Prevalent Introgression Underlies Convergent Evolution in the Diversification of Pungitius Sticklebacks.

New mutations and standing genetic variations contribute significantly to repeated phenotypic evolution in sticklebacks. However, less is known about the role of introgression in this process. We analyzed taxonomically and geographically comprehensive genomic data from Pungitius sticklebacks to decipher the extent of introgression and its consequences for the diversification of this genus. Our results demonstrate that introgression is more prevalent than suggested by earlier studies. Although gene flow was generally bidirectional, it was often asymmetric and left unequal genomic signatures in hybridizing species, which might, at least partly, be due to biased hybridization and/or population size differences. In several cases, introgression of variants from one species to another was accompanied by transitions of pelvic and/or lateral plate structures-important diagnostic traits in Pungitius systematics-and frequently left signatures of adaptation in the core gene regulatory networks of armor trait development. This finding suggests that introgression has been an important source of genetic variation and enabled phenotypic convergence among Pungitius sticklebacks. The results highlight the importance of introgression of genetic variation as a source of adaptive variation underlying key ecological and taxonomic traits. Taken together, our study indicates that introgression-driven convergence likely explains the long-standing challenges in resolving the taxonomy and systematics of this small but phenotypically highly diverse group of fish.

Recent Progress of Transition Metal Selenides for Electrochemical Oxygen Reduction to Hydrogen Peroxide: From Catalyst Design to Electrolyzers Application.

Hydrogen peroxide (H2O2) is a highly value-added and environmental-friendly chemical with various applications. The production of H2O2 by electrocatalytic 2e- oxygen reduction reaction (ORR) has emerged as a promising alternative to the energy-intensive anthraquinone process. High selectivity Catalysts combining with superior activity are critical for the efficient electrosynthesis of H2O2. Earth-abundant transition metal selenides (TMSs) being discovered as a classic of stable, low-cost, highly active and selective catalysts for electrochemical 2e- ORR. These features come from the relatively large atomic radius of selenium element, the metal-like properties and the abundant reserves. Moreover, compared with the advanced noble metal or single-atom catalysts, the kinetic current density of TMSs for H2O2 generation is higher in acidic solution, which enable them to become suitable catalyst candidates. Herein, the recent progress of TMSs for ORR to H2O2 is systematically reviewed. The effects of TMSs electrocatalysts on the activity, selectivity and stability of ORR to H2O2 are summarized. It is intended to provide an insight from catalyst design and corresponding reaction mechanisms to the device setup, and to discuss the relationship between structure and activity.

Classical swine fever virus NS5A protein activates autophagy via the PP2A-DAPK3-Beclin 1 axis.

IMPORTANCE: Autophagy is a conserved degradation process that maintains cellular homeostasis and regulates native and adaptive immunity. Viruses have evolved diverse strategies to inhibit or activate autophagy for their benefit. The paper reveals that CSFV NS5A mediates the dissociation of PP2A from Beclin 1 and the association of PP2A with DAPK3 by interaction with PPP2R1A and DAPK3, PP2A dephosphorylates DAPK3 to activate its protein kinase activity, and activated DAPK3 phosphorylates Beclin 1 to trigger autophagy, indicating that NS5A activates autophagy via the PP2A-DAPK3-Beclin 1 axis. These data highlight a novel mechanism by which CSFV activates autophagy to favor its replication, thereby contributing to the development of antiviral strategies.

Genome-Wide Identification and Expression Profiling of Potato (Solanum tuberosum L.) Universal Stress Proteins Reveal Essential Roles in Mechanical Damage and Deoxynivalenol Stress.

