Identifying selection signatures for immune response and resilience to Aleutian disease in mink using genotype data.

Aleutian disease (AD) brings tremendous financial losses to the mink industry. Selecting AD-resilient mink has been conducted to control AD. Such selections could have altered the patterns of genetic variation responding to selection pressures. This study aimed to identify selection signatures for immune response (IRE) and resilience to AD. A total of 1,411 mink from an AD-positive facility were used. For IRE, 264 animals were categorized according to the combined results of enzyme-linked immunosorbent assay (ELISA) and counterimmunoelectrophoresis (CIEP). For resilience, two grouping methods were used: 1) general resilience performance (GRP, n = 30) was evaluated based on the feed conversion ratio, Kleiber ratio, and pelt quality; and 2) female reproductive performance (FRP, n = 36) was measured based on the number of kits alive 24 h after birth. Detection methods were the pairwise fixation index, nucleotide diversity, and cross-population extended haplotype homozygosity. A total of 619, 569, and 526 SNPs were identified as candidates for IRE, GRP, and FRP, respectively. The annotated genes were involved in immune system process, growth, reproduction, and pigmentation. Two olfactory-related Gene Ontology (GO) terms were significant (q < 0.05) for all traits, suggesting the impact of AD on the sense of smell of infected mink. Differences in detected genes and GO terms among different color types for IRE indicated variations in immune response to AD among color types. The mitogen-activated protein kinase (MAPK) signaling pathway was significant (q < 0.05) for FRP, suggesting that AD may disrupt MAPK signaling and affect FRP. The findings of this research contribute to our knowledge of the genomic architecture and biological mechanisms underlying AD resilience in mink.

Identification of consensus homozygous regions and their associations with growth and feed efficiency traits in American mink.

The recent chromosome-based genome assembly and the newly developed 70K single nucleotide polymorphism (SNP) array for American mink (Neogale vison) facilitate the identification of genetic variants underlying complex traits in this species. The objective of this study was to evaluate the association between consensus runs of homozygosity (ROH) with growth and feed efficiency traits in American mink. A subsample of two mink populations (n = 2,986) were genotyped using the Affymetrix Mink 70K SNP array. The identified ROH segments were included simultaneously, concatenated into consensus regions, and the ROH-based association studies were carried out with linear mixed models considering a genomic relationship matrix for 11 growth and feed efficiency traits implemented in ASReml-R version 4. In total, 298,313 ROH were identified across all individuals, with an average length and coverage of 4.16 Mb and 414.8 Mb, respectively. After merging ROH segments, 196 consensus ROH regions were detected and used for genome-wide ROH-based association analysis. Thirteen consensus ROH regions were significantly (P < 0.01) associated with growth and feed efficiency traits. Several candidate genes within the significant regions are known for their involvement in growth and body size development, including MEF2A, ADAMTS17, POU3F2, and TYRO3. In addition, we found ten consensus ROH regions, defined as ROH islands, with frequencies over 80% of the population. These islands harbored 12 annotated genes, some of which were related to immune system processes such as DTX3L, PARP9, PARP14, CD86, and HCLS1. This is the first study to explore the associations between homozygous regions with growth and feed efficiency traits in American mink. Our findings shed the light on the effects of homozygosity in the mink genome on growth and feed efficiency traits, that can be utilized in developing a sustainable breeding program for mink.

Integrated metabolomics and transcriptomics reveal that HhERF9 positively regulates salt tolerance in Hibiscus hamabo Siebold & Zuccarini.

Hibiscus hamabo Siebold & Zuccarini is one of the few semi-mangrove plants in the genus Hibiscus that can survive in saline-alkali soil and flooded land, but the mechanism underlying its adaptation to salt soil remains unknown. Here, to uncover this unsolved mystery, we characterized the changes in the accumulation of specific metabolites under salt stress in H. hamabo by integrating physiological, metabolic, and transcriptomic data, and found that osmotic adjustment and abscisic acid (ABA) is highly associated with the salt stress response. Further, a weighted gene co-expression network analysis was performed on the root transcriptome data, which identified three key candidate transcription factors responsive to salt stress. Among them, the expression HhERF9 was significantly upregulated under salt stress and ABA treatment and was involved in regulating the expression of genes related to the salt stress response. Further research indicated that HhERF9 enhances the accumulation of proline and soluble sugars by regulating the expression of genes such as NHX2 and P5CS. These findings provide a reference for improving H. hamabo through targeted genetic engineering and lay a theoretical foundation for its future promotion and cultivation in saline-alkali areas.

