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Oncogenic stress induces DNA damage repair (DDR) that permits escape from mitotic catastrophe and allows early precursor lesions during the evolution of cancer. SAMHD1, a dNTPase protecting cells from viral infections, has been recently found to participate in DNA damage repair process. However, its role in tumorigenesis remains largely unknown. Here, we show that SAMHD1 is up-regulated in early-stage human carcinoma tissues and cell lines under oxidative stress or genotoxic insults. We further demonstrate that de-ubiquitinating enzyme USP7 interacts with SAMHD1 and de-ubiquitinates it at lysine 421, thus stabilizing SAMHD1 protein expression for further interaction with CtIP for DDR, which promotes tumor cell survival under genotoxic stress. Furthermore, SAMHD1 levels positively correlates with USP7 in various human carcinomas, and is associated with an unfavorable survival outcome in patients who underwent chemotherapy. Moreover, USP7 inhibitor sensitizes tumor cells to chemotherapeutic agents by decreasing SAMHD1 in vitro and in vivo. These findings suggest that de-ubiquitination of SAMHD1 by USP7 promotes DDR to overcome oncogenic stress and affect chemotherapy sensitivity.

Nutrient resorption and stoichiometry ratios are vital indicators to explore nutrient transfer and use efficiency for plants, particularly under the condition of nutrient limitation. However, the changing rules about nutrient resorption and ecological stoichiometry homeostasis are still unclear with the development of plantations. We determined carbon (C), nitrogen (N), and phosphorus (P) concentrations in soil and in fresh and senesced needles along a chronosequence of Pinus massoniana plantations (10, 20, 30, and 36 years old) in Guizhou Province, China. We also calculated the N and P resorption efficiency (NRE and PRE, respectively) and the homeostasis coefficient. The results showed that fresh and senesced needles’ C and N concentrations maintained an increasing trend, whereas their P concentrations decreased initially and subsequently increased as the plantations’ ages increased. Fresh needles’ N:P ratios indicated that N limitation existed before 20 years old, while P limitation appeared in the 30-year-old plantations. The NRE and PRE showed patterns of increasing initially and decreasing subsequently along the chronosequence of P. massoniana plantations, which was coupled with weak stoichiometric homeostasis to reduce nutrient deficiency. Therefore, the appropriate nutrient management measurements should be induced to promote tree growth and the sustainable development of P. massoniana plantations.

Reactive oxygen species (ROS) are generally small, short-lived and highly reactive molecules, initially thought to be a pathological role in the cell. A growing amount of evidence in recent years argues for ROS functioning as a signaling intermediate to facilitate cellular adaptation in response to pathophysiological stress through the regulation of autophagy. Autophagy is an essential cellular process that plays a crucial role in recycling cellular components and damaged organelles to eliminate sources of ROS in response to various stress conditions. A large number of studies have shown that DNA damage response (DDR) transducer ataxia-telangiectasia mutated (ATM) protein can also be activated by ROS, and its downstream signaling pathway is involved in autophagy regulation. This review aims at providing novel insight into the regulatory mechanism of ATM activated by ROS and its molecular basis for inducing autophagy, and revealing a new function that ATM can not only maintain genome homeostasis in the nucleus, but also as a ROS sensor trigger autophagy to maintain cellular homeostasis in the cytoplasm.

Progerin, a product of LMNA mutation, leads to multiple nuclear abnormalities in patients with Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging disorder. Progerin also accumulates during physiological aging. Here, we demonstrate that impaired insulin-like growth factor 1 receptor (IGF-1R)/Akt signaling pathway results in severe growth retardation and premature aging in Zmpste24 −/− mice, a mouse model of progeria. Mechanistically, progerin mislocalizes outside of the nucleus, interacts with the IGF-1R, and down-regulates its expression, leading to inhibited mitochondrial respiration, retarded cell growth, and accelerated cellular senescence. Pharmacological treatment with the PTEN (phosphatase and tensin homolog deleted on chromosome 10) inhibitor bpV (HOpic) increases Akt activity and improves multiple abnormalities in Zmpste24-deficient mice. These findings provide previously unidentified insights into the role of progerin in regulating the IGF-1R/Akt signaling in HGPS and might be useful for treating LMNA -associated progeroid disorders.