Universal stress proteins (USPs) play an important regulatory role in responses to abiotic stress. Most of the research related to USPs so far has been conducted on plant models such as Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa L.), and cotton (Gossypium hirsutum L.). The potato (Solanum tuberosum L.) is one of the four major food crops in the world. The potato is susceptible to mechanical damage and infection by pathogenic fungi during transport and storage. Deoxynivalenol (DON) released by Fusarium can seriously degrade the quality of potatoes. As a result, it is of great significance to study the expression pattern of the potato StUSP gene family under abiotic stress conditions. In this study, a total of 108 USP genes were identified from the genome of the Atlantic potato, divided into four subgroups. Based on their genetic structure, the physical and chemical properties of their proteins and other aspects of their biological characteristics are comprehensively analyzed. Collinear analysis showed that the homologous genes of StUSPs and four other representative species (Solanum lycopersicum, Arabidopsis, Oryza sativa L., and Nicotiana attenuata) were highly conserved. The cis-regulatory elements of the StUSPs promoter are involved in plant hormones, environmental stress, mechanical damage, and light response. RNA-seq analysis showed that there are differences in the expression patterns of members of each subgroup under different abiotic stresses. A Weighted Gene Coexpression Network Analysis (WGCNA) of the central gene showed that the differential coexpression gene is mainly involved in the plant-pathogen response process, plant hormone signal transduction, and the biosynthesis process of secondary metabolites. Through qRT-PCR analysis, it was confirmed that StUSP13, StUSP14, StUSP15, and StUSP41 may be important candidate genes involved in the response to adversity stress in potatoes. The results of this study provide a basis for further research on the functional analysis of StUSPs in the response of potatoes to adversity stress.

Necroptosis pathways in tumorigenesis.

Necroptosis is a caspase-independent form of programmed cell death executed by the receptor interacting protein kinase 1 (RIPK1)-RIPK3-mixed lineage kinase domain-like protein (MLKL) signaling cascade, deregulation of which can cause various human diseases including cancer. Escape from programmed cell death is a hallmark of cancer, leading to uncontrolled growth and drug resistance. Therefore, it is crucial to further understand whether necroptosis plays a key role in therapeutic resistance. In this review, we summarize the recent findings of the link between necroptosis and cancer, and discuss that targeting necroptosis is a new strategy to overcome apoptosis resistance in tumor therapy.

P-Block Metal-Based Electrocatalysts for Nitrogen Reduction to Ammonia: A Minireview.

Electrochemical nitrogen reduction reaction (NRR) to ammonia (NH3 ) using renewable electricity provides a promising approach towards carbon neutral. What's more, it has been regarded as the most promising alternative to the traditional Haber-Bosch route in current context of developing sustainable technologies. The development of a class of highly efficient electrocatalysts with high selectivity and stability is the key to electrochemical NRR. Among them, P-block metal-based electrocatalysts have significant application potential in NRR for which possessing a strong interaction with the N 2p orbitals. Thus, it offers a good selectivity for NRR to NH3 . The density of state (DOS) near the Fermi level is concentrated for the P-block metal-based catalysts, indicating the ability of P-block metal as active sites for N2 adsorption and activation by donating p electrons. In this work, we systematically review the recent progress of P-block metal-based electrocatalysts for electrochemical NRR. The effect of P-block metal-based electrocatalysts on the NRR activity, selectivity and stability are discussed. Specifically, the catalyst design, the nature of the active sites of electrocatalysts and some strategies for boosting NRR performance, the reaction mechanism, and the impact of operating conditions are unveiled. Finally, some challenges and outlooks using P-block metal-based electrocatalysts are proposed.

Major genetic locus with pleiotropism determined seed-related traits in cultivated and wild soybeans.

