Nanopatterning on silicon surface using atomic force microscopy with diamond-like carbon (DLC)-coated Si probe

Atomic force microscope (AFM) equipped with diamond-like carbon (DLC)-coated Si probe has been used for scratch nanolithography on Si surfaces. The effect of scratch direction, applied tip force, scratch speed, and number of scratches on the size of the scratched geometry has been investigated. The size of the groove differs with scratch direction, which increases with the applied tip force and number of scratches but decreases slightly with scratch speed. Complex nanostructures of arrays of parallel lines and square arrays are further fabricated uniformly and precisely on Si substrates at relatively high scratch speed. DLC-coated Si probe has the potential to be an alternative in AFM-based scratch nanofabrication on hard surfaces

The protective effect of PL 1-3 on D-galactose-induced aging mice

The aging population has become an issue that cannot be ignored, and research on aging is receiving increasing attention. PL 1-3 possesses diverse pharmacological properties including anti-oxidative stress, inhibits inflammatory responses and anti-apoptosis. This study showed that PL 1-3 could protect mice, especially the brain, against the aging caused by D-galactose (D-gal). D-gal could cause oxidative stress, inflammation, apoptosis and tissue pathological injury and so on in aging mice. The treatment of PL 1-3 could increase the anti-oxidative stress ability in the serum, liver, kidney and brain of aging mice, via increasing the total antioxidant capacity and the levels of anti-oxidative defense enzymes (superoxide dismutase, glutathione peroxidase, and catalase), and reducing the end product of lipid peroxidation (malondialdehyde). In the brain, in addition to the enhanced anti-oxidative stress via upregulating the level of the nuclear factor erythroid 2-related factor 2 and heme oxygenase 1, PL 1-3 could improve the dysfunction of the cholinergic system via reducing the active of acetylcholinesterase so as to increase the level of acetylcholine, increase the anti-inflammatory and anti-apoptosis activities via downregulating the expressions of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α) and pro-apoptosis proteins (Bcl-2 associated X protein and Caspase-3) in the D-gal-induced aging mice, to enhance the anti-aging ability via upregulating the expression of sirtuin 1 and downregulating the expressions of p53, p21, and p16. Besides, PL 1-3 could reverse the liver, kidney and spleen damages induced by D-gal in aging mice. These results suggested that PL 1-3 may be developed as an anti-aging drug for the prevention and intervention of age-related diseases

Effect of dexmedetomidine on blood T cell proliferation, T cell subsets and phagocytic function of alveolar macrophages in young rats subjected to splenectomy

Purpose: To study the effect of dexmedetomidine on blood T cell proliferation, T cell subsets and phagocytosis of alveolar macrophages in young rats undergoing splenectomy. Methods: Fifty-four healthy male rats were used for the establishment of an animal model of splenectomy. The young rats were randomly assigned to control, model (untreated) and medication groups, each with 18 rats. The rats in the control and model groups were given physiological saline at a dose of 10 ml/kg, while those in the treatment group were injected with dexmedetomidine at a dose of 50 µg/kg. All treatments were given intraperitoneally (i.p.). T cell proliferation, T cell subset level, phagocytic index and degree of phagocytosis of alveolar macrophages were compared among the rat groups. Results: Relative to control, CD4+, CD8+ and CD4+/CD8+ levels in model and medication groups decreased significantly (p < 0.05). CD4+ and CD8+ levels were lower in the medication group than in model group. Phagocytic index and degree of phagocytosis of alveolar macrophages in model and medication groups were significantly lower than those in the control group, while phagocytic index and degree of phagocytosis of alveolar macrophages in the medication group of rats were smaller than those in model rats (p < 0.05). Conclusion: Dexmedetomidine significantly reduces immune function in splenectomy rats. However, it should be used with caution in patients with splenectomy

Intramolecular borylation via sequential B-Mes bond cleavage for the divergent synthesis of B,N,B-doped benzo[4]helicenes

Authors thank the Natural Sciences and Engineering Research Council of Canada and the Leverhulme Trust (RPG-2016-47) for financial support. J. A. Knöller thanks the Baden Württemberg Stiftung for a scholarship as well as Queen's and Stuttgart University for enabling this research through the Dual Degree Masters program.New symmetric and unsymmetric B,N,B-doped benzo[4]helicenes 3 - 6a/b have been achieved in good yields, using a three-step process, starting from N(tolyl)3 in a highly divergent manner (7 examples). A borinic acid functionalized 1,4-B,N- anthracene 1 was found to display unprecedented reactivity, acting as a convenient and highly effective precursor for selective formation of bromo substituted B,N,B-benzo[4]helicenes 2a/2b via intramolecular borylation and sequential B-Mes bond cleavage in presence of BBr3. Subsequent reaction of 2a/2b with Ar-Li provided a highly effective toolbox for the preparation of symmetrically/unsymmetrically functionalized B,N,B-helicenes. Their high photoluminescence quantum yields along with the small ∆EST suggest the potential as thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs).PostprintPeer reviewe

Targeting mitochondria for ovarian aging: new insights into mechanisms and therapeutic potential

