HDAC6 down-regulation arrested cell cycle and induced apoptosis, but not affected senescence.

<p>(<b>A</b>) FACS analysis of NC-si-treated and H6-si-1 or-3-treated A375.S2 cell cycle. (<b>B</b>) The cell percentage at different phases was indicated. (<b>C</b>) Flow cytometric analysis of apoptosis following staining with PI/AnnexinV-FITC in H6-si-1 or-3-treated and NC-si-treated A375.S2 cells. (<b>D</b>) The percentage of PI positive and Annexin V positive cells was indicated. (<b>E</b>) The protein levels of caspase-3 and-9, Bax and Bcl-2 expressions were analyzed by Western blot in H6-si-1 or-3-treated and NC-si-treated A375.S2 cells. (<b>F</b>) Immunoblotting for cytochrome c using cytosolic and mitochondrial fractions. GAPDH or Cox IV antibody was used to normalize for protein loading. (<b>G</b>) Senescence was observed by the detection of SA-β-Gal-positive cells. Bars represent the mean ± S.E.M. values. (n = 4). Statistical significance (**<i>P</i> < 0.01, ***<i>P</i> < 0.001). NC-si, NC-siRNA treated group; H6-si-1, HDAC6-siRNA-1 treated group; H6-si-3, HDAC6-siRNA-3 treated group.</p

The expression of HDAC6 was up-regulated in melanoma tissues and cell lines.

<p>(<b>A</b>) Representative melanoma tissue (Mela) and adjacent normal dermatic tissue (Adjacent) samples of HDAC6 protein expression were determined by Western blot. β-actin was used as internal loading controls for the cell lysates in the Western blot analysis. (n = 23). (<b>B</b>) The protein expression of HDAC6 in 23 pairs of melanoma tissue (Mela) and adjacent normal dermatic tissue (Adjacent) samples. (<b>C</b>, <b>D</b>) The mRNA level and protein expression of HDAC6 were analyzed in several melanoma cell lines, A375.S2, SK-MEL-28, HT-144 and human immortalised keratinocytes (HaCaT) and normal human epidermal melanocytes (PIG1) by quantitative real time PCR (qRT-PCR) (<b>C</b>) and Western blot (<b>D</b>). (n = 4). Bars represent the mean ± S.E.M. values. Statistical significance (**<i>P</i> < 0.01, ***<i>P</i> < 0.001).</p

HDAC6 silencing inhibited A375.S2 cell proliferation and colony formation.

<p>(<b>A</b>, <b>B</b>) Selective down-regulation of HDAC6 expression in A375.S2 cells that were treated for 24 or 48 h with the negative control (NC-si) or targeting-HDAC6 (H-6-si-1, -2 and-3) siRNAs or cells alone. The mRNA and protein levels of HDAC6 were determined by qRT-PCR analysis (<b>A</b>) and Western blot (<b>B</b>). (<b>C</b>) A Cell Counting Kit-8 (CCK-8) assay determined the growth condition of H6-si-1 or-3 treated and NC-si-treated A375.S2 cells. (<b>D</b>) Colony formation and (<b>E</b>) quantification of colony number. Clonogenic assay showing the effect of a two weeks incubation with H6-si-1 or-3 on the formation of cell colonies compared with NC-si-transfected cells. Bars represent the mean ± S.E.M. values. (n = 4). Statistical significance (*<i>P</i> < 0.05, **<i>P</i> < 0.01, ^^<i>P</i> < 0.01, ***<i>P</i> < 0.001). NC-si, NC-siRNA treated group; H6-si-1, HDAC6-siRNA-1 treated group; H6-si-3, HDAC6-siRNA-3 treated group.</p

NAC blocked HDAC6 siRNA-induced apoptosis and mitochondrial dysfunction in A375.S2 cells.

