Novel Susceptibility Genes and Biomarkers for Obstructive Sleep Apnea: Insights from Genetic and Inflammatory Proteins.

STUDY OBJECTIVES: Numerous observational studies link obstructive sleep apnea (OSA) to inflammatory proteins, yet the directionality of these associations remains ambiguous. Therefore, we aimed to clarify the potential associations of gene-predicted inflammatory proteins with OSA. METHODS: Based on genome-wide association study data, we applied Mendelian randomization (MR) to explore potential connections between circulating inflammatory proteins and OSA, primarily using the inverse variance weighting method for robustness. Cochran's Q test, MR‒Egger intercept test, MR-PRESSO, and leave-one-out method were used to perform sensitivity tests for pleiotropy and heterogeneity. Replication analyses and meta-analyses were performed using other independent data. Steiger tests and multivariate MR assessed the independent effects of exposure factors, and the functional mapping and annotation (FUMA) platform was used to identify key genes to enhance the understanding of genetics. RESULTS: Our investigation revealed 21 circulating inflammatory proteins significantly associated with OSA-related phenotypes. Notably, IL-10RA, IL-18R1, TNFSF14, CCL23, ADA, and SLAMF1 had significant effects on multiple phenotypes. After FDR correction, IL-18R1, SLAMF1, IL-10RA, and IL-17C were identified as important candidates for OSA, and multivariate MR analysis strengthened the independent heritability of 20 inflammatory factors. The FUMA platform revealed seven overlapping genes: ROBO1, PRIM1, NACA, SHBG, HSD17B6, RBMS2, and WWOX. All reverse MR analyses and sensitivity analyses confirmed the robustness of these associations. CONCLUSIONS: Our results underscore crucial associations between inflammatory proteins and OSA pathogenesis, revealing new correlates and susceptibility genes. These findings advance biomarker identification for OSA risk and highlight the importance of genetic and inflammatory profiles in OSA management.

Influence of hypocalcemia on the prognosis of patients with multiple trauma.

BACKGROUND: Hypocalcemia is highly common in hospitalized patients, especially in those with trauma, On the other hand, abnormal calcium metabolism is an important metabolic challenge; however, it is often neglected and untreated, and certain factors may induce serious neurological and cardiovascular complications. AIM: To retrospectively analyze the impact of hypocalcemia on the prognosis of patients with multiple traumas. METHODS: The study was conducted from January 2020 to December 2021. Ninety-nine patients with multiple injuries were treated at the critical care medicine department of Fuyang People's Hospital. The selected indicators included sex, age, and blood calcium and hematocrit levels. Many indicators were observed, including within 24 h of hospitalization, and the prognosis was collected after 28 d. Based on the blood calcium levels, the patients were divided into the following two groups: Normocalcemia and hypocalcemia. Of the 99 patients included, 81 had normocalcemia, and 18 had hypocalcemia. Separate experiments were conducted for these two groups. RESULTS: There was an association between serum calcium levels and the prognosis of patients with polytrauma. CONCLUSION: Clinically, the prognosis of patients with multiple traumas can be preliminarily evaluated based on serum calcium levels.

Dynamic Changes in Intestinal Gene Expression and Microbiota across Chicken Egg-Laying Stages.

