Explore the vast range of titles available.

Lineage commitment and tumorigenesis, traits distinguishing stem cells, have not been well characterized and compared in mesenchymal stem cells derived from human dental pulp (DP-MSCs) and bone marrow (BM-MSCs). Here, we report DP-MSCs exhibit increased osteogenic potential, possess decreased adipogenic potential, form dentin pulp-like complexes, and are resistant to oncogenic transformation when compared to BM-MSCs. Genome-wide RNA-seq and differential expression analysis reveal differences in adipocyte and osteoblast differentiation pathways, bone marrow neoplasm pathway, and PTEN/PI3K/AKT pathway. Higher PTEN expression in DP-MSCs than in BM-MSCs is responsible for the lineage commitment and tumorigenesis differences in both cells. Additionally, the PTEN promoter in BM-MSCs exhibits higher DNA methylation levels and repressive mark H3K9Me2 enrichment when compared to DP-MSCs, which is mediated by increased DNMT3B and G9a expression, respectively. The study demonstrates how several epigenetic factors broadly affect lineage commitment and tumorigenesis, which should be considered when developing therapeutic uses of stem cells. Mesenchymal stem cells derived from dental pulp (DP-MSCs) differ in oncogenesic and developmental potential compared to those from bone marrow. Here, the authors show that decreased DNA methylation and histone H3K9Me2 enrichment along with higher PTEN activation in DP-MSCs promotes osteogenesis and reduces oncogenesis.

In 2022, the Event Horizon Telescope (EHT) collaboration has reported the first observations of Sagittarius A*(SgrA*). Applying the EHT observational results, we find out constraints on non-singular Hayward parameter of regular dark energy black hole. Considering these constraints and different thin disk accretion, we present a detailed investigation into influence of different dark energy and Hayward parameters on shadows from non-singular Hayward black holes. In the first second-order attenuation function model, corresponding shadow radius and peak for observed intensity from direct image decrease with increasing dark energy parameter and Hayward parameter. However, for the lensing ring and photon ring, corresponding peak become bigger as dark energy parameter increase in case of fixed Hayward parameter. In the second third-order attenuation function model, significantly different from model 1, above two rings completely overlay on the direct image, resulting in two distinct peaks in the observed intensity. As increase of Hayward and dark energy parameters, the difference between the two peaks decreases, and shadows and observed intensity decrease. In the final inverse trigonometric function attenuation model, the result shows corresponding lensing ring as well as photon ring can be distinguished within the superposition region, and the superposition region becomes larger. With the increase of the dark energy parameter, the shadow radius exhibits a decreasing trend, while observed intensity increases. However, with the increase of the Hayward parameter, both decreases. Compared with the first two models, the shadow radius becomes smaller, but the observed intensity becomes larger, making the bright ring wider and brighter. Therefore, different accretion models and non-singular Hayward parameters can give rise to interesting and distinguish characteristic for the black hole shadow and rings.

In the framework of holography, we discuss on the phase transition behavior from a novel Gauss–Bonnet AdS black hole discovered in [Phys. Rev. Lett. 124, 081301 (2020)] in both charged and neutral cases. First, we explore the thermodynamic behavior for the black hole entropy by investigating T - S diagram, specific heat capacity and free energy, and we find that, in the T - S plane, the black hole exhibits a van der Waals phase transition similar to that in P - V plane in extended phase space. Secondly, we detect thermodynamic phase transition for the two point correlation function, and find that, the van der Waals phase transition can also be displayed in the T - δ L plane which is completely similar to that of black hole entropy in the T - S plane. Our result turns out that, not only the charged but also neutral cases, we can observe holographic van der Waals phase transition for the novel Gauss–Bonnet AdS black hole by employing the black hole entropy and two point correlation function.