Five Larix species (L. griffithii, L. speciose, L. himalaica, L. kongboensis, and L. potaninii var. australis), have survived on the Qinghai-Tibet Plateau (QTP) under specific climate conditions for decades. The lack of genomic information seriously hinders research on the evolution, conservation and ecology of these Larix resources. In this study, complete chloroplast (cp) genomes of the 5 species were assembled and compared based on next generation sequencing technology combined with polymerase chain reaction validation. The results show that the 5 cp genomes are relatively conservative in size, gene content and arrangement, and border variation. Phylogenetic analysis showed that the species are closely related as well as to seven other species of the same genus. In addition, the 5 cp genomes contained few simple sequence repeats and relatively low nucleotide variability; thus, 12 candidate polymorphic cp DNA markers will be helpful for further research on relevant population genetics. These results will provide valuable genetic information for the conservation, evolution and ecology of these species and their relatives.

The sirtuins family is well known by its unique nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase function. The most-investigated member of the family, Sirtuin 1 (SIRT1), accounts for deacetylating a broad range of transcription factors and coregulators, such as p53, the Forkhead box O (FOXO), and so on. It serves as a pivotal regulator in various intracellular biological processes, including energy metabolism, DNA damage response, genome stability maintenance and tumorigenesis. Although the most attention has been focused on its intracellular functions, the regulatory effect on extracellular microenvironment remodeling of SIRT1 has been recognized by researchers recently. SIRT1 can regulate cell secretion process and participate in glucose metabolism, neuroendocrine function, inflammation and tumorigenesis. Here, we review the advances in the understanding of SIRT1 on remodeling the extracellular microenvironment, which may provide new ideas for pathogenesis investigation and guidance for clinical treatment.

Four evergreen broadleaf Rhododendron spp. (Rhododendrons), namely, Rhododendron aganniphum, R. nyingchiense, R. wardii, and R. triflorum, occur in harsh subalpine habitats in the southwest Qinghai-Tibet Plateau (QTP), China. Considering that the four Rhododendrons cannot escape their unique environment, they must evolve a set of adaptations to survive, but the information is lacking. To uncover their physiological adaptation characteristics, in the present study, we monitored their physiological characteristics by determination of their seasonal variation in antioxidant enzyme activity, osmotic adjustment substrates, and carbohydrate contents, and their pigment content and photosynthetic efficiency. The results showed that superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) activities and proline content of four Rhododendrons had a significant difference in autumn and were insignificant in summer. Specifically, R. aganniphum had the maximum protective enzyme activity and proline content in winter as well as chl a, b, and car contents. The values of maximal quantum yield (Fv/Fm), photochemical efficiency (ΦPSII), and non-photochemical quenching (NPQ) of four Rhododendrons were significantly higher in summer than in other seasons. The lower qP indicated the four Rhododendrons were susceptible to photoinhibition. Overall, the four Rhododendrons had similar physical characteristics in subalpine habitats. The parameters of the maximum quantum yield of photosystem II (PSII), the actual quantum yield of PSII, the non-photochemical chlorophyll fluorescence quenching, and chlorophyll a content increased in summer. Meanwhile, the protective enzyme activity and total soluble sugar content, proline content, and carotenoid content increased in spring, autumn, and winter. These results suggested that the four Rhododendrons can adapt to subalpine habitats by heat dissipation to avoid the damage of excessive radiation during the warm season while scavenging reactive oxygen and increasing the intracellular fluid concentration to avoid damage caused by chilling temperatures during the cold seasons. These findings would provide a reference for the conservation and application of these valuable ornamental evergreen broadleaf Rhododendrons, and enrich theory of plant eco-physiology in the high altitudes of the QTP.

DNA damage signals transducer RING finger protein 8 (RNF8) is involved in maintaining genomic stability by facilitating the repair of DNA double-strand breaks (DSB) via ubiquitin signaling. By analyzing the TCGA database and colon cancer tissue microarrays, we found that the expression level of RNF8 was positively correlated with that of c-Myc in colon cancer, which were closely associated with poor survival of colon cancer patients. Furthermore, overexpressing and knocking down RNF8 increased and decreased the expression of c-Myc in colon cancer cells, respectively. In addition, RNF8 interacted with β-catenin and facilitated its nuclear translocation by conjugating K63 polyubiquitination on it. These observations suggested a de novo role of RNF8 in promoting the progression of colon cancer by inducing β-catenin-mediated c-Myc expression.

