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Meta-analysis is a beneficial approach to reevaluating the outcomes of independent previous studies in the same scope. Saccharomyces cerevisiae, or the baker’s yeast, is a commonly used unicellular and eukaryotic model organism. In this study, 12 evolved S. cerevisiae strains that became resistant to diverse stress conditions (boron, caffeine, caloric restriction, cobalt, coniferyl aldehyde, ethanol, iron, nickel, oxidative stress, 2-phenylethanol, and silver stress) by adaptive laboratory evolution were reassessed to reveal the correlated stress/stressor clusters based on their transcriptomic and stress–cross-resistance data. Principal Component Analysis (PCA) with k-means clustering was performed. Five clusters for the transcriptomic data of strains and six clusters for cross-resistance stressors were identified. Through statistical evaluations, critical genes pertinent to each cluster were elucidated. The pathways associated with these genes were investigated using the KEGG database. The findings demonstrated that caffeine and coniferyl aldehyde stressors exhibit clear distinctions from other stressors in terms of both physiological stress-cross-resistance responses and transcriptomic profiles. Pathway analysis showed that ribosome biogenesis was downregulated, and starch and sucrose metabolism was upregulated across all clusters. Gene and pathway analyses have shown that stressors lead to distinct changes in yeast gene expression, and these alterations have been systematically documented for each cluster. Several of the highlighted genes are pivotal for further exploration and could potentially clarify new aspects of stress response mechanisms and multiple stress resistance in yeast.

Gastric cancer (GC) is one of the most lethal malignancies due to high metastatic rate, making the identification of new therapeutic targets critical for developing effective anti-GC treatments. Glutathione peroxidase 4 (GPx4), a key regulator of ferroptosis and redox homeostasis, contributes to progression and influences patient survival. However, the molecular mechanism by which GPx4 drives GC progression has not been fully illuminated. In this study, we found that GPx4 was overexpressed and negatively associated with poor prognosis and distant metastasis, as confirmed by single-cell RNA sequencing (scRNA-seq) and validation with retrospective clinical samples. GPx4 knockdown suppressed GC invasion, migration and peritoneal metastasis in vitro and in vivo. Proteomic analysis revealed that GPx4 expression regulated the Homeostasis of RCC2, an oncogene link to epithelial-mesenchymal transition (EMT). Furthermore, we demonstrated that the reactive oxygen species (ROS) accumulation induced by GPx4 inhibition or knockdown activated aurora A phosphorylation, leading to RCC2 ubiquitination and degradation, thereby suppressing peritoneal metastasis in GC. We also identified that the Thr418 phosphorylation site is crucial for RCC2 ubiquitination at the K377, initiating its degradation in response to ROS. In conclusion, our results indicate that GPx4 acts as an oncogene in GC, and that suppressing GPx4 prevents GC progression and metastasis by promoting ROS-induced RCC2 ubiquitination and degradation.

Background: Previous research has established that chronic kidney disease (CKD) and heart failure with preserved ejection fraction (HFpEF) often coexist. Although we have a preliminary understanding of the potential correlation between HFpEF and CKD, the underlying pathophysiological mechanisms remain unclear. This study aimed to elucidate the molecular mechanisms associated with CKD and HFpEF through bioinformatics analysis. Methods: Datasets for HFpEF and CKD were obtained from the Gene Expression Omnibus (GEO) database. The R software package “limma” was employed to conduct differential expression analysis. Functional annotation was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). We conducted weighted gene co-expression network analysis (WGCNA), correlation analysis with autophagy, ferroptosis, and immune-related processes, as well as transcriptional regulation analysis, immune infiltration analysis, and diagnostic performance evaluation. Finally, the diagnostic potential of the identified hub genes for CKD and HFpEF was assessed using ROC curve analysis (GSE37171). Results: Differential expression analysis revealed 58 overlapping genes, comprised of 40 up-regulated and 18 down-regulated genes. Both GO and KEGG analyses indicated enriched pathways relevant to both disorders. WGCNA identified 4086 genes associated with CKD. Further comparison with differentially expressed genes (DEGs) identified three hub genes (KLF4, SCD, and SEL1L3) that were linked to autophagy, ferroptosis, and immune processes in both conditions. Additionally, a miRNA-mRNA regulatory network involving 376 miRNAs and 12 transcription factors (TFs) was constructed. ROC curve analysis was performed to evaluate the diagnostic utility of the hub genes for CKD and HFpEF. Conclusion: This study elucidated shared pathogenic mechanisms and identified diagnostic markers common to both HFpEF and CKD. The identified hub genes show promise as potential tools for early diagnosis and treatment strategies for these conditions.