Eggs are a vital dietary component for humans, and it is beneficial to increase egg production to support poultry farming. Initially, the egg production rate rises rapidly with young hens until it reaches its peak, and then it declines gradually. By extending the duration of peak egg production, the hens' performance can be enhanced significantly. Previous studies found dynamic changes in gut microbiota during egg-laying, and several species of microbiota isolated from the chicken gut improved egg-laying performance. However, the interaction between microbes and host gene expression is still unclear. This study provides a more comprehensive understanding of chicken egg-laying by examining dynamic alterations in the microbiota of the entire intestinal tract (i.e., duodenum, jejunum, and ileum) and gene expression. The microbial community in the intestine underwent significant changes during different egg-laying periods (i.e., pre-, peak-, and late-laying periods). Metagenomic functional analysis showed that the relative abundance of biosynthesis of amino acids, secondary metabolites, and cofactors decreased significantly in the duodenum, jejunum, and ileum of aging hens. The relative levels of aldosterone, GnRH, insulin, growth hormone, and other hormone-related pathways increased dramatically in the intestinal microbiota during egg-laying, but only in the microbiota located in the duodenum and ileum. Transcriptome analysis suggested that genes associated with various transport processes were upregulated consistently in the small intestine during egg-laying; genes involved in the development of intestinal structure were down-regulated; and genes involved in response to DNA damage and stress were consistent with changes in laying rate. The abundance of Lactobacillus was related to the expression of ANGPTRL1, ANGPTRL2, ANGPT1L, and NOXO1 in the duodenum; Muricomes was correlated significantly with NFKBIZ, LYG2, and IRG1L expression in the jejunum; and Campylobacter was correlated positively with the expression of KMT2A and USF3 in the ileum. These results indicated that the intestinal microbiota and host gene expression may influence egg production jointly.

Undervalued dry riverbeds: A key factor in equating intermittent river CO2 emissions to perennial rivers.

Intermittent rivers in semiarid and arid regions, constituting over half of the world's rivers, alternate the carbon cycle interactions among the biosphere, hydrosphere, and atmosphere. Inadequate quantification of flow duration and river water surface area, along with overlooked CO2 emissions from dry riverbeds, result in notable inaccuracies in global carbon cycle assessments. High-resolution remote sensing images combined with intensive field measurements and hydrological modelling were used to estimate and extract the flow duration, river water surface area and dry riverbed area of Huangfuchuan, an intermittent river watershed that acts as a major tributary of the Yellow River in semiarid Northwest China. CO2 emission rates and partial pressures in water and air across the watershed were in-situ measured. In 2018, the flow duration of Huangfuchuan increased from less than 5 days in the first-order tributary to 150 days in the sixth-order mainstream. River water surface area estimated by remote sensing extraction plus the hydrodynamic model simulation varied from 3.9 to 88.6 km2 under 5 %-95 % discharge frequencies. CO2 emissions from the water-air interface and dry riverbed in 2018 were estimated at 582.3 × 103 and 355.2 × 103 ton, respectively. The estimated total annual emission (937.5 × 103 ton) aligns closely with the range of emissions (67.3 × 103-1377.2 × 103 ton) calculated for the water-air interface alone, derived using DEM river length and hydraulic geometry method. This similarity can be attributed to the overestimation of flow duration and flow velocity, as well as the over- or under-estimation of river water surface area and slope. The new method proposed in this study has large potential to be applied in estimating CO2 emissions from data-scarce intermittent rivers located in mountainous regions and provides a standardized solution in the estimation of CO2 emission. Results of this research reveal the spatiotemporal distribution of CO2 emissions along an intermittent river system and highlight the substantial role of dry riverbed in carbon cycle.

Identification and Characterization of the miRNA Transcriptome Controlling Green Pigmentation of Chicken Eggshells.

Green eggs are mainly caused by inserting an avian endogenous retrovirus (EVA-HP) fragment into the SLCO1B3 gene. Although the genotypes for this insertion allele are consistent, eggshell color (ESC) may vary after a peak laying period; light-colored eggs are undesired by consumers and farmers and result in financial loss, so it is necessary to resolve this problem. miRNAs are small non-coding RNAs that exert essential functions in animal development and diseases. However, the regulatory miRNAs and detailed molecular mechanisms regulating eggshell greenness remain unclear. In the present study, we determined the genotype of green-eggshell hens through the detection of a homozygous allele insertion in the SLCO1B3 gene. The shell gland epithelium was obtained from green-eggshell hens that produced white and green shell eggs to perform transcriptome sequencing and investigate the important regulatory mechanisms that influence the ESC. Approximately 921 miRNAs were expressed in these two groups, which included 587 known miRNAs and 334 novel miRNAs, among which 44 were differentially expressed. There were 22 miRNAs that were significantly upregulated in the green and white groups, respectively, which targeted hundreds of genes, including KIT, HMOX2, and several solute carrier family genes. A Gene Ontology enrichment analysis of the target genes showed that the differentially expressed miRNA-targeted genes mainly belonged to the functional categories of homophilic cell adhesion, gland development, the Wnt signaling pathway, and epithelial tube morphogenesis. A KEGG enrichment analysis showed that the Hedgehog signaling pathway was significantly transformed in this study. The current study provides an overview of the miRNA expression profiles and the interaction between the miRNAs and their target genes. It provides valuable insights into the molecular mechanisms underlying green eggshell pigmentation, screening more effective hens to produce stable green eggs and obtaining higher economic benefits.

