Objective. To investigate the expression patterns and prognostic values of STEAP family members in the occurrence and development of breast cancer. Materials and Methods. The Human Protein Atlas was ...used to analyze the expression level of STEAPs in human normal tissues and malignant tumors. ONCOMINE datasets were analyzed for the comparison of the STEAPs levels between malignant cancers and corresponding normal tissues. Kaplan-Meier plotter was used to analyze the prognostic value of STEAPs in breast cancer patients. Results. STEAPs were widely distributed in human normal tissues with diverse levels. Normally, it is predicted that STEAP1 and STEAP2 were involved in the mineral absorption process, while STEAP3 participated in the TP53 signaling pathway and iron apoptosis. The results from ONCOMINE showed downregulation of STEAP1, STEAP2, and STEAP4 in breast cancers. Survival analysis revealed that breast cancer patients with high levels of STEAP1, STEAP2, and STEAP4 had a good prognosis, while those with low expression had high overall mortality. Conclusion. STEAP1, STEAP2, and STEAP4 are predicted to be the potential prognostic biomarkers for breast cancer patients, providing novel therapeutic strategies for them.
As a zero-dimensional (0D) nanomaterial, graphene quantum dot (GQD) has a unique physical structure and electrochemical properties, which has been widely used in biomedical fields, such as ...bioimaging, biosensor, drug delivery, etc. Its biological safety and potential cytotoxicity to human and animal cells have become a growing concern in recent years. In particular, the potential DNA structure damage caused by GQD is of great importance but still obscure. In this study, molecular dynamics (MD) simulation was used to investigate the adsorption behavior and the structural changes of single-stranded (ssDNA) and double-stranded DNA (dsDNA) on the surfaces of GQDs with different sizes and oxidation. Our results showed that ssDNA can strongly adsorb and lay flat on the surface of GQDs and graphene oxide quantum dots (GOQDs), whereas dsDNA was preferentially oriented vertically on both surfaces. With the increase of GQDs size, more structural change of adsorbed ssDNA and dsDNA could be found, while the size effect of GOQD on the structure of ssDNA and dsDNA is not significant. These findings may help to improve the understanding of GQD biocompatibility and potential applications of GQD in the biomedical field.
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Disulfiram (DSF), a Food and Drug Administration (FDA)-approved drug for the treatment of alcoholism, has been found to have antitumor activity. DSF showed better antitumor efficiency ...when it was used in combination with certain antitumor drugs. DSF plays an important role in cancer treatment. It has been used as multidrug resistance (MDR) modulator to reverse MDR and can also combine with copper ions (Cu2+), which will produce copper diethyldithiocarbamate (CuDDC2) complex with antitumor activity. The synergistic targeted drug delivery for cancer treatment based on DSF, especially the combination with exogenous Cu2+ and its forms of administration, has attracted extensive attention in the biomedical field. In this review, we summarize these synergistic delivery systems, in the hope that they will contribute to the continuous optimization and development of more advanced drug delivery systems. Furthermore, we discuss the current limitation and future directions of DSF-based drug delivery systems in the field of tumor therapy. Hopefully, our work may inspire further innovation of DSF-based antitumor drug delivery systems.
Boron nitride nanotubes (BNNTs) are potential candidates for water desalination owing to their advantages of higher thermal and chemical stabilities as well as resistance to oxidation. In this work, ...four different types of functional groups were introduced to the end of BNNT (8,8), and the mechanism of water and ion transportation through functionalized BNNTs were investigated via molecular dynamics simulation. The effect of functional groups on desalination performance of BNNT was discussed. It was found that BNNT (8,8)-COO– and BNNT (8,8)-NH3+ systems show well water flux and high ions rejection due to the space-steric effect and electrostatic interaction. Our study also revealed that the water flux in aligned functionalized BNNTs is much higher than that in reverse osmosis (RO) membranes.
•BNNT (8,8)-COO– and BNNT (8,8)-NH3+ systems show high water flux and ions rejection•Ions need overcome a relative high energy barrier to pass through the functionalized BNNT•BNNT (8,8)-COO– and BNNT (8,8)-NH3+ were selected to construct aligned BNNT arrays•The water flux in functionalized BNNT (8, 8) arrays is 2 orders of magnitude higher than RO membranes
M7G modification, known as one of the common post-transcriptional modifications of RNA, is present in many different types of RNAs. With the accurate identification of m7G modifications within RNAs, ...their functional roles in the regulation of gene expression and different physiological functions have been revealed. In addition, there is growing evidence that m7G modifications are crucial in the emergence of cancer. Here, we review the most recent findings regarding the detection techniques, distribution, biological functions and Regulators of m7G. We also summarize the connections between m7G modifications and cancer development, drug resistance, and tumor microenvironment as well as we discuss the research's future directions and trends.
