MGAT5/TMEM163 variant is associated with prognosis in ursodeoxycholic acid-treated patients with primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic immune-mediated liver disease. Previous genome-wide meta-analysis has identified the association between variants in TMEM163 with PBC. Here we aimed to evaluate the association between variants near the reported risk loci of TMEM163 at 2q21.3 and prognosis of PBC patients. METHODS: We performed a retrospective analysis of 347 PBC patients treated with ursodeoxycholic acid (UDCA) for at least 1 year. We collected clinical data at diagnosis and 1 year after UDCA treatment. SNPs within 200 kb upstream and downstream of the lead variant were genotyped and screened. RESULTS: We identified that rs661899 near MGAT5 and TMEM163 showed the strongest association with prognosis in PBC patients. Patients carrying the rs661899 T allele tended to respond incompletely to UDCA treatment and had worse performances in laboratory values including aspartate aminotransferase (53.5 vs 32 vs 28.5 U/L, p = 0.001), alkaline phosphate (157.25 vs 125 vs 113 U/L, p = 0.001), albumin (41.5 vs 42.3 vs 43.7 g/L, p = 0.008) and bilirubin (19.2 vs 14.9 vs 12.85 µmol/L, p = 0.001). GLOBE scores (p = 4.8 × 10-5) and UK-PBC risk scores (p = 4.6 × 10-4) were strongly correlated with rs661899 genotype. Patients with TT genotype had a higher risk for adverse events compared with CC genotype (p = 0.039) during the 1-year follow-up. Results were also verified in an independent cohort. CONCLUSIONS: PBC patients carrying the rs661899 T allele are associated with poor prognosis and adverse outcomes after 1-year UDCA therapy.

A+T rich interaction domain protein 3a (Arid3a) impairs Mertk-mediated efferocytosis in cholestasis.

BACKGROUND & AIMS: Macrophages are key elements in the pathogenesis of cholestatic liver diseases. Arid3a plays a prominent role in the biologic properties of hematopoietic stem cells, B lymphocytes and tumor cells, but its ability to modulate macrophage function during cholestasis remains unknown. METHODS: Gene and protein expression and cellular localization were assessed by q-PCR, immunohistochemistry, immunofluorescence staining and flow cytometry. We generated myeloid-specific Arid3a knockout mice and established three cholestatic murine models. The transcriptome was analyzed by RNA-seq. A specific inhibitor of the Mertk receptor was used in vitro and in vivo. Promoter activity was determined by chromatin immunoprecipitation-seq against Arid3a and a luciferase reporter assay. RESULTS: In cholestatic murine models, myeloid-specific deletion of Arid3a alleviated cholestatic liver injury (accompanied by decreased accumulation of macrophages). Arid3a-deficient macrophages manifested a more reparative phenotype, which was eliminated by in vitro treatment with UNC2025, a specific inhibitor of the efferocytosis receptor Mertk. Efferocytosis of apoptotic cholangiocytes was enhanced in Arid3a-deficient macrophages via upregulation of Mertk. Arid3a negatively regulated Mertk transcription by directly binding to its promoter. Targeting Mertk in vivo effectively reversed the protective phenotype of Arid3a deficiency in macrophages. Arid3a was upregulated in hepatic macrophages and circulating monocytes in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Mertk was correspondingly upregulated and negatively correlated with Arid3a expression in PBC and PSC. Mertk+ cells were located in close proximity to cholangiocytes, while Arid3a+ cells were scattered among immune cells with greater spatial distances to hyperplastic cholangiocytes in PBC and PSC. CONCLUSIONS: Arid3a promotes cholestatic liver injury by impairing Mertk-mediated efferocytosis of apoptotic cholangiocytes by macrophages during cholestasis. The Arid3a-Mertk axis is a promising novel therapeutic target for cholestatic liver diseases. IMPACT AND IMPLICATIONS: Macrophages play an important role in the pathogenesis of cholestatic liver diseases. This study reveals that macrophages with Arid3a upregulation manifest a pro-inflammatory phenotype and promote cholestatic liver injury by impairing Mertk-mediated efferocytosis of apoptotic cholangiocytes during cholestasis. Although we now offer a new paradigm to explain how efferocytosis is regulated in a myeloid cell autonomous manner, the regulatory effects of Arid3a on chronic liver diseases remain to be further elucidated.