Vitamin D Deficiency Participates in Depression of Patients with Diabetic Peripheral Neuropathy by Regulating the Expression of Pro-Inflammatory Cytokines.

Objective: Vitamin D deficiency is associated with patients with diabetic peripheral neuropathy (DPN), and low levels of vitamin D are common in patients with depression. Depression is common in DPN patients and the definite pathogenesis remains unclear. This study aimed to determine vitamin D deficiency in the onset of depression in DPN and evaluate the effect of vitamin D supplementation on depression. Methods: A total of 192 patients with DPN were enrolled in this study. Clinical and laboratory information was collected. Chemiluminescent immunoassay was used to measure the level of 25(OH)D. Enzyme-linked immunosorbent assay was employed to measure the concentrations of interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), and IL-17A. Subjects with low 25(OH)D received 5000IU vitamin D daily for 12 weeks. Depression scores and levels of 25(OH)D, IL-1ß, TNF-α, and IL-17A were re-evaluated after supplementation. Results: The incidence of vitamin D deficiency and depression was high in DPN patients. Compared with vitamin D sufficient participants, Hamilton Depression Rating Scale (HAMD) scores and the levels of inflammatory markers IL-1ß, TNF-α, and IL-17A were significantly higher in insufficient group (all p<0.05). HAMD score, IL-1ß, TNF-α, and IL-17A were negatively correlated with 25(OH)D (all p<0.05). A linear relationship existed among IL-1ß, TNF-α, IL-17A, and 25(OH)D (p<0.05). HAMD scores, IL-1ß, TNF-α, and IL-17A were all reduced significantly after supplementation of vitamin D (p<0.05). Binary logistic analysis revealed that vitamin D insufficiency was an independent risk factor for depression in patients with DPN. Receiver operating characteristic (ROC) curve analysis showed a high sensitivity (87.20%) of 25(OH)D in discriminating DPN patients with depression. Conclusion: Vitamin D deficiency participated in occurrence of depression in DPN patients and could be mediated, at least in part, by upregulation of pro-inflammatory cytokines. Vitamin D supplementation may be effective in improving depressive symptoms in DPN patients.

Prognostic analysis of mutated genes and insight into effects of DNA damage and repair on mutational strand asymmetries in gastric cancer.

Gastric cancer (GACA) is a complex and multifaceted disease influenced by a variety of environmental and genetic factors. Somatic mutations play a major role in its development, and their characteristics, including the asymmetry between two DNA strands, are of great interest and appear as a signal of information and guidance, revealing mechanisms of DNA damage and repair. Here, we analyzed the impact of High-frequency mutated genes on patient prognosis and found that the effect of expression levels of tumor protein p53 (TP53) and lysine methyltransferase 2C (KMT2C) genes remained high throughout the development of GACA, with similar expression patterns. After investigating mutation asymmetry across mutagenic processes, we found that transcriptional asymmetry was dominated by T > G mutations under the influence of transcription couples repair and damage. The apolipoprotein B mRNA editing enzyme catalytic polypeptide like (APOBEC) enzyme that induces mutations during DNA replication has been identified here and we identified a replicative asymmetry, which was dominated by C > A mutations in left-replicating. Strand bias in different mutation classes at transcription factor binding sites and enhancer regions were also confirmed, which implies the important role of non-coding regulatory elements in the occurrence of mutations. This work systematically describes mutational strand asymmetries in specific genomic regions, shedding light on the DNA damage and repair mechanisms underlying somatic mutations in cohorts of GACA patients with gastric cancer.