<p>(<b>A</b>) ROS generation and (<b>B</b>) mitochondrial membrane potential (MMP) level were detected using DCFH2 and JC-1 staining respectively in H6-si-1 or-3-treated and NC-si-treated A375.S2 cells after pretreatment with or not with 5 mM NAC for 60 min. (<b>C</b>) The growth condition of H6-si-1 or-3 treated A375.S2 cells after pretreatment with or not with NAC (^##<i>P</i> < 0.01, compared to NC-si group; *<i>P</i> < 0.05, compared to H6-si-3 group, ^&<i>P</i> < 0.05, compared to H6-si-1 group). (<b>D</b>) The cell apoptosis was assayed by flow cytometry using PI and Annexin V-FITC double staining. (<b>E</b>) Quantitative mtDNA copy number was calculated for D-loop/18S rRNA ratio. (<b>F</b>) The mitochondrial biogenesis protein PPAR-coactivator-1alpha (PGC-1α) and the mitochondrial dynamics-related proteins Mfn2 and DRP1 were detected by Western blot. Bars represent the mean ± S.E.M. values. (n = 4). Statistical significance (*<i>P</i> < 0.05, **<i>P</i> < 0.01, ***<i>P</i> < 0.001). NC-si, NC-siRNA treated group; H6-si-1, HDAC6-siRNA-1 treated group; H6-si-3, HDAC6-siRNA-3 treated group.</p

Table_1_Sulodexide for Secondary Prevention of Recurrent Venous Thromboembolism: A Systematic Review and Meta-Analysis.DOCX

<p>Background: Patients with venous thromboembolism have high risk of recurrence after discontinuation of anticoagulant treatment. Extended anticoagulation, such as traditional anticoagulants, can reduce the risk of recurrence but is associated with increased risk of hemorrhage. Sulodexide is a natural glycosaminoglycan mixture which can prevent recurrent venous thromboembolism. However, its clinical efficiency and safety still remain controversial.</p><p>Methods: A systematic search in Medline, EMBASE, Cochrane Library, Web of Science and bibliographies of retrieved articles was performed. Prospective controlled studies reporting the efficacy and safety of sulodexide on the secondary prevention of recurrent venous thromboembolism were included. Two reviewers independently extracted the following data: first author, year of publication, study design, characteristics of patients, data of interventions, doses of sulodexide, overall duration of drug administration, time of follow-up, efficacy and safety outcomes, adverse effects, and the quality of the included studies. The primary efficacy outcomes were recurrent deep vein thrombosis (DVT) or pulmonary embolism. The secondary efficacy outcomes included distal or superficial vein thrombosis and nonfatal or fatal myocardial infarction, stroke, and acute ischemia of the lower limbs. Safety outcome was possible hemorrhagic episodes.</p><p>Results: Four studies involving 1,461 patients were enrolled in this study. Meta-analysis showed that sulodexide significantly reduced the recurrent venous thromboembolism [RR 0.51, 95 % CI [0.35, 0.74], P = 0.0004] and superficial vein thrombosis in the sulodexide group [RR 0.41, 95% CI [0.22, 0.76], P = 0.005]. The safety of sulodexide was also reliable. The rate of bleeding was 0.28% in the sulodexide group and 1.60% in the control group, and design of study did not influence these results.</p><p>Conclusions: Sulodexide could significantly reduce the recurrence of VTE after discontinuation of anticoagulation treatment as compared with placebo.</p

FedEWA: Federated Learning with Elastic Weighted Averaging

FedEWA: Federated Learning with Elastic Weighted Averagin

Table_1_Brain metastases: It takes two factors for a primary cancer to metastasize to brain.xlsx

Brain metastasis of a cancer is a malignant disease with high mortality, but the cause and the molecular mechanism remain largely unknown. Using the samples of primary tumors of 22 cancer types in the TCGA database, we have performed a computational study of their transcriptomic data to investigate the drivers of brain metastases at the basic physics and chemistry level. Our main discoveries are: (i) the physical characteristics, namely electric charge, molecular weight, and the hydrophobicity of the extracellular structures of the expressed transmembrane proteins largely affect a primary cancer cell’s ability to cross the blood-brain barrier; and (ii) brain metastasis may require specific functions provided by the activated enzymes in the metastasizing primary cancer cells for survival in the brain micro-environment. Both predictions are supported by published experimental studies. Based on these findings, we have built a classifier to predict if a given primary cancer may have brain metastasis, achieving the accuracy level at AUC = 0.92 on large test sets.</p

