The Evolution, Expression Patterns, and Domestication Selection Analysis of the Annexin Gene Family in the Barley Pan-Genome.

Plant annexins constitute a conserved protein family that plays crucial roles in regulating plant growth and development, as well as in responses to both biotic and abiotic stresses. In this study, a total of 144 annexin genes were identified in the barley pan-genome, comprising 12 reference genomes, including cultivated barley, landraces, and wild barley. Their chromosomal locations, physical-chemical characteristics, gene structures, conserved domains, and subcellular localizations were systematically analyzed to reveal the certain differences between wild and cultivated populations. Through a cis-acting element analysis, co-expression network, and large-scale transcriptome analysis, their involvement in growth, development, and responses to various stressors was highlighted. It is worth noting that HvMOREXann5 is only expressed in pistils and anthers, indicating its crucial role in reproductive development. Based on the resequencing data from 282 barley accessions worldwide, genetic variations in thefamily were investigated, and the results showed that 5 out of the 12 identified HvMOREXanns were affected by selection pressure. Genetic diversity and haplotype frequency showed notable reductions between wild and domesticated barley, suggesting that a genetic bottleneck occurred on the annexin family during the barley domestication process. Finally, qRT-PCR analysis confirmed the up-regulation of HvMOREXann7 under drought stress, along with significant differences between wild accessions and varieties. This study provides some insights into the genome organization and genetic characteristics of the annexin gene family in barley at the pan-genome level, which will contribute to better understanding its evolution and function in barley and other crops.

[Association between insomnia and type 2 diabetes: A two-sample Mendelian rando-mization study].

OBJECTIVE: To explore the robust relationship between insomnia and type 2 diabetes mellitus by two-sample Mendelian randomization analysis to overcome confounding factors and reverse causality in observational studies. METHODS: We identified strong, independent single nucleotide polymorphisms (SNPs) of insomnia from the most up to date genome wide association studies (GWAS) within European ancestors and applied them as instrumental variable to GWAS of type 2 diabetes mellitus. After excluding SNPs that were significantly associated with smoking, physical activity, alcohol consumption, educational attainment, obesity, or type 2 diabetes mellitus, we assessed the impact of insomnia on type 2 diabetes mellitus using inverse variance weighting (IVW) method. Weighted median and MR-Egger regression analysis were also conducted to test the robustness of the association. We calculated the F statistic of the selected SNPs to test the applicability of instrumental variable and F statistic over than ten indicated that there was little possibility of bias of weak instrumental variables. We further examined the existence of pleiotropy by testing whether the intercept term in MR-Egger regression was significantly different from zero. In addition, the leave-one-out method was used for sensitivity analysis to verify the stability and reliability of the results. RESULTS: We selected 248 SNPs independently associated with insomnia at the genome-wide level (P<5×10-8) as a preliminary candidate set of instrumental variables. After clumping based on the reference panel from 1000 Genome Project and removing the potential pleiotropic SNPs, a total of 167 SNPs associated with insomnia were included as final instrumental variables. The F statistic of this study was 39. 74, which was in line with the relevance assumption of Mendelian randomization. IVW method showed insomnia was associated with higher risk of type 2 diabetes mellitus that po-pulation with insomnia were 1. 14 times more likely to develop type 2 diabetes mellitus than those without insomnia (95% CI: 1.09-1.21, P<0.001). The weighted median estimator (WME) method and MR-Egger regression showed similar causal effect of insomnia on type 2 diabetes mellitus. And MR-Egger regression also showed that the effect was less likely to be triggered by pleiotropy. Sensitivity analyses produced directionally similar estimates. CONCLUSION: Insomnia is a risk factor of type 2 diabetes mellitus, which has positively effects on type 2 diabetes mellitus. Our study provides further rationale for indivi-duals at risk for diabetes to keep healthy lifestyle.

Loss of CBX2 causes genomic instability and Wnt activation in high grade serous ovarian carcinoma cells.