Lung cancer is the deadliest kind of cancer in the world, and the hypoxic tumor microenvironment can significantly lower the sensitivity of chemotherapeutic drugs and limit the efficacy of different therapeutic approaches. In order to overcome these problems, we have designed a drug-loaded targeted DNA nanoflowers encoding AS1411 aptamer and encapsulating chemotherapeutic drug doxorubicin and oxygen-producing drug horseradish peroxidase (DOX/HRP-DFs). These nanoflowers can release drugs in response to acidic tumor microenvironment and alleviate tumor tissue hypoxia, enhancing the therapeutic effects of chemotherapy synergistic with sonodynamic therapy. Owing to the encoded drug-loading sequence, the doxorubicin loading rate of DNA nanoflowers reached 73.24 ± 3.45%, and the drug could be released quickly by disintegrating in an acidic environment. Furthermore, the AS1411 aptamer endowed DNA nanoflowers with exceptional tumor targeting properties, which increased the concentration of chemotherapeutic drug doxorubicin in tumor cells. It is noteworthy that both in vitro and in vivo experiments demonstrated DNA nanoflowers could considerably improve the hypoxia of tumor cells, which enabled the generation of sufficient reactive oxygen species in combination with ultrasound, significantly enhancing the therapeutic effect of sonodynamic therapy and evidently inhibiting tumor growth and metastasis. Overall, this DNA nanoflowers delivery system offers a promising approach for treating lung cancer.

Telomeres, which are chromosomal end structures, play a crucial role in maintaining genome stability and integrity in eukaryotes. In the baker’s yeast Saccharomyces cerevisiae, the X- and Y’-elements are subtelomeric repetitive sequences found in all 32 and 17 telomeres, respectively. While the Y’-elements serve as a backup for telomere functions in cells lacking telomerase, the function of the X-elements remains unclear. This study utilized the S. cerevisiae strain SY12, which has three chromosomes and six telomeres, to investigate the role of X-elements (as well as Y’-elements) in telomere maintenance. Deletion of Y’-elements (SY12YΔ), X-elements (SY12XYΔ+Y), or both X- and Y’-elements (SY12XYΔ) did not impact the length of the terminal TG1-3 tracks or telomere silencing. However, inactivation of telomerase in SY12YΔ, SY12XYΔ+Y, and SY12XYΔ cells resulted in cellular senescence and the generation of survivors. These survivors either maintained their telomeres through homologous recombination-dependent TG1-3 track elongation or underwent microhomology-mediated intra-chromosomal end-to-end joining. Our findings indicate the non-essential role of subtelomeric X- and Y’-elements in telomere regulation in both telomerase-proficient and telomerase-null cells and suggest that these elements may represent remnants of S. cerevisiae genome evolution. Furthermore, strains with fewer or no subtelomeric elements exhibit more concise telomere structures and offer potential models for future studies in telomere biology.