Septin4 is a tumor suppressor protein that promotes cell programmed death in various cell types through specifically antagonizing XIAP (X linked inhibitor of apoptosis), little is known its other novel binding partner and role in colorectal cancer. In this study, we found that Septin4 significantly expressed lower in human colon cancer when compared to peri-tumor benign cells, and its low expression was significantly associated with worse prognostic outcomes. Furthermore, Septin4 participated in DOX-induced colon cancer cell death in vitro. Septin4-overexpressing colon cancer cells displayed augmented apoptotic cell death and ROS production. Additionally, Septin4-knockdown cells revealed a resistance of DOX-induced cell death and reduced ROS production. Importantly, we first identified that BAX is a novel Septin4 binding partner and the interaction is enhanced under DOX treatment. Finally, Septin4-knockdown promoted colon cells growth in vivo. These observations suggest that Septin4 as an essential molecule contribute to the occurrence and development of human colon cancer and provide new technical approaches for targeted treatment of this disease.

Oncogenic stress induces DNA damage response (DDR) that guards against genetic instability during the evolution of cancer. SAMHD1, a dNTPase protecting cells from viral infections, has been recently found to participate in DNA damage repair process. However, its role in tumorigenesis remains largely unknown. Here, we show that SAMHD1 is up-regulated in early-stage human carcinoma tissues and cell lines under oxidative stress or genotoxic insults. We further demonstrate that de-ubiquitinating enzyme USP7 interacts with SAMHD1 and de-ubiquitinates it at lysine 421, thus stabilizing SAMHD1 protein expression, and promotes tumor cell survival under genotoxic stress. Furthermore, SAMHD1 levels positively correlates with USP7 in various human carcinomas, and is associated with an unfavorable survival outcome in patients who underwent chemotherapy. Moreover, USP7 inhibitor sensitizes tumor cells to chemotherapeutic agents by decreasing SAMHD1 in vitro and in vivo. These findings suggest that targeting USP7 may help overcome chemoresistance, thus necessitating further investigation in the pursuit of precision medicine.

Both the stress-response protein, SIRT1, and the cell cycle checkpoint kinase, CHK2, play critical roles in aging and cancer via the modulation of cellular homeostasis and the maintenance of genomic integrity. However, the underlying mechanism linking the two pathways remains elusive. Here, we show that SIRT1 functions as a modifier of CHK2 in cell cycle control. Specifically, SIRT1 interacts with CHK2 and deacetylates it at lysine 520 residue, which suppresses CHK2 phosphorylation, dimerization, and thus activation. SIRT1 depletion induces CHK2 hyperactivation-mediated cell cycle arrest and subsequent cell death. In vivo, genetic deletion of Chk2 rescues the neonatal lethality of Sirt1−/− mice, consistent with the role of SIRT1 in preventing CHK2 hyperactivation. Together, these results suggest that CHK2 mediates the function of SIRT1 in cell cycle progression, and may provide new insights into modulating cellular homeostasis and maintaining genomic integrity in the prevention of aging and cancer.

Proliferative vitreoretinopathy (PVR) is the most serious fibrous complication that causes vision loss after intraocular surgery, and there is currently no effective treatment in clinical. Autophagy is an important cell biological mechanism in maintaining the homeostasis of tissues and cells, resisting the process of EMT. However, it is still unclear whether autophagy could resist intraocular fibrosis and prevent PVR progression. In this study, we investigated the expression of mesenchymal biomarkers in autophagy deficiency cells and found these proteins were increased. The mesenchymal protein transcription factor Twist can bind to autophagy related protein p62 and promote the degradation of Twist, which reduced the expression of mesenchymal markers. By constructing an EMT model of retinal pigment epithelial (RPE) cells in vitro, we found that autophagy was activated in the EMT process of RPE cells. Moreover, in autophagy deficient RPE cell line via knockdown autophagy related protein 7 (Atg7), the expression of epithelial marker claudin-1 was suppressed and the mesenchymal markers were increased, accompanied by an increase in cell migration and contractility. Importantly, RPE epithelial properties can be maintained by promoting autophagy and effectively reversing TFG-β2-induced RPE fibrosis. These observations reveal that autophagy may be an effective way to treat PVR.

