基于耦合协调度的黄土高原地区NDVI与降水关系的变异诊断

植被是地表生态系统的重要"指示器"，在能量交换、水循环、碳循环、生物地球化学循环和维持中发挥着重要作用，降水是影响植被变化的主要气候因子，研究两者之间的作用关系具有重要的意义和价值。利用Mann-Kendall趋势检验法和Hust指数分析了黄土高原地区归一化植被指数（NDVI）的变化趋势，使用相对发展率（RDR）指数和重心转移模型分析了NDVI变化的时空差异，并构建了基于耦合协调度理论和Pettitt检验方法的NDVI与降水关系的变异诊断方法，识别了黄土高原地区NDVI与降水关系的突变点，探讨了降水对NDVI变化的影响以及造成NDVI与降水关系变化的原因。结果表明：（1）黄土高原地区73.49%面积的NDVI在1998-2017年有呈现显著增加趋势（P<0.05），大部分地区NDVI在未来依旧呈现增加趋势；（2）黄土高原地区丘陵沟壑区与高原沟壑区的NDVI增加幅度大于黄土高原地区整体的增加幅度，而北部风沙区和农灌区以及黄土高原地区边界区域的NDVI增加滞后于区域整体变化；（3） NDVI与降水耦合协调程度逐年增强，两者关系在2006年发生显著突变（P<0.05）；（4） NDVI呈现显著增加区域降水明显高于不显著变化区域（P<0.05），降水对NDVI变化存在一定影响，在丘陵沟壑区、高原沟壑区北部和东部河谷及土石山区北部NDVI和降水存在显著正相关关系（P<0.05），然而黄土高原地区大部分区域的降水并不存在显著变化趋势（P>0.05），因此造成黄土高原地区NDVI与降水关系在2006年发生显著突变的主要原因应该是人类活动（P<0.05）。研究成果有助于进一步理解黄土高原植被变化与降水的相互作用，为黄土高原生态建设和水土流失治理提供一定的科学支撑。     

Bringing Dicynodonts Back to Life: Paleobiology and Anatomy of a New Emydopoid Genus from the Upper Permian of Mozambique

Dicynodontia represent the most diverse tetrapod group during the Late Permian. They survived the Permo-Triassic extinction and are central to understanding Permo-Triassic terrestrial ecosystems. Although extensively studied, several aspects of dicynodont paleobiology such as, neuroanatomy, inner ear morphology and internal cranial anatomy remain obscure. Here we describe a new dicynodont (Therapsida, Anomodontia) from northern Mozambique: Niassodon mfumukasi gen. et sp. nov. The holotype ML1620 was collected from the Late Permian K5 formation, Metangula Graben, Niassa Province northern Mozambique, an almost completely unexplored basin and country for vertebrate paleontology. Synchrotron radiation based micro-computed tomography (SRµCT), combined with a phylogenetic analysis, demonstrates a set of characters shared with Emydopoidea. All individual bones were digitally segmented allowing a 3D visualization of each element. In addition, we reconstructed the osseous labyrinth, endocast, cranial nerves and vasculature. The brain is narrow and the cerebellum is broader than the forebrain, resembling the conservative, “reptilian-grade” morphology of other non-mammalian therapsids, but the enlarged paraflocculi occupy the same relative volume as in birds. The orientation of the horizontal semicircular canals indicates a slightly more dorsally tilted head posture than previously assumed in other dicynodonts. In addition, synchrotron data shows a secondary center of ossification in the femur. Thus ML1620 represents, to our knowledge, the oldest fossil evidence of a secondary center of ossification, pushing back the evolutionary origins of this feature. The fact that the specimen represents a new species indicates that the Late Permian tetrapod fauna of east Africa is still incompletely known.     