High grade serous ovarian carcinoma (HGSOC) is lethal with insidious onset, rapid progression, poor prognosis, and limited treatment options. Polycomb repressor complexes (PRC) 1 and 2 are intimately involved in progression of many types of cancer including HGSOC. Unlike the consistent constitution of PRC2, PRC1 consists of diverse components whose clinical significance in HGSOC are not entirely clear. Here, prognosis-associated PRC1 components were identified through data-mining. CBX2 promoted proliferation and reduced apoptosis of HGSOC cell lines OVCAR4, OVCAR3, and CAOV3. Complete loss of CBX2 by CRISPR-cas9 editing (CBX2KO ) destabilized genome stability with increased spontaneous chromosomal breaks and tendency to polyploidy accompanied by disrupted cell cycle especially stalled G2/M transition and caused severe cell death. Wnt/ß-catenin/LEF1/TCF7L1 was activated in surviving OVCAR4-CBX2KO clones to bypass the crisis caused by loss of CBX2. The relieve of TCF7L1 core-promoter region occupied by CBX2 might be one of the possible explanations to TCF7L1 increase in OVCAR4-CBX2KO clones. Subcutaneous tumor model further validated that depletion of CBX2 repressed HGSOC cell line derived tumor growth. High immunohistochemistry score of CBX2 in primary ovarian cancer tissue associated with advanced clinical stage (p = 0.033), poor overall survival (HR = 3.056, 95% CI: 1.024-9.123), and progression free survival (HR = 4.455, 95% CI: 1.513-13.118) in HGSOC. Overall, our results suggested that CBX2 was a promising prognostic factor and therapeutic target in HGSOC.

Preparation of NH4Cl-Modified Carbon Materials via High-Temperature Calcination and Their Application in the Negative Electrode of Lead-Carbon Batteries.

The performance of lead-acid batteries could be significantly increased by incorporating carbon materials into the negative electrodes. In this study, a modified carbon material developed via a simple high-temperature calcination method was employed as a negative electrode additive, and we have named it as follows: N-doped chitosan-derived carbon (NCC). The performance of this material was compared with a control battery containing activated carbon (AC). X-ray diffraction (XRD), scanning electron microscopy (SEM) and Raman spectroscopy were engaged in analyzing the crystal structure and morphology of the material. Afterwards, the electrochemical and battery performance was examined through cyclic voltammetry (CV), linear voltammetry (LSV) and constant current charge-discharge testing. Markedly, the electrode plate containing 1 wt.% NCC indicates the highest specific capacity (106.48 F g-1) as compared to the control battery, which is 1.56 times higher than the AC electrode plate and 4.75 times higher than the blank electrode plate. The linear voltammetry shows that the hydrogen precipitation current density of the 1 wt.% NCC electrode plate is only -0.028 A cm-2, a much higher value than that of the AC electrode plate. In addition, the simulated battery containing 1 wt.% NCC has a cycle life of 4324 cycles, which is 2.36 times longer than that of the same amount of additive AC battery (1834 cycles) and 5.34 times longer than that of the blank battery (809 cycles). In summary, NCC carbon has the advantage of extending the life of lead-acid batteries, rendering it a promising candidate for lead-acid battery additives.

Disease patterns of coronary heart disease and type 2 diabetes harbored distinct and shared genetic architecture.

BACKGROUND: Coronary heart disease (CHD) and type 2 diabetes (T2D) are two complex diseases with complex interrelationships. However, the genetic architecture of the two diseases is often studied independently by the individual single-nucleotide polymorphism (SNP) approach. Here, we presented a genotypic-phenotypic framework for deciphering the genetic architecture underlying the disease patterns of CHD and T2D. METHOD: A data-driven SNP-set approach was performed in a genome-wide association study consisting of subpopulations with different disease patterns of CHD and T2D (comorbidity, CHD without T2D, T2D without CHD and all none). We applied nonsmooth nonnegative matrix factorization (nsNMF) clustering to generate SNP sets interacting the information of SNP and subject. Relationships between SNP sets and phenotype sets harboring different disease patterns were then assessed, and we further co-clustered the SNP sets into a genetic network to topologically elucidate the genetic architecture composed of SNP sets. RESULTS: We identified 23 non-identical SNP sets with significant association with CHD or T2D (SNP-set based association test, P < 3.70 × [Formula: see text]). Among them, disease patterns involving CHD and T2D were related to distinct SNP sets (Hypergeometric test, P < 2.17 × [Formula: see text]). Accordingly, numerous genes (e.g., KLKs, GRM8, SHANK2) and pathways (e.g., fatty acid metabolism) were diversely implicated in different subtypes and related pathophysiological processes. Finally, we showed that the genetic architecture for disease patterns of CHD and T2D was composed of disjoint genetic networks (heterogeneity), with common genes contributing to it (pleiotropy). CONCLUSION: The SNP-set approach deciphered the complexity of both genotype and phenotype as well as their complex relationships. Different disease patterns of CHD and T2D share distinct genetic architectures, for which lipid metabolism related to fibrosis may be an atherogenic pathway that is specifically activated by diabetes. Our findings provide new insights for exploring new biological pathways.

