Abstract
We present Atacama Large Millimeter/submillimeter Array subarcsecond-resolution observations of both continuum and molecular lines at 345 GHz toward the massive star-forming region IRAS ...16351-4722 (hereafter I16351). A total of 12 dust cores were detected based on high-spatial-resolution observations of the continuum. Among them, a high-mass core (11.6
M
⊙
) and a low-mass core (1.7
M
⊙
) show abundant molecular line emissions. 164 molecular transitions from 29 species and 104 molecular transitions from 25 species are identified in the high-mass and low-mass cores, respectively. Complex organic molecules (COMs) such as CH
3
OH, CH
3
OCHO, CH
3
OCH
3
, C
2
H
5
OH, and C
2
H
5
CN are detected in the two cores. Under the assumption of local thermodynamic equilibrium, the rotational temperatures and column densities of the COMs are derived with the XCLASS software. The maximum rotation temperature values in the low-mass core and the high-mass core were found to be approximately 130 K and 198 K, respectively. Additionally, the line widths in the high-mass core are larger than those in the low-mass one. The abundant COM line transitions, high gas temperatures, and smaller line widths indicate the presence of a low-mass line-rich core in the massive star formation region for the first time, while the high-mass line-rich core shows hot core properties. When comparing the molecular abundances of CH
3
OH, CH
3
OCHO, CH
3
OCH
3
, and C
2
H
5
OH of the two cores with other hot cores and hot corinos reported in the literature, we further confirm that both a hot core and a low-mass line-rich core are simultaneously detected in I16351.
In the hepatocellular carcinoma (HCC) microenvironment, chemokine receptors play a critical role in tumorigenesis and metastasis. Our previous studies have found that osteopontin (OPN) is a promoter ...for HCC metastasis. However, the role of chemokine receptors in OPN‐induced HCC metastasis remains unclear. In this study, we demonstrate that OPN is dramatically elevated in HCC tissues with metastasis and that high expression of OPN correlates with poorer overall survival and higher recurrence rate. OPN upregulates chemokine receptor expression, migration, invasion and pulmonary metastasis in HCC. We find that C‐C chemokine receptor type 1 (CCR1) and C‐X‐C chemokine receptor type 6 (CXCR6) are the most upregulated chemokine receptors induced by OPN. CCR1 knockdown results in reduction of migration, invasion and pulmonary metastasis induced by OPN in vitro and in vivo, whereas CXCR6 knockdown does not reverse OPN‐promoted migration and invasion. Moreover, OPN upregulates the expression of CCR1 through activating phosphoinositide 3‐kinase (PI3K)/AKT and hypoxia‐inducible factor 1α (HIF‐1α) in HCC cells. Furthermore, blockade of OPN‐CCR1 axis with CCR1 antagonist significantly restrains the promoting effects of OPN on HCC progression and metastasis. In human HCC tissues, OPN expression shows significantly positive correlation with CCR1 expression, and the patients with high levels of both OPN and CCR1 have the most dismal prognosis. Collectively, our results indicate that the OPN‐CCR1 axis in HCC is important for accelerating tumor metastasis and that CCR1 is a potential therapeutic target for controlling metastasis in HCC patients with high OPN.
In this study, we found that OPN up‐regulated the expression of C‐C chemokine receptor‐1(CCR1) via activating phosphoinositide 3‐kinase (PI3K)/AKT and hypoxia‐inducible factor 1α(HIF‐1α). Moreover, blockade of OPN/CCR1 signaling with CCR1 antagonist significantly restrained the promoting effects of OPN on HCC progression and metastasis. Our work proved that CCR1 may be a potential therapeutic target for controlling metastasis in HCC patients with high OPN.