Underwater light source changes microecosystem constructed by Vallisneria spinulosa Yan for water restoration: Efficiency of water purification, characteristics of growth, and rhizosphere.

Submerged macrophytes are effective in ecological restoration of water bodies polluted by nitrogen and phosphorus, and its restoration capacity depends on underwater illumination condition. This study explored the influencing mechanism of illumination on Vallisneria spinulosa Yan (V. spinulosa Yan) for water restoration. Addition of underwater light source increased the total nitrogen, ammonia nitrogen, total phosphorus, and phosphate removal loads of the V. spinulosa Yan growth system by 61.5, 39.2, 8.5, and 5.0 mg m-2 d-1, respectively. Meanwhile, the growth of V. spinulosa Yan was obviously promoted, even with high water turbidity. Although the biological nitrogen removal processes were inhibited by adding underwater light source, the growth of V. spinulosa Yan can be significantly improved, thus enhancing the efficiency of water purification via the absorption of nitrogen and phosphorus by V. spinulosa Yan. This study provides a theoretical foundation and technical support for application of submerged macrophytes in ecological water restoration.

Detection of optical properties of chiral substances by a photoconductive THz polarization detector.

Chiral enantiomers have significant differences in biochemical functions. The use of THz wave polarization detection to characterize the optical properties of chiral substances is of great significance to the development of life science and the identification and application of chiral substances. However, the traditional polarization detection procedures of THz waves are complex, which limits the study of chiral substances. Herein, we proposed a high-sensitivity THz polarization detector, which can simultaneously obtain the change information of amplitude, phase, and polarization state through a single measurement. The optical rotation and elliptical angle of solid and liquid D/L-Glutamic acid 5-methyl ester in the THz band are studied. Then it is verified that anisotropic interference may occur in the preparation of solid samples. Finally, the effects of sample content and thickness on polarization are obtained. The experimental results show that different chirality has the opposite effect on the state of polarization, and the difference between chiral enantiomers can be detected by this method. This work is of great significance for understanding the optical properties of chiral substances and promoting the development of chiral recognition.

Germline cis variant determines epigenetic regulation of the anti-cancer drug metabolism gene dihydropyrimidine dehydrogenase (DPYD).

Enhancers are critical for regulating tissue-specific gene expression, and genetic variants within enhancer regions have been suggested to contribute to various cancer-related processes, including therapeutic resistance. However, the precise mechanisms remain elusive. Using a well-defined drug-gene pair, we identified an enhancer region for dihydropyrimidine dehydrogenase (DPD, DPYD gene) expression that is relevant to the metabolism of the anti-cancer drug 5-fluorouracil (5-FU). Using reporter systems, CRISPR genome-edited cell models, and human liver specimens, we demonstrated in vitro and vivo that genotype status for the common germline variant (rs4294451; 27% global minor allele frequency) located within this novel enhancer controls DPYD transcription and alters resistance to 5-FU. The variant genotype increases recruitment of the transcription factor CEBPB to the enhancer and alters the level of direct interactions between the enhancer and DPYD promoter. Our data provide insight into the regulatory mechanisms controlling sensitivity and resistance to 5-FU.

Ubiquitinome Analysis Uncovers Alterations in Synaptic Proteins and Glucose Metabolism Enzymes in the Hippocampi of Adolescent Mice Following Cold Exposure.