Evaluating future water availability in Texas through the lens of a data-driven approach leveraged with CMIP6 general circulation models.

Climate change is escalating the frequency and intensity of extreme precipitation events, significantly influencing the spatial and temporal distributions of water resources. This is particularly evident in Texas, a rapidly growing state with a pronounced west-east gradient in water supply. This study utilizes Coupled Model Intercomparison Project Phase 6 (CMIP6) data and data-driven methodology to improve projections of Texas's future water resources, focusing on actual evapotranspiration (AET) and water availability through enhanced Multi-Model Ensembles. The results reveal that the data-driven model significantly outperforms the CMIP5 and CMIP6 models across all skill metrics, underscoring the potential of data-driven methodologies in advancing climate science. Furthermore, the study provides an in-depth analysis of the projected changes in net water availability (NWA) and estimated water demand for different regions in Texas over the next six decades from 2015 to 2074, which reveal fluctuating patterns of water stress, with the regions (nine out of sixteen water planning regions in Texas, especially for the most populated regions) poised for heightened challenges in reconciling water demand and availability. While increasing trends are found in precipitation, AET, and NWA for the northern region of Texas based on SSP2-4.5, decreasing trends are found over the southern region for all three parameters based on SSP5-8.5. These findings underscore the importance of factoring both spatial and temporal variations in water availability and demand for effective water management strategies and the need for adaptive water management strategies for the changing water availability scenarios.

Multi-omics Analyses Reveal Function of Apolipoprotein E in Alternative Splicing and Tumor Immune Microenvironment in Kidney Renal Clear Cell Carcinoma via Pan-cancer Analysis.

Apolipoprotein E (APOE) regulates lipid metabolism, associated with the development of various cancers. However, its precise prognostic significance and functions in alternative splicing and the tumor immune microenvironment remain unclear. In this study, we extracted APOE expression in pan-cancer from TCGA and analyzed mRNA transcriptome, cell lines, and protein levels. Furthermore, we analyzed the alternative splicing expression of the APOE gene transcript with prognostic profiles using the OncoSplicing database. We obtained 73 common APOE genes to perform functional enrichment analysis, assess the correlation between genes and immune cells using TIMER, EPIC, and ssGSEA methods, and examine the prognostic significance using the UALCAN database. Finally, single-cell data was employed to assess the correlation between APOE genes and cell functions. Our findings revealed that APOE expression varies across different tumor types and cancer cell lines. The alternative splicing analysis demonstrated that APOE transcript expression levels have prognostic value in cancers such as LGG, KIRC, and KIRP. Functional enrichment analysis indicated significant associations between APOE and various immune cells, such as macrophages, CD8 T cells, and NK cells, with significant implications for prognosis. Moreover, single-cell data indicated that APOE was primarily expressed in renal epithelial cells among stromal cells and in macrophages among immune cells, significantly negatively correlated with five functional states. Our study represents the first comprehensive exploration of APOE's function in pan-cancers and identifies APOE as a potential biomarker in cancer pathogenesis, prognosis, and immune therapeutic target.

Recent intensified erosion and massive sediment deposition in Tibetan Plateau rivers.

Recent climate change has caused an increase in warming-driven erosion and sediment transport processes on the Tibetan Plateau (TP). Yet a lack of measurements hinders our understanding of basin-scale sediment dynamics and associated spatiotemporal changes. Here, using satellite-based estimates of suspended sediment, we reconstruct the quantitative history and patterns of erosion and sediment transport in major headwater basins from 1986 to 2021. Out of 13 warming-affected headwater regions, 63% of the rivers have experienced significant increases in sediment flux. Despite such intensified erosion, we find that 30% of the total suspended sediment flux has been temporarily deposited within rivers. Our findings reveal a pronounced spatiotemporal heterogeneity within and across basins. The recurrent fluctuations in erosion-deposition patterns within river channels not only result in the underestimation of erosion magnitude but also drive continuous transformations in valley morphology, thereby endangering local ecosystems, landscape stability, and infrastructure project safety.