Magnetic resonance imaging (MRI) diagnosis, enhanced by deep learning methods, plays a crucial role in medical image processing, facilitating precise clinical diagnosis and optimal treatment planning. Current methodologies predominantly focus on feature extraction from the image domain, which often results in the loss of global features during down-sampling processes. However, the unique global representational capacity of MRI K-space is often overlooked. In this paper, we present a novel MRI K-space-based global feature extraction and dual-path attention fusion network. Our proposed method extracts global features from MRI K-space data and fuses them with local features from the image domain using a dual-path attention mechanism, thereby achieving accurate MRI segmentation for diagnosis. Specifically, our method consists of four main components: an image-domain feature extraction module, a K-space domain feature extraction module, a dual-path attention feature fusion module, and a decoder. We conducted ablation studies and comprehensive comparisons on the Brain Tumor Segmentation (BraTS) MRI dataset to validate the effectiveness of each module. The results demonstrate that our method exhibits superior performance in segmentation diagnostics, outperforming state-of-the-art methods with improvements of up to 63.82% in the HD95 distance evaluation metric. Furthermore, we performed generalization testing and complexity analysis on the Automated Cardiac Diagnosis Challenge (ACDC) MRI cardiac segmentation dataset. The findings indicate robust performance across different datasets, highlighting strong generalizability and favorable algorithmic complexity. Collectively, these results suggest that our proposed method holds significant potential for practical clinical applications.

Background: Diffusion-weighted imaging (DWI), a pivotal component of multiparametric magnetic resonance imaging (mpMRI), plays a pivotal role in the detection, diagnosis, and evaluation of gastric cancer. Despite its potential, DWI is often marred by substantial anatomical distortions and sensitivity artifacts, which can hinder its practical utility. Presently, enhancing DWI’s image quality necessitates reliance on cutting-edge hardware and extended scanning durations. The development of a rapid technique that optimally balances shortened acquisition time with improved image quality would have substantial clinical relevance. Objectives: This study aims to construct and evaluate the unsupervised learning framework called attention dual contrast vision transformer cyclegan (ADCVCGAN) for enhancing image quality and reducing scanning time in gastric DWI. Methods: The ADCVCGAN framework, proposed in this study, employs high b-value DWI (b = 1200 s/mm2) as a reference for generating synthetic b-value DWI (s-DWI) from acquired lower b-value DWI (a-DWI, b = 800 s/mm2). Specifically, ADCVCGAN incorporates an attention mechanism CBAM module into the CycleGAN generator to enhance feature extraction from the input a-DWI in both the channel and spatial dimensions. Subsequently, a vision transformer module, based on the U-net framework, is introduced to refine detailed features, aiming to produce s-DWI with image quality comparable to that of b-DWI. Finally, images from the source domain are added as negative samples to the discriminator, encouraging the discriminator to steer the generator towards synthesizing images distant from the source domain in the latent space, with the goal of generating more realistic s-DWI. The image quality of the s-DWI is quantitatively assessed using metrics such as the peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), feature similarity index (FSIM), mean squared error (MSE), weighted peak signal-to-noise ratio (WPSNR), and weighted mean squared error (WMSE). Subjective evaluations of different DWI images were conducted using the Wilcoxon signed-rank test. The reproducibility and consistency of b-ADC and s-ADC, calculated from b-DWI and s-DWI, respectively, were assessed using the intraclass correlation coefficient (ICC). A statistical significance level of p < 0.05 was considered. Results: The s-DWI generated by the unsupervised learning framework ADCVCGAN scored significantly higher than a-DWI in quantitative metrics such as PSNR, SSIM, FSIM, MSE, WPSNR, and WMSE, with statistical significance (p < 0.001). This performance is comparable to the optimal level achieved by the latest synthetic algorithms. Subjective scores for lesion visibility, image anatomical details, image distortion, and overall image quality were significantly higher for s-DWI and b-DWI compared to a-DWI (p < 0.001). At the same time, there was no significant difference between the scores of s-DWI and b-DWI (p > 0.05). The consistency of b-ADC and s-ADC readings was comparable among different readers (ICC: b-ADC 0.87–0.90; s-ADC 0.88–0.89, respectively). The repeatability of b-ADC and s-ADC readings by the same reader was also comparable (Reader1 ICC: b-ADC 0.85–0.86, s-ADC 0.85–0.93; Reader2 ICC: b-ADC 0.86–0.87, s-ADC 0.89–0.92, respectively). Conclusions: ADCVCGAN shows excellent promise in generating gastric cancer DWI images. It effectively reduces scanning time, improves image quality, and ensures the authenticity of s-DWI images and their s-ADC values, thus providing a basis for assisting clinical decision making.