Background Owing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in colorectal cancer (CRC) in multiple studies. Thus, the discovery of additional bacteria contributing to CRC development in various populations can be expected. We aimed to identify bacteria associated with the progression of colorectal adenoma to carcinoma and determine the contribution of these bacteria to malignant transformation in patients of Han Chinese origin. Methods Microbiota composition was determined through 16S rRNA V3–V4 amplicon sequencing of autologous adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissue samples (referred to as “tri-part samples”) in patients with CRC. Enriched taxa in adenocarcinoma tissues were identified through pairwise comparison. The abundance of candidate bacteria was quantified through genomic quantitative polymerase chain reaction (qPCR) in tissue samples from 116 patients. Associations of candidate bacteria with clinicopathological features and genomic and genetic alterations were evaluated through odds ratio tests. Additionally, the effects of candidate bacteria on CRC cell proliferation, migration, and invasion were evaluated through the co-culture of CRC cells with bacterial cells or with conditioned media from bacteria. Results Prevotella intermedia was overrepresented in adenocarcinomas compared with paired adenomatous polyps. Furthermore, co-abundance of P. intermedia and F. nucleatum was observed in tumor tissues. More notably, the coexistence of these two bacteria in adenocarcinomas was associated with lymph node involvement and distant metastasis. These two bacteria also exerted additive effects on the enhancement of the migration and invasion abilities of CRC cells. Finally, conditioned media from P. intermedia promoted the migration and invasion of CRC cells. Conclusion This report is the first to demonstrate that P. intermedia is enriched in colorectal adenocarcinoma tissues and enhances the migration and invasion abilities of CRC cells. Moreover, P. intermedia and F. nucleatum exert additive effects on the malignant transformation of colorectal adenomas into carcinomas. These findings can be used to identify patients at a high risk of malignant transformation of colorectal adenomas or metastasis of CRC, and they can accordingly be provided optimal clinical management.

SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although SARS-CoV-2 RNA or antigen has been identified in T cells from patients. Here, we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells (PBCs) or postmortem lung T cells, and the infectious virus could also be detected from viral antigen-positive PBCs. We next prove that SARS-CoV-2 infects T lymphocytes, preferably activated CD4 + T cells in vitro. Upon infection, viral RNA, subgenomic RNA, viral protein or viral particle can be detected in the T cells. Furthermore, we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments. Next, we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis. In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways. Finally, we demonstrated that LFA-1, the protein exclusively expresses in multiple leukocytes, is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells, compared to a list of other known receptors. Collectively, this work confirmed a SARS-CoV-2 infection of T cells, in a spike-ACE2-independent manner, which shed novel insights into the underlying mechanisms of SARS-CoV-2-induced lymphopenia in COVID-19 patients.

To address the non-renormalizability issue of general relativity in the realm of quantum gravity, Weinberg first proposed the theory of asymptotically safe gravity. Based on AdS/CFT duality, we investigate holographic Einstein rings from a quantum-corrected Schwarzschild spacetime in asymptotically safe gravity. By introducing a Gaussian wave and computing its response function, combined with a virtual convex lens optical system, we have successfully constructed a holographic image of Einstein ring. The study reveals that the observer’s position, horizon temperature, wave source frequency, and asymptotically safe gravity parameter significantly influence the shape and brightness of holographic Einstein ring. Notably, variations of observer’s position cause the ring image to gradually distort and even shrink into a unilateral bright spot. Unlike in Einstein gravity, the asymptotically safe gravity parameter in modified gravity can significantly alter the ring’s brightness. Furthermore, the results demonstrate consistency between wave optics and geometric optics, reinforcing the validity of the holographic principle in asymptotically safe gravity. This work provides new insights into optical behaviors in black hole gravitational fields and highlights the potential of holographic methods in gravitational physics research.

Personalized medical care focuses on prediction of disease risk and response to medications. To build the risk models, access to both large-scale genomic resources and human genetic studies is required. The Taiwan Biobank (TWB) has generated high-coverage, whole-genome sequencing data from 1492 individuals and genome-wide SNP data from 103,106 individuals of Han Chinese ancestry using custom SNP arrays. Principal components analysis of the genotyping data showed that the full range of Han Chinese genetic variation was found in the cohort. The arrays also include thousands of known functional variants, allowing for simultaneous ascertainment of Mendelian disease-causing mutations and variants that affect drug metabolism. We found that 21.2% of the population are mutation carriers of autosomal recessive diseases, 3.1% have mutations in cancer-predisposing genes, and 87.3% carry variants that affect drug response. We highlight how TWB data provide insight into both population history and disease burden, while showing how widespread genetic testing can be used to improve clinical care.