Although numerous long non-coding RNAs (lncRNAs) have been identified in mammals, many of their biological roles remain to be characterized. Early reports suggest that H19 contributes to ...carcinogenesis, including hepatocellular carcinoma (HCC). Examination of the Oncomine resource showed that most HCC cases express H19 at a level that is comparable with the liver, with a tendency toward lower expression. This is consistent with our previous microarray data and indicates a more complicated role of H19 in HCC that needs to be characterized. In this study, the expression level of H19 was assessed in different regions of HCC patients' liver samples. Loss- and gain-of-function studies on this lncRNA in the HCC cell lines, SMMC7721 and HCCLM3, were used to characterize its effects on gene expression and to assess its effect on HCC metastasis both in vitro and in vivo. In this study, we show that H19 was underexpressed in intratumoral HCC tissues (T), as compared with peritumoral tissues (L). Additionally, low T/L ratio of H19 predicted poor prognosis. H19 suppressed HCC progression metastasis and the expression of markers of epithelial-to-mesenchymal transition. Furthermore, H19 associated with the protein complex hnRNP U/PCAF/RNAPol II, activating miR-200 family by increasing histone acetylation. The results demonstrate that H19 can alter the miR-200 pathway, thus contributing to mesenchymal-to-epithelial transition and to the suppression of tumor metastasis. These data provide an explanation for the hitherto puzzling literature on the relationship between H19 and cancer, and could suggest the development of combination therapies that target H19 and the miR-200 family.
Abstract
Investigating the temperature and density structures of gas in massive protoclusters is crucial for understanding the chemical properties therein. In this study, we present observations of ...the continuum and thioformaldehyde (H
2
CS) lines at 345 GHz of 11 massive protoclusters using the Atacama Large Millimeter/submillimeter Array telescope. High spatial resolution and sensitivity observations have detected 145 continuum cores from the 11 sources. H
2
CS line transitions are observed in 72 out of 145 cores, including line-rich cores, warm cores, and cold cores. The H
2
column densities of the 72 cores are estimated from the continuum emission, which are larger than the density threshold value for star formation, suggesting that H
2
CS can be widely distributed in star-forming cores with different physical environments. The rotation temperature and column density of H
2
CS are derived using the XCLASS software. The results show that the H
2
CS abundances increase as temperature rises and higher gas temperatures are usually associated with higher H
2
CS column densities. The abundances of H
2
CS are positively correlated with its column density, suggesting that the H
2
CS abundances are enhanced from cold cores, warm cores, and line-rich cores in star-forming regions.
Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA ...sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation.
Aims. We aim to reveal the physical properties and chemical composition of the cores in the California molecular cloud (CMC), so as to better understand the initial conditions of star formation. ...Methods. We made a high-resolution column density map (18.2′′) with Herschel data, and extracted a complete sample of the cores in the CMC with the fellwalker algorithm. We performed new single-pointing observations of molecular lines near 90 GHz with the IRAM 30m telescope along the main filament of the CMC. In addition, we also performed a numerical modeling of chemical evolution for the cores under the physical conditions. Results. We extracted 300 cores, of which 33 are protostellar and 267 are starless cores. About 51% (137 of 267) of the starless cores are prestellar cores. Three cores have the potential to evolve into high-mass stars. The prestellar core mass function (CMF) can be well fit by a log-normal form. The high-mass end of the prestellar CMF shows a power-law form with an index α = −0.9 ± 0.1 that is shallower than that of the Galactic field stellar mass function. Combining the mass transformation efficiency (ε) from the prestellar core to the star of 15 ± 1% and the core formation efficiency (CFE) of 5.5%, we suggest an overall star formation efficiency of about 1% in the CMC. In the single-pointing observations with the IRAM 30m telescope, we find that 6 cores show blue-skewed profile, while 4 cores show red-skewed profile. HCO+/HNC and HCO+/N2H+ in protostellar cores are higher than those in prestellar cores; this can be used as chemical clocks. The best-fit chemical age of the cores with line observations is ~5 × 104 yr.
