, we investigate in lung cancer that SOX30 is sharply under-expressed in metastatic tumors compared with non-metastatic tumors, and suppresses plenty of metastasis related processes or pathways. SOX30 strongly inhibits tumor cell metastasis in vitro and in vivo. Sox30 deficiency promotes lung metastasis in Sox30−/− mice and this uncontrollable lung-metastasis is re-inhibited upon Sox30 re-expression. Mechanistically, SOX30 diminishes Wnt-signaling via directly transcriptional repressing β-catenin or interacting with β-catenin to compete with TCF for binding to β-catenin. The carboxyl-terminus of SOX30 is required for attenuating β-catenin transcriptional activity, whereas the amino-terminus of SOX30 is required for its interaction with β-catenin protein. Enhance of β-catenin attenuates the anti-metastatic role of SOX30. Moreover, Sox30 deficiency promotes tumor metastasis and reduces survival of mice. In addition, nuclear SOX30 expression is closely associated with metastasis and represents a favorable independent prognostic biomarker of lung cancer patients. Altogether, these results highlight an important role and mechanism of SOX30 in lung cancer metastasis, providing a potential therapeutic target for anti-metastasis. Keywords: Lung cancer, Metastasis, SOX30, Wnt-signaling, Molecular mechanism

Background/Aims: Bone morphogenetic proteins (BMPs) and BMP receptors widely participate in osteolytic metastasis of breast cancer, while their role in tumor-stromal interaction is largely unknown. In this study, we investigated whether BMP receptor type 1a (BMPR1a) can alter the interaction between metastatic cancer cells and osteoclast precursors. Methods: Adenovirus-mediated RNA interference was used to interrupt target genes of human breast cancer cell lines and nude mice were injected intratibially with the cancer cells. Tumor-bearing mice were examined by bioluminescence imaging and microCT. Sections of metastatic legs were measured by a series of staining methods. Murine bone marrow mononuclear cells or RAW264.7 cells were cultured with conditioned media of breast cancer cells. RT-PCR, Western blotting and ELISA were used to test mRNA and protein expressions of target molecules. Results: Expression of BMPR1a of MDA-MB-231-luc cells at tumor-bone interface was apparently stronger than that of cancer cells distant from the interface. Mice injected with BMPR1a-knockdown MDA-MB-231-luc cells showed reduced tumor growth and bone destruction compared with control groups. Knockdown (KD) of BMPR1a of MDA-MB-231-luc cells or MCF-7 cells decreased the level of receptor activator for NF-κB ligand (RANKL). Level of RANKL in MDA-MB-231-luc cells or MCF-7 cells was reduced by p38 inhibitor. Compared with control group, knockdown of p38 of breast cancer cells decreased cancer-induced osteoclastogenesis. Conclusion: Knockdown of BMPR1a of breast cancer cells suppresses their production of RANKL via p38 pathway and inhibits cancer-induced osteoclastogenesis, which indicates that BMPR1a might be a possible target in breast cancer-induced osteolytic metastasis.

It is well known that the harmonic sum $H_{n}(1)=\sum_{1\leq k\leq n}\frac{1}{k}$is never an integer for $n>1$. Erd\"{o}s and Niven proved in 1946 thatthe multiple harmonic sum$H_{n}(\{1\}^r)=\sum_{1\leq k_{1}

Optical network-on-chip (ONoC) is based on optical interconnects and optical routers (ORs), which have obvious advantages in bandwidth and power consumption. Transmission capacity is a significant performance in ONoC architecture, which has to be fully considered during the design process. Relying on mode-division multiplexing (MDM) technology, the system capacity of optical interconnection is greatly improved compared to the traditional multiplexing technology. With the explosion in MDM technology, the optical router supporting MDM came into being. In this paper, we design a multimode optical router (MDM-OR) model and analyze its indicators. Above all, we propose a novel multimode switching element and design an N-port universal multimode optical router (MDM-OR) model. Secondly, we analyze the insertion loss model of different optical devices and the crosstalk noise model of N-port MDM-OR. On this basis, a multimode router structure of a single-mode five-port optical router is proposed. At the same time, we analyze the transmission loss, crosstalk noise, signal-to-noise radio (OSNR), and bit error rate (BER) of different input–output pairs by inputting the 1550 nm TE0, TE1, and TE2 modes to the router.