Ultrastable Graphite-Potassium Anode through Binder Chemistry.

Graphite with abundant reserves has attracted enormous research interest as an anode of potassium-ion batteries (PIBs) owing to its high plateau capacity of 279 mAh g-1 at ≈0.2 V in conventional carbonate electrolytes. Unfortunately, it suffers from fast capacity decay during K+ storage. Herein, an ultrastable graphite-potassium anode is developed through binder chemistry. Polyvinyl alcohol (PVA) is utilized as a water-soluble binder to generate a uniform and robust KF-rich SEI film on the graphite surface, which can not only inhibit the electrolyte decomposition, but also withstand large volume expansion during K+ -insertion. Compared to the PVDF as binder, PVA-based graphite anode can operate for over 2000 cycles (running time of 406 days at C/3) with 97% capacity retention in KPF6 -based electrolytes. The initial Coulombic efficiency (ICE) of graphite anode is as high as 81.6% using PVA as the binder, higher than that of PVDF (40.1%). Benefiting from the strong adhesion ability of PVA, a graphite||fluorophosphate K-ion full battery is further built through 3D printing, which achieves a record-high areal energy of 8.9 mWh cm-2 at a total mass loading of 38 mg cm-2 . These results demonstrate the important role of binder in developing high-performance PIBs.

Synthesis of N-(acyloxy)-N-alkynylamides via generation of "C2" from hypervalent alkynyliodane and a weak base.

The first synthesis of N-(acyloxy)ynamides was realized through the coupling of N-(acyloxy)amides and hypervalent alkynyliodane under mild conditions. This reaction probably involves biradical species ("C2") generation and radical processes. Furthermore, we also demonstrated that N-(acyloxy)ynamide could be transformed into a N-sulfonylimidate derivative by a copper catalyst. This study provides new building blocks for synthetic organic chemistry reactions and improves understanding of the chemical reactivity of "C2".

A Potential Immune-Related miRNAs Regulatory Network and Corresponding Diagnostic Efficacy in Schizophrenia.

PURPOSE: Immune-related pathways actively participate in the progression of schizophrenia (SCZ), however, roles of immune-related miRNAs in SCZ are still unclear. METHODS: A microarray expression study was conducted to explored roles of immune-related genes in SCZ. Functional enrichment analysis by using "clusterProfiler" was used to identify molecular alterations of SCZ. Protein-protein interaction (PPI) network was constructed and helped core molecular factors identification. Based on The Cancer Genome Atlas (TCGA) database, clinical significances of hub immune-related genes in cancers were also been explored. Then, correlation analyses were used to determine immune-related miRNAs. We further validated that hsa-miR-1299 could be an effective diagnostic biomarker for SCZ via analyzing multi-cohorts' data and quantitative real-time PCR (qRT-PCR). RESULTS: A total of 455 mRNAs and 70 miRNAs that were differentially expressed between SCZ and control samples. Functional enrichment analysis based on differentially expressed genes (DEGs) hinted that immune-related pathways were significantly correlated with SCZ. Furthermore, a total of 35 immune-related genes that involved in disease onset and showed significant co-expressed relationships. Hub immune-related gene CCL4 and CCL22 are valuable in tumor diagnosis and survival prediction. Furthermore, we also identified 22 immune-related miRNAs that play important roles in this disease. An immune-related miRNAs-mRNAs regulatory network was constructed to provide miRNAs regulatory roles in SCZ. Core miRNAs expression status of hsa-miR-1299 were also validated in another cohort, which suggested its diagnostic performance for SCZ. CONCLUSIONS: Our study reports the downregulation of some miRNAs in the process of SCZ are important. Shared genomics characteristics between SCZ and cancers also provide novel insights for cancers. A significant alteration of hsa-miR-1299 expression is effective as biomarker for the diagnosis of SCZ, suggesting that this miRNA could be a specific biomarker.

