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Nanolayered Zr/Nb metals are considered promising for advanced nuclear reactors due to their superior resistance to irradiation. In this study, Zr/Nb multilayers were irradiated with 50 keV He+ ions to a fluence of 1 × 1017 ions/cm2 at temperatures of room temperature, 350 °C, and 500 °C to investigate irradiation-induced structural changes. X-ray diffraction (XRD) analysis indicated low-angle shifts of 0.08–0.54° and high-angle shifts of 0.08–0.42° in the irradiated Zr and Nb layers, suggesting tensile and compressive strains, respectively. At 500 °C, the selected-area electron diffraction (SAED) observed a 9.2% lattice expansion in Zr and a 0.13% contraction in Nb. Geometric phase analysis (GPA) revealed varying strain distributions, transitioning from incoherent to coherent interfaces with increasing irradiation damage. Transmission electron microscopy (TEM) identified the presence of He bubbles in the Zr layer as one of the reasons for strain differences. Nanoindentation tests showed an increase at a depth of 150 nm hardness of 0.831 GPa at 500 °C compared to 350 °C. These results are attributed to differences in crystal structure, vacancy dynamics, interfacial effects, and lattice strain influences. Stability of Zr/Nb interfaces after He irradiation was studied. This study provides insights into the radiation behavior of Zr/Nb nanoscale metallic materials, enhancing our understanding of their potential as structural materials in nuclear energy systems.

This study investigated the microstructure and mechanical properties of GdxCoCrFeNiV0.4 alloys. Various techniques such as XRD, SEM, EBSD, and TEM were utilized, alongside hardness and compression tests at room temperature. The findings revealed that the high-entropy alloy without Gd element exhibited a single face-centered cubic (FCC) phase. Upon the introduction of Gd element, the phase composition shifted to FCC + hexagonal structure (HS) phases, and further addition of Gd resulted in the presence of FCC + HS + body-centered cubic (BCC) phases. Additionally, the inclusion of Gd element led to the precipitation of Gd-rich particles within the alloy. The Vickers hardness test results revealed a significant increase in alloy hardness as the Gd content rose, from 177.5 HV for Gd0 to 848.4 HV for Gd0.4. This suggests that the presence of the HS phase and BCC phase notably influences alloy hardness. Furthermore, compressive test outcomes demonstrated that the alloy's yield strength rose from 173.74 MPa for Gd0 to 1356.17 MPa for Gd0.3 with increasing Gd content. However, the excessive addition of Gd elements results in significant precipitation of V and Cr elements, leading to grain coarsening, adversely affecting its mechanical properties. The high strength of Gd-containing high-entropy alloys can be attributed to various strengthening mechanisms, such as solid solution strengthening, the presence of the HS phase, the precipitation of a small number of Gd-rich particles, and the grain refinement caused by the addition of Gd.

Abstract For light-element materials, X-ray phase contrast imaging provides better contrast compared to absorption imaging. While the Fourier transform method has a shorter imaging time, it typically results in lower image quality; in contrast, the phase-shifting method offers higher image quality but is more time-consuming and involves a higher radiation dose. To rapidly reconstruct low-dose X-ray phase contrast images, this study developed a model based on Generative Adversarial Networks (GAN), incorporating custom layers and self-attention mechanisms to recover high-quality phase contrast images. We generated a simulated dataset using Kaggle’s X-ray data to train the GAN, and in simulated experiments, we achieved significant improvements in Peak Signal-to-Noise Ratio (PSNR) and Structural Similarity Index (SSIM). To further validate our method, we applied it to fringe images acquired from three phase contrast systems: a single-grating phase contrast system, a Talbot-Lau system, and a cascaded grating system. The current results demonstrate that our method successfully restored high-quality phase contrast images from fringe images collected in experimental settings, though it should be noted that these results were achieved using relatively simple sample configurations.