Cold exposure exerts negative effects on hippocampal nerve development in adolescent mice, but the underlying mechanisms are not fully understood. Given that ubiquitination is essential for neurodevelopmental processes, we attempted to investigate the effects of cold exposure on the hippocampus from the perspective of ubiquitination. By conducting a ubiquitinome analysis, we found that cold exposure caused changes in the ubiquitination levels of a variety of synaptic-associated proteins. We validated changes in postsynaptic density-95 (PSD-95) ubiquitination levels by immunoprecipitation, revealing reductions in both the K48 and K63 polyubiquitination levels of PSD-95. Golgi staining further demonstrated that cold exposure decreased the dendritic-spine density in the CA1 and CA3 regions of the hippocampus. Additionally, bioinformatics analysis revealed that differentially ubiquitinated proteins were enriched in the glycolytic, hypoxia-inducible factor-1 (HIF-1), and 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathways. Protein expression analysis confirmed that cold exposure activated the mammalian target of rapamycin (mTOR)/HIF-1α pathway. We also observed suppression of pyruvate kinase M2 (PKM2) protein levels and the pyruvate kinase (PK) activity induced by cold exposure. Regarding oxidative phosphorylation, a dramatic decrease in mitochondrial respiratory-complex I activity was observed, along with reduced gene expression of the key subunits NADH: ubiquinone oxidoreductase core subunit V1 (Ndufv1) and Ndufv2. In summary, cold exposure negatively affects hippocampal neurodevelopment and causes abnormalities in energy homeostasis within the hippocampus.

Defective transfer of parental histone decreases frequency of homologous recombination by increasing free histone pools in budding yeast.

Recycling of parental histones is an important step in epigenetic inheritance. During DNA replication, DNA polymerase epsilon subunit DPB3/DPB4 and DNA replication helicase subunit MCM2 are involved in the transfer of parental histones to the leading and lagging strands, respectively. Single Dpb3 deletion (dpb3Δ) or Mcm2 mutation (mcm2-3A), which each disrupts one parental histone transfer pathway, leads to the other's predominance. However, the biological impact of the two histone transfer pathways on chromatin structure and DNA repair remains elusive. In this study, we used budding yeast Saccharomyces cerevisiae to determine the genetic and epigenetic outcomes from disruption of parental histone H3-H4 tetramer transfer. We found that a dpb3Δ mcm2-3A double mutant did not exhibit the asymmetric parental histone patterns caused by a single dpb3Δ or mcm2-3A mutation, suggesting that the processes by which parental histones are transferred to the leading and lagging strands are independent. Surprisingly, the frequency of homologous recombination was significantly lower in dpb3Δ, mcm2-3A and dpb3Δ mcm2-3A mutants, likely due to the elevated levels of free histones detected in the mutant cells. Together, these findings indicate that proper transfer of parental histones during DNA replication is essential for maintaining chromatin structure and that lower homologous recombination activity due to parental histone transfer defects is detrimental to cells.

Characterization of runs of homozygosity islands in American mink using whole-genome sequencing data.

The genome-wide analysis of runs of homozygosity (ROH) islands can be an effective strategy for identifying shared variants within a population and uncovering important genomic regions related to complex traits. The current study performed ROH analysis to characterize the genome-wide patterns of homozygosity, identify ROH islands and annotated genes within these candidate regions using whole-genome sequencing data from 100 American mink (Neogale vison). After sequence processing, variants were called using GATK and Samtools pipelines. Subsequent to quality control, 8,373,854 bi-allelic variants identified by both pipelines remained for further analysis. A total of 34,652 ROH segments were identified in all individuals, among which shorter segments (0.3-1 Mb) were abundant throughout the genome, approximately accounting for 84.39% of all ROH. Within these segments, we identified 63 ROH islands housing 156 annotated genes. The genes located in ROH islands were associated with fur quality (EDNRA, FGF2, FOXA2 and SLC24A4), body size/weight (MYLK4, PRIM2, FABP2, EYS and PHF3), immune capacity (IL2, IL21, PTP4A1, SEMA4C, JAK2, CCNA2 and TNIP3) and reproduction (ADAD1, KHDRBS2, INSL6, PGRMC2 and HSPA4L). Furthermore, Gene Ontology and KEGG pathway enrichment analyses revealed 56 and 9 significant terms (FDR-corrected p-value < 0.05), respectively, among which cGMP-PKG signalling pathway, regulation of actin cytoskeleton, and calcium signalling pathway were highlighted due to their functional roles in growth and fur characteristics. This is the first study to present ROH islands in American mink. The candidate genes from ROH islands and functional enrichment analysis suggest possible signatures of selection in response to the mink breeding targets, such as increased body length, reproductive performance and fur quality. These findings contribute to our understanding of genetic characteristics, and provide complementary information to assist with implementation of breeding strategies for genetic improvement in American mink.

Molecular Mechanism of Different Rooting Capacity between Two Clones of Taxodium hybrid 'Zhongshanshan'.