Bioinformatics analysis based on high-throughput sequencing data to identify hub genes related to different clinical types of COVID-19.

This article aims to explore hub genes related to different clinical types of cases with COVID-19 and predict the therapeutic drugs related to severe cases. The expression profile of GSE166424 was divided into four data sets according to different clinical types of COVID-19 and then calculated the differential expression genes (DEGs). The specific genes of four clinical types of COVID-19 were obtained by Venn diagram and conducted enrichment analysis, protein-protein interaction (PPI) networks analysis, screening hub genes, and ROC curve analysis. The hub genes related to severe cases were verified in GSE171110, their RNA-specific expression tissues were obtained from the HPA database, and potential therapeutic drugs were predicted through the DGIdb database. There were 536, 266, 944, and 506 specific genes related to asymptomatic infections, mild, moderate, and severe cases, respectively. The hub genes of severe specific genes were AURKB, BRCA1, BUB1, CCNB1, CCNB2, CDC20, CDC6, KIF11, TOP2A, UBE2C, and RPL11, and also differentially expressed in GSE171110 (P < 0.05), and their AUC values were greater than 0.955. The RNA tissue specificity of AURKB, CDC6, KIF11, UBE2C, CCNB2, CDC20, TOP2A, BUB1, and CCNB1 specifically enhanced on lymphoid tissue; CCNB2, CDC20, TOP2A, and BUB1 specifically expressed on the testis. Finally, 55 drugs related to severe COVID-19 were obtained from the DGIdb database. Summary, AURKB, BRCA1, BUB1, CCNB1, CCNB2, CDC20, CDC6, KIF11, TOP2A, UBE2C, and RPL11 may be potential diagnostic biomarkers for severe COVID-19, which may affect immune and male reproductive systems. 55 drugs may be potential therapeutic drugs for severe COVID-19.

A regulatory variant at 19p13.3 is associated with primary biliary cholangitis risk and ARID3A expression.

Genome-wide association studies have identified 19p13.3 locus associated with primary biliary cholangitis (PBC). Here we aim to identify causative variant(s) and initiate efforts to define the mechanism by which the 19p13.3 locus variant(s) contributes to the pathogenesis of PBC. A genome-wide meta-analysis of 1931 PBC subjects and 7852 controls in two Han Chinese cohorts confirms the strong association between 19p13.3 locus and PBC. By integrating functional annotations, luciferase reporter assay and allele-specific chromatin immunoprecipitation, we prioritize rs2238574, an AT-Rich Interaction Domain 3A (ARID3A) intronic variant, as a potential causal variant at 19p13.3 locus. The risk allele of rs2238574 shows higher binding affinity of transcription factors, leading to an increased enhancer activity in myeloid cells. Genome-editing demonstrates the regulatory effect of rs2238574 on ARID3A expression through allele-specific enhancer activity. Furthermore, knock-down of ARID3A inhibits myeloid differentiation and activation pathway, and overexpression of the gene has the opposite effect. Finally, we find ARID3A expression and rs2238574 genotypes linked to disease severity in PBC. Our work provides several lines of evidence that a non-coding variant regulates ARID3A expression, presenting a mechanistic basis for association of 19p13.3 locus with the susceptibility to PBC.

CircFOXP1 alleviates brain injury after acute ischemic stroke by regulating STAT3/apoptotic signaling.