Clinical utility of 3D magnetic resonance elastography in patients with biliary obstruction.

OBJECTIVES: Three-dimensional magnetic resonance elastography (3D-MRE) allows for multiparametric modeling of both elastic and viscous tissue characteristics. Our aim was to compare 3D-MRE with conventional liver shear stiffness assessment in gauging obstructive jaundice (OJ), predicting the adequacy of biliary decompression after drainage, and discriminating OJ from liver fibrosis. METHODS: Patients with no histories of liver disease (n = 201) were studied in retrospect, grouped by bilirubin levels as no jaundice (NJ ≤ 2 mg/dL; n = 75), mild OJ (>2 mg/dL and ≤ 4 mg/dL; n = 56), and severe OJ (> 4 mg/dL; n = 70). For comparison, another 75 patients with chronic hepatitis B and C infections and histologically proven liver fibrosis were similarly analyzed. Each patient underwent spin-echo echo-planar-imaging MRE at 60 Hz with 3D wave postprocessing. Logistic regression and ordinary regression models were used to compare the 3D-MRE model with liver shear stiffness. RESULTS: Liver shear stiffness, loss modulus, and damping ratio were incorporated into a 3D-MRE model, which significantly outperformed shear stiffness in predicting OJ severity (accuracy: 0.801 vs 0.672; p < 0.001). Both the 3D-MRE model and liver shear stiffness performed equally well in predicting the outcome of biliary drainage procedure (C-statistics: 0.852 vs 0.847; p = 0.48). The 3D-MRE model also demonstrated significantly better C-statistics than that of liver shear stiffness in discriminating mild OJ from F1-F2 liver fibrosis (0.765 vs 0.641; p = 0.005) and severe OJ from F3-F4 liver fibrosis (0.750 vs 0.635; p = 0.031). CONCLUSIONS: 3D-MRE is an innovative imaging method for gauging OJ severity, predicting the outcome of biliary drainage procedure, and discriminating OJ from liver fibrosis. KEY POINTS: • 3D-MR elastography achieved promising results for predicting the severity of obstructive jaundice. • Advanced parameters of 3D-MR elastography demonstrated significantly better performance than that of shear stiffness of 2D-MR elastography in discriminating obstructive jaundice from liver fibrosis caused by chronic hepatitis B/C. • Both 3D-MR elastography and 2D-MR elastography were equivalent in predicting the outcome of biliary drainage procedure.

Hypermethylation-mediated downregulation of lncRNA PVT1 promotes granulosa cell apoptosis in premature ovarian insufficiency via interacting with Foxo3a.

Long noncoding RNA PVT1 is involved in the progression of female gynecological cancers. However, the role of PVT1 in ovarian granulosa cell apoptosis-mediated premature ovarian insufficiency (POI) remains unclear. This study aims to elucidate the role of PVT1 in ovarian granulosa cell apoptosis-mediated POI. The expression of PVT1 was compared between ovarian tissues from POI patients and normal controls. The methylation level in the PVT1 promoter region was detected by methylation-specific polymerase chain reaction. The interaction between PVT1 and forkhead box class O3A (Foxo3a) was confirmed by RNA pull-down and RNA immunoprecipitation assays. Granulosa cell apoptosis was detected using flow cytometry. The effect of PVT1 on transcription activity of Foxo3a was detected by luciferase reporter assay. The expression of PVT1 was low in the POI ovarian tissues compared with the controls, and such a low expression was related to the hypermethylation of the PVT1 promoter. PVT1 was localized in both the cytoplasm and the nucleus of granulosa cells. We determined that PVT1 could bind with Foxo3a and that downregulating PVT1 by small interfering RNAs inhibited Foxo3a phosphorylation by promoting SCP4-mediated Foxo3a dephosphorylation, resulting in an increase in Foxo3a transcription activity. Moreover, downregulating PVT1 promoted granulosa cell apoptosis by increasing the Foxo3a protein levels. An in vivo experiment showed that the injection of PVT1 overexpressing vectors restored the ovarian function in POI mice. Hypermethylation-induced downregulation of PVT1 promotes granulosa cell apoptosis in POI by inhibiting Foxo3a phosphorylation and increases the Foxo3a transcription activity.

Three-dimensional MR Elastography Depicts Liver Inflammation, Fibrosis, and Portal Hypertension in Chronic Hepatitis B or C.