Abstract LncRNAs are highly implicated in oxidative stress (OS) during the growth of mammalian follicles. TAK1 binding protein 2 gene (TAB2) has been suggested to involve in the normal apoptosis and proliferation of granulosa cells (GCs), the main supporting cells in ovarian follicles. In this study, we found that TAB2 increased the expressions of SOD1, P50, and P65 to suppress the OS, thereby inhibiting the apoptosis and promoting the proliferation in GCs. Notably, DNMTs appeared to mediate the expression of TAB2 without the changes of DNA methylation at TAB2’s promoter. We identified an antisense lncRNA of TAB2, discovered that DNA methylation regulated the transcription of TAB2-AS in GCs, and found TAB2-AS medicated the follicular growth of ovaries in vivo. Mechanistically, the hypomethylation of the CpG site (−1759/−1760) activated the transcription of TAB2-AS, and the 1–155 nt and 156-241 nt of TAB2-AS were respectively complementary to 4368–4534 nt and 4215–4300 nt of TAB2’s mRNA to increase the expression of TAB2. Moreover, TAB2-AS inhibited the OS and apoptosis of GCs, while promoted the proliferation of GCs to expedite the follicular growth, which was in line with that of TAB2. Collectively, these findings revealed the antisense lncRNA mechanism mediated by DNA methylation, and TAB2-AS might be the target to control OS during follicular growth in mammals.

Abstract Purpose DNA methylation prominently inactivates tumor suppressor genes and facilitates oncogenesis. Previously, we delineated a chromosome 18 deletion encompassing the erythrocyte membrane protein band 4.1-like 3 (EPB41L3) gene, a progenitor for the tumor suppressor that is differentially expressed in adenocarcinoma of the lung-1 (DAL-1) in gastric cancer (GC). Methods Our current investigation aimed to elucidate EPB41L3 expression and methylation in GC, identify regulatory transcription factors, and identify affected downstream pathways. Immunohistochemistry demonstrated that DAL-1 expression is markedly reduced in GC tissues, with its downregulation serving as an independent prognostic marker. Results High-throughput bisulfite sequencing of 70 GC patient tissue pairs revealed that higher methylation of non-CpGs in the EPB41L3 promoter was correlated with more malignant tumor progression and higher-grade tissue classification. Such hypermethylation was shown to diminish DAL-1 expression, thus contributing to the malignancy of GC phenotypes. The DNA methyltransferase inhibitor 5-aza-2’-deoxycytidine (5-aza-CdR) was found to partially restore DAL-1 expression. Moreover, direct binding of the transcription factor CDC5L to the upstream region of the EPB41L3 promoter was identified via chromosome immunoprecipitation (ChIP)-qPCR and luciferase reporter assays. Immunohistochemistry confirmed the positive correlation between CDC5L and DAL-1 protein levels. Subsequent RNA-seq analysis revealed that DAL-1 significantly influences the extracellular matrix and space-related pathways. GC cell RNA-seq post-5-Aza-CdR treatment and single-cell RNA-seq data of GC tissues confirmed the upregulation of AREG and COL17A1, pivotal tumor suppressors, in response to EPB41L3 demethylation or overexpression in GC epithelial cells. Conclusion In conclusion, this study elucidates the association between non-CpG methylation of EPB41L3 and GC progression and identifies the key transcription factors and downstream molecules involved. These findings enhance our understanding of the role of EPB41L3 in gastric cancer and provide a solid theoretical foundation for future research and potential clinical applications.

Abstract Background There is a scarcity of evidence regarding the potential relationship between the size and location of necrotic lesions, which must be understood to provide optimal joint-preserving treatment. The purpose of this study was to characterize the distribution patterns of necrotic lesions of varying sizes in early-stage osteonecrosis of femoral head (ONFH) with the use of three-dimensional mapping. Methods We retrospectively evaluated clinical CT images of the hips that were performed in the Third Hospital of Hebei Medical University from January 2018 to December 2022 and collected all CT images diagnosed with stage I and II ONFH. Three-dimensional structures that included both necrotic lesions and normal areas of the femoral heads were reconstructed and divided into eight regions to record their size and location. CT images for all lesions were superimposed onto a standard template, and three-dimensional mapping was created to determine the presence of concentrated areas of lesions. Results In a cohort of 143 patients with stage I and II ONFH, a total of 150 hips were reviewed. For lesions with less than 15% of the femoral head volume, necrotic lesions predominantly involve regions I, III, and V, with region I showing concentration. For lesions with volumes ranging from 15 to 30%, necrotic lesions exhibited a wider distribution across regions I, II, III, IV, V, and VII, with significant concentrations in regions I, III, and V. For lesions exceeding 30% of the femoral head volume, the necrotic lesions were extensively distributed across nearly the entire femoral head, with a notable expansion of the concentrated necrotic areas. Conclusions The distribution of necrotic lesions varies with lesion size, with smaller lesions primarily concentrated in the anterior and medial regions of the femoral head, particularly in the anterosuperior region, while larger lesions expand to the lateral and inferior regions. These findings enhance existing classification systems and provide crucial insights for guiding hip-preserving surgical planning and approaches.