The conifer Taxodium hybrid 'Zhongshanshan' (T. hybrid 'Zhongshanshan') is characterized by rapid growth, strong stress resistance, and high ornamental value and has significant potential for use in afforestation, landscaping, and wood production. The main method of propagating T. hybrid 'Zhongshanshan' is tender branch cutting, but the cutting rooting abilities of different T. hybrid 'Zhongshanshan' clones differ significantly. To explore the causes of rooting ability differences at a molecular level, we analyzed the transcriptome data of cutting base and root tissues of T. hybrid 'Zhongshanshan 149' with a rooting rate of less than 5% and T. hybrid 'Zhongshanshan 118' with rooting rate greater than 60%, at the developmental time points in this study. The results indicated that differentially expressed genes between the two clones were mainly associated with copper ion binding, peroxidase, and oxidoreductase activity, response to oxidative stress, phenylpropanoid and flavonoid biosynthesis, and plant hormone signal transduction, among others. The expression pattern of ThAP2 was different throughout the development of the adventitive roots of the two clone cuttings. Therefore, this gene was selected for further study. It was shown that ThAP2 was a nuclear-localized transcription factor and demonstrated a positive feedback effect on rooting in transgenic Nicotiana benthamiana cuttings. Thus, the results of this study explain the molecular mechanism of cutting rooting and provide candidate gene resources for developing genetic breeding strategies for optimizing superior clones of T. hybrid 'Zhongshanshan'.

The Role of Hexokinases in Epigenetic Regulation: Altered Hexokinase Expression and Chromatin Stability in Yeast.

Background . Human hexokinase 2 ( HK2 ) plays an important role in regulating Warburg effect, which metabolizes glucose to lactate acid even in the presence of ample oxygen and provides intermediate metabolites to support cancer cell proliferation and tumor growth. HK2 overexpression has been observed in various types of cancers and targeting HK2 -driven Warburg effect has been suggested as a potential cancer therapeutic strategy. Given that epigenetic enzymes utilize metabolic intermediates as substrates or co-factors to carry out post-translational modification of DNA and histones in cells, we hypothesized that altering HK2 expression-mediated cellular glycolysis rates could impact the epigenome and, consequently, genome stability in yeast. To test this hypothesis, we established genetic models with different yeast hexokinase 2 ( HXK2) expression in Saccharomyces cerevisiae yeast cells and investigated the effect of HXK2 -dependent metabolism on parental nucleosome transfer, a key DNA replication-coupled epigenetic inheritance process, and chromatin stability. Results . By comparing the growth of mutant yeast cells carrying single deletion of hxk1Δ , hxk2Δ , or double-loss of hxk1Δ hxk2Δ to wild-type cells, we demonstrated that HXK2 is the dominant HXK in yeast cell growth. Surprisingly, manipulating HXK2 expression in yeast, whether through overexpression or deletion, had only a marginal impact on parental nucleosome assembly, but a noticeable trend with decrease chromatin instability. However, targeting yeast cells with 2-deoxy-D-glucose (2-DG), a HK2 inhibitor that has been proposed as an anti-cancer treatment, significantly increased chromatin instability. Conclusion . Our findings suggest that in yeast cells lacking HXK2 , alternative HXK s such as HXK1 or glucokinase 1 ( GLK1 ) play a role in supporting glycolysis at a level that adequately maintain epigenomic stability. While our study demonstrated an increase in epigenetic instability with 2-DG treatment, the observed effect seemed to occur independently of Hxk2-mediated glycolysis inhibition. Thus, additional research is needed to identify the molecular mechanism through which 2-DG influences chromatin stability.

Genome-wide association studies for economically important traits in mink using copy number variation.

Copy number variations (CNVs) are structural variants consisting of duplications and deletions of DNA segments, which are known to play important roles in the genetics of complex traits in livestock species. However, CNV-based genome-wide association studies (GWAS) have remained unexplored in American mink. Therefore, the purpose of the current study was to investigate the association between CNVs and complex traits in American mink. A CNV-based GWAS was performed with the ParseCNV2 software program using deregressed estimated breeding values of 27 traits as pseudophenotypes, categorized into traits of growth and feed efficiency, reproduction, pelt quality, and Aleutian disease tests. The study identified a total of 10,137 CNVs (6968 duplications and 3169 deletions) using the Affymetrix Mink 70K single nucleotide polymorphism (SNP) array in 2986 American mink. The association analyses identified 250 CNV regions (CNVRs) associated with at least one of the studied traits. These CNVRs overlapped with a total of 320 potential candidate genes, and among them, several genes have been known to be related to the traits such as ARID1B, APPL1, TOX, and GPC5 (growth and feed efficiency traits); GRM1, RNASE10, WNT3, WNT3A, and WNT9B (reproduction traits); MYO10, and LIMS1 (pelt quality traits); and IFNGR2, APEX1, UBE3A, and STX11 (Aleutian disease tests). Overall, the results of the study provide potential candidate genes that may regulate economically important traits and therefore may be used as genetic markers in mink genomic breeding programs.

