Although native to North America, the invasion of the aphid-like grape phylloxera Daktulosphaira vitifoliae across the globe altered the course of grape cultivation. For the past 150 years, viticulture relied on grafting-resistant North American Vitis species as rootstocks, thereby limiting genetic stocks tolerant to other stressors such as pathogens and climate change. Limited understanding of the insect genetics resulted in successive outbreaks across the globe when rootstocks failed. Here we report the 294-Mb genome of D. vitifoliae as a basic tool to understand host plant manipulation, nutritional endosymbiosis, and enhance global viticulture.

The honeybee is a model organism for studying learning and memory formation and its underlying molecular mechanisms. While DNA methylation is well studied in caste differentiation, its role in learning and memory is not clear in honeybees. Here, we analyzed genome-wide DNA methylation changes during olfactory learning and memory process in A. mellifera using whole genome bisulfite sequencing (WGBS) method. A total of 853 significantly differentially methylated regions (DMRs) and 963 differentially methylated genes (DMGs) were identified. We discovered that 440 DMRs of 648 genes were hypermethylated and 274 DMRs of 336 genes were hypomethylated in trained group compared to untrained group. Of these DMGs, many are critical genes involved in learning and memory, such as Creb, GABA B R and Ip3k, indicating extensive involvement of DNA methylation in honeybee olfactory learning and memory process. Furthermore, key enzymes for histone methylation, RNA editing and miRNA processing also showed methylation changes during this process, implying that DNA methylation can affect learning and memory of honeybees by regulating other epigenetic modification processes.

MicroRNAs are considered as potential regulators in various biological pathways and contribute to the diagnosis and prognosis of cancers. MicroRNA-214-3p (miR-214-3p) was proved to be correlated with various cancers in recent studies. However, the biological functions of miR-214-3p in hepatocellular carcinoma (HCC) and its association with the prognosis of HCC after liver transplantation are still unevaluated. Here we intended to elucidate the functional implication of miR-214-3p in regulation of cell proliferation and apoptosis and its potential prediction of clinical prognosis of HCC patients.

Cell proliferation and migration are the determinants of malignant tumor progression, and a better understanding of related genes will lead to the identification of new targets aimed at preventing the spread of cancer. Some studies have shown that KIAA1199 (CEMIP) is a transmembrane protein expressed in many types of noncancerous cells and cancer cells. However, the potential role of KIAA1199 in the progression of cholangiocarcinoma (CCA) remains unclear.

Our previous study suggested that the synapse-associated protein 97 (SAP97) gene rs3915512 polymorphism may influence neurocognition in schizophrenia patients. Neuroimaging studies have shown a possible association between cognitive function and brain activity/connectivity. Considering the poor understanding of whether the disease state and SAP97 rs3915512 polymorphism have interactive effects on brain activity/connectivity, 52 first-episode schizophrenia (FES) patients and 52 healthy controls were genotyped using blood DNA samples and underwent magnetic resonance imaging scanning. A two-way ANCOVA model was performed with rs3915512 genotypes and disease state as the between-subject factors. A significant disease × SAP97 interactive effect was found for the amplitude of low-frequency fluctuation (ALFF) in the right supplementary motor area, left rolandic opercularis area (ROC-L), and bilateral middle occipital gyrus (MOG). In addition, among auditory/visual-related brain areas, a significant interactive effect was found for resting-state functional connectivity (RSFC) between the MOG-L and bilateral superior temporal gyrus (STG) in the STG-L with ROC-R, right cuneus (Cu-R), left fusiform (Fu-L), and left lingual gyrus (LG-L). Positive correlations were found between ALFF in the ROC-L and motor speed scores, between RSFC in the STG-L and LG-L and between Brief Assessment of Cognition in Schizophrenia verbal memory scores in FES. The SAP97 rs3915512 polymorphism may affect neurocognitive function in patients with schizophrenia by changing the brain activity and connectivity of auditory/visual-related brain areas.