Electron transfer coupled spin transition in cyano-bridged mixed-valence {FeIII2FeII2} molecular squares.

The research on electron transfer coupled spin transition regulating the valence state and spin state transition of metal ions is promising and challenging. Herein, we report a cyano-bridged {FeIII2FeII2} molecular square complex, {[Fe(Tp)(CN)3]2 [Fe(bnbpen)]2}(ClO4)2·8CH3OH (1·8CH3OH, bnbpen = N,N'-bis-(2-naphthylmethyl)-N,N'-bis(2-picolayl)-ethylenediamine), and its free of solvents form (1). Combined single-crystal X-ray diffraction, temperature-dependent infrared (IR) spectra, magnetic measurements, and Mössbauer spectra reveal that 1·8CH3OH and 1 exhibit reversible one-step and two-step electron transfer coupled spin transition (ETCST) with temperature change, between the low-temperature state {FeII,LS(µ-CN)FeIII,LS}2 (LS = low spin, HS = high spin) and the high-temperature state {FeIII,LS(µ-CN)FeII,HS}2, respectively.

Impact of Vision Impairment and Ocular Morbidity and Their Treatment on Quality of Life in Children: A Systematic Review.

TOPIC: This review summarizes existing evidence of the impact of vision impairment and ocular morbidity and their treatment on children's quality of life (QoL). CLINICAL RELEVANCE: Myopia and strabismus are associated with reduced QoL among children. Surgical treatment of strabismus significantly improves affected children's QoL. METHODS: We conducted a systematic review and meta-analysis by screening articles in any language in 9 databases published from inception through August 22, 2022, addressing the impact of vision impairment, ocular morbidity, and their treatment on QoL in children. We reported pooled standardized mean differences (SMDs) using random-effects meta-analysis models. Quality appraisal was performed using Joanna Briggs Institute and National Institutes of Health tools. This study was registered with the International Prospective Register of Systematic Reviews (identifier, CRD42021233323). RESULTS: Our search identified 29 118 articles, 44 studies (0.15%) of which were included for analysis that included 32 318 participants from 14 countries between 2005 and 2022. Seventeen observational and 4 interventional studies concerned vision impairment, whereas 10 observational and 13 interventional studies described strabismus and other ocular morbidities. Twenty-one studies were included in the meta-analysis. The QoL scores did not differ between children with and without vision impairment (SMD, -1.04; 95% confidence interval [CI], -2.11 to 0.03; P = 0.06; 9 studies). Myopic children demonstrated significantly lower QoL scores than those with normal vision (SMD, -0.60; 95% CI, -1.09 to -0.11; P = 0.02; 7 studies). Children with strabismus showed a significantly lower QoL score compared with those without (SMD, -1.19; 95% CI, -1.66 to -0.73; P < 0.001; 7 studies). Strabismus surgery significantly improved QoL in children (SMD, 1.36; 95% CI, 0.48-2.23; P < 0.001; 7 studies). No randomized controlled trials (RCTs) concerning refractive error and QoL were identified. Among all included studies, 35 (79.5%) were scored as low to moderate quality; the remaining met all quality appraisal tools criteria. DISCUSSION: Reduced QoL was identified in children with myopia and strabismus. Surgical correction of strabismus improves the QoL of affected children, which supports insurance coverage of strabismus surgery. Further studies, especially RCTs, investigating the impact of correction of myopia on QoL are needed. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Patterns of sleep quality and its influence factors: A latent class model among students of medical university in Hubei Province, China.