Aging is a primary risk factor for neurodegenerative diseases, such as Alzheimer's disease (AD). SIRT2, an NAD

The lamellar body (LB), a concentric structure loaded with surfactant proteins and phospholipids, is an organelle specific to type 2 alveolar epithelial cells (AT2). However, the origin of LBs has not been fully elucidated. We have previously reported that autophagy regulates Weibel-Palade bodies (WPBs) formation, and here we demonstrated that autophagy is involved in LB maturation, another lysosome-related organelle. We found that during development, LBs were transformed from autophagic vacuoles containing cytoplasmic contents such as glycogen. Fusion between LBs and autophagosomes was observed in wild-type neonate mice. Moreover, the markers of autophagic activity, microtubule-associated protein 1 light chain 3B (LC3B), largely co-localized on the limiting membrane of the LB. Both

Male sterility caused by stamen petalody is a key factor for a low fruit set rate and a low yield of Camellia oleifera but can serve as a useful genetic tool because it eliminates the need for artificial emasculation. However, its molecular regulation mechanism still remains unclear. In this study, transcriptome was sequenced and analyzed on two types of bud materials, stamen petalody mutants and normal materials, at six stages of stamen development based on integrated single-molecule real-time (SMRT) technology with unique molecular identifiers (UMI) and RNA-seq technology to identify the hub genes responsible for stamen petalody in C. oleifera. The results show that a large number of alternative splicing events were identified in the transcriptome. A co-expression network analysis of MADSs and all the differentially expressed genes between the mutant stamens and the normal materials showed that four MADS transcription factor genes, CoSEP3.1, CoAGL6, CoSEP3.2, and CoAP3, were predicted to be the hub genes responsible for stamen petalody. Among these four, the expression patterns of CoAGL6 and CoSEP3.2 were consistently high in the mutant samples, but relatively low in the normal samples at six stages, while the patterns of CoSEP3.1 and CoAP3 were initially low in mutants and then were upregulated during development but remained relatively high in the normal materials. Furthermore, the genes with high connectivity to the hub genes showed significantly different expression patterns between the mutant stamens and the normal materials at different stages. qRT-PCR results showed a similar expression pattern of the hub genes in the RNA-seq. These results lay a solid foundation for the directive breeding of C. oleifera varieties and provide references for the genetic breeding of ornamental Camellia varieties.

Knowledge of altitudinal patterns in soil C, N and P distribution is important for understanding biogeochemical processes in mountainous forests, yet the influence of slope aspects on soil stoichiometry has been largely neglected in previous studies. In this paper, a total number of 150 topsoil samples at four altitudes (3700, 3900, 4100, 4380 m a.s.l.) on sunny and shady slopes of Sygera mountains in the Southeastern Tibet were collected. Soil C, N and P contents, and pH, were measured. Soil temperature, moisture and richness of plant species were investigated at each sampling site. The results showed that: 1) in sunny slope, soil C, N and P concentrations increased with the increase in altitude, whereas soil C:N, C:P, and N:P decreased along the altitudinal gradient on s. Soil moisture was the main regulator of soil nutrition and stoichiometric ratios. 2) In shady slope, soil C and N contents had no significant difference along the altitudinal gradient except the higher values at low altitude, whereas soil P increased first and then decreased. Soil C:N increased with the increase in altitude, whereas C:P and N:P decreased first and then increased. Soil temperature and species richness were the main factors influencing soil nutrition and stoichiometric ratios. 3) Decoupling of soil C:N:P stoichiometry was observed in shady slope owing to changes in soil pH and temperature. 4) The rich contents of soil C and P were observed at two slopes along the altitudinal gradient, and high capacity of N supply existed at the topsoil in shady slope. These results suggested that slope aspect plays an important role in shaping the altitudinal pattern of soil C:N:P stoichiometry in mountainous forests.