E2F Inhibition Synergizes with Paclitaxel in Lung Cancer Cell Lines

The CDK/Rb/E2F pathway is commonly disrupted in lung cancer, and thus, it is predicted that blocking the E2F pathway would have therapeutic potential. To test this hypothesis, we have examined the activity of HLM006474 (a small molecule pan-E2F inhibitor) in lung cancer cell lines as a single agent and in combination with other compounds. HLM006474 reduces the viability of both SCLC and NSCLC lines with a biological IC₅₀ that varies between 15 and 75 µM, but with no significant difference between the groups. Combination of HLM006474 with cisplatin and gemcitabine demonstrate little synergy; however, HLM006474 synergizes with paclitaxel. Surprisingly, we discovered that brief treatment of cells with HLM006474 led to an increase of E2F3 protein levels (due to de-repression of these promoter sites). Since paclitaxel sensitivity has been shown to correlate with E2F3 levels, we hypothesized that HLM006474 synergy with paclitaxel may be mediated by transient induction of E2F3. To test this, H1299 cells were depleted of E2F3a and E2F3b with siRNA and treated with paclitaxel. Assays of proliferation showed that both siRNAs significantly reduced paclitaxel sensitivity, as expected. Taken together, these results suggest that HLM006474 may have efficacy in lung cancer and may be useful in combination with taxanes.     

LncRNA TP73-AS1 enhances the malignant properties of pancreatic ductal adenocarcinoma by increasing MMP14 expression through miRNA -200a sponging

Pancreatic ductal adenocarcinoma (PDAC) is an invasive and aggressive cancer that remains a major threat to human health across the globe. Despite advances in cancer treatments and diagnosis, the prognosis of PDAC patients remains poor. New and more effective PDAC therapies are therefore urgently required. In this study, we identified a novel host factor, namely the LncRNA TP73-AS1, as overexpressed in PDAC tissues compared to adjacent healthy tissue samples. The overexpression of TP-73-AS1 was found to correlate with both PDAC stage and lymph node metastasis. To reveal its role in PDCA, we targeted TP73-AS1 using LnRNA inhibitors in a range of pancreatic cancer (PC) cell lines. We found that the inhibition of TP73-AS1 led to a loss of MMP14 expression in PC cells and significantly inhibited their migratory and invasive capacity. No effects of TP73-AS1 on cell survival or proliferation were observed. Mechanistically, we found that TP73-AS1 suppressed the expression of the known oncogenic miR-200a. Taken together, these data highlight the prognostic potential of TP73-AS1 for PC patients and highlight it as a potential anti-PDAC therapeutic target.     

A Statistical Physics View of Pitch Fluctuations in the Classical Music from Bach to Chopin: Evidence for Scaling

Because classical music has greatly affected our life and culture in its long history, it has attracted extensive attention from researchers to understand laws behind it. Based on statistical physics, here we use a different method to investigate classical music, namely, by analyzing cumulative distribution functions (CDFs) and autocorrelation functions of pitch fluctuations in compositions. We analyze 1,876 compositions of five representative classical music composers across 164 years from Bach, to Mozart, to Beethoven, to Mendelsohn, and to Chopin. We report that the biggest pitch fluctuations of a composer gradually increase as time evolves from Bach time to Mendelsohn/Chopin time. In particular, for the compositions of a composer, the positive and negative tails of a CDF of pitch fluctuations are distributed not only in power laws (with the scale-free property), but also in symmetry (namely, the probability of a treble following a bass and that of a bass following a treble are basically the same for each composer). The power-law exponent decreases as time elapses. Further, we also calculate the autocorrelation function of the pitch fluctuation. The autocorrelation function shows a power-law distribution for each composer. Especially, the power-law exponents vary with the composers, indicating their different levels of long-range correlation of notes. This work not only suggests a way to understand and develop music from a viewpoint of statistical physics, but also enriches the realm of traditional statistical physics by analyzing music.     

