Orbital-scale nonlinear response of East Asian summer monsoon to its potential driving forces in the late Quaternary

We conducted a statistical study to characterize the nonlinear response of the East Asian summer monsoon (EASM) to its potential forcing factors over the last 260 ka on orbital timescales. We find that both variation in solar insolation and global ice volume were responsible for the nonlinear forcing of orbital-scale monsoonal variations, accounting for similar to 80% of the total variance. Specifically, EASM records with dominated precession variance exhibit a more sensitive response to changes in solar insolation during intervals of enhanced monsoon strength, but are less sensitive during intervals of reduced monsoon strength. In the case of global ice volume with 100-ka variance, this difference is not one of sensitivity but rather a difference in baseline conditions, such as the relative areas of land and sea which affected the land-sea thermal gradient. We therefore suggest that EASM records with dominated precession variance recorded the signal of a shift in the location of the Inter-tropical Convergence Zone, and the associated changes in the incidence of torrential rainfall; while for proxies with dominated 100-ka variance, it recorded changes in the land-sea thermal gradient via its effects on non-torrential precipitation

PRMT5 Cooperates with pICln to Function as a Master Epigenetic Activator of DNA Double-Strand Break Repair Genes

DNA double-strand break (DSB) repair is critical for cell survival and genome integrity. Upon recognition of DSBs, repair proteins are transiently upregulated to facilitate repair through homologous recombination (HR) or non-homologous end joining (NHEJ). We present evidence that PRMT5 cooperates with pICln to function as a master epigenetic activator of DNA damage response (DDR) genes involved in HR, NHEJ, and G2 arrest (including RAD51, BRCA1, and BRCA2) to upregulate gene expression upon DNA damage. Contrary to the predominant role of PRMT5 as an epigenetic repressor, our results demonstrate that PRMT5 and pICln can activate gene expression, potentially independent of PRMT5's obligate cofactor MEP50. Targeting PRMT5 or pICln hinders repair of DSBs in multiple cancer cell lines, and both PRMT5 and pICln expression positively correlates with DDR genes across 32 clinical cancer datasets. Thus, targeting PRMT5 or pICln may be explored in combination with radiation or chemotherapy for cancer treatment

Clinical and immunological characteristics of TGM3 in pan-cancer: A potential prognostic biomarker

Background: Recent studies have identified that transglutaminases (TGMs) are involved in a widespread epigenetic modification in tumorigenesis. However, it remains unclear how transglutaminase 3 (TGM3) affects in pan-cancer. The present study aimed to explore the clinical and prognostic function of TGM3 in pan-cancer as well as to explore the relationship of TGM3 expression with clinical stage, survival rate, prognosis condition, immune infiltration and mutation indicators.Methods: The relevant data of tumors were obtained from The Cancer Genome Atlas (TCGA), TARGET, Cancer Cell Line Encyclopedia (CCLE) and Genotype-Tissue Expression (GTEx) databases. According to the Human Protein Atlas (HPA) and TIMER databases, we evaluated the protein expression levels of TGM3 in different organs and tissues as well as their association with immune cell infiltration and immunotherapeutic response in pan-cancers. Expression differences between normal and tumor tissues as well as survival and prognosis situation, clinical data characteristics, tumor mutational burden (TMB), microsatellite instability (MSI), and RNA methylation were also assessed. Oncogenic analyses were also evaluated by GSEA.Results: Compared to normal tissues, some tumor tissues had a lower expression level of TGM3, while other tumor tissues had a high expression level of TGM3. Further studies showed that high TGM3 expression had a certain risk impact on pan-cancer as high TGM3 expression levels were detrimental to the survival of several cancers, except for pancreatic cancer (PAAD). High expression level of TGM3 was also related to higher clinical stages in most cancers. The expression level of TGM3 was significantly negatively correlated with the expression of immune infiltration-related cells, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages and dendritic cells (DCs). Furthermore, in most cancer types, TGM3 was inversely correlated with TMB, MSI, and methylation, suggesting that TGM3 expression can be used to assess potential therapeutic response, especially immune-related targeted therapy. GSEA analysis elucidated the biological and molecular function of TGM3 in various cancer types. Taken together, these bioinformatic analyses identified TGM3 as an important biomarker for clinical tumor prognosis and evaluation of treatment efficacy.Conclusion: We comprehensively analyzed the clinical characteristics, tumor stages, immune infiltration, methylation level, gene mutation, functional enrichment analysis and immunotherapeutic value of TGM3 in pan-cancer, providing implications for the function of TGM3 and its role in clinical treatment

A weighted network model based on the correlation degree between nodes

Many complex networks in practice can be described by weighted network models, and the BBV model is one of the most classical ones. In this paper, by introducing the concept of correlation degree between nodes, a new weighted network model based on the BBV model is proposed. The model takes the both node strength and node correlation into consideration during the network evolution, which better reveals the evolving mechanisms behind various real-world networks. Results from theoretical analysis and numerical simulation have demonstrated the scale-free property and small-world property of the network model, which have been widely observed in many real-world networks. Compared with the BBV model, the added correlation preferential attachment rule in the model leads to a faster network propagation velocity.Location : Shenzhen, ChinaDate : 16-18 December 201

Highly responsive ground state of PbTaSe2_2: structural phase transition and evolution of superconductivity under pressure