Camellia oleifera (Abel) is an economic tree species and one of the four largest oil plants in the world. The leaf and twig responses and plasticity indices of C. oleifera were investigated under four light regimes in Pinus massoniana understory plantations, namely, 100% light intensity (CK), 75% of CK (HL), 50% of CK (ML), and 30% of CK (LL). The morphological characteristics, biomass allocation, and physiological characteristics of C. oleifera leaves and twigs under different light regimes, as well as their plasticity indexes, were comprehensively evaluated. The results showed that leaf area, and specific leaf area, leaf total carbon, total nitrogen, total phosphorus and chlorophyll contents, and photosynthesis increased, which indicates that plants have the strongest adaptability under HL. No fruit appeared in twigs under LL and ML. The plastic morphological traits were greater than the biomass allocation and physiological traits. The plasticity of palisade/sponge tissue thickness and lower epidermis thickness were the lowest. In conclusion, C. oleifera have differences in sensitivity and regulation mechanism according to their differences in leaf morphological characteristics, biomass allocation physiological indicators, and response to light regimes. C. oleifera plants showed obvious phenotypic inhibition under CK, while they can adjust their strategies for using light energy to maintain their own growth and development under HL. The wide range of light adaptation and strong plasticity of C. oleifera may be two important reasons for its existence in heterogeneous habitats, but it needs at least 75% light regimes to complete its normal growth development and fruit setting. The study provides insights into the optimum light regimes for the improvement of the quality and efficiency of C. oleifera in P. massoniana understory plantations.

Fungi play key roles in forest ecosystems and help to shape the forest’s diverse functions. However, little is known about the diversity of phyllospheric fungi or their possible relationships with fungal communities residing in different micro-environments of Pinus massoniana forests. We investigated seven different sample types: mature needles (NM), dead needles (ND), needles falling as litter (L), fermenting needles (F), humus (H), top soil (0–20 cm) (TS), and secondary soil (20–40 cm) (SS). These seven fungal communities were examined and compared with ITS amplicons using a high-throughput sequencing technique. A total of 1213 fungal operational taxonomic units (OTUs) were obtained at a 97% sequence similarity level. Distinct fungal communities were associated with different sample types. A greater number of OTUs were present in both NM and F samples than those shared by both NM and TS samples, indicating that phyllospheric fungi may play crucial roles in litter decomposition. Sixty OTUs (the core microbiome) were found in all sample types, and they may probably play different ecological roles in different sample types. These findings extend our knowledge of the fungal diversity of the phyllosphere and its possible interactions with fungal communities found in distinct forest micro-habitats.

SIRT2-mediated deacetylation of SMC1A promotes its phosphorylation and overcomes the oncogenic stress for tumor cell survival., Improper distribution of chromosomes during mitosis can contribute to malignant transformation. Higher eukaryotes have evolved a mitotic catastrophe mechanism for eliminating mitosis-incompetent cells; however, the signaling cascade and its epigenetic regulation are poorly understood. Our analyses of human cancerous tissue revealed that the NAD-dependent deacetylase SIRT2 is up-regulated in early-stage carcinomas of various organs. Mass spectrometry analysis revealed that SIRT2 interacts with and deacetylates the structural maintenance of chromosomes protein 1 (SMC1A), which then promotes SMC1A phosphorylation to properly drive mitosis. We have further demonstrated that inhibition of SIRT2 activity or continuously increasing SMC1A-K579 acetylation causes abnormal chromosome segregation, which, in turn, induces mitotic catastrophe in cancer cells and enhances their vulnerability to chemotherapeutic agents. These findings suggest that regulation of the SIRT2-SMC1A axis through deacetylation-phosphorylation permits escape from mitotic catastrophe, thus allowing early precursor lesions to overcome oncogenic stress.

Background Peritoneal metastasis (PM) is an important pathological process in the progression of gastric cancer (GC). The metastatic potential of tumor and stromal cells is governed by hypoxia, which is a key molecular feature of the tumor microenvironment. Mesothelial cells also participate in this complex and dynamic process. However, the molecular mechanisms underlying the hypoxia-driven mesothelial-tumor interactions that promote peritoneal metastasis of GC remain unclear. Methods We determined the hypoxic microenvironment in PM of nude mice by immunohistochemical analysis and screened VEGFA by human growth factor array kit. The crosstalk mediated by VEGFA between peritoneal mesothelial cells (PMCs) and GC cells was determined in GC cells incubated with conditioned medium prepared from hypoxia-treated PMCs. The association between VEGFR1 and integrin α5 and fibronectin in GC cells was enriched using Gene Set Enrichment Analysis and KEGG pathway enrichment analysis. In vitro and xenograft mouse models were used to evaluate the impact of VEGFA/VEGFR1 on gastric cancer peritoneal metastasis. Confocal microscopy and immunoprecipitation were performed to determine the effect of hypoxia-induced autophagy. Results Here we report that in the PMCs of the hypoxic microenvironment, SIRT1 is degraded via the autophagic lysosomal pathway, leading to increased acetylation of HIF-1α and secretion of VEGFA. Under hypoxic conditions, VEGFA derived from PMCs acts on VEGFR1 of GC cells, resulting in p-ERK/p-JNK pathway activation, increased integrin α5 and fibronectin expression, and promotion of PM. Conclusions Our findings have elucidated the mechanisms by which PMCs promote PM in GC in hypoxic environments. This study also provides a theoretical basis for considering autophagic pathways or VEGFA as potential therapeutic targets to treat PM in GC.