Kernel number per row (KNR) is an essential component of maize (Zea mays L.) grain yield (GY), and understanding its genetic mechanism is crucial to improve GY. In this study, two F7 recombinant inbred line (RIL) populations were created using a temperate–tropical introgression line TML418 and a tropical inbred line CML312 as female parents and a backbone maize inbred line Ye107 as the common male parent. Bi-parental quantitative trait locus (QTL) mapping and genome-wide association analysis (GWAS) were then performed on 399 lines of the two maize RIL populations for KNR in two different environments using 4118 validated single nucleotide polymorphism (SNP) markers. This study aimed to: (1) detect molecular markers and/or the genomic regions associated with KNR; (2) identify the candidate genes controlling KNR; and (3) analyze whether the candidate genes are useful in improving GY. The authors reported a total of 7 QTLs tightly linked to KNR through bi-parental QTL mapping and identified 21 SNPs significantly associated with KNR through GWAS. Among these, a highly confident locus qKNR7-1 was detected at two locations, Dehong and Baoshan, with both mapping approaches. At this locus, three novel candidate genes (Zm00001d022202, Zm00001d022168, Zm00001d022169) were identified to be associated with KNR. These candidate genes were primarily involved in the processes related to compound metabolism, biosynthesis, protein modification, degradation, and denaturation, all of which were related to the inflorescence development affecting KNR. These three candidate genes were not reported previously and are considered new candidate genes for KNR. The progeny of the hybrid Ye107 × TML418 exhibited strong heterosis for KNR, which the authors believe might be related to qKNR7-1. This study provides a theoretical foundation for future research on the genetic mechanism underlying KNR in maize and the use of heterotic patterns to develop high-yielding hybrids.

NUPR1 binds to PARP1 and inhibits PARP1 activity in pancreatic cancer cells, with the NUPR1 inhibitor ZZW-115 abolishing the protective effect of NUPR1, inducing strong hyperPARylation and cell death by mitochondrial dysfunction.

With the increasing complexity of engineering environments in tunnel construction, some projects are located in areas with adverse geological conditions, including areas prone to fault movements and other geological hazards. Fiber-reinforced concrete can significantly enhance structural performance in such challenging conditions. Currently, the application of high-performance steel-polypropylene fiber in tunnel linings and its anti-fault performance are quite limited. Therefore, this paper focuses on studying the application of steel-polypropylene mixed fiber-reinforced concrete in tunnel lining under reverse fault movements. In this paper, the constitutive relationship of mixed fiber-reinforced concrete is modified based on literature data. Utilizing the Najar formula, fiber-related variables were designed, and a three-dimensional numerical simulation model of a reverse fault tunnel was established. By designing various parameter combination cases, the structural response of tunnel linings was calculated and studied. then the influence patterns of mixed fiber parameters on the anti-fault performance of tunnel linings are summarized, the relationships between main variables are explored, and a reasonable value range for the two fibers is determined, which can provide guidance for practical engineering.