According to previous studies, circular RNAs (circRNAs) are involved in multiple pathological processes of acute ischemic stroke (AIS). However, the relationship between circFOXP1 and IS has not yet been reported. Here, we found that circFOXP1 expression was significantly decreased in the peripheral blood of AIS patients compared to controls and was associated with the severity and prognosis of AIS. Functionally, knockdown and overexpression of circFOXP1 promoted and inhibited apoptotic signaling, respectively, following oxygen-glucose deprivation/reperfusion (OGD/R) treatment in vitro. Adeno-associated virus (AAV)-mediated circFOXP1 overexpression attenuated neurological deficits and improved functional recovery after transient middle cerebral artery occlusion (tMCAO) treatment in vivo. Mechanistically, decreased QKI expression inhibited circFOXP1 biogenesis under hypoxic conditions. Decreased circFOXP1 expression accelerated signal transducer and activator of transcription 3 (STAT3) protein degradation by binding to and increasing STAT3 protein ubiquitination, ultimately aggravating brain injury after cerebral ischemia by activating apoptotic signaling. In summary, our study is the first to reveal that circFOXP1 alleviates brain injury after cerebral ischemia by regulating STAT3/apoptotic signaling, which provides a potentially novel therapeutic target for AIS.

Phylogeny, Morphology, Distribution, and Pathogenicity of Seven Calonectria Species from Leaf-Blighted Eucalyptus in HaiNan Island, China.

Leaf blight caused by Calonectria species constrains Eucalyptus trees in China. Calonectria leaf disease on Eucalyptus in China was first reported in HaiNan Island in 1985. No systematic investigation of Calonectria species associated with diseased Eucalyptus in HaiNan has been performed. To understand the species diversity, distribution, and pathogenicity of these Calonectria, 400 Calonectria isolates were obtained from 278 diseased Eucalyptus planted in 17 sites in five regions. All 400 isolates were identified by DNA sequences of translation elongation factor 1-alpha, ß-tubulin, calmodulin, and histone H3 gene regions and on morphology. Seven species, C. acaciicola (198 isolates), C. pseudoreteaudii (161 isolates), C. reteaudii (29 isolates), C. hawksworthii (6 isolates), C. hongkongensis (4 isolates), C. auriculiformis (1 isolate), and C. chinensis (1 isolate), were identified. This is the first report of C. acaciicola in China. C. acaciicola, C. pseudoreteaudii, and C. reteaudii belong to the C. reteaudii species complex and accounted for 97% of all isolates. The three species overlapped in vesicle shape, macroconidia size, and macroconidia septa number. Region significantly influenced C. acaciicola and C. pseudoreteaudii distribution. Representative isolates of C. acaciicola, C. pseudoreteaudii, C. reteaudii, and C. hawksworthii producing abundant macroconidia were used in conidial suspension inoculation on Eucalyptus seedlings; all were highly pathogenic to the two tested genotypes. The tolerances of two Eucalyptus genotypes were significantly different. This first systematic investigation of Calonectria species associated with Eucalyptus leaf blight in HaiNan will aid selection of disease-resistant genotypes for managing Eucalyptus leaf blight caused by Calonectria species in China.

Exploring biomarkers for ischemic stroke through integrated microarray data analysis.

Stroke is the third leading cause of disability-adjusted life years worldwide, and drugs available for its treatment are limited. This study aimed to explore high-confidence candidate genes associated with ischemic stroke (IS) through bioinformatics analysis and identify potential diagnostic biomarkers and gene-drug interactions. Weighted gene coexpression network analysis (WGCNA) and differentially expressed genes (DEGs) were integrated to identify overlapping genes. Then, high-confidence candidate genes were screened by least absolute shrinkage and selection operator (LASSO) regression. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of high-confidence candidate genes as biomarkers for IS. The NetworkAnalyst database was used to construct the TF-gene network and miRNA-TF regulatory network of the high-confidence candidate genes. The DGIdb database was used to identified gene-drug interactions. Through the comprehensive analysis of GSE58294 and GSE16561, 10 high-confidence candidate genes were identified by LASSO regression: ARG1, LY96, ABCA1, SLC22A4, CD163, TPM2, SLC25A42, ID3, FAM102A and CD79B. FAM102A had the highest diagnostic value, and the area under curve (AUC), sensitivity and specificity values were 0.974, 0.919 and 0.936, respectively. The HPA database demonstrated that 10 high-confidence candidate genes were expressed in the brain and blood in normal humans. Finally, DGIdb database analysis identified 8 gene-drug interactions. We identified IS-related diagnostic biomarkers and gene-drug interactions that potentially provide new insights into the diagnosis and treatment of IS.