MuscleX is an integrated, open-source computer software suite for data reduction of X-ray fiber diffraction patterns from striated muscle and other fibrous systems. It is written in Python and runs on Linux, Microsoft Windows or macOS. Most modules can be run either from a graphical user interface or in a `headless mode' from the command line, suitable for incorporation into beamline control systems. Here, we provide an overview of the general structure of the MuscleX software package and describe the specific features of the individual modules as well as examples of applications.

The variability of soil organic carbon (SOC) extends across three dimensions. However, quantitative analyses of the factors influencing spatiotemporal variations of SOC in various soil depth is scarce. This study leverages legacy data from two soil surveys conducted in the Dongting Lake Basin during the 1980s and the 2010s, employing Random Forest models to generate three-dimensional SOC maps. Through correlation analysis and permutation importance, we identified the primary factors driving temporal and spatial changes of SOC. The results showed that in the 2010s, SOC storage up to a depth of 1 m in the Dongting Lake Basin was approximately 2.95 Pg, increasing at an average rate of 0.0047 Pg C per year since the 1980s. Regions with higher average SOC contents were predominantly found in the western, southern, and eastern parts of the basin, despite significant losses over the 30-year period. In contrast, the central and northern areas, which initially had lower SOC contents in the 1980s, exhibited increases by the 2010s. Soil depth was the most influential predictor of SOC patterns in both the 1980s and 2010s. Meanwhile, relief and organism factors were primarily responsible for spatial variations in SOC, with the influence of organism factors diminishing by the 2010s. The temporal variations of SOC were chiefly attributed to changes in soil conservation practices, extreme precipitation events, and grain production. Consequently, it is imperative to prioritize ecological restoration and conservation tillage practices to mitigate the impacts of extreme weather conditions and safeguard food security.

Abstract Age at first farrowing (AFF) is a reproductive trait with low heritability and high importance in the pig industry. To enhance the statistical power of genome‐wide association study (GWAS) and further explore the genetic nature of AFF, we first conducted GWAS meta‐analysis using three Yorkshire populations, and then integrated the Pig Genotype‐Tissue Expression (PigGTEx) resources to interpret their potential regulatory mechanism. Additionally, we compared the AFF in pig with the age at first birth (AFB) of human using GWAS summary statistics. We detected 18 independent variants in GWAS meta‐analysis and 8 genes in gene‐based association analysis significantly associated with AFF. By integrating the PigGTEx resource, we conducted transcriptome‐wide association study (TWAS) and colocalization analysis on 34 pig tissues. In TWAS, we detected 18 significant gene‐tissue pairs, such as DCAF6 in uterus and CREG1 in blood. In colocalization, we found 111 potential candidate tissue‐gene pairs, such as GJD4 and LYPLAL1. We found that the homologous gene, CHST10, might be the potential candidate gene between humans in AFB and pigs in AFF. In conclusion, integrating GWAS meta‐analysis and PigGTEx resources is a meaningful way to decipher the genetic architecture of complex traits. We found that DCAF6, CREG1, GJD4, and LYPLAL1 are candidate genes with high reliability for AFF in swine. The comparative analysis showed that CHST10 might play a potentially critical role in AFB/AFF across human and pigs.