BACKGROUND: Sleep problem among undergraduate students has become one of the most pressing public health problems. This study aimed to explore the latent class of sleep patterns and the factors affecting sleep in Chinese students of medical university. METHODS: 3423 students participated in the cross-sectional study. The survey consisted of the reduced Morningness-Evening Questionnaire, the Pittsburgh Sleep Quality Index, and Health-Promoting Lifestyle Profile-II. Latent profile analysis and multinominal logistic regression analysis were performed. RESULTS: Three potential sleep categories were identified: "sleep disorder group" (1.87 %), "daytime dysfunction group" (24.42 %), and "good sleep group" (73.71 %). Compared with the "good sleep group," the "sleep disorder group" showed monthly living expenses (RMB) ≥ 3000 yuan (OR) = 13.04), interpersonal relationships as poor (OR = 3.71), health status as poor (OR = 45.09), circadian rhythm as eveningness (OR = 6.17), and poor health-promoting lifestyles (OR = 2.090) as its risk factors (all p < 0.05). Meanwhile, sophomore (OR = 1.75), junior (OR = 1.52), interpersonal relationships as poor (OR = 1.88), health status as poor (OR = 4.62), intermediate-chronotype (OR = 2.19), eveningness chronotype (OR = 5.66), and health-promoting lifestyles as poor (OR = 1.55) were identified as risk factors for the "daytime dysfunction group" (all p < 0.05). LIMITATIONS: Causal conclusions can not be drawn and recall bias in data collection. CONCLUSIONS: Significant population heterogeneity was found in the sleep quality. Implementing targeted interventions focusing on circadian rhythm and lifestyle is crucial to improve the sleep quality of students with different conditions.

Shifted sediment-transport regimes by climate change and amplified hydrological variability in cryosphere-fed rivers.

Climate change affects cryosphere-fed rivers and alters seasonal sediment dynamics, affecting cyclical fluvial material supply and year-round water-food-energy provisions to downstream communities. Here, we demonstrate seasonal sediment-transport regime shifts from the 1960s to 2000s in four cryosphere-fed rivers characterized by glacial, nival, pluvial, and mixed regimes, respectively. Spring sees a shift toward pluvial-dominated sediment transport due to less snowmelt and more erosive rainfall. Summer is characterized by intensified glacier meltwater pulses and pluvial events that exceptionally increase sediment fluxes. Our study highlights that the increases in hydroclimatic extremes and cryosphere degradation lead to amplified variability in fluvial fluxes and higher summer sediment peaks, which can threaten downstream river infrastructure safety and ecosystems and worsen glacial/pluvial floods. We further offer a monthly-scale sediment-availability-transport model that can reproduce such regime shifts and thus help facilitate sustainable reservoir operation and river management in wider cryospheric regions under future climate and hydrological change.

Influence of Baseline Diastolic Blood Pressure on the Effects of Intensive Blood Pressure Lowering: Results From the STEP Randomized Trial.

BACKGROUND: The STEP (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) trial demonstrated that intensive systolic blood pressure (SBP) lowering has cardiovascular benefits. However, the influence of baseline diastolic blood pressure (DBP) on the effects of intensive blood pressure lowering on cardiovascular outcomes has not been fully elucidated. METHODS: We performed a post hoc analysis of the STEP trial. Participants were randomly allocated to intensive (110 to <130 mm Hg) or standard (130 to <150 mm Hg) treatment groups. The effects of intensive SBP lowering on the primary composite outcome (stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, and cardiovascular death), major adverse cardiac event (a composite of the individual components of the primary outcome except for stroke), and all-cause mortality were analyzed according to baseline DBP as both a categorical and a continuous variable. RESULTS: The 8259 participants had a mean age of 66.2±4.8 years, and 46.5% were men. Participants with lower DBP were slightly older and had greater histories of cardiovascular disease, diabetes, and hyperlipidemia. Within each baseline DBP quartile, the mean achieved DBP was lower in the intensive versus standard group. The effects of intensive SBP lowering were not modified by baseline DBP as a continuous variable or as a categorical variable (quartiles, or <70, 70 to <80, and ≥80 mm Hg; all P value for interaction >0.05). CONCLUSIONS: The beneficial effects of intensive SBP lowering on cardiovascular outcomes were unaffected by baseline DBP. Lower DBP should not be an obstacle to intensive SBP control. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03015311.

Observation of protonation-induced intra-molecular metal-to-metal charge transfer in cyano-bridged [Fe-CN-Mn/Ni] dinuclear complexes.