Background The value of measuring mechanical properties to categorize various pathophysiologic states of the liver is as yet undetermined in chronic hepatitis B (CHB) or C (CHC). Purpose To evaluate multiparametric three-dimensional (3D) MR elastography as a means of detecting early necroinflammation, distinguishing necroinflammation from fibrosis, and gauging the severity of portal hypertension (PH) in CHB or CHC. Materials and Methods From January 2015 to September 2019, participants with CHB or CHC were prospectively enrolled from a single institution and were divided into two groups: those with liver biopsy and no evidence of PH (group 1) and those with PH and a hepatic venous pressure gradient (HVPG) measurement (group 2). For group 3, healthy volunteers were separately recruited from a nearby community. Multiple viscoelastic parameters (shear stiffness [SS], storage modulus, loss modulus, and damping ratio [DR]) were determined at 3D MR elastography at 60 Hz, and multivariable logistic or linear regression analysis was used to assess associations of mechanical parameters with histologic scores and HVPG. Results A total of 155 participants (median age, 41 years [interquartile range, 32-48 years]; 85 women) were in group 1 (training set: n = 78, validation set: n = 77), 85 participants (median age, 57 years [interquartile range, 43-61 years]; 51 women) in group 2, and 60 healthy volunteers (median age, 49 years [interquartile range, 27-64 years]; 38 men) in group 3. The liver DR was higher in participants with necroinflammation (DR, 0.13 ± 0.03) versus those without (at liver fibrosis stage F0) (DR, 0.10 ± 0.02; P < .001). Liver DR and SS together performed well in the diagnosis of necroinflammation (area under the receiver operating characteristic curve [AUC], 0.88 [95% CI: 0.79, 0.96]) and the scoring of moderate to severe activity (AUC, 0.88 [95% CI: 0.81, 0.95]) in the validation data set. Liver DR (regression coefficient [ß] = -30.3 [95% CI: -58.0, -2.5]; P = .03) and splenic SS (ß = 2.3 [95% CI: 1.7, 2.9]; P < .001) were independently associated with HVPG. Conclusion Three-dimensional MR elastography may detect early necroinflammation, distinguish necroinflammation from liver fibrosis, and correlate with hepatic venous pressure gradient in chronic hepatitis B and C. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Reeder in this issue.

The Selection of Treatment Modality for Breast Ductal Carcinoma In Situ: Experience From a Single Institution.

PURPOSE: Although breast conservation surgery(BCS) followed by adjuvant radiotherapy is now the mainstream treatment method for breast ductal carcinoma in situ(DCIS), mastectomy is still performed in some patients who refuse to undergo radiation. However, the most effective treatment method for these patients is still unknown. In the current study, we aimed to compare the survival rates between mastectomy and BCS plus adjuvant radiotherapy in patients with DCIS. MATERIALS AND METHODS: We performed a retrospective study of 333 patients with DCIS from May 2004 to December 2016. There were 209 patents who were treated with BCS and adjuvant radiotherapy, while the remaining of 124 patients underwent mastectomy. The disease-free survival (DFS) and local recurrence-free survival(LRFS) rates were compared between the 2 treatment groups. Cox proportional hazards regression was performed to explore factors associated with DFS and LRFS. RESULTS: The 10-year local recurrence(LR) rates in the mastectomy and BCS plus adjuvant radiotherapy groups were 2.6% and 7.5%, respectively. There was no difference in the LR rate between the 2 groups. Furthermore the DFS rate was also similar between the mastectomy and BCS plus adjuvant radiotherapy groups. Based on the multivariable analysis, age and tumor grade were significantly correlated with the LRFS and DFS rates. In the subgroup analysis based on the factors of age and tumor grade, patients with a tumor grade of III who underwent mastectomy had better LRFS and DFS rates compared to those who received BCS plus radiotherapy. CONCLUSION: In patients with DCIS, the long-term efficacy was similar between mastectomy and BCS followed by adjuvant radiotherapy. However, in the subgroup of patients with grade III tumors, mastectomy seems to offer a better LRFS and DFS than BCS plus radiotherapy.

Excess Heritability Contribution of Alcohol Consumption Variants in the "Missing Heritability" of Type 2 Diabetes Mellitus.