Abstract N-terminal pro-Brain-type natriuretic peptide (NT-proBNP) has a predictive value of cardiovascular disease (CVD). Pro-inflammatory diet has been proven to be related to CVD. Our study investigated whether the association between NT-proBNP and mortality differed among general U.S. adults with different dietary inflammatory index (DII) scores. This study utilized the National Health and Nutrition Examination Surveys (NHANES) database from 1999 to 2004. Non-pregnant U.S. adults aged ≥ 20 years and without CVD were included. Cox regression model and restricted cubic splines were used to investigate the associations between NT-proBNP, DII, and mortality. A total of 9788 adults were included, and 2386 all-cause deaths with 668 CVD deaths occurred over 17.08 years of follow-up. NT-proBNP was positively associated with DII scores (P

Abstract Purpose This study aimed to preliminarily investigate the association and possible mechanisms between Helicobacter. pylori (H. pylori) infection and type 2 diabetes mellitus (T2DM) through data collection, statistical analysis, and bioinformatics analysis. Methods A retrospective cohort study, including a total of 4406 participants who attended annual health checkups at Xian GEM Flower Changqing Hospital, was conducted to explore the correlation between the incidence of T2DM and H. pylori infection. To uncover the potential mechanisms underlying the interaction between the two diseases, differentially expressed genes (DEGs) common to T2DM and H. pylori infection were identified using the GEO database and Venn diagrams. These DEGs were then analyzed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) analysis. Results In total, 2053 participants were classified into the H. pylori-positive group and 2353 into the H. pylori-negative group. H. pylori infection was associated with a higher risk of T2DM occurrence (adjusted HR 1.59; 95% CI 1.17–2.15, P = 0.003). The average disease-free survival time was 34.81 months (95% CI 34.60-35.03 months) in the H. pylori positive group and 35.42 months (95% CI 35.28–35.56 months) in the H. pylori negative group. Multivariate analysis and subgroup analyses also showed that H. pylori infection increased the risk of developing T2DM. A total of 21 DEGs between T2DM and H. pylori infection were identified and enriched in 7 signaling pathways, indicating specific protein interactions. Conclusions The prevalence of T2DM was associated with H. pylori infection. T2DM and H. pylori infection may interact with each other through metabolic and immune pathways.

Abstract Background Studies have reported that polyphyllin I (PPI) had effective anti-tumor activity against hepatocellular carcinoma (HCC). However, the precise molecular mechanism of this action and the direct target remain unclear. The aim of this study was to discover the molecular targets and the exact mechanism of PPI in the treatment of HCC. Methods Various HCC cells and Zebrafish xenotransplantation models were used to examine the efficacy of PPI against HCC. A proteome microarray, surface plasmon resonance (SPR) analysis, small molecule transfection, and molecular docking were conducted to confirm the direct binding targets of PPI. Transcriptome and Western blotting were then used to determine the exact responding mechanism. Finally, the anticancer effect and its precise mechanism, as well as the safety of PPI, were verified using a mouse tumor xenograft study. Results The results demonstrated that PPI had significant anticancer activity against HCC in both in vitro studies of two cells and the zebrafish model. Notably, PPI selectively enhanced the action of the Zinc finger and BTB domain-containing 16 (ZBTB16) protein by directly binding to it. Furthermore, specific knockdown of ZBTB16 markedly attenuated PPI-dependent inhibition of HCC cell proliferation and migration caused by overexpression of the gene. The transcriptome and Western blotting also confirmed that the interaction between ZBTB16 and PPI also activated the PPARγ/RXRα pathway. Finally, the mouse experiments confirmed the efficacy and safety of PPI to treat HCC. Conclusions Our results indicate that ZBTB16 is a promising drug target for HCC and that PPI as a potent ZBTB16 agonist has potential as a therapeutic agent against HCC by regulating the ZBTB16/PPARγ/RXRα signaling axis.

