Small interfering RNA targeting CDC25B inhibits liver tumor growth in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Using gene expression profiling, we previously identified CDC25B to be significantly highly expressed in hepatocellular carcinoma (HCC) compared to non-tumor liver. CDC25B is a cell cycle-activating phosphatase that positively regulates the activity of cyclin-dependent kinases, and is over-expressed in a variety of human malignancies. In this study, we validated the over-expression of CDC25B in HCC, and further investigated its potential as a therapeutic target for the management of HCC.</p> <p>Results</p> <p>Quantitative real-time polymerase chain reaction and immunohistochemical staining of patient samples confirmed the significant over-expression of CDC25B in HCC compared to non-tumor liver samples (<it>P </it>< 0.001). Thus, intefering with the expression and activity of CDC25B may be a potential way to intervene with HCC progression. We used RNA interference to study the biological effects of silencing CDC25B expression in HCC cell lines (Hep3B and Hep40), in order to validate its potential as a therapeutic target. Using small oligo siRNAs targeting the coding region of CDC25B, we effectively suppressed CDC25B expression by up to 90%. This was associatetd with significant reductions in cell growth rate, cell migration and invasion through the matrigel membrane, and caused significant cell cycle delay at the G2 phase. Finally, suppression of CDC25B significantly slowed the growth of Hep40 xenografts in nude mice.</p> <p>Conclusion</p> <p>Our data provide evidence that the inhibition of CDC25B expression and activity lead to suppression of tumor cell growth and motility, and may therefore be a feasible approach in the clinical management of HCC.</p

Distinguishing Neural Speech Synthesis Models Through Fingerprints in Speech Waveforms

Recent strides in neural speech synthesis technologies, while enjoying widespread applications, have nonetheless introduced a series of challenges, spurring interest in the defence against the threat of misuse and abuse. Notably, source attribution of synthesized speech has value in forensics and intellectual property protection, but prior work in this area has certain limitations in scope. To address the gaps, we present our findings concerning the identification of the sources of synthesized speech in this paper. We investigate the existence of speech synthesis model fingerprints in the generated speech waveforms, with a focus on the acoustic model and the vocoder, and study the influence of each component on the fingerprint in the overall speech waveforms. Our research, conducted using the multi-speaker LibriTTS dataset, demonstrates two key insights: (1) vocoders and acoustic models impart distinct, model-specific fingerprints on the waveforms they generate, and (2) vocoder fingerprints are the more dominant of the two, and may mask the fingerprints from the acoustic model. These findings strongly suggest the existence of model-specific fingerprints for both the acoustic model and the vocoder, highlighting their potential utility in source identification applications.Comment: Submitted to ICASSP 202

Effects of additional food availability and pulse control on the dynamics of a Holling-(p+1) type pest-natural enemy model

In this paper, a novel pest-natural enemy model with additional food source and Holling-($p$+1) type functional response is put forward for plant pest management by considering multiple food sources for predators. The dynamical properties of the model are investigated, including existence and local asymptotic stability of equilibria, as well as the existence of limit cycles. The inhibition of natural enemy on pest dispersal and the impact of additional food sources on system dynamics are elucidated. In view of the fact that the inhibitory effect of the natural enemy on pest dispersal is slow and in general deviated from the expected target, an integrated pest management model is established by regularly releasing natural enemies and spraying insecticide to improve the control effect. The influence of the control period on the global stability and system persistence of the pest extinction periodic solution is discussed. It is shown that there exists a time threshold, and as long as the control period does not exceed that threshold, pests can be completely eliminated. When the control period exceeds that threshold, the system can bifurcate the supercritical coexistence periodic solution from the pest extinction one. To illustrate the main results and verify the effectiveness of the control method, numerical simulations are implemented in MATLAB programs. This study not only enriched the related content of population dynamics, but also provided certain reference for the management of plant pest

System Fingerprint Recognition for Deepfake Audio: An Initial Dataset and Investigation

The malicious use of deep speech synthesis models may pose significant threat to society. Therefore, many studies have emerged to detect the so-called ``deepfake audio". However, these studies focus on the binary detection of real audio and fake audio. For some realistic application scenarios, it is needed to know what tool or model generated the deepfake audio. This raises a question: Can we recognize the system fingerprints of deepfake audio? Therefore, in this paper, we propose a deepfake audio dataset for system fingerprint recognition (SFR) and conduct an initial investigation. We collected the dataset from five speech synthesis systems using the latest state-of-the-art deep learning technologies, including both clean and compressed sets. In addition, to facilitate the further development of system fingerprint recognition methods, we give researchers some benchmarks that can be compared, and research findings. The dataset will be publicly available.Comment: 12 pages, 3 figures. arXiv admin note: text overlap with arXiv:2208.0964

