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الكرز أثمر على شجر الرمان : رواية
كان الجو جميلا، فبعد هطول الأمطار، تحول لون القمح إلى اللون الأخضر، وسيطرت على الجو رائحة العشب الأخضر. هذه الرائحة حلوة بعض الشيء ومريرة بعض الشيء، دافئة قليلا وباردة قليلا، كم يُفرح هذا الجوّ القلب وينعش الذهن ! في ذلك الحين، كان قلب \"فان خوا\" يشعر بالراحة والطمأنينية. وفي المساء أثناء موعد عقد الاجتماع شعرت أن رؤوس الحيوانات المفترسة التي تعلو جانبي سقف المسرح جميلة المنظر، وضوء القمر أيضاً ساحر للغاية يشبه ثغر فتاة جميلة تضحك. لذا ابتسمت، إلا أن ضحكتها لم تكن ظاهرة على وجهها، بل كانت مختفية داخل قلبها.
The m6A/m5C/m1A Regulated Gene Signature Predicts the Prognosis and Correlates With the Immune Status of Hepatocellular Carcinoma
RNA modification of m6A/m5C/m1A contributes to the occurrence and development of cancer. Consequently, this study aimed to investigate the functions of m6A/m5C/m1A regulated genes in the prognosis and immune microenvironment of hepatocellular carcinoma (HCC). The expression levels of 45 m6A/m5C/m1A regulated genes in HCC tissues were determined. The functional mechanisms and protein–protein interaction network of m6A/m5C/m1A regulated genes were investigated. The Cancer Genome Atlas (TCGA) HCC gene set was categorized based on 45 m6A/m5C/m1A regulated genes, and survival analysis was used to determine the relationship between the overall survival of HCC patients in subgroups. Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to construct the risk model and nomogram for m6A/m5C/m1A regulated genes. The relationships between m6A/m5C/m1A regulated gene subsets and risk model and immune cell infiltration were analyzed using CIBERSORT. m6A/m5C/m1A regulated genes were involved in mRNA and RNA modifications, mRNA and RNA methylation, mRNA and RNA stability, and other processes. There was a statistically significant difference between cluster1 and cluster2 groups of genes regulated by m6A/m5C/m1A. The prognosis of cluster1 patients was significantly better than that of cluster2 patients. There were statistically significant differences between the two cluster groups in terms of fustat status, grade, clinical stage, and T stage of HCC patients. The risk model comprised the overexpression of YBX1, ZC3H13, YTHDF1, TRMT10C, YTHDF2, RRP8, TRMT6, LRPPRC, and IGF2BP3, which contributed to the poor prognosis of HCC patients. The high-risk score was associated with prognosis, fustat status, grade, clinical stage, T stage, and M stage and was an independent risk factor for poor prognosis in HCC patients. High-risk score mechanisms included spliceosome, RNA degradation, and DNA replication, among others, and high-risk was closely related to stromal score, CD4 memory resting T cells, M0 macrophages, M1 macrophages, resting mast cells, CD4 memory activated T cells, and follicular helper T cells. In conclusion, the cluster subgroup and risk model of m6A/m5C/m1A regulated genes were associated with the poor prognosis and immune microenvironment in HCC and are expected to be the new tools for assessing the prognosis of HCC patients.
Journal Article
FINANCIAL BUBBLE IMPLOSION AND REVERSE REGRESSION
Expansion and collapse are two key features of a financial asset bubble. Bubble expansion may be modeled using a mildly explosive process. Bubble implosion may take several different forms depending on the nature of the collapse and therefore requires some flexibility in modeling. This paper first strengthens the theoretical foundation of the real time bubble monitoring strategy proposed in Phillips, Shi and Yu (2015a,b, PSY) by developing analytics and studying the performance characteristics of the testing algorithm under alternative forms of bubble implosion which capture various return paths to market normalcy. Second, we propose a new reverse sample use of the PSY procedure for detecting crises and estimating the date of market recovery. Consistency of the dating estimators is established and the limit theory addresses new complications arising from the alternative forms of bubble implosion and the endogeneity effects present in the reverse regression. A real-time version of the strategy is provided that is suited for practical implementation. Simulations explore the finite sample performance of the strategy for dating market recovery. The use of the PSY strategy for bubble monitoring and the new procedure for crisis detection are illustrated with an application to the Nasdaq stock market.
Journal Article
Ceramic particles reinforced copper matrix composites manufactured by advanced powder metallurgy: preparation, performance, and mechanisms
The progress of advanced powder metallurgy techniques for manufacturing copper matrix composites and their advantages are reviewed. Influence mechanisms of ceramic particles on mechanical and thermophysical properties of composites are analyzed. The content, size, morphology and interfacial bonding of particles directly determine the comprehensive performance of composites. Research limitations and future perspectives of ceramic particles reinforced copper matrix composites are outlined. Copper matrix composites doped with ceramic particles are known to effectively enhance the mechanical properties, thermal expansion behavior and high-temperature stability of copper while maintaining high thermal and electrical conductivity. This greatly expands the applications of copper as a functional material in thermal and conductive components, including electronic packaging materials and heat sinks, brushes, integrated circuit lead frames. So far, endeavors have been focusing on how to choose suitable ceramic components and fully exert strengthening effect of ceramic particles in the copper matrix. This article reviews and analyzes the effects of preparation techniques and the characteristics of ceramic particles, including ceramic particle content, size, morphology and interfacial bonding, on the diathermancy, electrical conductivity and mechanical behavior of copper matrix composites. The corresponding models and influencing mechanisms are also elaborated in depth. This review contributes to a deep understanding of the strengthening mechanisms and microstructural regulation of ceramic particle reinforced copper matrix composites. By more precise design and manipulation of composite microstructure, the comprehensive properties could be further improved to meet the growing demands of copper matrix composites in a wide range of application fields.