Additional file 1 of Classification of colorectal carcinoma subtypes based on ferroptosis-associated molecular markers

Additional file 1: Table S1. Clinical characteristics of TCGA and GEO sets. N/A, not available; BMI, body mass index. Table S2. The 60 ferroptosis-related genes. Table S3. Correlations between PD-L1 and 49 ferroptosis-associated genes. Supplementary Fig. S1. Principal component analysis showed the distribution of samples in GEO and TCGA datasets. Supplementary Fig. S2. Differences in antitumor drug (sorafenib(a), dasatinib(b) and cytarabine(c)) sensitivity in ferroptosis subclasses of CRC patients. Supplementary Fig. S3. (A) Differences in the tumor mutation burden (TMB) in ferroptosis-associated subtypes in patients with colorectal carcinoma (CRC). (B) Differences in microsatellite instability (MSI) scores in ferroptosis-associated subtypes in patients with colorectal carcinoma (CRC)

A Systematic Literature Review of Robust Federated Learning: Issues, Solutions, and Future Research Directions

Federated Learning (FL) has emerged as a promising paradigm for training machine learning models across distributed devices while preserving their data privacy. However, the robustness of FL models against adversarial data and model attacks, noisy updates, and label-flipped data issues remain a critical concern. In this paper, we present a systematic literature review using the PRISMA framework to comprehensively analyze existing research on robust FL. Through a rigorous selection process using six key databases (ACM Digital Library, IEEE Xplore, ScienceDirect, Springer, Web of Science, and Scopus), we identify and categorize 244 studies into eight themes of ensuring robustness in FL: objective regularization, optimizer modification, differential privacy employment, additional dataset requirement and decentralization orchestration, manifold, client selection, new aggregation algorithms, and aggregation hyperparameter tuning. We synthesize the findings from these themes, highlighting the various approaches and their potential gaps proposed to enhance the robustness of FL models. Furthermore, we discuss future research directions, focusing on the potential of hybrid approaches, ensemble techniques, and adaptive mechanisms for addressing the challenges associated with robust FL. This review not only provides a comprehensive overview of the state-of-the-art in robust FL but also serves as a roadmap for researchers and practitioners seeking to advance the field and develop more robust and resilient FL systems

Image_2_Phenotypic Plasticity of Staphylococcus aureus in Liquid Medium Containing Vancomycin.JPEG

Phenotypic plasticity enables individuals to develop different phenotypes in a changing environment and promotes adaptive evolution. Genome-wide association study (GWAS) facilitates the study of the genetic basis of bacterial phenotypes, and provides a new opportunity for bacterial phenotypic plasticity research. To investigate the relationship between growth plasticity and genotype in bacteria, 41 Staphylococcus aureus strains, including 29 vancomycin-intermediate S. aureus (VISA) strains, were inoculated in the absence or presence of vancomycin for 48 h. Growth curves and maximum growth rates revealed that strains with the same minimum inhibitory concentration (MIC) showed different levels of plasticity in response to vancomycin. A bivariate GWAS was performed to map single-nucleotide polymorphisms (SNPs) associated with growth plasticity. In total, 227 SNPs were identified from 14 time points, while 15 high-frequency SNPs were mapped to different annotated genes. The P-values and growth variations between the two cultures suggest that non-coding region (SNP 738836), ebh (SNP 1394043), drug transporter (SNP 264897), and pepV (SNP 1775112) play important roles in the growth plasticity of S. aureus. Our study provides an alternative strategy for dissecting the adaptive growth of S. aureus in vancomycin and highlights the feasibility of bivariate GWAS in bacterial phenotypic plasticity research.</p