Vehicle detection in aerial images is a challenging task. The complexity of the background information and the redundancy of the detection area are the main obstacles that limit the successful operation of vehicle detection based on anchors in very-high-resolution (VHR) remote sensing images. In this paper, an anchor-free target detection method is proposed to solve the problems above. First, a multi-attention feature pyramid network (MA-FPN) was designed to address the influence of noise and background information on vehicle target detection by fusing attention information in the feature pyramid network (FPN) structure. Second, a more precise foveal area (MPFA) is proposed to provide better ground truth for the anchor-free method by determining a more accurate positive sample selection area. The proposed anchor-free model with MA-FPN and MPFA can predict vehicles accurately and quickly in VHR remote sensing images through direct regression and predict the pixels in the feature map. A detailed evaluation based on remote sensing image (RSI) and vehicle detection in aerial imagery (VEDAI) data sets for vehicle detection shows that our detection method performs well, the network is simple, and the detection is fast.

Abstract Background ALX4 is a paired-like homedomain transcription factor mainly expressed in the mesenchymal compartment of variety of developing tissues, but its functions, regulation mechanisms and clinical values in breast cancer remains unclear. Methods The expression of ALX4 in breast cancer cell lines and patients’ tissues were detected by RT-PCR, qPCR and western blot. Furthermore TCGA database was applied to confirm these results. MSP and BSP methods were used to assess the methylation of ALX4 promoter region. In vitro proliferation, metastasis and in vivo nude mice model were used to evaluate the anti-tumor effect of ALX4 on breast cancer cell lines. Luciferase reporter assay, western blot and TCGA database were used to investigate the tumor suppression mechanisms of ALX4. TMA of 142 breast patients was generated to evaluate the clinical significance of ALX4. Results Expression analysis revealed that ALX4 expression is down regulated in breast cancer cell lines and tissues. MSP study showed that the promoter region of ALX4 was hyper-methylated 100% (3/3) in breast cancer cell lines and 69.44% (75/108) in primary breast tumors tissues while 0% (0/8) in normal breast tissues. 5-aza-dc de-methylation treatment restored ALX4 expression in breast cancer cell lines. Functional studies showed that ectopic expression of ALX4 in breast cancer cells inhibited cell proliferation, metastasis in vitro and in vivo. Mechanism study found that ALX4 exerted its anti-tumor function by suppressing the Wnt/β-catenin pathway through promoting the phosphorylation degradation of β-catenin in a GSK3β dependent manner. Clinically multivariate analysis showed that ALX4 expression was an independent favorable prognostic factor in breast cancer patients. Conclusions We reveal for the first time that ALX4 acts as a novel functional tumor suppressor inactivated by DNA methylation and is an independent prognostic factor in breast cancer.

The performance of silicon single-photon avalanche detectors is currently limited by the trade-off between photon detection efficiency and timing jitter. Here, the authors demonstrate how a CMOS-compatible, nanostructured, thin junction structure can make use of tailored light trapping to break this trade-off.

In recent years because of the increasing number and types of scientific payloads on a probe, the constraints between payload and probe and the constraints among payloads have become increasingly complex. The technology of constraint processing has gradually become a focus of research in deep space planning. In this paper, we propose a constrained-programmed planner called DSPlan for deep space planning problems based on table constraints. We first propose a technique for automatically converting the planning domain definition language model used in planning into the form of table constraints. Following the common practice of coding a planning problem as a constraint satisfaction problem with multiple levels, we propose a dynamic constraint set and a corresponding mutex filtering algorithm to express the different combinations of constraints on varying levels that need to be satisfied. This new form of data structure uses explicit domain information to maintain the generalized arc consistency of table constraints. Empirical analyses demonstrate the efficiency of table constraints over the international planning competition problem and classic deep space instances in general arc consistency schema algorithms. Experimental results also prove that DSPlan and table constraints are highly promising general-purpose tools for deep space planning problems compared with other planners.