In vitro Studies and Clinical Observations Imply a Synergistic Effect Between Epstein-Barr Virus and Dengue Virus Infection.

Dengue virus (DENV) infection can lead to a complex spectrum of clinical outcomes, ranging from asymptomatic infection to life-threatening severe dengue. The reasons for thus drastically varying manifestations of the disease remain an enigma. Herein, we reported an original discovery of the synergistic effect between preexisting Epstein-Barr virus (EBV) infection and DENV superinfection in vitro and of a strong correlation of these two viruses in the clinical samples from dengue patients. We showed that (I) DENV-2 infection of an EBV-positive cell line (EBV + Akata cell) reactivated EBV, and it could be blocked by wortmannin treatment. (II) Examination of human peripheral blood mononuclear cell (PBMC) samples from dengue patients revealed significantly elevated cell-associated EBV DNA copy number at the time of hospitalization vs. at the time of disease recovery in most individuals. (III) EBV infection promoted DENV propagation in both EBV-hosting B cells and indirectly in THP-1 cells, supported by the following evidence: (A) EBV + Akata cells were more permissive to DENV-2 infection compared with Akata cells harboring no EBV virus (EBV- Akata cells). (B) Low-molecular weight fraction secreted from EBV + Akata cells could enhance DENV-2 propagation in monocytic THP-1 cells. (C) While reactivation of EBV in EBV + Akata cells further increased DENV-2 yield from this cell line, pharmacological inhibition of EBV replication by acyclovir had the opposite effect. To our knowledge, this is the first investigation demonstrating a positive correlation between EBV and DENV in vitro and in human biospecimens.

Intestinal bacterial overgrowth in the early stage of severe acute pancreatitis is associated with acute respiratory distress syndrome.

BACKGROUND: In the early stage of acute pancreatitis (AP), a large number of cytokines induced by local pancreatic inflammation seriously damage the intestinal barrier function, and intestinal bacteria and endotoxins enter the blood, causing inflammatory storm, resulting in multiple organ failure, infectious complications, and other disorders, eventually leading to death. Intestinal failure occurs early in the course of AP, accelerating its development. As an alternative method to detect small intestinal bacterial overgrowth, the hydrogen breath test is safe, noninvasive, and convenient, reflecting the number of intestinal bacteria in AP indirectly. This study aimed to investigate the changes in intestinal bacteria measured using the hydrogen breath test in the early stage of AP to clarify the relationship between intestinal bacteria and acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Early clinical intervention and maintenance of intestinal barrier function would be highly beneficial in controlling the development of severe acute pancreatitis (SAP). AIM: To analyze the relationship between intestinal bacteria change and ALI/ARDS in the early stage of SAP. METHODS: A total of 149 patients with AP admitted to the intensive care unit of the Digestive Department, Xuanwu Hospital, Capital Medical University from 2016 to 2019 were finally enrolled, following compliance with the inclusion and exclusion criteria. The results of the hydrogen breath test within 1 wk of admission were collected, and the hydrogen production rates at admission, 72 h, and 96 h were calculated. The higher the hydrogen production rates the more bacteria in the small intestine. First, according to the improved Marshall scoring system in the 2012 Atlanta Consensus on New Standards for Classification of Acute Pancreatitis, 66 patients with a PaO2/FiO2 score ≤ 1 were included in the mild AP (MAP) group, 18 patients with a PaO2/FiO2 score ≥ 2 and duration < 48 h were included in the moderately SAP (MSAP) group, and 65 patients with a PaO2/FiO2 score ≥ 2 and duration > 48 h were included in the SAP group, to analyze the correlation between intestinal bacterial overgrowth and organ failure in AP. Second, ALI (PaO2/FiO2 = 2) and ARDS (PaO2/FiO2 > 2) were defined according to the simplified diagnostic criteria proposed by the 1994 European Union Conference. The MSAP group was divided into two groups according to the PaO2/FiO2 score: 15 patients with PaO2/FiO2 score = 2 were included in group A, and three patients with score > 2 were included in group B. Similarly, the SAP group was divided into two groups: 28 patients with score = 2 were included in group C, and 37 patients with score > 2 were included in group D, to analyze the correlation between intestinal bacterial overgrowth and ALI/ARDS in AP. RESULTS: A total of 149 patients were included: 66 patients in the MAP group, of whom 53 patients were male (80.3%) and 13 patients were female (19.7%); 18 patients in the MSAP group, of whom 13 patients were male (72.2%) and 5 patients were female (27.8%); 65 patients in the SAP group, of whom 48 patients were male (73.8%) and 17 patients were female (26.2%). There was no significant difference in interleukin-6 and procalcitonin among the MAP, MSAP, and SAP groups (P = 0.445 and P = 0.399, respectively). There was no significant difference in the growth of intestinal bacteria among the MAP, MSAP, and SAP groups (P = 0.649). There was no significant difference in the growth of small intestinal bacteria between group A and group B (P = 0.353). There was a significant difference in the growth of small intestinal bacteria between group C and group D (P = 0.038). CONCLUSION: Intestinal bacterial overgrowth in the early stage of SAP is correlated with ARDS.