KEY MESSAGE: Here, a novel pleiotropic QTL qSS14 simultaneously regulating four seed size traits and two consistently detected QTLs qSW17 and qSLW02 were identified across multiple years. Seed-related traits were the key agronomic traits that have been artificially selected during the domestication of wild soybean. Identifying the genetic loci and genes that regulate seed size could clarify the genetic variations in seed-related traits and provide novel insights into high-yield soybean breeding. In this study, we used a high-density genetic map constructed by F10 RIL populations from a cross between Glycine max and Glycine soja to detect additive QTLs for seven seed-related traits over the last three years. As a result, we identified one novel pleiotropic QTL, qSS14, that simultaneously controlled four seed size traits (100-seed weight, seed length, seed width, and seed thickness) and two consistently detected QTLs, qSW17, and qSLW02, in multiple years of phenotypic data. Furthermore, we predicted two, two and three candidate genes within these three critical loci based on the parental resequencing data and gene function annotations. And the relative expression of four candidate genes GLYMA_14G155100, GLYMA_17G061000, GLYMA_02G273100, and GLYMA_02G273300 showed significant differences among parents and the extreme materials through qRT-PCR analysis. These findings could facilitate the determination of beneficial genes in wild soybean and contribute to our understanding of the soybean domestication process.

Uptake, translocation, and metabolism of thiamethoxam in soil by leek plants.

Thiamethoxam (TMX) is commonly applied on leek plants by root irrigation. It might be taken up by leek plants and thus has lasting dietary risk. In this study, the uptake, translocation, and metabolism of TMX in leek plants were investigated. The results obtained from both the hydroponic and soil experiments indicated that TMX could be easily translocated upward and accumulated in leek shoots after being absorbed by roots. The total absorbed TMX amount (Mtotal) in leek plants from the tested soils varied greatly with its adsorption governed by soil characteristics. Interestingly, Mtotal was closely correlated with the concentration of TMX in in situ pore water, indicating that TMX in in situ pore water could be a useful approach to predict uptake of this chemical by leek plants from various soils. Profoundly, clothianidin (CLO) was detected with concentration of 0.07-1.54 mg/kg in roots and 0.27-4.12 mg/kg in shoots at 14 d, respectively, suggesting that TMX is easily converted into CLO in leek plants. The results showed that TMX used in soil is easily absorbed by leek and accumulated in edible parts accompanying with formation of CLO.

Role of HIF-2α/NF-κB pathway in mechanical stress-induced temporomandibular joint osteoarthritis.

OBJECTIVES: Many activities overload temporomandibular joint (TMJ) and cause mandibular condylar cartilage (MCC) degradation by inducing the expression of hypoxia-inducible factor-2α (HIF-2α). Although NF-κB signaling pathway has been reported to induce HIF-2α expression, the underlying mechanisms need to be verified. The aim was to investigate the effects of NF-κB/HIF-2α on MCC degradation induced by mechanical stress and the regulatory mechanism of NF-κB in the HIF-2α pathway. METHODS: Chondrocytes were subjected to cyclic compressive forces in a hypoxic environment. Western blotting was used to test the effects of stress on the expression of NF-κB and HIF-2α. HIF-2α siRNA and shRNA were constructed and transfected into MCC cells in vitro and in vivo to inhibit HIF-2α expression. To test the regulatory effect of the NF-κB pathway on HIF-2α, siRNA p65 was transfected into MCC. RESULTS: The results showed that mechanical stress could cause cartilage degradation and significantly increased the expression of NF-κB, HIF-2α, and downstream degradation factors (MMP13 and ADAMTs-4). Blockade of HIF-2α decreased cartilage degradation and related degradation factors. Suppression of p65 significantly decreased the expression of HIF-2α. CONCLUSIONS: Our results indicated that the upstream NF-κB pathway exerted a regulatory effect on HIF-2α in the degradation of MCC induced by stress.

Uptake, Accumulation, and translocation of azoxystrobin by Vegetable plants in soils: influence of soil characteristics and plant species.

Although azoxystrobin has been widely applied on various crops, little is known about the bioavailability of azoxystrobin in the soil-vegetable system. In this study, the uptake, accumulation and translocation of azoxystrobin as affected by soil characteristics and plant species were respectively investigated. The accumulation amount of azoxystrobin in pakchoi increased as soil adsorption decreased and was positively associated with its concentration in pore water (Cpw), which was mainly affected by soil organic matter content. Therefore, Cpw could be a candidate for the estimation of azoxystrobin accumulation in pakchoi. In all the tested vegetables, azoxystrobin was mainly accumulated in roots, and its upward translocation was limited. Root lipid content was a major factor affecting the uptake and translocation of azoxystrobin in different vegetables.