Abstract Muscle invasive bladder cancers (BCs) can be divided into 2 major subgroups-basal/squamous (BASQ) tumors and luminal tumors. Since Pparg has low or undetectable expression in BASQ tumors, we tested the effects of rosiglitazone, Pparg agonist, in a mouse model of BASQ BC. We find that rosiglitazone reduces proliferation while treatment with rosiglitazone plus trametinib, a MEK inhibitor, induces apoptosis and reduces tumor volume by 91% after 1 month. Rosiglitazone and trametinib also induce a shift from BASQ to luminal differentiation in tumors, which our analysis suggests is mediated by retinoid signaling, a pathway known to drive the luminal differentiation program. Our data suggest that rosiglitazone, trametinib, and retinoids, which are all FDA approved, may be clinically active in BASQ tumors in patients.

Salmonella is an important cause of foodborne diseases worldwide, with a high detection rate in fresh meat. Rapid, accurate and sensitive detection of Salmonella is crucial in safeguarding food safety and people’s health. Electrochemical aptamer-based sensors, integrating the advantages of both aptamers and electrochemical sensors in terms of recognition specificity and sensitivity, attract much attention, thus having the potential for application in qualitative and quantitative detection of Salmonella. However, most existing reviews focus on the preparation process of sensors, while little information is available regarding the correlation between the structure and properties of Salmonella, leading to the lack of a direct theoretical basis for the design and improvement of sensors. Therefore, based on the structure and properties of Salmonella, this article establishes its internal connection with aptamer-based sensors, and summarizes the electrode modification materials, aptamer fixation on the working electrode, the signal sensing strategies and the signal amplification strategies, in order to provide a reference for the rapid detection of Salmonella and other foodborne pathogenic bacteria.

Abstract Background Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive. Results In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo. Conclusions In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment.

Abstract Slow-controlled release fertilizers are experiencing a popularity in rice cultivation due to their effectiveness in yield and quality with low environmental costs. However, the underlying mechanism by which these fertilizers regulate grain quality remains inadequately understood. This study investigated the effects of five fertilizer management practices on rice yield and quality in a two-year field experiment: CK, conventional fertilization, and four applications of slow-controlled release fertilizer (UF, urea formaldehyde; SCU, sulfur-coated urea; PCU, polymer-coated urea; BBF, controlled-release bulk blending fertilizer). In 2020 and 2021, the yields of UF and SCU groups showed significant decreases when compared to conventional fertilization, accompanied by a decline in nutritional quality. Additionally, PCU group exhibited poorer cooking and eating qualities. However, BBF group achieved increases in both yield (10.8 t hm−2 and 11.0 t hm−2) and grain quality reaching the level of CK group. The adequate nitrogen supply in PCU group during the grain-filling stage led to a greater capacity for the accumulation of proteins and amino acids in the PCU group compared to starch accumulation. Intriguingly, BBF group showed better carbon–nitrogen metabolism than that of PCU group. The optimal nitrogen supply present in BBF group suitable boosted the synthesis of amino acids involved in the glycolysis/ tricarboxylic acid cycle, thereby effectively coordinating carbon–nitrogen metabolism. The application of the new slow-controlled release fertilizer, BBF, is advantageous in regulating the carbon flow in the carbon–nitrogen metabolism to enhance rice quality.

Abstract Purpose To validate the safety and clinical results of single-stage bilateral versus unilateral medial opening wedge high tibial osteotomy (HTO). Methods A propensity-matched cohort study was performed from March 2020 to March 2021 in our medical center. Data were prospectively collected. Including 34 patients who underwent single-stage bilateral medial opening HTO(SSBHTO), and 68 cases in the unilateral group. Propensity-matched ration was 2:1 based on age, sex, and body mass index using R software. Comparisons of the length of hospital stay, operative time, blood loss, postoperative adverse events, 90-day readmission rate, conversion to TKA rate, self-reported VAS and WOMAC scores were made to investigate the safety and clinical results of bilateral HTO. Results The mean length of hospital stay was 7.36 ± 2.23 days for SSBHTO and 7 days (IQR, 3 days; range, 4 to 23 days) for the unilateral group (P = 0.219). The mean operative time was 144 ± 47 min for bilateral HTO and 105(37.5) mins for a unilateral OWHTO (P 0.05). Conclusions A single-stage bilateral medial opening wedge high tibial osteotomy is advisable for patients with knee osteoarthritis. Patients benefit from avoiding secondary anesthesia, postoperative complications, and substantial cost savings. Level of Evidence Therapeutic Level III.