Development and Validation of Non-Integrative, Self-Limited, and Replicating Minicircles for Safe Reporter Gene Imaging of Cell-Based Therapies

Reporter gene (RG) imaging of cell-based therapies provides a direct readout of therapeutic efficacy by assessing the fate of implanted cells. To permit long-term cellular imaging, RGs are traditionally required to be integrated into the cellular genome. This poses a potential safety risk and regulatory bottleneck for clinical translation as integration can lead to cellular transformation. To address this issue, we have developed non-integrative, replicating minicircles (MCs) as an alternative platform for safer monitoring of cells in living subjects. We developed both plasmids and minicircles containing the scaffold/matrix attachment regions (S/MAR) of the human interferon-beta gene, driven by the CMV promoter, and expressing the bioluminescence RG firefly luciferase. Constructs were transfected into breast cancer cells, and expanded S/MAR minicircle clones showed luciferase signal for greater than 3 months in culture and minicircles remained as episomes. Importantly, luciferase activity in clonal populations was slowly lost over time and this corresponded to a loss of episome, providing a way to reversibly label cells. To monitor cell proliferation in vivo, 1.5×10(6) cells carrying the S/MAR minicircle were implanted subcutaneously into mice (n = 5) and as tumors developed significantly more bioluminescence signal was noted at day 35 and 43 compared to day 7 post-implant (p<0.05). To our knowledge, this is the first work examining the use of episomal, self-limited, replicating minicircles to track the proliferation of cells using non-invasive imaging in living subjects. Continued development of S/MAR minicircles will provide a broadly applicable vector platform amenable with any of the numerous RG technologies available to allow therapeutic cell fate to be assessed in individual patients, and to achieve this without the need to manipulate the cell's genome so that safety concerns are minimized. This will lead to safe tools to assess treatment response at earlier time points and improve the precision of cell-based therapies.The authors would like to acknowledge the imaging support provided by the Stanford Small Animal Imaging FacilityPublicad

CFAD: A Chinese Dataset for Fake Audio Detection

Fake audio detection is a growing concern and some relevant datasets have been designed for research. However, there is no standard public Chinese dataset under complex conditions.In this paper, we aim to fill in the gap and design a Chinese fake audio detection dataset (CFAD) for studying more generalized detection methods. Twelve mainstream speech-generation techniques are used to generate fake audio. To simulate the real-life scenarios, three noise datasets are selected for noise adding at five different signal-to-noise ratios, and six codecs are considered for audio transcoding (format conversion). CFAD dataset can be used not only for fake audio detection but also for detecting the algorithms of fake utterances for audio forensics. Baseline results are presented with analysis. The results that show fake audio detection methods with generalization remain challenging. The CFAD dataset is publicly available at: https://zenodo.org/record/8122764.Comment: FAD renamed as CFA

Impact of central venous pressure on the mortality of patients with sepsis-related acute kidney injury: a propensity score-matched analysis based on the MIMIC IV database