Evolution-based Shape and Behavior Co-design of Virtual Agents.

We introduce a novel co-design method for autonomous moving agents' shape attributes and locomotion by combining deep reinforcement learning and evolution with user control. Our main inspiration comes from evolution, which has led to wide variability and adaptation in Nature and has significantly improved design and behavior simultaneously. Our method takes an input agent with optional user-defined constraints, such as leg parts that should not evolve or are only within the allowed ranges of changes. It uses physics-based simulation to determine its locomotion and finds a behavior policy for the input design that is used as a baseline for comparison. The agent is randomly modified within the allowed ranges, creating a new generation of several hundred agents. The generation is trained by transferring the previous policy, which significantly speeds up the training. The best-performing agents are selected, and a new generation is formed using their crossover and mutations. The next generations are then trained until satisfactory results are reached. We show a wide variety of evolved agents, and our results show that even with only 10 the overall performance of the evolved agents improves by 50 experiments' performance will improve even more to 150 structures, and it does not require considerable computation resources as it works on a single GPU and provides results by training thousands of agents within 30 minutes.

Characterization of Methane Extraction during ScCO2-ECBM: Consideration of Competitive Adsorption of ScCO2 and CH4.

The supercritical CO2 enhanced coalbed methane (ScCO2-ECBM) technology is still in the development stage, and many simulation experiments and theoretical studies related to ScCO2-ECBM are being improved. Previous research works have conducted many studies on the competitive adsorption of CO2 and CH4 in coal, but there is less research on the competitive adsorption of ScCO2 and CH4 and its impact on methane extraction characteristics. In this study, a permeability model considering the competitive effects of effective stress and adsorption swelling on permeability was established. Based on the assumed conditions and permeability evolution model, different injected pressure and initial methane pressure conditions were set to obtain quantitative results of the competitive adsorption of ScCO2 and CH4, permeability changes, and CH4 production. By obtaining the competitive adsorption relationship between ScCO2 and CH4, we analyzed the evolution law of permeability and its impact on CH4 production. It was found that ScCO2 has a stronger competitive adsorption capacity, and the competitive adsorption capacity of ScCO2 and CH4 is more sensitive to injected pressure. Under two different conditions, it was found that the higher the injected pressure or injected differential pressure, the higher the initial permeability. However, due to the greater sensitivity of the competitive adsorption capacity of ScCO2 and CH4 to injected pressure, the greater the injected pressure in the later stage, the greater the decrease in permeability, resulting in a situation where the permeability at an injected pressure of 10 MPa is lower than that at an injected pressure of 8 MPa. A simple comparison was made between gaseous CO2 and ScCO2, and it was found that although injecting ScCO2 has a stronger adsorption swelling capacity that affects permeability changes, its stronger adsorption capacity can effectively displace methane and higher injected pressure, injected temperature, and advantages such as fracturing and extraction that are not yet reflected in the model. This study provides some guidance for numerical simulation of the ScCO2-ECBM process and the enhancement of coalbed methane extraction.

Germline cis variant determines epigenetic regulation of the anti-cancer drug metabolism gene dihydropyrimidine dehydrogenase (DPYD).

Enhancers are critical for regulating tissue-specific gene expression, and genetic variants within enhancer regions have been suggested to contribute to various cancer-related processes, including therapeutic resistance. However, the precise mechanisms remain elusive. Using a well-defined drug-gene pair, we identified an enhancer region for dihydropyrimidine dehydrogenase (DPD, DPYD gene) expression that is relevant to the metabolism of the anti-cancer drug 5-fluorouracil (5-FU). Using reporter systems, CRISPR genome edited cell models, and human liver specimens, we demonstrated in vitro and vivo that genotype status for the common germline variant (rs4294451; 27% global minor allele frequency) located within this novel enhancer controls DPYD transcription and alters resistance to 5-FU. The variant genotype increases recruitment of the transcription factor CEBPB to the enhancer and alters the level of direct interactions between the enhancer and DPYD promoter. Our data provide insight into the regulatory mechanisms controlling sensitivity and resistance to 5-FU.