Abstract Recently, the significant benefits of cancer immunotherapy for most cancers have been demonstrated in clinical and preclinical studies. However, the efficacy of these immunotherapies for gliomas is limited, owing to restricted drug delivery and insufficient immune activation. As drug carriers, exosomes offer the advantages of low toxicity, good biocompatibility, and intrinsic cell targeting, which could enhance glioma immunotherapy efficacy. However, a review of exosome-based drug delivery systems for glioma immunotherapy has not been presented. This review introduces the current problems in glioma immunotherapy and the role of exosomes in addressing these issues. Meanwhile, preparation and application strategies of exosome-based drug delivery systems for glioma immunotherapy are discussed, especially for enhancing immunogenicity and reversing the immunosuppressive tumor microenvironment. Finally, we briefly describe the challenges of exosome-based drug delivery systems in clinical translation. We anticipate that this review will guide the use of exosomes as drug carriers for glioma immunotherapy. Graphical Abstract

Abstract Introduction Recent advancements in androgenetic alopecia (AGA) treatment have highlighted the efficacy of botulinum toxin (BoNT). However, inconsistencies in injection sites and depths warrant attention. It remains unclear which injection strategy is most beneficial for patients. Methods This split-scalp randomized controlled trial divided each enrolled participant’s scalp along the midline: one side was randomized to receive intramuscular BoNT injections in the surrounding muscles, while the other side received intradermal BoNT injections directly into the balding areas. This study evaluated the impact of treatment on hair density and diameter through trichoscopic examinations conducted at baseline and 12 weeks post treatment. Additionally, assessments of pain and overall safety were integrated into the study protocol. Results Twenty-nine patients completed the study, with significant improvements in hair density observed in the intramuscular injection group compared to the intradermal group (p

Abstract Genome organization is thought to underlie cell type specific gene expression, yet how it is regulated in progenitors to produce cellular diversity is unknown. In Drosophila, a developmentally-timed genome reorganization in neural progenitors terminates competence to produce early-born neurons. These events require downregulation of Distal antenna (Dan), part of the conserved pipsqueak DNA-binding superfamily. Here we find that Dan forms liquid-like condensates with high protein mobility, and whose size and subnuclear distribution are balanced with its DNA-binding. Further, we identify a LARKS domain, a structural motif associated with condensate-forming proteins. Deleting just 13 amino acids from LARKS abrogates Dan’s ability to retain the early-born neural fate gene, hunchback, in the neuroblast nuclear interior and maintain competence in vivo. Conversely, domain-swapping with LARKS from known phase-separating proteins rescues Dan’s effects on competence. Together, we provide in vivo evidence for condensate formation and the regulation of progenitor nuclear architecture underlying neuronal diversification.

Abstract Background The exploration of gene-disease associations is crucial for understanding the mechanisms underlying disease onset and progression, with significant implications for prevention and treatment strategies. Advances in high-throughput biotechnology have generated a wealth of data linking diseases to specific genes. While graph representation learning has recently introduced groundbreaking approaches for predicting novel associations, existing studies always overlooked the cumulative impact of functional modules such as protein complexes and the incompletion of some important data such as protein interactions, which limits the detection performance. Results Addressing these limitations, here we introduce a deep learning framework called ModulePred for predicting disease-gene associations. ModulePred performs graph augmentation on the protein interaction network using L3 link prediction algorithms. It builds a heterogeneous module network by integrating disease-gene associations, protein complexes and augmented protein interactions, and develops a novel graph embedding for the heterogeneous module network. Subsequently, a graph neural network is constructed to learn node representations by collectively aggregating information from topological structure, and gene prioritization is carried out by the disease and gene embeddings obtained from the graph neural network. Experimental results underscore the superiority of ModulePred, showcasing the effectiveness of incorporating functional modules and graph augmentation in predicting disease-gene associations. This research introduces innovative ideas and directions, enhancing the understanding and prediction of gene-disease relationships.