Background We recently showed that fucosyltransferase 8 (FUT8)-mediated core fucosylation of transforming growth factor-β receptor enhances its signaling and promotes breast cancer invasion and metastasis. However, the complete FUT8 target glycoproteins and their downstream signaling networks critical for breast cancer progression remain largely unknown. Method We performed quantitative glycoproteomics with two highly invasive breast cancer cell lines to unravel a comprehensive list of core-fucosylated glycoproteins by comparison to parental wild-type and FUT8-knockout counterpart cells. In addition, ingenuity pathway analysis (IPA) was performed to highlight the most enriched biological functions and signaling pathways mediated by FUT8 targets. Novel FUT8 target glycoproteins with biological interest were functionally studied and validated by using LCA ( Lens culinaris agglutinin ) blotting and LC–MS/MS (liquid chromatography–tandem mass spectrometry) analysis. Results Loss-of-function studies demonstrated that FUT8 knockout suppressed the invasiveness of highly aggressive breast carcinoma cells. Quantitative glycoproteomics identified 140 common target glycoproteins. Ingenuity pathway analysis (IPA) of these target proteins gave a global and novel perspective on signaling networks essential for breast cancer cell migration and invasion. In addition, we showed that core fucosylation of integrin αvβ5 or IL6ST might be crucial for breast cancer cell adhesion to vitronectin or enhanced cellular signaling to interleukin 6 and oncostatin M, two cytokines implicated in the breast cancer epithelial–mesenchymal transition and metastasis. Conclusions Our report reveals a comprehensive list of core-fucosylated target proteins and provides novel insights into signaling networks crucial for breast cancer progression. These findings will assist in deciphering the complex molecular mechanisms and developing diagnostic or therapeutic approaches targeting these signaling pathways in breast cancer metastasis.

The significance of DNA hydroxymethylation in replicative senescence of mesenchymal stem cells (MSCs) and aging-related osteoporosis remains unknown. Here, we reveal 5hmC levels positively regulate MSC self-renewal and osteoblast differentiation. Mechanistically, PARP1 recruits TET1 to hydrolyze methylated nucleotides on DNMT1 exons, aiding CTCF in preventing DNMT1 alternative splicing in early MSCs. Additionally, ATM phosphorylates TRIM37 at Th203, promoting its nuclear entry and the monoubiquitination of PARP1, stabilizing the protein. CTCF or TRIM37 knockdown induces replicative senescence of MSCs with loss of full-length DNMT1. Co-treatment with resveratrol (ATM activator) and vitamin C (TET1 activator) rejuvenates late MSCs via the TRIM37/PARP1/DNMT1 pathway and alleviates osteoporosis in aged mice. Gene knockout experiments further reveal the participation of TRIM37 and PARP1 in MSC aging, contributing significantly to bone maintenance and repair in vivo. This study emphasizes the role of DNA hydroxymethylation in stemness, suggesting therapeutic strategies, especially for osteoporosis. TRIM37–PARP1–TET1 signalling preserves stem cell function and prevents osteoporosis by regulating DNMT1 splicing through 5hmC maintenance, revealing a mechanism linking epigenetic control to stem cell function and bone health.

In this paper, taking into account a black hole solution of Finsler theory, we study the remnant and its phase transition close to the Planck scale. Based on the corrected Dirac equation, the quantum tunneling method is applied to derive a revised Hawking temperature-uncertainty relation. Further, with the generalized uncertainty principle(GUP), when the Finsler black hole reaches the Planck scale, the remnant after evaporation is calculated. Meanwhile, according to the phase transition and heat capacity, we analyze thermodynamic stability of the black hole remnant.