Highly Sensitive Electrochemical Sensor for the Determination of 8-Hydroxy-2 \u27-deoxyguanosine Incorporating SWCNTs-Nafion Composite Film

8-Hydroxy-2\u27-deoxyguanosine (8-OHdG) is a typical biomarker of oxidative DNA damage and has attracted much attention in recent years since the level of 8-OHdG in body fluids is typically associated with various diseases. In this work, a simple and highly sensitive electrochemical sensor for the determination of 8-OHdG was fabricated incorporating single wall carbon nanotubes-(SWCNTs-) Nafion composite film coated on glassy carbon electrode. Nafion was chosen as an optimal adhesive agent from a series of adhesive agents and acted as a binder, enrichment, and exclusion film. Due to the strong cation-exchange ability of Nafion and the outstanding electronic properties ofSWCNTs, the prepared SWCNTs-Nafion film can strongly enhance the electrochemical response to oxidation of 8-OHdG and efficiently alleviate the interferences from uric acid and ascorbic acid. The oxidation peak currents are linear with the concentration of 8-OHdG in the range of 0.03 to 1.25 mu M with a detection limit of 8.0 nM (S/N = 3). This work demonstrates that SWCNTs-Nafion film can improve the sensitivity, selectivity, reproducibility, and stability, making it an ideal candidate for electrochemical detection of 8-OHdG

Evaluating the effect of database inflation in proteogenomic search on sensitive and reliable peptide identification

Comparison of novel peptides identified from real proteogenomic databases. (DOCX 68 kb

Structural and Topological Nature of Plasticity in Sheared Granular Materials

Upon mechanical loading, granular materials yield and undergo plastic deformation. The nature of plastic deformation is essential for the development of the macroscopic constitutive models and the understanding of shear band formation. However, we still do not fully understand the microscopic nature of plastic deformation in disordered granular materials. Here we used synchrotron X-ray tomography technique to track the structural evolutions of three-dimensional granular materials under shear. We establish that highly distorted coplanar tetrahedra are the structural defects responsible for microscopic plasticity in disordered granular packings. The elementary plastic events occur through flip events which correspond to a neighbor switching process among these coplanar tetrahedra (or equivalently as the rotation motion of 4-ring disclinations). These events are discrete in space and possess specific orientations with the principal stress direction.Comment: 26 pages, 11 figures, 2 tables, to be published in Nature Communication

The connection between tricarboxylic acid cycle enzyme mutations and pseudohypoxic signaling in pheochromocytoma and paraganglioma

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors originating from chromaffin cells, holding significant clinical importance due to their capacity for excessive catecholamine secretion and associated cardiovascular complications. Roughly 80% of cases are associated with genetic mutations. Based on the functionality of these mutated genes, PPGLs can be categorized into distinct molecular clusters: the pseudohypoxia signaling cluster (Cluster-1), the kinase signaling cluster (Cluster-2), and the WNT signaling cluster (Cluster-3). A pivotal factor in the pathogenesis of PPGLs is hypoxia-inducible factor-2α (HIF2α), which becomes upregulated even under normoxic conditions, activating downstream transcriptional processes associated with pseudohypoxia. This adaptation provides tumor cells with a growth advantage and enhances their ability to thrive in adverse microenvironments. Moreover, pseudohypoxia disrupts immune cell communication, leading to the development of an immunosuppressive tumor microenvironment. Within Cluster-1a, metabolic perturbations are particularly pronounced. Mutations in enzymes associated with the tricarboxylic acid (TCA) cycle, such as succinate dehydrogenase (SDHx), fumarate hydratase (FH), isocitrate dehydrogenase (IDH), and malate dehydrogenase type 2 (MDH2), result in the accumulation of critical oncogenic metabolic intermediates. Notable among these intermediates are succinate, fumarate, and 2-hydroxyglutarate (2-HG), which promote activation of the HIFs signaling pathway through various mechanisms, thus inducing pseudohypoxia and facilitating tumorigenesis. SDHx mutations are prevalent in PPGLs, disrupting mitochondrial function and causing succinate accumulation, which competitively inhibits α-ketoglutarate-dependent dioxygenases. Consequently, this leads to global hypermethylation, epigenetic changes, and activation of HIFs. In FH-deficient cells, fumarate accumulation leads to protein succination, impacting cell function. FH mutations also trigger metabolic reprogramming towards glycolysis and lactate synthesis. IDH1/2 mutations generate D-2HG, inhibiting α-ketoglutarate-dependent dioxygenases and stabilizing HIFs. Similarly, MDH2 mutations are associated with HIF stability and pseudohypoxic response. Understanding the intricate relationship between metabolic enzyme mutations in the TCA cycle and pseudohypoxic signaling is crucial for unraveling the pathogenesis of PPGLs and developing targeted therapies. This knowledge enhances our comprehension of the pivotal role of cellular metabolism in PPGLs and holds implications for potential therapeutic advancements

TRIM37 interacts with PTEN to promote the growth of human T-cell acute lymphocytic leukemia cells through regulating PI3K/AKT pathway