Desmin is a type III intermediate filament protein specifically expressed in muscle cells, which is encoded by the DES gene. Defects in the desmin protein and cytoskeletal instability may interfere with cardiac muscle conduction signals, a fundamental mechanism for arrhythmias in patients with desmin-related myopathy. This current case report presents a female patient in her early 20s who presented with early-onset complete atrioventricular block and complete left bundle branch block over the previous decade. More recently, she had developed ventricular tachycardia, ventricular fibrillation, atrial fibrillation and other arrhythmias. Echocardiography revealed non-compaction of the ventricular myocardium and pulmonary hypertension. Whole-exome sequencing analysis identified a heterozygous missense mutation in the DES gene: c.1216C>T (p.Arg406Trp). She was eventually diagnosed with arrhythmias due to desmin-related myopathy. A literature review of international databases was undertaken to summarise the clinical characteristics of the cardiac involvement associated with this DES gene mutation.

Summary: The strategy of lowering cholesterol levels by promoting cholesterol excretion is still lacking, and few molecular targets act on multiple cholesterol metabolic processes. In this study, we find that Nogo-B deficiency/inhibition simultaneously promotes hepatic uptake of cholesterol and cholesterol excretion. Nogo-B deficiency decreases cholesterol levels by activating ATP-binding cassette transporters (ABCs), apolipoprotein E (ApoE), and low-density lipoprotein receptor (LDLR) expression. We discover that Nogo-B interacts with liver X receptor α (LXRα), and Nogo-B deficiency inhibits ubiquitination degradation of LXRα, thereby enhancing its function on cholesterol excretion. Decreased cellular cholesterol levels further activate SREBP2 and LDLR expression, thereby promoting hepatic uptake of cholesterol. Nogo-B inhibition decreases atherosclerotic plaques and cholesterol levels in mice, and Nogo-B levels are correlated to cholesterol levels in human plasma. In this study, Nogo-B deficiency/inhibition not only promotes hepatic uptake of blood cholesterol but also facilitates cholesterol excretion. This study reports a strategy to lower cholesterol levels by inhibiting Nogo-B expression to promote hepatic cholesterol uptake and cholesterol excretion.

The Jiamusi section of the Songhua River is one of the first 17 model river construction sections in China. The implementation of river health assessments can determine the health dynamics of rivers and test the management's effectiveness. Targeting seven rivers, this study conducted river zoning and monitoring point deployment to conduct sufficient field research and monitoring. The authors selected hydrological and water resources, physical structure, water quality, aquatic life, social service functions, and management as guideline layers and 15 indicator layers. Subsequently, the authors established an evaluation index system to evaluate and analyze the ecological status and social service status of each river. The results showed that the Yindamu, Alingda, and Gejie rivers scored well as healthy rivers, with health evaluation scores of 78.98, 76.06, and 75.83, respectively. The Wangsanwu, Lujiagang, and Lingdangmai rivers are generally sub-healthy rivers with scores of 71.55, 67.97, and 60.7, respectively. The Yinggetu River has a score of 54.52 and is therefore assessed as unhealthy. Based on the scientific evaluation index method, this study analyses the current river health state in Jiamusi City to provide the basis for the evaluation of the river chief's work and future river management. HIGHLIGHTS Established a river health evaluation system using a graded index scoring method.; Assessed the health status of seven rivers in Jiamusi City.; Some measures and suggestions for the future management of water resources are given.;

Abstract Introduction The aim of this study was to assess the efficacy and safety of 15% azelaic acid (AzA) gel in treating acne-induced post-inflammatory erythema (PIE) and post-inflammatory hyperpigmentation (PIH). The effects of 15% AzA gel on acne, skin barrier function, and quality of life were also evaluated. Methods A total of 72 patients with mild to moderate acne were enrolled in a randomized, double-blind, placebo-controlled trial. Patients were divided into two groups: patients in the AzA group applied 15% AzA gel twice daily for 12 weeks, and those in the placebo group applied AzA-free gel. Clinical evaluations using non-invasive skin detection technologies, including VISIA skin analysis, dermoscopy, and skin physiological function tests, were performed at 0, 4, 8, and 12 weeks. Main outcome measures included the post-acne hyperpigmentation index (PAHPI), melanin, hemoglobin, individual typology angle, water content, transepidermal water loss, and sebum. Investigator Global Assessment) and Dermatology Life Quality Index (DLQI) assessments were conducted at weeks 0 and 12. Adverse reactions were recorded. Results Of the 72 patients at study initiation, 60 completed the trial. At 8 and 12 weeks, patients in the AzA group showed significantly reduced PAHPI for PIE lesions compared to baseline and patients receiving placebo (P