A study on cholesterol-cholesteryl ester metabolic homeostasis and drug intervention in hyperlipidemic hamsters using UHPLC-MS/MS.

Hyperlipidemia is a global metabolic disorder characterized by dysregulation of lipid metabolism. This dysregulation is closely associated with the altered homeostasis of cholesterol-cholesteryl ester (CE) metabolism in systemic circulation, and some organs. Additionally, the relationship between oxidized cholesteryl ester (oxCE) and the disease has also gained attention. Currently, there is a lack of comprehensive research on the alterations in cholesterol-CE metabolism in the context of hyperlipidemia, as well as the characteristics of lipid-lowering agents in regulating this metabolic state. Therefore, 40 oxCEs were identified in the hamster liver sample, and novel ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) methods were established for simultaneous analysis of cholesterol, 57 CEs, and 40 oxCEs in the serum, liver, adipose tissue, and intestine of hyperlipidemic hamsters. This study investigated the metabolic alterations between cholesterol-CE/oxCE in hyperlipidemic hamsters and those treated with lipid-lowering agents, including the Niemann-Pick-C1 like-1 protein (NPC1L1) inhibitor ezetimibe and the acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitor avasimibe. The study findings demonstrate metabolic disorders in cholesterol-CE/oxCE homeostasis in hyperlipidemic hamsters. Lipid-lowering agent therapy can improve the metabolic dysregulation caused by hyperlipidemia, with distinct characteristics: ezetimibe is more effective in reducing cholesterol, while avasimibe is more effective in reducing CEs/oxCEs. Eight potential biomarkers indicating the dysregulation of cholesterol-CE metabolism caused by hyperlipidemia and its improvement by lipid-lowering agents have been identified in the serum. This study offers new insights into the hyperlipidemia pathophysiology and the mechanisms of lipid-lowering agents from a novel perspective on cholesterol-CE/oxCE metabolic homeostasis.

Prognostic Value of Platelet-to-Lymphocyte Ratio Combined with CHA2DS2-VASc Score for Nonvalvular Atrial Fibrillation Induced Cardiogenic Cerebral Embolism.

Aim: To determine the predictive significance of the platelet-to-lymphocyte ratio (PLR) combined with the CHA2DS2-VASc score for cardiogenic cerebral embolism (CCE) in patients with nonvalvular atrial fibrillation (NVAF). Methods: A total of 553 patients with NVAF were included in this retrospective study. The general data, PLR, CHA2DS2-VASc score and echocardiography indicators were compared. The risk factors for CCE and the predictive value of PLR and CHA2DS2-VASc were analyzed. Stratified analysis was performed based on the cut-off value. Least absolute shrinkage and selection operator (LASSO) regression analysis was utilized to build a model. The relationship between risk score and different anticoagulants was evaluated. Results: Multiple regression analysis showed hypertension (OR=3.95, 95% CI=2.12-7.35, p=1.40×10-5), diabetes mellitus (OR=2.95, 95% CI=1.57-5.58, p=7.65×10-4), PLR (OR=1.01, 95% CI=1.00-1.01, p<10-6), creatinine level (OR=1.01, 95% CI=1.00-1.02, p=7.44×10-3), left atrial diameter (LAD) (OR=1.90, 95% CI=1.13-3.19, p=1.51×10-2), ejection fraction (EF) (OR=0.93, 95% CI=0.87-0.98, p=8.06×10-3) and CHA2DS2-VASc score (OR=3.79, 95% CI=2.95-4.85, p<10-6) were independent risk factors for CCE. A one-way linear analysis also showed the above seven indexes were significantly correlated with CCE (F=56.4, p<10-6). The area under the receiver operating characteristic (ROC) curve of PLR and CHA2DS2-VASc score was 0.760 (95% CI:0.721-0.800), and 0.855 (95% CI: 0.824-0.886), respectively. Pearson correlation analysis showed that PLR was correlated with CHA2DS2-VASc score (r=0.331, p<10-6). Stratified analysis indicated there was a positive correlation between different risk group (p<10-6). Using the LASSO model, a composite indicator displayed differential power for distinguishing CCE with an AUC value of 0.884 (95% CI: 0.857-0.911). Patients with dabigatran and rivaroxaban exhibited higher risk score than those with warfarin (warfarin vs dabigatran, p=1.40×10-2; warfarin vs rivaroxaban p=3.00×10-3). Conclusion: PLR and CHA2DS2-VASc score are independent risk factors for CCE with NVAF, and the combination of the two indices can improve the prediction of CCE.