A novel approach for the forensic diagnosis of drowning by microbiological analysis with next-generation sequencing and unweighted UniFrac-based PCoA.

The diagnosis of drowning is one of the major challenges in forensic practice, especially when the corpse is in a state of decomposition. Novel indicators of drowning are desired in the field of forensic medicine. In the past decade, aquatic bacteria have attracted great attention from forensic experts because they can easily enter the blood circulation with drowning medium, and some of them can proliferate in the corpse. Recently, the advent of next-generation sequencing (NGS) has created new opportunities to efficiently analyze whole microbial communities and has catalyzed the development of forensic microbiology. We presumed that NGS could be a potential method for diagnosing drowning. In the present study, we verified this hypothesis by fundamental experiments in drowned and postmortem-submersed rat models. Our study revealed that detecting the bacterial communities with NGS and processing the data in a transparent way with unweighted UniFrac-based principal coordinates analysis (PCoA) could clearly discriminate the skin, lung, blood, and liver specimens of the drowning group and postmortem submersion group. Furthermore, the acquired information could be used to identify new cases. Taken together, these results suggest that we could build a microbial database of drowned and postmortem-submersed victims by NGS and subsequently use a bioinformatic method to diagnose drowning in future forensic practice.

Epidemiological investigation of Helicobacter pylori infection in elderly people in Beijing.

BACKGROUND: The Helicobacter pylori (H. pylori) infection rate in China is approximately 50%. H. pylori is a pathogenic factor of peptic ulcer and chronic gastritis. In addition, H. pylori infection may also be associated with a variety of cardiovascular diseases in elderly people, such as arteriosclerosis, coronary heart disease, and cerebral infarction, having deleterious effect on their health. With the aging of the population, the disease characteristics of the elderly population have been increasingly valued by the whole society. We conducted an epidemiological survey of H. pylori infection among elderly people in Beijing to provide a basis for health management of H. pylori infection. AIM: To understand the epidemiological characteristics of H. pylori infection in elderly people in Beijing. METHODS: A total of 1090 elderly people aged more than 60 years from different parts of Beijing (urban and rural areas) were selected using the random cluster sampling method. Structured questionnaires were completed during home visits and the 13C-urea breath test was conducted for H. pylori detection. RESULTS: The prevalence of H. pylori infection was 46.5% (507/1090). The infection rate in men was 51.8%, which was significantly higher than that in women (42.5%; P < 0.05). The H. pylori infection rate in illiterate people was significantly higher than that in literate persons (53.5% vs 44.8%, P < 0.05). The total infection rate of H. pylori gradually increased with age and the difference was statistically significant (P < 0.01). The H. pylori infection rate in smokers was significantly higher than that in non-smokers and those who had quit smoking (P < 0.05). CONCLUSION: The prevalence of H. pylori infection among elderly people is 46.5% and the infection rate gradually increases with age. Sex, education level, age, and smoking were determined to be H. pylori infection risk factors. The relationship of H. pylori infection with region, occupation, drinking, and diet structure needs to be further studied.