Background Rhododendron delavayi Franch. var. delavayi is a wild ornamental plant species in Guizhou Province, China. The lack of its plastid genome information seriously hinders the further application and conservation of the valuable resource. Methods The complete plastid genome of R. delavayi was assembled from long sequence reads. The genome was then characterized, and compared with those of other photosynthetic Ericaceae species. Results The plastid genome of R. delavayi has a typical quadripartite structure, and a length of 202,169 bp. It contains a large number of repeat sequences and shows preference for codon usage. The comparative analysis revealed the irregular recombination of gene sets, including rearrangement and inversion, in the large single copy region. The extreme expansion of the inverted repeat region shortened the small single copy, and expanded the full length of the genome. In addition, consistent with traditional taxonomy, R. delavayi with nine other species of the same family were clustered into Ericaceae based on the homologous protein-coding sequences of the plastid genomes. Thus, the long-read assembly of the plastid genome of R. delavayi would provide basic information for the further study of the evolution, genetic diversity, and conservation of R. delavayi and its relatives.

The homeostatic link between oxidative stress and autophagy plays an important role in cellular responses to a wide variety of physiological and pathological conditions. However, the regulatory pathway and outcomes remain incompletely understood. Here, we show that reactive oxygen species (ROS) function as signaling molecules that regulate autophagy through ataxia‐telangiectasia mutated (ATM) and cell cycle checkpoint kinase 2 (CHK2), a DNA damage response (DDR) pathway activated during metabolic and hypoxic stress. We report that CHK2 binds to and phosphorylates Beclin 1 at Ser90/Ser93, thereby impairing Beclin 1‐Bcl‐2 autophagy‐regulatory complex formation in a ROS‐dependent fashion. We further demonstrate that CHK2‐mediated autophagy has an unexpected role in reducing ROS levels via the removal of damaged mitochondria, which is required for cell survival under stress conditions. Finally, CHK2(−/−) mice display aggravated infarct phenotypes and reduced Beclin 1 p‐Ser90/Ser93 in a cerebral stroke model, suggesting an in vivo role of CHK2‐induced autophagy in cell survival. Taken together, these results indicate that the ROS‐ATM‐CHK2‐Beclin 1‐autophagy axis serves as a physiological adaptation pathway that protects cells exposed to pathological conditions from stress‐induced tissue damage.

Additional file 3. Supplementary Fig. S2. VEGFR1 is activated with VEGFA treatment and mediates GC cell adhesion and migration. A. Immunoblotting of p-VEGFR1 in GC cells in response to 100 ng/mL VEGFA at the indicated time points. Cells were treated with VEGFA, synchronously with Bevacizumab (100 μg/ml) for 24 h. p-VEGFR1 was detected by immunoblotting. B. Immunoblotting of VEGFR1 in the indicated cells in response to sgRNA-VEGFR1/sgRNA-NC. C. SGC-7901 cells were exposed to CM from hypoxic PMCs or exogenous VEGFA, synchronously with knockout of VEGFR1. Representative photographs of adherent and migratory cells are shown. Scale bars represent 100 μm. Bars represent SD of the mean. *P < 0.05. **P < 0.01. ***P < 0.001.

Sophora moorcroftiana (Benth.) Baker is an endemic woody species distributed in the Qinghai–Tibet Plateau (QTP), a part of the world characterized by high altitude and cold weather. In this study, the genetic diversity of S. moorcroftiana was evaluated based on 300 representative samples of 15 populations using 20 polymorphic SSR markers, and its potential distribution was predicted according to 19 bioclimatic factors using MaxEnt modeling. Results showed the population genetic diversity of S. moorcroftiana was generally not high (around 0.5), and the range of variation was small (0.437–0.539). Altitude, rather than other environmental factors, was the key factor affecting the present genetic diversity. Moreover, due to climate change in the QTP, the suitable area is increasing and will continue to increase by 48.35%, 84.44%, 101.98%, and 107.30% in the four future periods of 2030s, 2050s, 2070s, and 2090s, respectively, compared to the present, which is beneficial for S. moorcroftiana. These results will provide a theoretical basis for the development of germplasm conservation strategies for S. moorcroftiana and enrich information on the impacts of climate change on plants in the QTP.