A key challenge in the design of magnetic molecules with intramolecular charge transfer behavior is to obtain reversible magnetic bistability triggered by external stimuli. Here, we show that two dinuclear metal complexes, [(bbp)Fe(CN)3Mn(Py5Me2)]·2.5CH3OH (4) and [(bbp)Fe(CN)3Ni(Py5Me2)]·2.5CH3OH (5) (Py5Me2 = 2,6-bis(1,1-di(pyridine-2-yl)ethyl)pyridine, H2bbp = 2,6-bis(benzimidazole-2-yl)pyridine), were self-assembly synthesized by (Bu4N)2[(bbp)FeIII(CN)3] and [Mn(Py5Me2)(OH2)](ClO4)2 or [Ni(Py5Me2)(OH2)](ClO4)2, respectively. Complexes 4 and 5 exhibited intramolecular metal-to-metal charge transfer with the addition of acids or bases in solution by UV-visible spectrophotometric measurements and electrochemistry studies, and concomitant switching of the {FeIII(µ-CN)MnII/NiII} state to the {FeII(µ-CN)MnIII/NiIII} state.

A Molecular Dynamics Study on the Dislocation-Precipitate Interaction in a Nickel Based Superalloy during the Tensile Deformation.

In the present paper, the dislocation-precipitate interaction in the Inconel 718 superalloy is studied by means of molecular dynamics simulation. The atomistic model composed of the ellipsoidal Ni3Nb precipitate (γ″ phase) and the Ni matrix is constructed, and tensile tests on the composite Ni3Nb@Ni system along different loading directions are simulated. The dislocation propagation behaviors in the precipitate interior and at the surface of the precipitate are characterized. The results indicate that the dislocation shearing and bypassing simultaneously occur during plastic deformation. The contact position of the dislocation on the surface of the precipitate could affect the penetration depth of the dislocation. The maximum obstacle size, allowing for the dislocation shearing on the slip planes, is found to be close to 20 nm. The investigation of anisotropic plastic deformation behavior shows that the composite system under the loading direction along the major axis of the precipitate experiences stronger shear strain localizations than that with the loading direction along the minor axis of the precipitate. The precipitate size effect is quantified, indicating that the larger the precipitate, the lower the elastic limit of the flow stress of the composite system. The dislocation accumulations in the precipitate are also examined with the dislocation densities given on specific slip systems. These findings provide atomistic insights into the mechanical behavior of nickel-based superalloys with nano-precipitates.

Exploration of Key Immune-Related Transcriptomes Associated with Doxorubicin-Induced Cardiotoxicity in Patients with Breast Cancer.

Based on a few studies, heart failure patients with breast cancer were assessed to find potential biomarkers for doxorubicin-induced cardiotoxicity. However, key immune-related transcriptional markers linked to doxorubicin-induced cardiotoxicity in breast cancer patients have not been thoroughly investigated. We used GSE40447, GSE76314, and TCGA BRCA cohorts to perform this study. Then, we performed various bioinformatics approaches to identify the key immune-related transcriptional markers and their association with doxorubicin-induced cardiotoxicity in patients with breast cancer. We found 255 upregulated genes and 286 downregulated genes in patients with doxorubicin-induced heart failure in breast cancer. We discovered that in patients with breast cancer comorbidity doxorubicin-induced cardiotoxicity, the 58 immunological genes are elevated (such as CPA3, VSIG4, GATA2, RFX2, IL3RA, and LRP1), and the 60 genes are significantly suppressed (such as MS4A1, FCRL1, CD200, FCRLA, FCRL2, and CD79A). Furthermore, we revealed that the immune-related differentially expressed genes (DEGs) are substantially associated with the enrichment of KEGG pathways, including B-cell receptor signaling pathway, primary immunodeficiency, chemokine signaling pathway, hematopoietic cell lineage, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, MAPK signaling pathway, focal adhesion, dilated cardiomyopathy, cell adhesion molecule, etc. Moreover, we discovered that the doxorubicin-induced immune-related genes are crucially involved in the protein-protein interaction and gene clusters. The immune-related genes, including IFIT5, XCL1, SPIB, BTLA, MS4A1, CD19, TCL1A, CD83, CD200, FCRLA, CD79A, BIRC3, and IGF2R are significantly associated with a poor survival prognosis of breast cancer patients and showed diagnostic efficacy in patients with breast cancer and heart failure. Molecular docking revealed that the survival-associated genes interact with the doxorubicin with appreciable binding affinity. Finally, we validated the expression level of immune-related genes in breast cancer patients-derived cardiomyocytes with doxorubicin-induced cardiotoxicity and found that the level of RAD9A, HSPA1B, GATA2, IGF2R, CD200, ERCC8, and BCL11A genes are consistently dysregulated. Our findings offered a basis for understanding the mechanism and pathogenesis of the cardiotoxicity caused by doxorubicin in breast cancer patients and predicted the interaction of immune-related potential biomarkers with doxorubicin.