Histone deacetylase gene PtHDT902 modifies adventitious root formation and negatively regulates salt stress tolerance in poplar.

Histone deacetylases (HDACs) regulate gene transcription, and play a critical role in plant growth, development and stress responses. HD2 proteins are plant specific histone deacetylases. In woody plants, functions of HD2s are not known. In this study, we cloned an HD2 gene PtHDT902 from Populus trichocarpa and investigated its sequence, expression, subcellular localization, and functions in root development and salt stress responses. Our findings indicated that PtHDT902 was a nuclear protein and its expression was regulated by abiotic stresses. The over-expression of PtHDT902 in both Arabidopsis and poplar increased the expression levels of gibberellin (GA) biosynthetic genes. The expression of PtHDT902 in Arabidopsis enhanced primary root growth, and its over-expression in poplar inhibited adventitious root formation. These phenotypes resulted from over-expression of PtHDT902 were consistent with the GA-overproduction phenotypes. In addition, the poplar plants over-expressing PtHDT902 exhibited lower tolerance to salt than non-transgenic plants. These findings indicated that PtHDT902 worked as an important regulator in adventitious root formation and salt stress tolerance in poplar.

[Spatial and temporal changes of farmland soil acidification and their influencing factors in different regions of Guangdong Province, Chin]. / å¹¿ä¸œçœä¸åŒåŒºåŸŸå†œç”°åœŸå£¤é ¸åŒ–æ—¶ç©ºå˜åŒ–åŠå ¶å½±å“å› ç´ .

Based on the three datasets from 1980s, 2010 and 2015 in Guangdong Province, we analyzed the spatial and temporal variations of soil pH in farmlands in different regions of Guangdong Province and analyzed the driving factors for such variations. The results showed that the spatial distribution of soil pH in Guangdong Province changed significantly in different periods. During 1980s to 2010, soil pH showed an acidification trend with a decline of 0.3, and increased by 0.09 from 2010 to 2015, with more uneven trend and more obvious acid base differentiation. From the perspective of each region, there was generally a trend of acidification from the 1980s to 2010. From 2010 to 2015, the average pH value of farmland soil in the Pearl River Delta increased by 0.27, while that on the east wing and west wing decreased by 0.05 and 0.15 respectively, showing a unapparent change of soil pH in the mountainous area. Our results showed that soil acidification in diffe-rent areas of Guangdong Province was affected by natural factors such as soil itself and precipitation. In addition, anthropogenic factors such as acid rain, unreasonable fertilization and the planting structure of high-yielding crops were also the main causes of soil acidification. Industrialization, urbanization, mining development, and the spread of soil testing formula fertilization increased soil pH in local areas. Our results could provide theoretical guidance for controlling and alleviating soil acidification and improving the quality of cultivated land in different areas.

A research roadmap for next-generation sequencing informatics.

Next-generation sequencing technologies are fueling a wave of new diagnostic tests. Progress on a key set of nine research challenge areas will help generate the knowledge required to advance effectively these diagnostics to the clinic.

Association of genetic variants in CDK6 and XRCC1 with the risk of dysplastic nevi in melanoma-prone families.