Journal Article
Afforestation in China cools local land surface temperature
China has the largest afforested area in the world (∼62 million hectares in 2008), and these forests are carbon sinks. The climatic effect of these new forests depends on how radiant and turbulent energy fluxes over these plantations modify surface temperature. For instance, a lower albedo may cause warming, which negates the climatic benefits of carbon sequestration. Here, we used satellite measurements of land surface temperature (LST) from planted forests and adjacent grasslands or croplands in China to understand how afforestation affects LST. Afforestation is found to decrease daytime LST by about 1.1 ± 0.5 °C (mean ± 1 SD) and to increase nighttime LST by about 0.2 ± 0.5 °C, on average. The observed daytime cooling is a result of increased evapotranspiration. The nighttime warming is found to increase with latitude and decrease with average rainfall. Afforestation in dry regions therefore leads to net warming, as daytime cooling is offset by nighttime warming. Thus, it is necessary to carefully consider where to plant trees to realize potential climatic benefits in future afforestation projects.
Journal Article
The substrate and inhibitor binding mechanism of polyspecific transporter OAT1 revealed by high-resolution cryo-EM
Organic anion transporters (OATs) of the SLC22 family have crucial roles in the transport of organic anions, including metabolites and therapeutic drugs, and in transporter-mediated drug-drug interactions. In the kidneys, OATs facilitate the elimination of metabolic waste products and xenobiotics. However, their transport activities can lead to the accumulation of certain toxic compounds within cells, causing kidney damage. Moreover, OATs are important drug targets, because their inhibition modulates the elimination or retention of substrates linked to diseases. Despite extensive research on OATs, the molecular basis of their substrate and inhibitor binding remains poorly understood. Here we report the cryo-EM structures of rat OAT1 (also known as SLC22A6) and its complexes with
para
-aminohippuric acid and probenecid at 2.1, 2.8 and 2.9 Å resolution, respectively. Our findings reveal a highly conserved substrate binding mechanism for SLC22 transporters, wherein four aromatic residues form a cage to accommodate the polyspecific binding of diverse compounds.
Here the authors report the structures of OAT1, a drug transporter implicated in transporter-mediated drug interactions, unveiling the mechanism of its polyspecific substrate binding.
Journal Article
Simulation of heat transfer in a landfill with layered new and old municipal solid waste
Due to rapid degradation of the newly filled municipal solid waste (MSW), the local temperature of the waste layer increases greatly. The mechanical parameters related to waste degradation and the deformation of high-density polyethylene (HDPE) pipes in the waste body will be affected by the elevated temperature. To predict the temperature distribution in the anaerobic landfill, a one-dimensional heat transfer model is established in this study. This model considers the stratification of the saturated and unsaturated zones, and the layering of new and old waste. Furthermore, a single peak model for heat production is applied as the source term of heat production. The stratification of the unsaturated and saturated zones is considered by distinguishing the difference in heat conductivity and specific heat capacity. The layering of the new and old waste layers is considered by distinguishing the difference in the length of time that waste has been degraded to produce heat. Based on the numerical calculation method, the temperature distribution in a landfill with layered new and old MSW is well simulated. The position where the maximum temperature occurs and the variation in the temperature at the edge of new and old waste are elucidated. The sensitivity analysis shows that the influence of the density on the temperature distribution is more significant. Besides, the stratification of saturated–unsaturated waste should also be considered in landfills.
Journal Article
Effect of Temperature on the Development, Survival, and Fecundity of Heliothis viriplaca (Lepidoptera: Noctuidae)
Heliothis viriplaca (Hüfnagel) (Lepidoptera: Noctuidae) is worldwide an important economic pest of major agricultural crops. The effect of temperature on the biology, in particular the duration of the different developmental stages, of this insect pest was examined.The development, survival, and fecundity of H. viriplaca at five different temperatures (22, 25, 28, 31, and 34°C) were investigated, and experimental population life tables calculated.The results show that the developmental time of larvae, pupae, pre-oviposition, adults, and the entire generation decreases with increasing temperature. Larvae emerged fastest from the eggs at 28°C.The percentage of larvae that reached the seventh instar stage was 32.69, 38.60, 19.67, 3.61, and 20.88% at 22, 25, 28, 31, and 34°C, respectively.The developmental threshold temperature of the eggs, larvae, pupae, pre-oviposition and total pre-oviposition period was 10.53, 12.34, 5.60, 11.47, and 10.01°C, respectively.The effective accumulative temperature was 42.90, 239.68, 309.19, 77.72, and 767.64 degree-days, respectively.The population trend index (I) and the intrinsic rate of increase (r) of H. viriplaca were the highest at 31°C (133.97 and 0.12 d-1, respectively).The results of this study may be useful for predicting the population dynamics of H. viriplaca and thus provides information on this important insect pest that may assist in its management.
Journal Article
Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001)
There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4–11.0) versus 8.0 months (95% CI, 6.6–9.5) (adjusted hazard ratio [HR], 0.70,
P
= 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1–27.3] vs. 15.7 months [13.0–20.2]; adjusted HR, 0.63,
P
= 0.001; ORR, 60.1% vs. 32.0%;
P
< 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.
Journal Article