Central venous pressure (CVP); Database; MortalityPressió venosa central (PVC); Base de dades; MortalitatPresión venosa central (PVC); Base de datos; MortalidadBackground: Sepsis has long been a life-threatening organ dysfunction. Sepsis associated acute kidney injury (SA-AKI) is an important complication of sepsis, as an important hemodynamic index, the impact of central venous pressure (CVP) on sepsis patients needs to be explored. Thus this study aimed to investigate the relationship between CVP and the mortality of SA-AKI. Methods: Clinical data of adult patients with sepsis-related acute kidney injury, defined as met both the Sepsis 3.0 criteria and the Kidney Disease Improving Global Outcomes Clinical Practice Guideline (KDIGO) criteria, were obtained from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. The included cohort was divided into a high CVP and a low CVP group were determined based on the cuf-off value from receiver operating characteristic curve, with propensity score-matched analysis of the 28-day mortality for both groups and sensitivity analysis using inverse the probability-weighting model, multifactorial regression, and doubly robust estimation, patients acquired chronic coronary syndrome (CCS) and diabetes were also taken into consideration. Results: Of 1,377 patients with sepsis-related acute kidney injury, low CVP group (<13 mmHg) was 67.4% (n=928) and high CVP group (≥13 mmHg) was 32.6% (n=449). The two groups were matched 1:1 by propensity score to obtain a matched cohort (n=288). The mortality rates in the low versus high CVP group (19.4% vs. 34.7%) were statistically difference (odds ratio OR: 0.454; 95% confidence interval 0.263, 0.771). Moreover, the bistable analysis of logistic regression of the matched cohort (OR: 0.434; 95% CI: 0.244, 0.757), propensity score inverse probability weighting (IPW) (OR: 0.547; 95% CI: 0.454, 0.658), and multifactorial logistic regression (OR: 0.352; 95% CI: 0.127, 0.932) all yielded the same results. Conclusions: In patients with sepsis-related acute kidney injury, a lower CVP level (<13 mmHg) is an independent variable associated with decreased mortality. The threshold of CVP needs to be controlled in clinical work to improve the prognosis of patients with SA-AKI

Sulfur-doped TiO2 anchored on a large-area carbon sheet as a high-performance anode for sodium-ion battery

Well-tailored sulfur-doped anatase titanium dioxide nanoparticles anchored on a large-area carbon sheet are designed, where the in situ sulfur-doped titanium dioxide directly comes from titanium oxysulfate and the large-area carbon sheet is derived from glucose. When applied as an anode material for sodium-ion batteries, it exhibits an excellent electrochemical performance including a high capacity [256.4 mA h g–1 at 2 C (1 C = 335 mA h g–1) after 500 cycles] and a remarkable rate of cycling stability (100.5 mA h g–1 at 30 C after 500 cycles). These outstanding sodium storage behaviors are ascribed to the nanosized particles (about 8–12 nm), good electronic conductivity promoted by the incorporation of carbon sheet and sulfur, as well as the unique chemical bond based on the electrostatic interaction

Characterization and insight mechanism of an acid-adapted β-Glucosidase from Lactobacillus paracasei and its application in bioconversion of glycosides

Introduction: β-glucosidase is one class of pivotal glycosylhydrolase enzyme that can cleavage glucosidic bonds and transfer glycosyl group between the oxygen nucleophiles. Lactobacillus is the most abundant bacteria in the human gut. Identification and characterization of new β-glucosidases from Lactobacillus are meaningful for food or drug industry.Method: Herein, an acid-adapted β-glucosidase (LpBgla) was cloned and characterized from Lactobacillus paracasei. And the insight acid-adapted mechanism of LpBgla was investigated using molecular dynamics simulations.Results and Discussion: The recombinant LpBgla exhibited maximal activity at temperature of 30°C and pH 5.5, and the enzymatic activity was inhibited by Cu2+, Mn2+, Zn2+, Fe2+, Fe3+ and EDTA. The LpBgla showed a more stable structure, wider substrate-binding pocket and channel aisle, more hydrogen bonds and stronger molecular interaction with the substrate at pH 5.5 than pH 7.5. Five residues including Asp45, Leu60, Arg120, Lys153 and Arg164 might play a critical role in the acid-adapted mechanism of LpBgla. Moreover, LpBgla showed a broad substrate specificity and potential application in the bioconversion of glycosides, especially towards the arbutin. Our study greatly benefits for the development novel β-glucosidases from Lactobacillus, and for the biosynthesis of aglycones

Flavonoids improve type 2 diabetes mellitus and its complications: a review

The prevalence of type 2 diabetes mellitus (T2DM) is increasing every year. Medications are currently the most common therapy for T2DM. However, these medications have certain adverse effects. In order to find safe and effective ways to improve this disease, researchers have discovered that some natural products can decrease blood sugar. Flavonoids are one of the most essential low molecular weight phenolic chemicals in the plant world, which widely exist in plant roots, stems, leaves, flowers, and fruits. They possess a variety of biological activities, including organ protection, hypoglycemic, lipid-lowering, anti-oxidative and anti-inflammatory effects. Some natural flavonoids ameliorate T2DM and its complications through anti-oxidation, anti-inflammatory action, glucose and lipid metabolism regulation, insulin resistance management, etc. Hence, this review aims at demonstrating the potential benefits of flavonoids in T2DM and its complications. This laid the foundation for the development of novel hypoglycemic medications from flavonoids