We aim to compare the relative heritability contributed by variants of behavior-related environmental phenotypes and elucidate the role of these factors in the conundrum of "missing heritability" of type 2 diabetes. Methods: We used Linkage-Disequilibrium Adjusted Kinships (LDAK) and LDAK-Thin models to calculate the relative heritability of each variant and compare the relative heritability for each phenotype. Biological analysis was carried out for the phenotype whose variants made a significant contribution. Potential hub genes were prioritized based on topological parameters of the protein-protein interaction network. We included 16 behavior-related phenotypes and 2607 valid variants. In the LDAK model, we found the variants of alcohol consumption and caffeine intake were identified as contributing higher relative heritability than that of the random variants. Compared with the relative expected heritability contributed by the variants associated with type 2 diabetes, the relative expected heritability contributed by the variants associated with these two phenotypes was higher. In the LDAK-Thin model, the relative heritability of variants of 11 phenotypes was statistically higher than random variants. Biological function analysis showed the same distributions among type 2 diabetes and alcohol consumption. We eventually screened out 31 hub genes interacting intensively, four of which were validated and showed the upregulated expression pattern in blood samples seen in type 2 diabetes cases. Conclusion: We found that alcohol consumption contributed higher relative heritability. Hub genes may influence the onset of type 2 diabetes by a mediating effect or a pleiotropic effect. Our results provide new insight to reveal the role of behavior-related factors in the conundrum of "missing heritability" of type 2 diabetes.

Association between vascular endothelial growth factor gene polymorphisms and PCOS risk: a meta-analysis.

Vascular endothelial growth factor (VEGF) plays important roles in the pathogenesis of polycystic ovary syndrome (PCOS). Several single nucleotide polymorphisms (SNP) of the VEGF gene have been identified and are associated with the aberrant secretion of VEGF protein. This meta-analysis aimed to evaluate the impact of the VEGF +405G>C (rs2010963), -460C>T (rs833061) and -2578A>C (rs699947) polymorphisms on PCOS susceptibility. A systematic search of the Embase, PubMed, Web of Science and Wanfang databases was carried out to identify relevant studies published before 19 July 2019. Seven eligible studies were included in this meta-analysis involving 1100 patients with PCOS and 1141 control individuals. The pooled analysis revealed no significant association between PCOS risk and the +405G>C (rs2010963), -460C>T (rs833061) or -2578A>C (rs699947) polymorphisms in women. Subgroup analysis by ethnicity indicated that Asian women carrying the VEGF +405C allele had a lower risk of PCOS (C versus G: odds ratio [OR] 0.731, 95% confidence interval [CI] 0.544-0.982, P < 0.05, I2 = 46.4%; CG versus GG: OR 0.667, 95% CI 0.469-0.948, P < 0.05, I2 = 18.4%; CC versus GG: OR 0.611, 95% CI 0.390-0.958, P < 0.05, I2 = 24.3%). The study demonstrates that for all women regardless of ethnicity, no significant associations between VEGF SNP and PCOS were observed; however, +405G>C (rs2010963) may protect Asian women from PCOS.

Evaluation of fixed-jaw IMRT and tangential partial-VMAT radiotherapy plans for synchronous bilateral breast cancer irradiation based on a dosimetric study.

PURPOSE: To investigate the fixed-jaw intensity-modulated radiotherapy (F-IMRT) and tangential partial volumetric modulated arc therapy (tP-VMAT) treatment plans for synchronous bilateral breast cancer (SBBC). MATERIALS AND METHOD: Twelve SBBC patients with pTis-2N0M0 stages who underwent whole-breast irradiation after breast-conserving surgery were planned with F-IMRT and tP-VMAT techniques prescribing 42.56 Gy (2.66 Gy*16f) to the breast. The F-IMRT used 8-12 jaw-fixed tangential fields with single (sF-IMRT) or two (F-IMRT) isocenters located under the sternum or in the center of the left and right planning target volumes (PTVs), and tP-VMAT used 4 tangential partial arcs with two isocenters located in the center of the left and right PTVs. Plan evaluation was based on dose-volume histogram (DVH) analysis. Dosimetric parameters were calculated to evaluate plan quality; total monitor units (MUs), and the gamma analysis for patient-specific quality assurance (QA) were also evaluated. RESULTS: For PTVs, the three plans had similar Dmean and conformity index (CI) values. F-IMRT showed a slightly better target coverage according to the V100% values and demonstrated an obvious reduction in V105% and Dmax compared with the values observed for sF-IMRT and tP-VMAT. Compared with tP-VMAT, sF-IMRT was slightly better in terms of V100% , V105% and Dmax . In addition, F-IMRT achieved the best homogeneity index (HI) values for PTVs. Concerning healthy tissue, tP-VMAT had an advantage in minimizing the high dose volume. The MUs of the tP-VMAT plan were decreased approximately 1.45 and 1 times compared with the sF-IMRT and F-IMRT plans, respectively, and all plans passed QA. For the lungs, heart and liver, F-IMRT achieved the smallest values in terms of Dmean and showed a significant difference compared with tP-VMAT. Simultaneously, sF-IMRT was also superior to tP-VMAT. For the coronary artery, tP-VMAT achieved the lowest Dmean , while the value for F-IMRT was 2.24% lower compared with sF-IMRT. For all organs at risk (OARs), tP-VMAT was superior at the high dose level. In contrast, sF-IMRT and F-IMRT were obviously superior at the low dose level. The sF-IMRT and F-IMRT plans showed consistent trends. CONCLUSION: All treatment plans for the provided techniques were of high quality and feasible for SBBC patients. However, we recommend F-IMRT with a single isocenter as a priority technique because of the tremendous advantage of local hot spot control in PTVs and the reduced dose to OARs at low dose levels. When the irradiated dose to the lungs and heart exceed the clinical restriction, two isocenter F-IMRT can be used to maximize OAR sparing. Additionally, tP-VMAT can be adopted for improving cold spots in PTVs or high-dose exposure to normal tissue when the interval between PTVs is narrow.