Endogenous retroviruses (ERVs), remnants of ancient viral invasions, make up a significant part of the mammalian genomes. ERVs are typically held in check by complex epigenetic mechanisms, which serve to limit their expansion and potential adverse effects on the genome. However, ERVs can become aberrantly activated in response to stressful challenges, contributing to progression in pathological conditions, including cancer, inflammation, auto-immune disorders, and aging, through various mechanisms. Notably, ERV activation is also detected in the brain and is increasingly recognized as an important factor in neuropsychiatric disorders. In this review, we encapsulate the general understanding of ERVs in both physiological and pathological states and compiled evidence for ERV activation across a spectrum of neuropsychiatric disorders, along with current studies exploring the underlying mechanisms. Despite the accumulating body of evidence, research in this field remains in its infancy and faces substantial challenges. Further studies are warranted to enhance our understanding of ERV activation mechanisms and their roles in neuropsychological conditions, potentially contributing to the development of innovative therapeutic interventions.

Abstract Background This study aims to investigate the expression of UBQLN1 in lung cancer (LC) tissue and the diagnostic capability of autoantibody to UBQLN1 (anti-UBQLN1) in the detection of LC and the discrimination of pulmonary nodules (PNs). Methods Sera from 798 participants were used to discover and validate the level of autoantibodies via HuProt microarray and Enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was applied to establish model. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the diagnostic potential. Immunohistochemistry was performed to detect UBQLN1 expression in 88 LC tissues and 88 para-tumor tissues. qRT-PCR and western blotting were performed to detect the expression of UBQLN1 at the mRNA and protein levels, respectively. Trans-well assay and cell counting kit-8 (CCK-8) was used to investigate the function of UBQLN1. Results Anti-UBQLN1 was identified with the highest fold change by protein microarray. The level of anti-UBQLN1 in LC patients was obviously higher than that in NC or patients with benign lung disease of validation cohort 1 (P

In this paper, the microstructure and tensile mechanical properties of Mg-8.5Gd-4.5Y-0.8Zn-0.4Zr rare-earth (RE) magnesium alloy in the as-cast state and its solid solution state were investigated by means of optical microscopy (OM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), electron backscatter diffraction (EBSD), X-ray diffraction (XRD), differential scanning calorimeter (DSC) and the first-principles simulation. The results show that the mechanical properties were improved after solution treatment. The CS520-12 alloy, treated at 520 °C for 12 h, exhibited excellent mechanical properties, possessing an ultimate tensile strength (UTS) of 343 ± 5 MPa and an elongation of 18.9 ± 0.8 %. These main reasons for the improving of mechanical properties was attributed the formation of I1 stacking faults (SFs) and accumulated-dislocations. The Y element, originating from the melt of the eutectic phase during solution treatment, resulted in a reduction in stacking faults energy (SFE) and facilitated the formation of I1 faults. The presence of numerous SFs hindered dislocation slip. The other key factors for elongation improving were that the weaken of texture, and geometrically necessary dislocation (GND) density decreased from 1.52 × 1013m−2 to 1.22 × 1013m−2. 14H-LPSO phase played an important role in the improving mechanical properties for CS480-12, CS480-24 and CS520-24 alloys. The higher elastic modulus of LPSO compared to Mg matrix, according to the first-principles calculated results, enabled its function as a short-fiber, thus strengthened the mechanical properties. Block-shaped 14H-LPSO in CS480-12 alloys, distributed at the grain boundaries (GBs), suppressed the grow of cracks. The lamellar 14H-LPSO within the grains of CS480-24 and CS520-24 alloys were parallel to the dislocations, which compared with SFs of CS520-12 alloy, can't effectively inhibit the movement of dislocations.