A comprehensive review on immune checkpoint inhibitors induced cardiotoxicity characteristics and associated factors.

Newly approved cancer drugs called ICIs have shown remarkable success in improving patient survival rates, but they also have the potential for inflammatory and immune-related side effects, including those affecting the cardiovascular system. Research has been conducted to understand the development of these toxicities and identify risk factors. This review focuses on the characteristics of ICI-induced cardiotoxicity and discusses the reported risk factors. It is important for cardio-oncologists to understand the basic concepts of these drugs to better understand how cardiotoxicities occur. It might be hard to find reports, where all patients treated with ICIs had developed cardiac toxicity, because there could be other existing and variable factors that influence the likelihood or risk of developing cardiotoxicity during treatment. Various clinical parameters have been explored as potential risk factors, and further investigation is needed through large-scale studies.

Variations in Post-Operative Electrolyte in Coronary Artery Intervention.

Background: Low volume change and minimal trauma observed during angiography are the reason why physicians often overlook any changes affecting pre-operative electrolytes levels after coronary intervention. However, few studies have addressed the issue of electrolyte changes after the coronary intervention. Therefore, our study investigates coronary angiography's effect on electrolytes and provides the quick identification of groups more prone to electrolyte changes. Methods: From the department of cardiology of the second affiliated hospital of Shandong's first medical university, 374 patients undergoing coronary angiography were selected. Pre-intervention and post-intervention serums, sodium (Na+), potassium (K+), chloride (Cl-), magnesium (Mg2+) and renal function were analyzed. The correlation between influential factors was also assessed. The association of hypokalemia with short-major adverse cardiac events (MACE) and arrhythmia was evaluated. Results: Among the 374 subjects including 264 patients who had a simple angiography and 110 patients who received coronary artery interventional therapy. A decrease in potassium levels was found in 81.8% of the patients, and post-interventional hypokalemia was observed in 15.0%. After the intervention, the hypokalemia among males was 2.18 times than that of females, and the pre-operative serum potassium level was 3.5mmol/L≤K+<4.0mmol/L and was 2.09 times than that of K+≥4.0 mmol/L, but was not associated with age and either simple coronary angiography or PCI (percutaneous coronary intervention). Hypernatremia was also prevalent in males under 60 years and with pre-operative hypernatremia. Significant variations were found between hypokalemia and influential factors like hypertension, diabetes, and gastrointestinal disease. We also found that there was no obvious correlation between hypokalemia and recurrent angina, heart failure and death, but significantly increased the risk of some arrhythmias. Conclusion: Male patients are more likely to suffer from electrolyte disturbance after coronary intervention. There is a need to emphasize monitoring and managing electrolyte changes to prevent severe complications in the peri-operative period.

Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation.

Parental histones, the carriers of posttranslational modifications, are deposited evenly onto the replicating DNA of sister chromatids in a process dependent on the Mcm2 subunit of DNA helicase and the Pole3 subunit of leading-strand DNA polymerase. The biological significance of parental histone propagation remains unclear. Here we show that Mcm2-mutated or Pole3-deleted mouse embryonic stem cells (ESCs) display aberrant histone landscapes and impaired neural differentiation. Mutation of the Mcm2 histone-binding domain causes defects in pre-implantation development and embryonic lethality. ESCs with biased parental histone transfer exhibit increased epigenetic heterogeneity, showing altered histone variant H3.3 and H3K27me3 patterning at genomic sites regulating differentiation genes. Our results indicate that the lagging strand pattern of H3.3 leads to the redistribution of H3K27me3 in Mcm2-2A ESCs. We demonstrate that symmetric parental histone deposition to sister chromatids contributes to cellular differentiation and development.