Computed Tomography Features of Septic Pulmonary Embolism Caused by Klebsiella pneumoniae Liver Abscess Associated With Extrapulmonary Metastatic Infection.

OBJECTIVES: The aims of the study were to investigate the computed tomography (CT) features and clinical course of septic pulmonary embolism (SPE) caused by Klebsiella pneumoniae liver abscess (KPLA) and to explore the possible mechanism underlying the spread of infection. METHODS: Twenty-one patients with KPLA-induced SPE admitted to our hospital between January 2010 and May 2015 were evaluated. According to the presence or absence of extrapulmonary metastatic infection (EMI), they were divided into EMI and non-EMI groups and clinical and CT features of the 2 groups were compared. Hepatic vein thrombophlebitis was evaluated on liver CT images. Chest CT features included nodules, wedge-shaped lesions, ground-glass opacity, consolidation, cavitation, feeding vessel sign, pleural effusion, and lymphadenopathy. RESULTS: All the vessels within the so-called feeding vessel sign were confirmed as pulmonary veins by multiplanar reconstruction, so we used an alternative name draining vessel sign (DVS) instead. Peripheral nodules, DVS, and consolidation were the main CT features of KPLA-induced SPE. Peripheral nodules and DVS were more frequently seen in the EMI group than in the non-EMI group (P = 0.019 and 0.008, respectively). Five of 8 patients with hepatic vein thrombophlebitis had lung consolidation, whereas only 3 of 13 patients without hepatic vein thrombophlebitis had lung consolidation, although the difference was not significant (P = 0.09). CONCLUSIONS: Multiple pulmonary nodules and DVS were associated with EMI. Hepatic and pulmonary vein invasion are possible causes underlying the metastatic spread of infection.

Shared Genetic Architectures between Coronary Artery Disease and Type 2 Diabetes Mellitus in East Asian and European Populations.

Coronary artery disease (CAD) is a common comorbidity of type 2 diabetes mellitus (T2DM). However, the pathophysiology connecting these two phenotypes remains to be further understood. Combined analysis in multi-ethnic populations can help contribute to deepening our understanding of biological mechanisms caused by shared genetic loci. We applied genetic correlation analysis and then performed conditional and joint association analyses in Chinese, Japanese, and European populations to identify the genetic variants jointly associated with CAD and T2DM. Next, the associations between genes and the two traits were also explored. Finally, fine-mapping and functional enrichment analysis were employed to identify the potential causal variants and pathways. Genetic correlation results indicated significant genetic overlap between CAD and T2DM in the three populations. Over 10,000 shared signals were identified, and 587 were shared by East Asian and European populations. Fifty-six novel shared genes were found to have significant effects on both CAD and T2DM. Most loci were fine-mapped to plausible causal variant sets. Several similarities and differences of the involved genes in GO terms and KEGG pathways were revealed across East Asian and European populations. These findings highlight the importance of immunoregulation, neuroregulation, heart development, and the regulation of glucose metabolism in shared etiological mechanisms between CAD and T2DM.

Effect of sucrose-based carbon foams as negative electrode additive on the performance of lead-acid batteries under high-rate partial-state-of-charge condition.