Transport and magnetic studies of PbTaSe$_2$ under pressure suggest existence of two superconducting phases with the low temperature phase boundary at $\sim 0.25$ GPa that is defined by a very sharp, first order, phase transition. The first order phase transition line can be followed via pressure dependent resistivity measurements, and is found to be near 0.12 GPa near room temperature. Transmission electron microscopy and x-ray diffraction at elevated temperatures confirm that this first order phase transition is structural and occurs at ambient pressure near $\sim 425$ K. The new, high temperature / high pressure phase has a similar crystal structure and slightly lower unit cell volume relative to the ambient pressure, room temperature structure. Based on first-principles calculations this structure is suggested to be obtained by shifting the Pb atoms from the $1a$ to $1e$ Wyckoff position without changing the positions of Ta and Se atoms. PbTaSe$_2$ has an exceptionally pressure sensitive, structural phase transition with $\Delta T_s/\Delta P \approx - 1700$ K/GPa near 4 K, this first order transition causes an $\sim 1$ K ($\sim 25 \%$) step - like decrease in $T_c$ as pressure is increased through 0.25 GPa

Clay mineralogy indicates a mildly warm and humid living environment for the Miocene hominoid from the Zhaotong Basin, Yunnan, China

Global and regional environmental changes have influenced the evolutionary processes of hominoid primates, particularly during the Miocene. Recently, a new Lufengpithecus cf. lufengensis hominoid fossil with a late Miocene age of ~6.2 Ma was discovered in the Shuitangba (STB) section of the Zhaotong Basin in Yunnan on the southeast margin of the Tibetan Plateau. To understand the relationship between paleoclimate and hominoid evolution, we have studied sedimentary, clay mineralogy and geochemical proxies for the late Miocene STB section (~16 m thick; ca. 6.7–6.0 Ma). Our results show that Lufengpithecus cf. lufengensis lived in a mildly warm and humid climate in a lacustrine or swamp environment. Comparing mid to late Miocene records from hominoid sites in Yunnan, Siwalik in Pakistan, and tropical Africa we find that ecological shifts from forest to grassland in Siwalik are much later than in tropical Africa, consistent with the disappearance of hominoid fossils. However, no significant vegetation changes are found in Yunnan during the late Miocene, which we suggest is the result of uplift of the Tibetan plateau combined with the Asian monsoon geographically and climatically isolating these regions. The resultant warm and humid conditions in southeastern China offered an important refuge for Miocene hominoids

Insolation driven biomagnetic response to the Holocene Warm Period in semi-arid East Asia

The Holocene Warm Period (HWP) provides valuable insights into the climate system and biotic responses to environmental variability and thus serves as an excellent analogue for future global climate changes. Here we document, for the first time, that warm and wet HWP conditions were highly favourable for magnetofossil proliferation in the semi-arid Asian interior. The pronounced increase of magnetofossil concentrations at ~9.8 ka and decrease at ~5.9 ka in Dali Lake coincided respectively with the onset and termination of the HWP, and are respectively linked to increased nutrient supply due to postglacial warming and poor nutrition due to drying at ~6 ka in the Asian interior. The two-stage transition at ~7.7 ka correlates well with increased organic carbon in middle HWP and suggests that improved climate conditions, leading to high quality nutrient influx, fostered magnetofossil proliferation. Our findings represent an excellent lake record in which magnetofossil abundance is, through nutrient availability, controlled by insolation driven climate changes.This research was supported by the NSFC grant 41330104 and the 973 program grant 2012CB821900. J.X. was supported by the 973 program grant 2010CB833400 and the NSFC grant 41130101. J.L. received support from the NSFC grant 41374004. C.D. acknowledges further support from the NSFC grant 40925012 and the CAS Bairen Program

Catestatin Enhances Neuropathic Pain Mediated by P2X4 Receptor of Dorsal Root Ganglia in a Rat Model of Chronic Constriction Injury

Background/Aims: Neuropathic pain (NPP) is the consequence of a number of central nervous system injuries or diseases. Previous studies have shown that NPP is mediated by P2X4 receptors that are expressed on satellite glial cells (SGCs) of dorsal root ganglia (DRG). Catestatin (CST), a neuroendocrine multifunctional peptide, may be involved in the pathogenesis of NPP. Here, we studied the mechanism through which CST affects NPP. Methods: We made rat models of chronic constriction injury (CCI) that simulate neuropathic pain. Rat behavioral changes were estimated by measuring the degree of hyperalgesia as assessed by the mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL). P2X4 mRNA expression was detected by quantitative real-time reverse transcription-polymerase chain reaction. P2X4 protein level and related signal pathways were assessed by western blot. Additionally, double-labeled immunofluorescence was employed to visualize the correspondence between the P2X4 receptor and glial fibrillary acidic protein. An enzyme-linked immunosorbent assay was performed to determine the concentration of CST and inflammatory factors. Results: CST led to lower MWT and TWL and increased P2X4 mRNA and protein expression on the SGCs of model rats. Further, CST upregulated the expression of phosphor-p38 and phosphor-ERK 1/2 on the SGCs of CCI rats. However, the expression level of phosphor-JNK and phosphor-p65 did not obviously change. Conclusion: Taken together, CST might boost NPP by enhancing the sensitivity of P2X4 receptors in the DRG of rats, which would provide us a novel perspective and research direction to explore new therapeutic targets for NPP

Front Cover Picture: Light-Controlled Nanosystems: Light-Controlled Nanosystem with Size-Flexibility Improves Targeted Retention for Tumor Suppression (Adv. Funct. Mater. 27/2021)

In article number 2101262, Gang Chen, Hélder A. Santos, Wenguo Cui, and co-workers construct a light-controlled nanosystem with in situ modulated particle size by near-infrared irradiation with a synergistic effect using photochemotherapy for tumor suppression. The nanosystem at the tumor leads to rapid shedding of polye thylene glycol by near-infrared irradiation and enhanced cellular uptake. The versatile design of this light-controlled nanosystem with in situ size flexibility opens new avenues in cancer therapy.Peer reviewe