Background. This study is aimed at to establish an effective prognostic nomogram for patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI). Methods. The nomogram was based on a retrospective study of 977 patients with AF and ACS who underwent PCI who were admitted to any of the 11 tertiary hospitals in the Beijing area between 2009 and 2015. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index) and calibration curve and were compared using current risk scores such as GRACE, CRUSADE, CHA2DS2-VASc, and HAS-BLED. The results were validated using bootstrap resampling and a retrospective cohort study of 409 patients enrolled in Fuwai Hospital at the same institution. Results. Independent factors derived from multivariable analysis of the primary cohort to predict all-cause mortality were age, pattern of ACS, red blood cell distribution width, N-terminal proBNP, and serum creatinine, all of which were assembled into the nomogram. The calibration curve for the probability of recurrence showed that the nomogram-based predictions were in good agreement with actual observations. The C-index of the nomogram for predicting mortality was 0.764 (95% CI, 0.718-0.810), which was statistically higher than the C-index values for the current risk scores (from 0.573 to 0.681). In the validation cohort, the C-index of the nomogram for predicting all-cause death was 0.706 (95% CI 0.601-0.811), with no significant differences compared with GRACE and CRUSADE, but better than that of CHA2DS2-VASc and HAS-BLED. Conclusions. The nomogram has good prognostic prediction for patients with AF and ACS who underwent PCI.

Coordinated AP-1 and clathrin coat assembly mediate secretory sorting on the trans-Golgi network (TGN) during conventional secretion. Here we found that SMAP-1/SMAPs deficiency caused the apical protein ERM-1 to accumulate on the basolateral side of the TGN. In contrast, the basolateral protein SLCF-1 appeared abnormally on the apical membrane. SMAP-1 colocalized with AP-1 on the TGN. The integrity of AP-1 is required for the subcellular presence of SMAP-1. Moreover, we found that the loss of SMAP-1 reduced clathrin-positive structures in the cytosol, suggesting that SMAP-1 has a regulatory role in clathrin assembly on the TGN. Functional experiments showed that overexpressing clathrin effectively alleviated exocytic defects due to the lack of SMAP-1, corroborating the role of SMAP-1 in promoting the assembly of clathrin on the TGN. Together, our results suggested that the AP-1 complex regulates the TGN localization of SMAP-1, promoting clathrin assembly to ensure polarized conventional secretion in C. elegans intestinal epithelia.

We aimed to investigate differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in atherosclerosis and validate the expression of lncRNAs and co-expressed target genes in proliferation and migration models of human coronary artery smooth muscle cells (HCASMCs). Ten coronary artery specimens from a subject who died from a heart attack were employed. The pathological analysis was analyzed by hematoxylin and eosin (H&E) staining, and the lncRNAs and mRNAs were identified by RNA sequencing. Bioinformatic analyses were performed to predict possible mechanisms. The proliferation and migration of HCASMCs were induced with oxidized low-density lipoprotein (ox-LDL). Differentially expressed lncRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). In this study, 68 lncRNAs and 222 mRNAs were identified differentially expressed in atherosclerosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the Fanconi anemia pathway may be involved in atherosclerosis. GON4L was found to be the co-localized target gene of LNC_000439, and 14 genes had high correlations with the expression of seven lncRNAs. In addition, nine lncRNA–miRNA–mRNA networks were constructed, and 53 co-expressed gene modules were detected with weighted gene co-expression network analysis (WGCNA). LNC_000684, LNC_001046, LNC_001333, LNC_001538, and LNC_002115 were downregulated, while LNC_002936 was upregulated in proliferation and migration models of HCASMCs. In total, six co-expressed mRNAs were upregulated in HCASMCs. This study suggests that the differentially expressed lncRNAs identified by RNA sequencing and validated in smooth muscle cells may be a target for regulating HCASMC proliferation and migration in atherosclerosis, which will provide a new diagnostic basis and therapeutic target for the treatment of cardiovascular diseases.