Lead-acid batteries are noted for simple maintenance, long lifespan, stable quality, and high reliability, widely used in the field of energy storage. However, during the use of lead-acid batteries, the negative electrode is prone to irreversible sulfation, failing to meet the requirements of new applications such as maintenance-free hybrid vehicles and solar energy storage. In this study, in order to overcome the sulfation problem and improve the cycle life of lead-acid batteries, active carbon (AC) was selected as a foaming agent and foam fixing agent, and carbon foams (CF) with layered porous structure was prepared by mixing with molten sucrose. Sucrose as raw material is green and cheap, and the material preparation process is simple. The prepared CF material was then added as an additive to the negative electrode plate, and the electrochemical performance of the electrode plate and the battery was studied. The results proved that the addition of CF could effectively inhibit the sulfate formation of the negative electrode plate, with the 1.0 % CF negative electrode plate showing the best electrochemical performance. Specifically, according to the result of battery cycle testing, the simulated battery with CF had a cycle life of 3642 times, which was 2.87 times that of the blank group and 2.39 times of the AC group. Meanwhile, rate testing showed that the simulated battery with CF could maintain a high capacity even under high-rate discharge conditions.

Association between periodontitis and COVID-19 infection: a two-sample Mendelian randomization study.

Background and Objective: Epidemiological studies report associations between coronavirus disease 2019 (COVID-19) and periodontitis; however, causality has not been proven. The aim of this study is to assess the associations between COVID-19 susceptibility and periodontitis with two-sample Mendelian randomization (MR) analyses. Methods: A two-sample summary MR analysis was performed using data for outcome and exposure from the OpenGWAS database on people of European descent. Periodontal complex traits (PCTs) were chosen as a proxy for the periodontitis phenotype. The causal association between PCT3 (Aggregatibacter actinomycetemcomitans), PCT5 (Porphyromonas gingivalis), and gingival crevicular fluid (GCF) interleukin-1ß (IL-1ß) and COVID-19 were considered. Genome-wide association study (GWAS) data with the two largest sample sizes were selected as COVID-19 outcomes (datasets ebi-a-GCST010776 and ebi-a-GCST010777). Single-nucleotide polymorphisms (SNPs) associated with PCT3, PCT5, and GCF IL-1ß at statistical significance at genome-wide level (P < 5 × 10-8) were identified as genetic instruments. We used two-sample summary MR methods and tested the existence of a pleiotropic effect with MR-Egger. Results: Inverse-variance weighted (IVW) estimates showed that there was a positive association between COVID-19 risk and periodontitis (ebi-a-GCST010776: odds ratio [OR] = 1.02 (95% confidence interval (CI), 1.00-1.05), P = 0.0171; ebi-a-GCST010777: OR = 1.03 (95% CI, 1.00-1.05), P = 0.0397). The weighted median also showed directionally similar estimates. Exploration of the causal associations between other PCTs and COVID-19 identified a slight effect of local inflammatory response (GCF IL-1ß) on COVID-19 risk across the two datasets (ebi-a-GCST010776: IVW OR = 1.02 (95% CI, [1.01-1.03]), P < 0.001; ebi-a-GCST010777: IVW OR = 1.03 (95% CI, [1.02-1.04]), P < 0.001). The intercepts of MR-Egger yielded no proof for significant directional pleiotropy for either dataset (ebi-a-GCST010776: P = 0.7660; ebi-a-GCST010777: P = 0.6017). Conclusions: The findings suggests that periodontitis and the higher GCF IL-1ß levels is causally related to increase susceptibility of COVID-19. However, given the limitations of our study, the well-designed randomized controlled trials are needed to confirm its findings, which may represent a new non-pharmaceutical intervention for preventing COVID-19.

Factors associated with compassion fatigue and compassion satisfaction in obstetrics and gynaecology nurses: A cross-sectional study.