Anthocyanins are distributed ubiquitously to terrestrial plants and chalcone isomerase (CHI) catalyzes the stereospecific isomerization of chalcones - a committed step in the anthocyanin biosynthesis pathway. In this study, one gene encoding CHI was isolated from Ophiorrhiza japonica and designated as OjCHI. Multiple sequence alignments and phylogenetic analysis revealed that OjCHI had the conserved CHI active site residues and was classified into type I CHI group. In order to better understand the mechanisms of anthocyanin synthesis in O. japonica, integrative analysis between metabolites and OjCHI expression was conducted. The results showed OjCHI expression matched the accumulation patterns of anthocyanins not only in different tissues but also during the flower developmental stages, suggesting the potential roles of OjCHI in the biosynthesis of anthocyanin. Then biochemical analysis indicated that recombinant OjCHI protein exhibited a typical type I CHI activity which catalyzed the production of naringenin from naringenin chalcone. Moreover, expressing OjCHI in Arabidopsis tt5 mutant restored the anthocyanins and flavonols phenotype of hypocotyl, cotyledon and seed coat, indicating its function as a chalcone isomerase in vivo. In summary, our findings reveal the in vitro as well as in vivo functions of OjCHI and provide a resource to understand the mechanism of anthocyanin biosynthesis in O. japonica.

Gene fusions that contribute to oncogenicity can be explored for identifying cancer biomarkers and potential drug targets. To investigate the nature and distribution of fusion transcripts in cancer, we examined the transcriptome data of about 9,000 primary tumors from 33 different cancers in TCGA (The Cancer Genome Atlas) along with cell line data from CCLE (Cancer Cell Line Encyclopedia) using ChimeRScope, a novel fusion detection algorithm. We identified several fusions with sense (canonical, 39%) or antisense (non-canonical, 61%) transcripts recurrent across cancers. The majority of the recurrent non-canonical fusions found in our study are novel, unexplored, and exhibited highly variable profiles across cancers, with breast cancer and glioblastoma having the highest and lowest rates, respectively. Overall, 4,344 recurrent fusions were identified from TCGA in this study, of which 70% were novel. Additional analysis of 802 tumor-derived cell line transcriptome data across 20 cancers revealed significant variability in recurrent fusion profiles between primary tumors and corresponding cell lines. A subset of canonical and non-canonical fusions was validated by examining the structural variation evidence in whole-genome sequencing (WGS) data or by Sanger sequencing of fusion junctions. Several recurrent fusion genes identified in our study show promise for drug repurposing in basket trials and present opportunities for mechanistic studies.

Background and Aim: DOT1L regulates various genes involved in cancer onset and progression by catalyzing H3K79 methylation, but how DOT1L activity itself is regulated is unclear. Here, we aimed to identify specific DOT1L post-translational modifications that might regulate DOT1L activity and thus impact on colorectal cancer (CRC) progression. Methods: We conducted affinity purification and mass spectrometry to explore DOT1L post-translational modifications. We then established transwell migration and invasion assays to specifically investigate the role of DOT1L(K358) acetylation on CRC cellular behavior in vitro and a bioluminescence imaging approach to determine the role of DOT1L(K358) acetylation in CRC metastasis in vivo. We performed chromatin immunoprecipitation to identify DOT1L acetylation-controlled target genes. Finally, we used immunohistochemical staining of human tissue arrays to examine the relevance of DOT1L(K358) acetylation in CRC progression and metastasis and the correlation between DOT1L acetylation and CBP. Results: We found that CBP mediates DOT1L K358 acetylation in human colon cancer cells and positively correlates with CRC stages. Mechanistically, DOT1L acetylation confers DOT1L stability by preventing the binding of RNF8 to DOT1L and subsequent proteasomal degradation, but does not affect its enzyme activity. Once stabilized, DOT1L can catalyze the H3K79 methylation of genes involved in epithelial-mesenchymal transition, including SNAIL and ZEB1. An acetylation mimic DOT1L mutant (Q358) could induce a cancer-like phenotype in vitro, characterized by metastasis and invasion. Finally, DOT1L(K358) acetylation correlated with CRC progression and a poor survival rate as well as with high CBP expression. Conclusions: DOT1L acetylation by CBP drives CRC progression and metastasis. Targeting DOT1L deacetylation signaling is a potential therapeutic strategy for DOT1L-driven cancers.

Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middle-income countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018.

Inflammasome activation is essential for host defence against invading pathogens, but is also involved in various forms of inflammatory diseases. The processes that control inflammasome activity are thus important for averting excessive immune responses and tissue damage. Here we show that the deubiquitinase POH1 negatively regulates the immune response triggered by inflammasome activation. POH1 deficiency in macrophages enhances mature IL-1β production without significant alterations in inflammasome priming and ASC-caspase-1 activation. In WT macrophages, POH1 interacts with and deubiquitinates pro-IL-1β by decreasing the K63-linked polyubiquitin chains, as well as decreases the efficacy of pro-IL-1β cleavage. Furthermore, myeloid cell-specific deletion of POH1 aggravates lipopolysaccharide-induced systemic inflammation and alum-induced peritonitis inflammatory responses in vivo. Our study thereby reveals that POH1-mediated deubiquitination of pro-IL-1β is an important regulatory event that restrains inflammatory responses for the maintenance of immune homeostasis.

Much of the world's Li deposits occurs as basinal brines in magmatic orogens, particularly in continental volcanic arcs. However, the exact origin of Li enrichment in arc magmatic systems is not clear. Here, we show that, globally, primitive arc magmas have Li contents and Li/Y ratios similar to mid-ocean ridge basalts, indicating that the subducting slab has limited contribution to Li enrichment in arc magmas. Instead, we find that Li enrichment is enhanced by lower degrees of sub-arc mantle melting and higher extents of intracrustal differentiation. These enrichment effects are favored in arcs with thick crust, which explains why magmatism and differentiation in continental arcs, like the Andes, reach greater Li contents than their island arc counterparts. Weathering of these enriched source rocks mobilizes and transports such Li into the hydrologic system, ultimately developing Li brines with the combination of arid climate and the presence of landlocked extensional basins in thickened orogenic settings.

Styrax wuyuanensis S. M. Hwang is an endemic species distributed in China. In this study, we characterized its complete chloroplast genome. The circular genome of S. wuyuanensis is 157,969 bp in length, and includes two inverted repeat (IRa and IRb) regions of 25,954 bp in length separated by a large single copy (LSC) region of 87,575 bp and a small single copy (SSC) region of 18,486 bp. The total GC content of the S. wuyuanensis chloroplast genome is 37.0%, and a total of 132 functional genes are encoded, including 87 protein-coding genes, 37 tRNA, and eight rRNA. The phylogenetic analysis has shown that S. wuyuanensis is positioned in the Styracaceae clade, as a sister taxon to S. faberi and S. fortunei, confirming the close relationship of S. wuyuanensis with the latter two species.

Background: To explore the changes in lipids in exosomes of hormone-sensitive and hormone-resistant prostate cancer cells and develop an inexpensive and rapid technique for screening lipid-based biomarkers of prostate cancer. Methods: Exosomes were extracted from LnCap, PC3 and DU-145 cells, and their lipid composition was analyzed quantitatively using high-throughput mass spectrometry. Exosomes released by LnCap prostate cancer cells were also purified using a modified procedure based on polyethylene glycol (PEG) precipitation. Results: Exosomes extracted from LnCap cells contained higher proportions of phosphatidyl choline, phosphatidyl ethanolamine and phosphatidyl inositol lipids than whole LnCap cells. Lysophosphatidylcholine, a harmful intermediate product of phosphatidylcholine metabolism in vivo, was not found in LnCap cells but in exosomes. Phospholipids were different in exosomes from LnCap, PC3 and DU-145 prostate cancer cells. The main lipid pathways involved, i.e., glycerophospholipid metabolism, autophagy, and ferroptosis pathways, were also different in these cells. Exosomes isolated by this modified PEG precipitation technique were similar in purity to those obtained using a commercial kit. Conclusions: This study demonstrates that phosphatidylcholine and its harmful product lysophosphatidylcholine may play important roles in hormone-sensitive prostate cancer. Phospholipid exosome metabolism was changed in hormone-sensitive and hormone-resistant prostate cancer cells. The LPC, lipid pathway of autophagy and ferroptosis may act as therapeutic targets. The possibility of purifying prostate cancer cell exosomes using modified PEG precipitation is suitable for cancer screening.