BackgroundTRIM37 has been reported to be associated with the tumorigenesis of cancers. However, the role of TRIM37 in T-cell acute lymphoblastic leukemia (T-ALL) remains unclear. This study aimed to characterize the effect of TRIM37 on T-ALL.MethodsTRIM37 expression in T-ALL patients and T-ALL cell lines was determined by qRT-PCR and Western blot. Knockdown or overexpression of TRIM37 was conducted by transferring small-interfering TRIM37 or lentivirus-mediated transducing into T-ALL cells. CCK-8 assay and flow cytometry assay were conducted to analyze the proliferation and apoptosis of T-ALL cells. Co-immunoprecipitation experiments were conducted to investigate the relationship between TRIM37 and PTEN and the ubiquitination of PTEN.ResultsOur results suggested that TRIM37 expression was upregulated in the blood of T-ALL patients and T-ALL cell lines. Knockdown of TRIM37 noticeably inhibited the proliferation and promoted apoptosis of T-ALL cells. Ectopic expression of TRIM37 promoted the proliferation and suppressed the apoptosis rate of MOLT-4 cells and enhanced the phosphorylation of AKT. Moreover, TRIM37 interacted with PTEN and accelerated the degradation of PTEN via TRIM37-mediated ubiquitination in T-ALL cells. Moreover, TRIM37 reduced the sensitivity of T-ALL cells to bortezomib treatment. Additionally, PI3K/AKT signaling pathway was involved in the function of TRIM37 in T-ALL. TRIM37 contributed to the proliferation of T-ALL cells and reduced the susceptibility of T-ALL cells to bortezomib treatment through ubiquitination of PTEN and activating PI3K/AKT signaling pathway.ConclusionsOur study suggested that TRIM37 could be considered as a therapeutic target for T-ALL

Transgenic Technology can Accelerate Cotton Breeding: Transgenic <em>ScALDH21</em> Cotton Significantly Improve Drought Tolerance in Southern and Northern Xinjiang

Aldehyde dehydrogenases (ALDHs) contribute to cellular protection against oxidative stress. These enzymes are crucial to organisms’ ability to cope with environmental stress. The ALDH21 gene was introduced into upland cotton (Gossypium hirsutum L.) from desiccant-tolerant Syntrichia caninervis moss, created stable genetic transgenic lines. As a result, drought tolerance is increased and yield penalty is reduced in those transgenic lines. The first study to demonstrate overexpression of ALDH21 enhances drought tolerance in cotton under multi-location field experiments is presented here. Cotton genotypes containing ScALDH21 exhibit significant morphological, physiological, and economic benefits. ScALDH21 functions in the physiology of cotton plants to protect them by scavenging ROS and reducing osmotic stress. The yield of transgenic cotton in northern Xinjiang showed up to 10% improvement under full irrigation and up to 18% improvement in deficit irrigation conditions on fields with purple clay loam soils. Additionally, transgenic cotton can be grown in sandy loam soil in southern Xinjiang with an average yield increase of 40% on different irrigation levels in the desert-oasis ecotone. Using ScALDH21 as a candidate gene for cotton improvement in arid and semi-arid regions was demonstrated. In addition, we assessed different irrigation protocols and optimized irrigation methods with minimal water requirements for ScALDH21-transgenic cotton that could be used in production agriculture

Development and Application of a Multiple Cross Displacement Amplification Combined With Nanoparticle-Based Lateral Flow Biosensor Assay to Detect Candida tropicalis

Candida tropicalis is an increasingly opportunistic pathogen that causes serious invasive candidiasis threatening a patient’s life. Traditional methods to detect C. tropicalis infection depends on time-consuming, culture-based gold-standard methods. So, we sought to establish a new method that could detect target pathogens quickly, accurately, and straightforwardly. Herein, a combination of multiple cross displacement amplification (MCDA) and lateral flow biosensors (LFB) was employed to detect C. tropicalis. In the MCDA system, 10 primers were designed to identify the specific genes of C. tropicalis and amplify the genes in an isothermal amplification device. Then, MCDA amplification reaction products could be identified visibly by color change, and all the amplification products would be tested by LFB with no special equipment. The results demonstrated that the optimal reaction condition of C. tropicalis-MCDA assay was 64°C within 30 min, and only 10 fg DNA was required in each reaction. No cross-reaction was found between C. tropicalis strains and non-C. tropicalis strains. For 300 sputum samples, the results showed that MCDA-LFB assay could rapidly and successfully detect all of the C. tropicalis-positive (28/300) samples detected by the gold-standard method. The entire procedure, including specimen processing (40 min), isothermal reaction (30 min) and result reporting (within 2 min), could be completed within 75 min. Briefly, the study results demonstrated that the detection ability of C. tropicalis-MCDA-LFB assay was better than culture methods with more simplicity, rapidity, sensitivity and specificity. Hence, MCDA-LFB strategy is an effective tool to rapidly detect C. tropicalis in clinical samples, especially in resource-poor areas