The two tree peony species, namely, Paeonia ludlowii (Stern & G. Taylor) D. Y. Hong and P. delavayi Franch, belongs to the section Moutan Paeonia (Paeoniaceae). They are the only sources of yellow pigment in tree peony cultivar breeding. P. ludlowii has been listed as “critically endangered”, whereas P. delavayi has been listed as “near threatened” species according to the China Species Red List. The complete chloroplast genome sizes of P. ludlowii and P. delavayi are 152,687 and 154,405 bp respectively. Both contain a 17,056 bp long small single copy region (SSC). The large single copy region (LSC) in P. ludlowii is 84,613 bp, whereas the inverted repeat regions (IRs) are 25,644 bp. In addition, LSC in P. delavayi is 86,142 bp, whereas the IRs is 25,650 bp. The genomes of the two species encode the same set of 134 genes, including 86 protein-coding genes, 8 ribosomal RNA genes and 40 transfer RNA genes. Phylogenetic analysis revealed that all five Paeonia species clustered together, and P. ludlowii and P. delavayi are most closely related to each other. These newly characterized chloroplast genomes will provide essential data for the further conservation of P. ludlowii and P. delavayi.

// Xiaochen Xie 1 , Xiaoguang Shi 1 , Haixia Guan 1 , Qiqiang Guo 2 , Chenling Fan 1 , Wenwu Dong 3 , Guiling Wang 4 , Feng Li 4 , Zhongyan Shan 1 , Liu Cao 2 , Weiping Teng 1 1 Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, P.R. China 2 Key Laboratory of Medical Cell Biology, College of Translational Medicine, China Medical University, Shenyang, P.R. China 3 Department of Thyroid Surgery, The First Affiliated Hospital of China Medical University, Shenyang, P.R. China 4 Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, P.R. China Correspondence to: Weiping Teng, email: twp@vip.163.com Keywords: p21-activated kinase 4, thyroid-stimulating hormone, PKA Cα, papillary thyroid cancer, cell proliferation Received: April 21, 2016 Accepted: November 23, 2016 Published: February 04, 2017 ABSTRACT Papillary thyroid cancer is a common endocrine malignancy. Although p21-activated kinase 4 (PAK4) is involved in the development of different types of tumor, its function has not been investigated in papillary thyroid cancer. Here, we identified a role for PAK4 in papillary thyroid cancer progression. Levels of PAK4 and PAK4 phosphorylated at serine 474 correlated significantly with tumor size and TNM stage. Furthermore, stable knockdown of PAK4 retarded cellular proliferation, migration, and invasion. Moreover, thyroid stimulating hormone-induced cellular proliferation in papillary thyroid cancer was found to be dependent on TSHR/cAMP/PKA/PAK4 signaling, with levels of phosphorylated PAK4 correlating positively with serum thyroid stimulating hormone and PKA Cα levels in patients with papillary thyroid cancer. These findings revealed a novel function of PAK4 in thyroid stimulating hormone-induced papillary thyroid cancer progression and suggest that PAK4 may become a promising diagnostic and therapeutic target for this disease.

Hutchinson-Gilford progeria syndrome (HGPS) arises when a truncated form of farnesylated prelamin A accumulates at the nuclear envelope, leading to misshapen nuclei. Previous studies of adult Zmpste24-deficient mice, a mouse model of progeria, have reported a metabolic response involving inhibition of the mTOR (mammalian target of rapamycin) kinase and activation of autophagy. However, exactly how mTOR or autophagy is involved in progeria remains unclear. Here, we investigate this question by crossing Zmpste24+/- mice with mice hypomorphic in mTOR (mTOR△/+ ), or mice heterozygous in autophagy-related gene 7 (Atg7+/- ). We find that accumulation of prelamin A induces premature aging through mTOR overactivation and impaired autophagy in newborn Zmpste24-/- mice. Zmpste24-/- mice with genetically reduced mTOR activity, but not heterozygosity in Atg7, show extended lifespan. Moreover, mTOR inhibition partially restores autophagy and S6K1 activity. We also show that progerin interacts with the Akt phosphatase to promote full activation of the Akt/mTOR signaling pathway. Finally, although we find that genetic reduction of mTOR postpones premature aging in Zmpste24 KO mice, frequent embryonic lethality occurs. Together, our findings show that over-activated mTOR contributes to premature aging in Zmpste24-/- mice, and suggest a potential strategy in treating HGPS patients with mTOR inhibitors.