The purpose of this study is to explore the expression of miRNA-590-5p, an exosome of gastric cancer (GC), and to evaluate the suitability of miR-590-5p, an exosome with its own clinical characteristics. Serum samples from 168 gastric cancer patients and 50 matched controls were collected and exosomal RNAs were extracted. After that, miR-590-5p is analyzed by quantitative polymerase chain reaction (qRT-PCR), which is more related to clinical and pathological parameters and patient monitoring data. MGC-803 and HGC-27 cells were treated by miR-590-5p mimics, and then the changes of cell fluidity and invasiveness were monitored. The results showed that the expression level of miR-590-5p in exosomes of healthy observation group, early (I and II) stage group, and late stage (III) group was 30.34 ± 6.35, 6.19 ± 0.81, and 2.9 ± 0.19, respectively (all p < 0.05). ROC (receiver-operating characteristic curve) showed that the AUC (area under the curve) of exosomal miR-590-5p was 0.810 with 63.7% sensitivity and 86% specificity. The expression of exosomal miR-590-5p in serum was related to clinical stage (p = 0.008), infiltration depth, and the expression level of ki-67 (p < 0.001). In addition, Kaplan-Meier analysis showed that the decrease of explicit level of exosomal miR-590-5p was related to the decrease of overall survival rate (p < 0.001). Cox regression analysis showed that miR-590-5p can be used as an independent predictor. Furthermore, upregulation of miR-590-5p inhibited cell migration and invasion in MGC-803 cells and HGC-27 cells. The serum expression level of exosomal miR-590-5p may be a biomarker, which is potentially useful and noninvasive for early detection and prediction of GC. In addition, miR-590-5p can play a role in eliminating carcinogens by actively regulating the malignant potential of gastric cancer.

Canonical Notch signaling is one of the most conserved signaling cascades. It regulates cell proliferation, cell differentiation, and cell fate maintenance in a variety of biological systems during development and cancer (Fortini, 2009; Kopan and Ilagan, 2009; Andersson et al., 2011; Ntziachristos et al., 2014). For the hematopoietic system, during embryonic development, Notch1 is essential for the emergence of hematopoietic stem cells (HSCs) at the aorta-gornado-mesonephro regions of the dorsal aorta. At adult stage, Notch receptors and Notch targets are expressed at different levels in diverse hematopoietic cell types and influence lineage choices. For example, Notch specifies T cell lineage over B cells. However, there has been a long-lasting debate on whether Notch signaling is required for the maintenance of adult HSCs, utilizing transgenic animals inactivating different components of the Notch signaling pathway in HSCs or niche cells. The aims of the current mini-review are to summarize the evidence that disapproves or supports such hypothesis and point at imperative questions waiting to be addressed; hence, some of the seemingly contradictory findings could be reconciled. We need to better delineate the Notch signaling events using biochemical assays to identify direct Notch targets within HSCs or niche cells in specific biological context. More importantly, we call for more elaborate studies that pertain to whether niche cell type (vascular endothelial cells or other stromal cell)-specific Notch ligands regulate the differentiation of T cells in solid tumors during the progression of T-lymphoblastic lymphoma (T-ALL) or chronic myelomonocytic leukemia (CMML). We believe that the investigation of vascular endothelial cells' or other stromal cell types' interaction with hematopoietic cells during homeostasis and stress can offer insights toward specific and effective Notch-related therapeutics.