Necroptosis in pathogenesis of osteoarthritis and its therapeutic implications.

Osteoarthritis is a progressive degenerative joint disease induced by many causes, for which there is no radical cure currently. Necroptosis is a newly reported programmed cell death, and its related factors are also inseparable from the progress of osteoarthritis. For examples, damage-associated molecular pattern promotes the release of various inflammatory factors, so as to recruit macrophages and promote local inflammation of the joint; inhibition of receptor-interacting protein kinase can reduce the death of cell and the expression of inflammatory factors, so as to reduce cartilage damage. Therefore, in-depth study of the regulatory mechanism of necroptosis in osteoarthritis will help to further reveal the pathogenesis of osteoarthritis, so as to provide potential targets for the treatment of osteoarthritis.

Targeted resequencing showing novel common and rare genetic variants increases the risk of asthma in the Chinese Han population.

BACKGROUND: Although studies have identified hundreds of genetic variants associated with asthma risk, a large fraction of heritability remains unexplained, especially in Chinese individuals. METHODS: To identify genetic risk factors for asthma in a Han Chinese population, 211 asthma-related genes were first selected based on database searches. The genes were then sequenced for subjects in a Discovery Cohort (284 asthma patients and 205 older healthy controls) using targeted next-generation sequencing. Bioinformatics analysis and statistical association analyses were performed to reveal the associations between rare/common variants and asthma, respectively. The identified common risk variants underwent a validation analysis using a Replication Cohort (664 patients and 650 controls). RESULTS: First, we identified 18 potentially functional rare loss-of-function (LOF) variants in 21/284 (7.4%) of the asthma cases. Second, using burden tests, we found that the asthma group had nominally significant (p < 0.05) burdens of rare nonsynonymous variants in 10 genes. Third, 23 common single-nucleotide polymorphisms were associated with the risk of asthma, 7/23 (30.4%) and 9/23 (39.1%) of which were modestly significant (p < 9.1 × 10-4 ) in the Replication Cohort and Combined Cohort, respectively. According to our cumulative risk model involving the modestly associated alleles, middle- and high-risk subjects had a 2.0-fold (95% CI: 1.621-2.423, p = 2.624 × 10-11 ) and 6.0-fold (95% CI: 3.623-10.156, p = 7.086 × 10-12 ) increased risk of asthma, respectively, compared with low-risk subjects. CONCLUSION: This study revealed novel rare and common genetic risk factors for asthma, and provided a cumulative risk model for asthma risk prediction and stratification in Han Chinese individuals.

A nonsynonymous polymorphism (rs117179004, T392M) of hyaluronidase 1 (HYAL1) is associated with increased risk of idiopathic pulmonary fibrosis in Southern Han Chinese.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. Hyaluronidase 1 (HYAL1) was found to be upregulated in fibroblasts from IPF patients, and overexpression of HYAL1 could prevent human fetal lung fibroblast proliferation. However, the genetic correlation between the HYAL1 and IPF or connective tissue diseases related interstitial lung disease (CTD-ILD) has not been determined. METHODS: A two-stage study was conducted in Southern Han Chinese population. We sequenced the coding regions and flanking regulatory regions of HYAL1 in stage one (253 IPF cases and 125 controls). A statistically significant variant was further genotyped in stage two (162 IPF cases, 182 CTD-ILD cases, and 225 controls). RESULTS: We identified a nonsynonymous polymorphism (rs117179004, T392M) significantly associated with increased IPF risk (dominant model: OR = 2.239, 95% CI = 1.212-4.137, p = 0.010 in stage one; OR = 2.383, 95% CI = 1.376-4.128, p = 0.002 in stage two). However, we did not observe this association in CTD-ILD (OR = 1.401, 95% CI = 0.790-2.485, p = 0.248). CONCLUSION: Our findings suggest that the nonsynonymous polymorphism (rs117179004, T392M) may confer susceptibility to IPF in Southern Han Chinese, but is not associated with susceptibility to CTD-ILD.