Characteristics of Autophagy-Related Genes, Diagnostic Models, and Their Correlation with Immune Infiltration in Keratoconus.

Purpose: Keratoconus (KTCN) is one of the most common degenerative keratopathies, significantly affecting vision and even leading to blindness. This study identifies potential biomarkers of KTCN based on the characterization of autophagy-related genes (ARGs) and the construction of a diagnostic model; and explores their relevance to immune infiltrating cells in KTCN. Methods: Gene Expression Omnibus (GEO) data were downloaded and ARGs were acquired from GeneCards and Molecular Signatures Database (MSigDB). Autophagy-related differential expression genes (ARDEGs) were discovered through the integration of differentially expressed genes (DEGs) with ARGs, while hub genes of KTCN were discovered by protein-protein interaction (PPI) network analysis. The probable biological roles of these hub ARDEGs were examined using functional enrichment analysis, and a KTCN diagnostic model was generated using the least absolute shrinkage and selection operator (LASSO) regression analysis. We also employed the CIBERSORTx and ssGSEA algorithms to identify potential regulatory pathways to compare the abundance of immune cell infiltrates and their association with hub genes. Finally, the hub gene expression levels were confirmed using validation datasets as well as blood samples from KTCN and healthy individuals. Results: In this study, we identified 12 hub ARDEGs, of which 9 genes were substantially distinct between KTCN patients and normal groups. The LASSO risk score was used to generate the nomogram, and the calibration curve evaluated the model's effective diagnostic performance (C index of 0.961). Patients with KTCN had greater percentages of M2 Macrophages and Gamma delta T cells, according to CIBERSORTx and ssGSEA. The outcomes of the bioinformatics analysis were supported by the DDIT3 and BINP3 expression levels in KTCN patients and healthy controls, according to the qRT-PCR data. Conclusion: Five biomarkers (CFTR, PLIN2, DDIT3, BAG3, and BNIP3) and diagnostic models offer fresh perspectives on identifying and managing KTCN.

Determining the Transformation Kinetics of Water Oxidation Intermediates on Hematite Photoanode.

The oxygen evolution reaction (OER) from water is a sequential oxidation reaction process, involved in transformation of multiple reaction intermediates. For photo(electro)catalytic OER, revealing the intermediates transformation kinetics is quite challenging due to its coupling with photogenerated charge dynamics. Herein, we specifically study the transformation kinetics of the OER intermediates in rationally thin hematite photoanodes through increasing the ratio between surface intermediates and photogenerated charges in bulk. We directly identify the formation and consumption kinetics of one-hole OER intermediate (FeIV═O) in photoelectrochemical water oxidation using operando transient absorption (TA) spectroscopy. The microsecond formation kinetics of the FeIV═O species are sensitively changed by the excitation mode of Fe2O3. The subsecond consumption kinetics are closely dependent on surface FeIV═O species density, demonstrating that the cooperation of FeIV═O intermediates is the key to accelerating water oxidation kinetics on the Fe2O3 surface. This work provides insight into understanding and controlling water oxidation reaction kinetics on Fe2O3 surface.