Overactivation of androgen receptor (AR)-mediated signal has been extensively implicated in prostate cancer (CaP) development, progression, and recurrence, which makes it an attractive therapeutic target. Meanwhile, as an endogenous inhibitor of histone deacetylase 1 (HDAC 1), tumor-suppressive mammary serine protease inhibitor (maspin) was reported to sensitize drug-induced apoptosis with a better therapeutic outcome in CaP, but the relationship between AR and maspin remains unclear. In the current study, treatment of 5′-Aza or MS-275/enzalutamide induced poly (ADP-ribose) polymerase (PARP) cleavage and p-H2A.X in CaP cells with an increase of maspin expression but a decrease of AR. Then, treatment with protease inhibitor MG132 did not rescue the above drug-induced loss of AR. In addition, modulation of maspin expression by gene recombinant or siRNA technology showed an inverse correlation between expression of maspin and AR, consequently affecting the AR-regulated downstream gene transcription (e.g., NKX3.1 and TMPRSS2). Bioinformatics analysis of the data extracted from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) database also revealed an inverse correlation between low maspin expression and high AR level in advanced CaP. Furthermore, chromatin immunoprecipitation (ChIP) assay using anti-maspin antibody identified that a portion of AR promoter sequence was co-precipitated and presented in the immunoprecipitated complex. Finally, maspin-mediated repression of AR was induced by treatment of MS-275, which promoted enzalutamide treatment efficacy with decrease of prostate-specific antigen (PSA) expression in LNCaP and 22RV1 cells. Taken together, the data not only demonstrated maspin-mediated repression of AR to augment drug anti-tumor activity but also provided in-depth support for combination of HDAC inhibitors with AR antagonist in CaP therapy.

Meteorin-like (METRNL) protein is a newly identified myokine that functions to modulate energy expenditure and inflammation in adipose tissue. Herein, we aim to investigate the potential role and molecular basis of METRNL in doxorubicin (DOX)-induced cardiotoxicity. METRNL was found to be abundantly expressed in cardiac muscle under physiological conditions that was decreased upon DOX exposure. Cardiac-specific overexpression of METRNL by adeno-associated virus serotype 9 markedly improved oxidative stress, apoptosis, cardiac dysfunction and survival status in DOX-treated mice. Conversely, knocking down endogenous METRNL by an intramyocardial injection of adenovirus exacerbated DOX-induced cardiotoxicity and death. Meanwhile, METRNL overexpression attenuated, while METRNL silence promoted oxidative damage and apoptosis in DOX-treated H9C2 cells. Systemic METRNL depletion by a neutralizing antibody aggravated DOX-related cardiac injury and dysfunction in vivo, which were notably alleviated by METRNL overexpression within the cardiomyocytes. Besides, we detected robust METRNL secretion from isolated rodent hearts and cardiomyocytes, but to a less extent in those with DOX treatment. And the beneficial effects of METRNL in H9C2 cells disappeared after the incubation with a METRNL neutralizing antibody. Mechanistically, METRNL activated SIRT1 via the cAMP/PKA pathway, and its antioxidant and antiapoptotic capacities were blocked by SIRT1 deficiency. More importantly, METRNL did not affect the tumor-killing action of DOX in 4T1 breast cancer cells and tumor-bearing mice. Collectively, cardiac-derived METRNL activates SIRT1 via cAMP/PKA signaling axis in an autocrine manner, which ultimately improves DOX-elicited oxidative stress, apoptosis and cardiac dysfunction. Targeting METRNL may provide a novel therapeutic strategy for the prevention of DOX-associated cardiotoxicity.

Summary: To explore the mechanism of Rab5/RAB-5 activation during endocytic recycling, we perform a genome-wide RNAi screen and identify a recycling regulator, LET-502/ROCK. LET-502 preferentially interacts with RAB-5(GDP) and activates RABX-5 GEF activity toward RAB-5, presumably by disrupting the self-inhibiting conformation of RABX-5. Furthermore, we find that the concomitant loss of LET-502 and another CED-10 effector, TBC-2/RAB-5-GAP, results in an endosomal buildup of RAB-5, indicating that CED-10 directs TBC-2-mediated RAB-5 inactivation and re-activates RAB-5 via LET-502 afterward. Then, we compare the functional position of LET-502 with that of RME-6/RAB-5-GEF. Loss of LET-502-RABX-5 module or RME-6 leads to diminished RAB-5 presence in spatially distinct endosome groups. We conclude that in the intestine of C. elegans, RAB-5 resides in discrete endosome subpopulations. Under the oversight of CED-10, LET-502 synergizes with RABX-5 to revitalize RAB-5 on a subset of endosomes in the deep cytosol, ensuring the progress of basolateral recycling.