Research progress on tissue engineering in repairing tempomandibular joint.

Temporomandibular joint osteoarthritis (TMJOA) is mainly manifested as perforation of temporomandibular joint disc (TMJD) and destruction of condylar osteochondral complex (COCC). In recent years, tissue engineering technology has become one of the effective strategies in repairing this damage. With the development of scaffold material technology, composite scaffolds have become an important means to optimize the performance of scaffolds with the combined advantages of natural materials and synthetic materials. The gelling method with the minimally invasive concept can greatly solve the problems of surgical trauma and material anastomosis, which is beneficial to the clinical transformation of temporomandibular joint tissue engineering. Extracellular matrix scaffolds technology can solve the problem of scaffold source and maximize the simulation of the extracellular environment, which provides an important means for the transformation of temporo joint tissue engineering to animal level. Due to the limitation of the source and amplification of costal chondrocytes, the use of mesenchymal stem cells from different sources has been widely used for temporomandibular joint tissue engineering. The fibrochondral stem cells isolated from surface layer of articular cartilage may provide one more suitable cell source. Transforming growth factor ß superfamily, due to its osteochondrogenesis activity has been widely used in tissue engineering, and platelet-rich derivative as a convenient preparation of compound biological factor, gradually get used in temporomandibular joint tissue engineering. With the deepening of research on extracellular microenvironment and mechanical stimulation, mesenchymal stem cells, exosomes and stress stimulation are increasingly being used to regulate the extracellular microenvironment. In the future, the combination of complex bioactive factors and certain stress stimulation may become a trend in the temporomandibular joint tissue engineering research. In this article, the progress on tissue engineering in repairing COCC and TMJD, especially in scaffold materials, seed cells and bioactive factors, are reviewed, so as to provide information for future research design and clinical intervention.

Population transcriptomics reveals weak parallel genetic basis in repeated marine and freshwater divergence in nine-spined sticklebacks.

The degree to which adaptation to similar selection pressures is underlain by parallel versus non-parallel genetic changes is a topic of broad interest in contemporary evolutionary biology. Sticklebacks provide opportunities to characterize and compare the genetic underpinnings of repeated marine-freshwater divergences at both intra- and interspecific levels. While the degree of genetic parallelism in repeated marine-freshwater divergences has been frequently studied in the three-spined stickleback (Gasterosteus aculeatus), much less is known about this in other stickleback species. Using a population transcriptomic approach, we identified both genetic and gene expression variations associated with marine-freshwater divergence in the nine-spined stickleback (Pungitius pungitius). Specifically, we used a genome-wide association study approach, and found that ~1% of the total 173,491 identified SNPs showed marine-freshwater ecotypic differentiation. A total of 861 genes were identified to have SNPs associated with marine-freshwater divergence, but only 12 of these genes have also been reported as candidates associated with marine-freshwater divergence in the three-spined stickleback. Hence, our results indicate a low degree of interspecific genetic parallelism in marine-freshwater divergence. Moreover, 1,578 genes in the brain and 1,050 genes in the liver were differentially expressed between marine and freshwater nine-spined sticklebacks, ~5% of which have also been identified as candidates associated with marine-freshwater divergence in the three-spined stickleback. However, only few of these (e.g., CLDND1) appear to have been involved in repeated marine-freshwater divergence in nine-spined sticklebacks. Taken together, the results indicate a low degree of genetic parallelism in repeated marine-freshwater divergence both at intra- and interspecific levels.

Effect of lung function on the apnea-hypopnea index in patients with overlap syndrome: a multicenter cross-sectional study.

PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are referred to as having overlap syndrome (OVS). However, the relationship of lung function with the apnea-hypopnea index (AHI) in patients with OVS has not been evaluated. This multicenter study aimed to evaluate the relationship. METHODS: COPD patients diagnosed by spirometry were recruited from four Chinese tertiary hospitals. Those patients were requested to attend an overnight polysomnography (PSG). The relationships between parameters of lung function and sleep respiration in patients with OVS were assessed using multiple regression analyses. RESULTS: A total of 520 OVS patients and 246 patients with COPD only finally met inclusion criteria for study. After adjustment for age, sex, body mass index, neck circumference, economic status, smoking status, alcohol consumption, and hypertension, the forced expiratory volume in the first second (FEV1) had a positive correlation with the AHI in patients with OVS (ß, 0.17; 95% CI, 0.06-0.28; P < 0.01). However, when the severity of lung function of patients with OVS was stratified, the correlation with the FEV1 of each grade and the AHI was absent (P > 0.05). Additionally, The FEV1 was positively correlated with the nadir oxygen saturation (SaO2) (ß, 0.18; 95% CI, 0.08-0.27; P < 0.01) and was negatively correlated with the percentage of time spent with an SaO2 below 90% (TS90%) (ß,- 0.41; 95% CI,- 0.61-0.21; P < 0.01) in patients with OVS using multiple regression analyses. CONCLUSION: Lung function was associated with the AHI in patients with OVS. The lower FEV1 may play some protective role in the severity of AHI in OVS patients. Trial registry ClinicalTrials.gov , No.: NCT03182309, URL: www.clinicaltrials.gov .

LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) play nonnegligible roles in the epigenetic regulation of cancer cells. This study aimed to identify a specific lncRNA that promotes the colorectal cancer (CRC) progression and could be a potential therapeutic target. METHODS: We screened highly expressed lncRNAs in human CRC samples compared with their matched adjacent normal tissues. The proteins that interact with LINRIS (Long Intergenic Noncoding RNA for IGF2BP2 Stability) were confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assays. The proliferation and metabolic alteration of CRC cells with LINRIS inhibited were tested in vitro and in vivo. RESULTS: LINRIS was upregulated in CRC tissues from patients with poor overall survival (OS), and LINRIS inhibition led to the impaired CRC cell line growth. Moreover, knockdown of LINRIS resulted in a decreased level of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), a newly found N6-methyladenosine (m6A) 'reader'. LINRIS blocked K139 ubiquitination of IGF2BP2, maintaining its stability. This process prevented the degradation of IGF2BP2 through the autophagy-lysosome pathway (ALP). Therefore, knockdown of LINRIS attenuated the downstream effects of IGF2BP2, especially MYC-mediated glycolysis in CRC cells. In addition, the transcription of LINRIS could be inhibited by GATA3 in CRC cells. In vivo experiments showed that the inhibition of LINRIS suppressed the proliferation of tumors in orthotopic models and in patient-derived xenograft (PDX) models. CONCLUSION: LINRIS is an independent prognostic biomarker for CRC. The LINRIS-IGF2BP2-MYC axis promotes the progression of CRC and is a promising therapeutic target.

Chemotherapy With or Without Anti-EGFR Agents in Left- and Right-Sided Metastatic Colorectal Cancer: An Updated Meta-Analysis.

BACKGROUND: Previous meta-analyses have suggested primary tumor location as a predictive factor for efficacy of anti-epidermal growth factor receptor (EGFR) therapies in patients with metastatic colorectal cancer (mCRC). However, the recent phase III TAILOR trial addressing this issue was not included in those analyses. This meta-analysis incorporated data from the TAILOR trial to evaluate the efficacy of chemotherapy plus anti-EGFR agents (cetuximab [Cet] or panitumumab [Pani]) versus chemotherapy alone for RAS wild-type (wt) right- and left-sided mCRC. PATIENTS AND METHODS: A PubMed-based literature search was conducted to identify randomized controlled trials (RCTs) studying the additional efficacy of Cet/Pani in combination with chemotherapy versus chemotherapy alone in RAS wt left- and right-sided mCRC. Study-level pooled analyses of hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and odds ratios (ORs) for objective response rate (ORR) were performed. RESULTS: Three first-line RCTs (CRYSTAL, PRIME, and TAILOR) and one second-line RCT (20050181) were included. Significant OS benefits from Cet/Pani were observed in the left-sided (HR, 0.76; 95% CI, 0.66-0.86) but not right-sided subgroups (HR, 0.99; 95% CI, 0.78-1.27). However, the addition of Cet/Pani to chemotherapy significantly improved PFS and ORR in both the left-sided (HR, 0.70; 95% CI, 0.57-0.86, and OR, 3.28; 95% CI, 1.95-5.51, respectively) and right-sided subgroups (HR, 0.76; 95% CI, 0.59-0.99, and OR, 1.78; 95% CI, 1.08-2.93, respectively). CONCLUSIONS: The addition of Cet/Pani to chemotherapy significantly benefits PFS and ORR in patients with RAS wt right-sided mCRC, indicating that anti-EGFR therapies may remain an option for selected patients.