AIMS: To examine the factors influencing compassion fatigue and compassion satisfaction in obstetrics and gynaecology nurses and to explore the combined results of multiple factors. DESIGN: An online cross-sectional study was conducted. REVIEW METHODS: Data were collected from 311 nurses using a convenience sampling method from January to February 2022. Stepwise multiple linear regression analysis and mediation tests were performed. RESULTS: Compassion fatigue in obstetrics and gynaecology nurses was in the moderate to high levels. Physical status, number of children, emotional labour, lack of professional efficacy, emotional exhaustion and the none-only-child can influence compassion fatigue; lack of professional efficacy, cynicism, social support, work experience, employment status and night shift were predictive of compassion satisfaction. Social support partially mediated between lack of professional efficacy and compassion fatigue/compassion satisfaction; emotional labour moderated in the mediated analysis model. CONCLUSION: Moderate to high levels of compassion fatigue was present in 75.88% of obstetrics and gynaecology nurses. Some factors affect compassion fatigue and compassion satisfaction. Thus, nursing managers should consider factors and construct a monitoring system to reduce compassion fatigue and improve compassion satisfaction. IMPLICATIONS FOR THE PROFESSION: The results will provide a theoretical basis for improving job satisfaction and the quality of care in obstetrics and gynaecology nurses. And this may raise concerns about the occupational health of obstetrics and gynaecology nurses in China. REPORTING METHOD: The study was reported according to the STROBE. PATIENT OR PUBLIC CONTRIBUTION: The nurses spent time filling out the questionnaires during the data collection phase and answered the questions sincerely. WHAT DOES THIS ARTICLE CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: Obstetrics and gynaecology nurses with 4-16 years of experience are prone to experience compassion fatigue. The effect of lack of professional efficacy on compassion fatigue and compassion satisfaction can be improved by social support. RELEVANCE TO CLINICAL PRACTICE: Reducing nurse compassion fatigue and improving compassion satisfaction are important for providing quality nursing care to obstetrics and gynaecology patients. In addition, clarifying the influencing factors of compassion fatigue and compassion satisfaction can improve nurses' work efficiency and job satisfaction, and provide theoretical guidance for managers to implement interventions.

Safety and Effectiveness of a Novel Tips Access Set with Steerable Cannula in a Swine Model.

PURPOSE: This study aimed to assess the safety, effectiveness, and feasibility of the Liverty™ transjugular intrahepatic portosystemic shunt (TIPS) access set, which has an ergonomic handle that allows for in situ cannula tip deflection and a distal steerable cannula angle, versus the COOK® Rosch-Uchida Transjugular Liver Access Set (RUPS-100) in healthy pigs. METHODS: Twelve pigs randomly underwent TIPS with the Liverty™ set or the RUPS-100 set. Three interventionalists performed 4 TIPS procedures, 2 with each set. The primary outcome was procedural success, defined as successful establishment of the intrahepatic portosystemic shunt and stent placement. RESULTS: The shunt was successfully established in 11 pigs. The procedural success was achieved in all 6 pigs in the Liverty™ group and 5 out of 6 pigs for the RUPS-100 group (Fisher exact test, P > 0.999). The mean duration of puncture was shorter in the Liverty™ group versus the RUPS-100 group (12.3 ± 4.5 min vs. 16.2 ± 8.5 min), but without significant statistical difference (two sample t test, P = 0.359). The cannula angle was adjusted 69% of passes in the Liverty™ group, which was significantly higher than that in the RUPS-100 group (12%, P = 0.004). Overall, the TIPS procedural performance was comparable between the groups. Both sets were safe. No intraabdominal hemorrhage, vascular injuries, tissue or organ injuries, porto-biliary fistula, biliary peritonitis, and infection or abscess occurred in either group. CONCLUSION: The Liverty™ set is safe and has similar procedural metrics to the COOK® RUPS-100 set. It allows in situ adjustment of the angle of the stiffening cannula without increasing procedure time and lessens the occurrences of periprocedural complications.

Primary Treatment for Clinically Early Cervical Cancer with Lymph Node Metastasis: Radical Surgery or Radiation?

OBJECTIVE: To compare survival outcomes between primary radical surgery and primary radiation in early cervical cancer. METHODS: Patient information was extracted from the Surveillance, Epidemiology, and Results database. Patients diagnosed with early cervical cancer of stage T1a, T1b, and T2a (American Joint Committee on Cancer, 7th edition) from 1998 to 2015 were included in this study after propensity score matching. Overall survival (OS) was analyzed using the Kaplan-Meier method. RESULTS: Among the 4964 patients included in the study, 1080 patients were identified as having positive lymph nodes (N1), and 3884 patients were identified as having negative lymph nodes (N0). Patients with primary surgery had significantly longer 5-year OS than those with primary radiotherapy in both the N1 group (P<0.001) and N0 group (P<0.001). In the subgroup analysis, similar results were found in patients with positive lymph nodes of stage T1a (100.0% vs. 61.1%), T1b (84.1% vs. 64.3%), and T2a (74.4% vs. 63.8%). In patients with T1b1 and T2a1, primary surgery resulted in longer OS than primary radiation, but not in patients with T1b2 and T2a2. In multivariate analysis, the primary treatment was identified as an independent prognostic factor in both N1 and N0 patients (HRN1=2.522, 95% CI=1.919-3.054, PN1<0.001; HRN0=1.895, 95% CI=1.689-2.126, PN0<0.001). CONCLUSION: In early cervical cancer stage T1a, T1b1, and T2a1, primary surgery may result in longer OS than primary radiation for patients with and without lymph node metastasis.