Ovarian aging is a complex process characterized by a decline in oocyte quantity and quality, directly impacting fertility and overall well-being. Recent researches have identified mitochondria as pivotal players in the aging of ovaries, influencing various hallmarks and pathways governing this intricate process. In this review, we discuss the multifaceted role of mitochondria in determining ovarian fate, and outline the pivotal mechanisms through which mitochondria contribute to ovarian aging. Specifically, we emphasize the potential of targeting mitochondrial dysfunction through innovative therapeutic approaches, including antioxidants, metabolic improvement, biogenesis promotion, mitophagy enhancement, mitochondrial transfer, and traditional Chinese medicine. These strategies hold promise as effective means to mitigate age-related fertility decline and preserve ovarian health. Drawing insights from advanced researches in the field, this review provides a deeper understanding of the intricate interplay between mitochondrial function and ovarian aging, offering valuable perspectives for the development of novel therapeutic interventions aimed at preserving fertility and enhancing overall reproductive health

Full-length single-cell RNA-seq applied to a viral human cancer:applications to HPV expression and splicing analysis in HeLa S3 cells

Background: Viral infection causes multiple forms of human cancer, and HPV infection is the primary factor in cervical carcinomas Recent single-cell RNA-seq studies highlight the tumor heterogeneity present in most cancers, but virally induced tumors have not been studied HeLa is a well characterized HPV+ cervical cancer cell line Result: We developed a new high throughput platform to prepare single-cell RNA on a nanoliter scale based on a customized microwell chip Using this method, we successfully amplified full-length transcripts of 669 single HeLa S3 cells and 40 of them were randomly selected to perform single-cell RNA sequencing Based on these data, we obtained a comprehensive understanding of the heterogeneity of HeLa S3 cells in gene expression, alternative splicing and fusions Furthermore, we identified a high diversity of HPV-18 expression and splicing at the single-cell level By co-expression analysis we identified 283 E6, E7 co-regulated genes, including CDC25, PCNA, PLK4, BUB1B and IRF1 known to interact with HPV viral proteins Conclusion: Our results reveal the heterogeneity of a virus-infected cell line It not only provides a transcriptome characterization of HeLa S3 cells at the single cell level, but is a demonstration of the power of single cell RNA-seq analysis of virally infected cells and cancers

Comparison of variations detection between whole-genome amplification methods used in single-cell resequencing

Background: Single-cell resequencing (SCRS) provides many biomedical advances in variations detection at the single-cell level, but it currently relies on whole genome amplification (WGA). Three methods are commonly used for WGA: multiple displacement amplification (MDA), degenerate-oligonucleotide-primed PCR (DOP-PCR) and multiple annealing and looping-based amplification cycles (MALBAC). However, a comprehensive comparison of variations detection performance between these WGA methods has not yet been performed. Results: We systematically compared the advantages and disadvantages of different WGA methods, focusing particularly on variations detection. Low-coverage whole-genome sequencing revealed that DOP-PCR had the highest duplication ratio, but an even read distribution and the best reproducibility and accuracy for detection of copy-number variations (CNVs). However, MDA had significantly higher genome recovery sensitivity (~84 %) than DOP-PCR (~6 %) and MALBAC (~52 %) at high sequencing depth. MALBAC and MDA had comparable single-nucleotide variations detection efficiency, false-positive ratio, and allele drop-out ratio. We further demonstrated that SCRS data amplified by either MDA or MALBAC from a gastric cancer cell line could accurately detect gastric cancer CNVs with comparable sensitivity and specificity, including amplifications of 12p11.22 (KRAS) and 9p24.1 (JAK2, CD274, and PDCD1LG2). Conclusions: Our findings provide a comprehensive comparison of variations detection performance using SCRS amplified by different WGA methods. It will guide researchers to determine which WGA method is best suited to individual experimental needs at single-cell level

Genetic and functional characterization of disease associations explains comorbidity

Understanding relationships between diseases, such as comorbidities, has important socio-economic implications, ranging from clinical study design to health care planning. Most studies characterize disease comorbidity using shared genetic origins, ignoring pathway-based commonalities between diseases. In this study, we define the disease pathways using an interactome-based extension of known disease-genes and introduce several measures of functional overlap. The analysis reveals 206 significant links among 94 diseases, giving rise to a highly clustered disease association network. We observe that around 95% of the links in the disease network, though not identified by genetic overlap, are discovered by functional overlap. This disease network portraits rheumatoid arthritis, asthma, atherosclerosis, pulmonary diseases and Crohn's disease as hubs and thus pointing to common inflammatory processes underlying disease pathophysiology. We identify several described associations such as the inverse comorbidity relationship between Alzheimer's disease and neoplasms. Furthermore, we investigate the disruptions in protein interactions by mapping mutations onto the domains involved in the interaction, suggesting hypotheses on the causal link between diseases. Finally, we provide several proof-of-principle examples in which we model the effect of the mutation and the change of the association strength, which could explain the observed comorbidity between diseases caused by the same genetic alterations