Salt-adaptive strategies in oil seed crop Ricinus communis early seedlings (cotyledon vs. true leaf) revealed from proteomics analysis.

Soil salinity is a major abiotic stress affecting crop growth and productivity. Ricinus communis has good salt tolerance and is also an important oilseed crop throughout the world. Early seedling stage (such as cotyledon expansion stage) is the most vulnerable period for plant under stresses. However, little information exist concerning the physiological and molecular mechanisms of Ricinus communis seedlings and the role play by cotyledons and true leaf under salt stress. In the present study, biomass, photosynthesis, chlorophyll fluorescence, inorganic ions and organic solutes contents were measured, and two dimensional gel electrophoresis-based proteomic technology was employed to identify the differentially abundant proteins in the salt-treated Ricinus communis cotyledons and true leaves. The results showed that salt stress reduced growth and photosynthesis in the seedlings. With increasing salinity, the Na+ content increased and K+ content decreased in both cotyledons and leaves, but the true leaves had lower Na+ and higher K+ contents. Soluble sugars and proline are the primary organic solutes to cope with osmotic stress. In addition, proteomic analysis revealed 30 and 42 differentially accumulated protein spots in castor cotyledon and true leaf under salt stress, respectively. Most of the identified proteins were involved in carbohydrate and energy metabolism, photosynthesis, genetic information process, reactive oxygen species metabolism, amino acid metabolism and cell structure. The physiological and proteomic results highlighted that cotyledons accumulated a large number of Na+ and provided more energy to help true leaves cope with salt stress. The true leaves saved carbon structures to synthesize osmotic substances, and the enhancement of chlorophyll synthesis and electron transfer in true leaves could also maintain photosynthesis under salt stress. These findings provide new insights into different physiological mechanisms in cotyledon and true leaf of Ricinus communis response to salt stress during early seedling stage.

Targeted resequencing reveals genetic risks in patients with sporadic idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. However, a large fraction of genetic cause remains unexplained, especially in sporadic IPF (∼80% IPF). By systemically reviewing related literature and potential pathogenic pathways, 92 potentially IPF-related genes were selected and sequenced in genomic DNAs from 253 sporadic IPF patients and 125 matched health controls using targeted massively parallel next-generation sequencing. The identified risk variants were confirmed by Sanger sequencing. We identified two pathogenic and 10 loss-of-function (LOF) candidate variants, accounting for 4.74% (12 out of 253) of all the IPF cases. In burden tests, rare missense variants in three genes (CSF3R, DSP, and LAMA3) were identified that have a statistically significant relationship with IPF. Four common SNPs (rs3737002, rs2296160, rs1800470, and rs35705950) were observed to be statistically associated with increased risk of IPF. In the cumulative risk model, high risk subjects had 3.47-fold (95%CI: 2.07-5.81, P = 2.34 × 10-6 ) risk of developing IPF compared with low risk subjects. We drafted a comprehensive map of genetic risks (including both rare and common candidate variants) in patients with IPF, which could provide insights to help in understanding mechanisms, providing genetic diagnosis, and predicting risk for IPF.