Fabric defect detection is very important in the textile quality process. Current deep learning algorithms are not effective in detecting tiny and extreme aspect ratio fabric defects. In this paper, we proposed a strong detection method, Priori Anchor Convolutional Neural Network (PRAN-Net), for fabric defect detection to improve the detection and location accuracy of fabric defects and decrease the inspection time. First, we used Feature Pyramid Network (FPN) by selected multi-scale feature maps to reserve more detailed information of tiny defects. Secondly, we proposed a trick to generate sparse priori anchors based on fabric defects ground truth boxes instead of fixed anchors to locate extreme defects more accurately and efficiently. Finally, a classification network is used to classify and refine the position of the fabric defects. The method was validated on two self-made fabric datasets. Experimental results indicate that our method significantly improved the accuracy and efficiency of detecting fabric defects and is more suitable to the automatic fabric defect detection.

The aim of this preliminary study was to establish a primary insect cell culture from total embryos and embryonic brain tissues of Periplaneta americana, collected from Izmir, Turkey. Cells were cultured at 29ºC in Grace’s insect medium for one month. In the embryonic brain tissue culture, single cells and cell clumps containing spherical and ovoid as well as dividing cells were observed. Single bipolar neurons were detected after 4 days in culture. Network systems comprised of bipolar neurons were observed on the 5th day of incubation. In addition, presumably glia cells were observed in the embryonic brain culture. In the total embryo culture, the cell population exhibited variable morphologies, including spherical, spindle-like, polygonal and giant cells after nearly 20 days; the culture covered almost half of the Petri dish area within 30 days. This preliminary study associated with Periplaneta americana primary cell culture is the first of its kind in Turkey. These results should contribute to the development of new insect cell lines that are indigenous to Turkey.

Excitation-emission fluorescence spectra is very effective to predict the concentration of organics in samples. However, redundant information and noises in the excitation-emission matrix (EEM) decrease the accuracy of the prediction concentration. Here we proposed a method to select more useful excitation and emission spectra from the EEM to increase the accuracy of prediction concentration and reduce the processing time. First, the excitation wavelengths were selected based on the clustering method to limit the redundant information in the EEM. Then the emission wavelengths were selected based on the Monte-Carlo method. To validate this method, we established the concentration prediction model with the spectra corresponding to the selected wavelengths by partial least square regression and predicted the multi component concentrations in the test samples. Our studies indicate that incorporation of this method increases the accuracy of the prediction concentration of organics and reduces the processing time.

Iron plays an essential role in all organisms and is involved in the structure of many biomolecules. It also regulates the Fenton reaction where highly reactive hydroxyl radicals occur. Iron is also important for microbial biodiversity, health and nutrition. Excessive iron levels can cause oxidative damage in cells. Saccharomyces cerevisiae evolved mechanisms to regulate its iron levels. To study the iron stress resistance in S. cerevisiae, evolutionary engineering was employed. The evolved iron stress-resistant mutant “M8FE” was analysed physiologically, transcriptomically and by whole genome re-sequencing. M8FE showed cross-resistance to other transition metals: cobalt, chromium and nickel and seemed to cope with the iron stress by both avoidance and sequestration strategies. PHO84, encoding the high-affinity phosphate transporter, was the most down-regulated gene in the mutant, and may be crucial in iron-resistance. M8FE had upregulated many oxidative stress response, reserve carbohydrate metabolism and mitophagy genes, while ribosome biogenesis genes were downregulated. As a possible result of the induced oxidative stress response genes, lower intracellular oxidation levels were observed. M8FE also had high trehalose and glycerol production levels. Genome re-sequencing analyses revealed several mutations associated with diverse cellular and metabolic processes, like cell division, phosphate-mediated signalling, cell wall integrity and multidrug transporters.