Dysplastic nevi (DN) is a strong risk factor for cutaneous malignant melanoma (CMM), and it frequently occurs in melanoma-prone families. To identify genetic variants for DN, we genotyped 677 tagSNPs in 38 melanoma candidate genes that are involved in pigmentation, DNA repair, cell cycle control, and melanocyte proliferation pathways in a total of 504 individuals (310 with DN, 194 without DN) from 53 melanoma-prone families (23 CDKN2A mutation positive and 30 negative). Conditional logistic regression, conditioning on families, was used to estimate the association between DN and each single-nucleotide polymorphism (SNP) separately, adjusted for age, sex, CMM, and CDKN2A status. P-values for SNPs in the same gene were combined to yield gene-specific P-values. Two genes, CDK6 (cyclin-dependent kinase 6) and XRCC1, were significantly associated with DN after Bonferroni correction for multiple testing (P=0.0001 and 0.00025, respectively), whereas neither gene was significantly associated with CMM. Associations for CDK6 SNPs were stronger in CDKN2A mutation-positive families (rs2079147, Pinteraction=0.0033), whereas XRCC1 SNPs had similar effects in mutation-positive and -negative families. The association for one of the associated SNPs in XRCC1 (rs25487) was replicated in two independent data sets (random-effect meta-analysis: P<0.0001). Our findings suggest that some genetic variants may contribute to DN risk independently of their association with CMM in melanoma-prone families.

KIAA1462, a coronary artery disease associated gene, is a candidate gene for late onset Alzheimer disease in APOE carriers.

Alzheimer disease (AD) is a devastating neurodegenerative disease affecting more than five million Americans. In this study, we have used updated genetic linkage data from chromosome 10 in combination with expression data from serial analysis of gene expression to choose a new set of thirteen candidate genes for genetic analysis in late onset Alzheimer disease (LOAD). Results in this study identify the KIAA1462 locus as a candidate locus for LOAD in APOE4 carriers. Two genes exist at this locus, KIAA1462, a gene associated with coronary artery disease, and "rokimi", encoding an untranslated spliced RNA The genetic architecture at this locus suggests that the gene product important in this association is either "rokimi", or a different isoform of KIAA1462 than the isoform that is important in cardiovascular disease. Expression data suggests that isoform f of KIAA1462 is a more attractive candidate for association with LOAD in APOE4 carriers than "rokimi" which had no detectable expression in brain.

Familial aggregation of acute myeloid leukemia and myelodysplastic syndromes.

PURPOSE: Apart from rare pedigrees with multiple cases of acute myeloid leukemia (AML), there is limited data on familial aggregation of AML and myelodysplastic syndromes (MDSs) in the population. PATIENTS AND METHODS: Swedish population-based registry data were used to evaluate risk of AML, MDS, and other malignancies among 24,573 first-degree relatives of 6,962 patients with AML and 1,388 patients with MDS compared with 106,224 first-degree relatives of matched controls. We used a marginal survival model to calculate familial aggregation. RESULTS: AML and/or MDS did not aggregate significantly in relatives of patients with AML. There was a modest risk ratio (RR, 1.3; 95% CI, 0.9 to 1.8) in myeloproliferative/myeloid malignancies combined. The risks for any hematologic or any solid tumor were modestly but significantly increased. Relatives of patients with MDS did not show an increased risk for any hematologic tumors. In contrast, we found a significantly increased risk (RR, 6.5; 95% CI, 1.1 to 38.0) of AML/MDS and of all myeloid malignancies combined (RR, 3.1; 95% CI, 1.0 to 9.8) among relatives of patients diagnosed at younger than age 21 years. CONCLUSION: We did not find evidence for familial aggregation of the severe end of the spectrum of myeloid malignancies (AML and MDS). The risks of myeloproliferative neoplasms were modestly increased with trends toward significance, suggesting a possible role of inheritance. In contrast, although limited in sample size, relatives of young patients with AML were at increased risk of AML/MDS, suggesting that germline genes may play a stronger role in these patients. The increased risk of all hematologic malignancies and of solid tumors among relatives of patients with AML suggests that genes for malignancy in general and/or other environmental factors may be shared.