Current biodiversity loss is generally considered to have been caused by anthropogenic disturbance, but it is unclear when anthropogenic activities began to affect biodiversity loss. One hypothesis ...suggests it began with the Industrial Revolution, whereas others propose that anthropogenic disturbance has been associated with biodiversity decline since the early Holocene. To test these hypotheses, we examined the unique vegetation of evergreen broadleaved forests (EBLFs) in East Asia, where humans have affected landscapes since the early Holocene. We adopted a genomic approach to infer the demographic history of a dominant tree (Litsea elongata) of EBLFs. We used Holocene temperature and anthropogenic disturbance factors to calculate the correlation between these variables and the historical effective population size of L. elongata with Spearman statistics and integrated the maximum‐entropy niche model to determine the impact of climate change and anthropogenic disturbance on fluctuation in its effective population size. We identified 9 well‐defined geographic clades for the populations of L. elongata. Based on the estimated historical population sizes of these clades, all the populations contracted, indicating persistent population decline over the last 11,000 years. Demographic history of L. elongata and human population change, change in cropland use, and change in irrigated rice area were significantly negatively correlated, whereas climate change in the Holocene was not correlated with demographic history. Our results support the early human impact hypothesis and provide comprehensive evidence that early anthropogenic disturbance may contribute to the current biodiversity crisis in East Asia.
摘要
当前生物多样性丧失的主因普遍被认为是人类活动的干扰, 但人类活动何时开始导致地球生物多样性的丧失这一重大的科学问题仍不清楚。一些学者的研究认为, 生物多样性的丧失始于工业革命; 另一些研究者则发现, 人类活动所导致的生物多样性下降至少可以追溯到全新世早期。为了检验这两种假说, 本研究立足东亚亚热带地区的特征植被类型, 即亚热带常绿阔叶林(EBLFs), 选取其优势树种樟科木姜子属黄丹木姜子(Litsea elongata)为研究对象, 基于基因组重测序方法研究黄丹木姜子种群在万年尺度下的动态历史。通过生态位模拟, 相关性分析等方法推测全新世气候变化, 人类活动因素(人口增长变化, 耕地面积变化, 灌溉稻作面积变化)与黄丹木姜子有效种群大小变化之间的相关性。研究结果发现, 依据地理分布范围, 黄丹木姜子的种群可划分为九大地理分支, 种群动态历史揭示其大分支在11,000年以来有效种群大小持续下降的历史过程。相关性分析发现, 有效种群大小在11,000年以来的下降与东亚亚热带地区人口增长变化, 耕地面积变化, 灌溉稻作面积变化呈现显著的负相关, 而与全新世期间的气候变化则不呈现相关性。因此，本研究结果支持早全新世人类活动干扰的假说, 并且为东亚地区早期人类活动与当今生物多样性危机的关联机制提供了全新的证据和认识。
Cold stress is an important factor that limits apple production. In this study, we examined the tissue-cultured plantlets of apple rootstocks ‘M9T337’ and ‘60-160’, which are resistant and sensitive ...to cold stress, respectively. The enriched pathways of differentially expressed genes (DEGs) and physiological changes in ‘M9T337’ and ‘60-160’ plantlets were clearly different after cold stress (1°C) treatment for 48 h, suggesting that they have differential responses to cold stress. The differential expression of WRKY transcription factors in the two plantlets showed that MdWRKY40is and MdWRKY48 are potential regulators of cold tolerance. When we overexpressed MdWRKY40is and MdWRKY48 in apple calli, the overexpression of MdWRKY48 had no significant effect on the callus, while MdWRKY40is overexpression promoted anthocyanin accumulation, increased callus cold tolerance, and promoted the expression of anthocyanin structural gene MdDFR and cold-signaling core gene MdCBF2. Yeast one-hybrid screening and electrophoretic mobility shift assays showed that MdWRKY40is could only bind to the MdDFR promoter. Yeast two-hybrid screening and bimolecular fluorescence complementation showed that MdWRKY40is interacts with the CBF2 inhibitor MdMYB15L through the leucine zipper (LZ). When the LZ of MdWRMY40is was knocked out, MdWRKY40is overexpression in the callus did not affect MdCBF2 expression or callus cold tolerance, indicating that MdWRKY40is acts in the cold signaling pathway by interacting with MdMYB15L. In summary, MdWRKY40is can directly bind to the MdDFR promoter in order to promote anthocyanin accumulation, and it can also interact with MdMYB15L to interfere with its inhibitory effect on MdCBF2, indirectly promoting MdCBF2 expression, and thereby improving cold tolerance. These results provide a new perspective for the cold-resistance mechanism of apple rootstocks and a molecular basis for the screening of cold-resistant rootstocks.
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