Transplantation of Oligodendrocyte Precursor Cells Improves Locomotion Deficits in Rats with Spinal Cord Irradiation Injury

Demyelination contributes to the functional impairment of irradiation injured spinal cord. One potential therapeutic strategy involves replacing the myelin-forming cells. Here, we asked whether transplantation of Olig2⁺-GFP⁺-oligodendrocyte precursor cells (OPCs), which are derived from Olig2-GFP-mouse embryonic stem cells (mESCs), could enhance remyelination and functional recovery after spinal cord irradiation injury. We differentiated Olig2-GFP-mESCs into purified Olig2⁺-GFP⁺-OPCs and transplanted them into the rats’ cervical 4–5 dorsal spinal cord level at 4 months after irradiation injury. Eight weeks after transplantation, the Olig2⁺-GFP⁺-OPCs survived and integrated into the injured spinal cord. Immunofluorescence analysis showed that the grafted Olig2⁺-GFP⁺-OPCs primarily differentiated into adenomatous polyposis coli (APC⁺) oligodendrocytes (54.6±10.5%). The staining with luxol fast blue, hematoxylin & eosin (LFB/H&E) and electron microscopy demonstrated that the engrafted Olig2⁺-GFP⁺-OPCs attenuated the demyelination resulted from the irradiation. More importantly, the recovery of forelimb locomotor function was enhanced in animals receiving grafts of Olig2⁺-GFP⁺-OPCs. We concluded that OPC transplantation is a feasible therapy to repair the irradiated lesions in the central nervous system (CNS).     

Effect of Chronic Administration of Low Dose Rapamycin on Development and Immunity in Young Rats

Mammalian target of rapamycin (mTOR) regulates cell growth, cell differentiation and protein synthesis. Rapamycin, an inhibitor of mTOR, has been widely used as an immunosuppressant and anti-cancer drug. Recently, mTOR inhibitors have also been reported to be a potential anti-epileptic drug, which may be effective when used in young patients with genetic epilepsy. Thus, a suitable dose of rapamycin which can maintain the normal function of mTOR and has fewer side effects ideally should be identified. In the present study, we first detected changes in marker proteins of mTOR signaling pathway during development. Then we determined the dose of rapamycin by treating rats of 2 weeks of age with different doses of rapamycin for 3 days and detected its effect on mTOR pathway. Young rats were then treated with a suitable dose of rapamycin for 4 weeks and the effect of rapamycin on mTOR, development and immunity were investigated. We found that the expression of the marker proteins of mTOR pathway was changed during development in brain hippocampus and neocortex. After 3 days of treanent, 0.03 mg/kg rapamycin had no effect on phospho-S6, whereas 0.1, 0.3, 1.0 and 3.0 mg/kg rapamycin inhibited phospho-S6 in a dose-dependent manner. However, only 1.0 mg/kg and 3.0 mg/kg rapamycin inhibited phospho-S6 after 4 weeks treatment of rapamycin. Parallel to this result, rats treated with 0.1 and 0.3 mg/kg rapamycin had no obvious adverse effects, whereas rats treated with 1.0 and 3.0 mg/kg rapamycin showed significant decreases in body, spleen and thymus weight. Additionally, rats treated with 1.0 and 3.0 mg/kg rapamycin exhibited cognitive impairment and anxiety as evident by maze and open field experiments. Furthermore, the content of IL-1β, IL-2, IFN-γ, TNF-α in serum and cerebral cortex were significantly decreased in 1.0 and 3.0 mg/kg rapamycin-treated rats. The expression of DCX was also significantly decreased in 1.0 and 3.0 mg/kg rapamycin-treated rats. However, rats treated with 1.0 mg/ kg rapamycin exhibited fewer and milder side effects than those treated with 3.0 mg/kg. In summary, all these data suggest that there is not a rapamycin dose that can inhibit mTOR for epilepsy without causing any side effects, but 1 mg /kg may be the optimal dose for young rats for suppressing mTOR with relatively few side effects.