Nuclear casein kinase and cyclin-dependent kinase substrate 1 (nucks1) are considered a potential susceptibility gene for certain neurological diseases, such as Parkinson's disease (PD). In our study, we genotyped three single nucleotide polymorphisms (SNPs) (rs4951261, rs823114 and rs951366) of the nucks1 gene in 774 schizophrenic patients and 819 healthy controls using the improved multiplex ligation detection reaction (imLDR) technique. Furthermore, we also studied the relationship between the above SNPs and the clinical psychiatric symptoms and neurocognitive function of the patients. Genotype distributions and allele frequencies of these SNPs showed no significant differences and were found between patients and healthy controls. However, in an analysis of the positive symptom score of rs823114 among male patients, we found that the score of the A/A genotype was lower than that of the G/A+G/G genotypes (P = 0.001, P(corr) = 0.003]. Additionally, we also found that among the female patients, G allele carriers with rs823114 had lower semantic fluency scores than subjects with the A/A genotype (P = 0.010, P(corr) = 0.030]. Our data show for the first time that rs823114 polymorphism of nucks1 may affect positive symptoms and neurocognitive function in patients with schizophrenia in parts of southern China.

Objective: To investigate the effects of microRNA-137 (MIR137) polymorphisms (rs1198588 and rs2660304) on the risk of schizophrenia in a Han Chinese population. Methods: Schizophrenia was diagnosed according to the DSM-5. Clinical symptoms and cognitive functions were assessed with the Positive and Negative Symptom Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS), respectively. The polymorphisms were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 1,116 patients with schizophrenia and 1,039 healthy controls. Results: Significant associations were found between schizophrenia and MIR137 in the distributions of genotypes (p = 0.037 for rs1198588; p = 0.037 for rs2660304, FDR corrected) and alleles (p = 0.043 for rs1198588; p = 0.043 for rs2660304, FDR corrected) of two SNPs. When the population was stratified by sex, we found female-specific associations between MIR137 and schizophrenia in terms of genotype and allele distributions of rs1198588 (χ 2 = 4.41, p = 0.036 and χ 2 = 4.86, p = 0.029, respectively, FDR corrected) and rs2660304 (χ 2 = 4.74, p=0.036 and χ 2 = 4.80, p = 0.029, respectively, FDR corrected). Analysis of the MIR137 haplotype rs1198588-rs2660304 showed a significant association with schizophrenia in haplotype T-T [χ 2 = 4.60, p = 0.032, OR = 1.32, 95% CI (1.02-1.70)]. Then, significant female-specific associations were found with the haplotypes T-T and G-A [χ 2 = 4.92, p = 0.027, OR = 1.62, 95% CI (1.05-2.50); χ 2 = 4.42, p = 0.035, OR = 0.62, 95% CI (0.39-0.97), respectively]. When the TT genotype of rs1198588 was compared to the GT+GG genotype, a clinical characteristics analysis also showed a female-specific association in category instances (t = 2.76, p = 0.042, FDR corrected). Conclusion: The polymorphisms within the MIR137 gene are associated with susceptibility to schizophrenia, and a female-specific association of MIR137 with schizophrenia was reported in a Han Chinese population.