Background Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer with high malignancy and bad prognosis, consisted of lung adenocarcinomas (LUAD) and lung squamous cell carcinomas (LUSC) chiefly. Multiple studies have indicated that competing endogenous RNA (ceRNA) network centered long noncoding RNAs (lncRNAs) can regulate gene expression and the progression of various cancers. However, the research about lncRNAs-mediated ceRNA network in LUAD is still lacking. Methods In this study, we analyzed the RNA-seq database from The Cancer Genome Atlas (TCGA) and obtained dysregulated lncRNAs in NSCLC, then further identified survival associated lncRNAs through Kaplan–Meier analysis. Quantitative real time PCR (qRT-PCR) was performed to confirm their expression in LUAD tissues and cell lines. The ceRNA networks were constructed based on DIANA-TarBase and TargetScan databases and visualized with OmicShare tools. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to investigate the potential function of ceRNA networks. Results In total, 1,437 and 1,699 lncRNAs were found to be up-regulated in LUAD and LUSC respectively with 895 lncRNAs overlapping (|log2FC| > 3, adjusted P value 3, adjusted P value < 0.02). We selected 3 lncRNAs (CASC8, LINC01842 and VPS9D1-AS1) out of these 18 lncRNAs and confirmed their overexpression in lung cancer tissues and cells. CeRNA networks were further constructed centered CASC8, LINC01842 and VPS9D1-AS1 with 3 miRNAs and 100 mRNAs included respectively. Conclusion Through comprehensively analyses of TCGA, our study identified specific lncRNAs as candidate diagnostic and prognostic biomarkers for LUAD. The novel ceRNA network we created provided more insights into the regulatory mechanisms underlying LUAD.

Sterile alpha motif and histidine/aspartic acid domain‑containing protein 1 (SAMHD1), the only deoxynucleotide triphosphate (dNTP) hydrolase in eukaryotes, plays a crucial role in regulating the dynamic balance and ratio of cellular dNTP pools. Furthermore, SAMHD1 has been reported to be involved in the pathological process of several diseases. Homozygous SAMHD1 mutations have been identified in immune system disorders, such as autoimmune disease Aicardi‑Goutieres syndrome (AGS), whose primary pathogenesis is associated with the abnormal accumulation and disproportion of dNTPs. SAMHD1 is also considered to be an intrinsic virus‑restriction factor by suppressing the viral infection process, including reverse transcription, replication, packaging and transmission. In addition, SAMHD1 has been shown to promote genome integrity during homologous recombination following DNA damage, thus being considered a promising candidate for oncotherapy applications. The present review summarizes the molecular mechanisms of SAMHD1 regarding the regulation of dNTP homeostasis and DNA damage response. Additionally, its potential effects on tumorigenesis and oncotherapy are reported.

Cupressus gigantea and C. torulosa are ecologically and economically important endemic species of the conifer family Cupressaceae on the Qinghai-Tibetan plateau. C. gigantea was previously classified as a subspecies of C. torulosa because of their similar morphological characteristics and close distribution. In this study, 401 individuals were sampled from 16 populations of the two Cupressus species. The specimens were genotyped using 10 polymorphic microsatellite loci through fluorescence polymerase chain reaction (PCR). The genetic diversity of C. gigantea and C. torulosa populations was generally low, with the highest genetic diversity detected in the population LLS of C. gigantea. Distance-based phylogenetic and principal co-ordinates analyses indicated a clear genetic structures for the 16 populations of the two Cupressus species. Moreover, Mantel test results showed indistinctive correlations between population-pairwise Fst values and geographic distances, as well as between genetic distances and geographic distances in C. gigantea and C. torulosa, respectively. AMOVA suggested that genetic variation mostly resided within populations. Sixteen naturalpopulations were evidently clustered into two major groups in the constructed neighbour-joining tree. The results demonstrated that C. gigantea and C. torulosa are different Cupressus species. The genetic information provided important theoretical references for conservation and management of the two endangered Cupressus species.