Constraining thickness and geothermal gradient of Archean continental crust are crucial to understanding geodynamic regimes of the early Earth. Archean crust-sourced tonalitic-trondhjemitic-granodioritic gneisses are ideal lithologies for reconstructing the thermal state of early continental crust. Integrating experimental results with petrochemical data from the Eastern Block of the North China Craton allows us to establish temporal-spatial variations in thickness, geothermal gradient and basal heat flow across the block, which we relate to cooling mantle potential temperature and resultant changing geodynamic regimes from vertical tectonics in the late Mesoarchean (~2.9 Ga) to plate tectonics with hot subduction in the early to late Neoarchean (~2.7-2.5 Ga). Here, we show the transition to a plate tectonic regime plays an important role in the rapid cooling of the mantle, and thickening and strengthening of the lithosphere, which in turn prompted stabilization of the cratonic lithosphere at the end of the Archean.

Copper (Cu) has been implicated in the progression of Alzheimer's disease (AD), and aggregation of Cu and amyloid β peptide (Aβ) are considered key pathological features of AD. Metal chelators are considered to be potential therapeutic agents for AD because of their capacity to reduce metal ion-induced Aβ aggregation through the regulation of metal ion distribution. Here, we used phage display technology to screen, synthesize, and evaluate a novel Cu(II)-binding peptide that specifically blocked Cu-triggered Aβ aggregation. The Cu(II)-binding peptide (S-A-Q-I-A-P-H, PCu) identified from the phage display heptapeptide library was used to explore the mechanism of PCu inhibition of Cu2+-mediated Aβ aggregation and Aβ production. In vitro experiments revealed that PCu directly inhibited Cu2+-mediated Aβ aggregation and regulated copper levels to reduce biological toxicity. Furthermore, PCu reduced the production of Aβ by inhibiting Cu2+-induced BACE1 expression and improving Cu(II)-mediated cell oxidative damage. Cell culture experiments further demonstrated that PCu had relatively low toxicity. This Cu(II)-binding peptide that we have identified using phage display technology provides a potential therapeutic approach to prevent or treat AD.

Human parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global burden of hPIV in childhood ALRI. We aimed to estimate the global and regional hPIV-associated and hPIV-attributable ALRI incidence, hospital admissions, and mortality for children younger than 5 years and stratified by 0-5 months, 6-11 months, and 12-59 months of age.

Understanding the risk factors for poor outcomes among COVID-19 patients could help identify vulnerable populations who would need prioritisation in prevention and treatment for COVID-19. We aimed to critically appraise and synthesise published evidence on the risk factors for poor outcomes in hospitalised COVID-19 patients.

Emerging evidence suggests that the long noncoding RNA (lncRNA) growth arrest special 5 (GAS5) plays crucial roles in the pathogenesis of ischemic stroke (IS). The current research is aimed at assessing the correlation between two functional GAS5 variants (rs145204276 and rs55829688) and susceptibility to IS in a Han Chinese population. This study genotyped the two GAS5 variants in 1086 IS patients as well as 1045 age-matched healthy controls by using an improved multitemperature ligase detection reaction (iMLDR-TM) genotyping technology. We observed a considerable change in the frequencies of the rs145204276 allele and genotype among the IS patients and healthy control group. The del-T haplotype was substantially more prevalent in the IS cases compared to the control individuals. When study participants were stratified according to environmental factors, we found that the rs145204276 del allele was correlated with a higher risk of IS in male, smokers, hypertensive, and those ≥65 years old. Additional stratification conforming to IS subtypes exhibited that individuals carrying the rs145204276 del allele conferred a higher risk of expanding a larger artery atherosclerosis stroke subset. Moreover, there was a significant association between the rs145204276 del allele and elevated expression of GAS5 in IS patients. In contrast, the frequency of the allele related to rs55829688 was not statistically correlated with IS in all analysis. Our study supports a model wherein the rs145204276 variant in the GAS5 lncRNA is associated with IS risk, thus representing a potentially viable biomarker for IS prevention and treatment.