The microstructure and mechanical properties of pseudo-binary (TiZrHf)
50
(NiCoCu)
50
high entropy alloys (HEAs) with B2 matrix were investigated in this study. The studied HEAs includes Ti
40
Zr
10
...Ni
40
Co
5
Cu
5
, Ti
30
Zr
20
Ni
30
Co
10
Cu
10
, Ti
25
Zr
25
Ni
16.67
Co
16.67
Cu
16.67
, Ti
30
Zr
10
Hf
10
Ni
30
Co
10
Cu
10
, Ti
20
Zr
15
Hf
15
Ni
20
Co
15
Cu
15
, and Ti
16.67
Zr
16.67
Hf
16.67
Ni
16.67
Co
16.67
Cu
16.67
. XRD and SEM analyses revealed that all studied HEAs were a mixture of B2 and C15 intermetallic phases, instead of a single solid solution, due to their highly negative enthalpy of mixing and the relatively large difference in atomic radii. The B2 matrix was found capable of forming a solid solution of all six elements in a wide composition range. The lattice constants of B2 and C15 phases increase linearly with increasing the difference in atomic radii. Additionally, the microhardness of these HEAs increases from 409 to 595 HV with the increasing difference in atomic radii as well. Compression tests demonstrated substitution of Zr with Hf can improve the ductility. In all studied HEAs, the Ti
30
Zr
10
Hf
10
Ni
30
Co
10
Cu
10
HEA achieves a great balance between yield strength, ultimate compressive strength, and fracture strain of 1574 MPa, 1933 MPa, and 6.5%, respectively.
Graphic Abstract
Repetitive elements (REs) compose ∼50% of the human genome and are normally transcriptionally silenced, although the mechanism has remained elusive. Through an RNAi screen, we identified FBXO44 as an ...essential repressor of REs in cancer cells. FBXO44 bound H3K9me3-modified nucleosomes at the replication fork and recruited SUV39H1, CRL4, and Mi-2/NuRD to transcriptionally silence REs post-DNA replication. FBXO44/SUV39H1 inhibition reactivated REs, leading to DNA replication stress and stimulation of MAVS/STING antiviral pathways and interferon (IFN) signaling in cancer cells to promote decreased tumorigenicity, increased immunogenicity, and enhanced immunotherapy response. FBXO44 expression inversely correlated with replication stress, antiviral pathways, IFN signaling, and cytotoxic T cell infiltration in human cancers, while a FBXO44-immune gene signature correlated with improved immunotherapy response in cancer patients. FBXO44/SUV39H1 were dispensable in normal cells. Collectively, FBXO44/SUV39H1 are crucial repressors of RE transcription, and their inhibition selectively induces DNA replication stress and viral mimicry in cancer cells.
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•FBXO44 promotes H3K9me3-mediated repetitive element silencing in cancer cells•FBXO44 recruits SUV39H1, CRL4, and Mi-2/NuRD at the replication fork•Targeting FBXO44 stimulates antiviral pathways and replication stress in cancer cells•FBXO44/SUV39H1 inhibition overcomes resistance to immune checkpoint blockade therapy
Targeting FBXO44, which regulates the transcriptional silencing of repetitive elements in the human cancer genome, promotes antiviral signaling and decreases tumorigenesis as well as overcomes resistance to immune checkpoint blockade.
The purpose of the present study was to examine the protective action and mechanisms of quercetin on the blood-brain barrier (BBB) in rats subjected to transient middle cerebral artery occlusion ...(tMCAO) and reperfusion. Quercetin (10, 30, 50 mg/kg) was intraperitoneally administered at the onset of reperfusion. The results showed that quercetin significantly reduced cerebral infarct volume, neurological deficit, BBB permeability and ROS generation via Sirt1/Nrf2/HO-1 signaling pathway. Moreover, EX527, a selective inhibitor of Sirt1, reversed these neuroprotective effects. Our findings indicate that quercetin has neuroprotective effects against cerebral ischemia-reperfusion injury by protecting BBB through Sirt1 signaling pathway in MCAO rats.
Owing to their extraordinary electrical, chemical, optical, mechanical and structural properties, two-dimensional (2D) materials (mainly including graphene, boron nitride, MoS2 etc.) have stimulated ...exploding interests in sensor applications. 2D-material based nanoscale DNA sequencing is a single-molecule technique with revolutionary potential. In this paper, we review the methodology of DNA sequencing based on the measurements of ionic current, force peak, and transverse electrical currents etc. by 2D materials. The advantages and disadvantages of DNA sequencing by 2D materials are discussed. Besides the recent development of experiments, we will focus on the theoretical calculations of DNA sequencing, which have been played a critical role in the development of this field. Special emphasis will focus on the disagreements between experiments and theoretical calculations, and the explanations for the discrepancy will be highlighted. Finally, some new plausible sequencing methods from computational studies will be discussed, which may be applied in the realistic DNA sequencing experiments in future.
•2D materials have shown the promising applications on DNA sequencing.•Recent development of computations and experiments on DNA sequencing are summarized.•Cross point of computations and experiments on DNA sequencing has been discussed.•The future and the challenge of DNA sequencing by 2D materials were highlighted.
The human Interleukin-33 (IL-33), a member of the IL-1 family, is the cytokine as a cell endogenous alarmin, released by damaged or necrotic barrier cells (endothelial and epithelial cells). The ...signal transduction of IL-33 relies on recognition and interaction with specific receptor ST2, mainly expressed in immune cells. In both innate and adoptive immunity, IL-33 regulates the homeostasis in response to stress from within/out the microenvironment. Various, even negative biofunctions of IL-33 pathways have now been widely verified in pathogenesis among immunological mechanisms, like Th2-related immune-stimuli, inflammation/infection-induced tissue protectors. A larger versatility in studies of IL-33 on malignancies now focuses on: (1) promoting myeloid-derived suppressor cells (MDSC), (2) intervention toward CD8
T, Natural Killer (NK) cell infiltration, group 2 innate lymphoid cells (ILC2) proliferation, dendritic cells (DC) activation, and (3) inhibiting tumor growth and/or further metastasis as an immunoadjuvant. Although IL-33 functioned pro-tumorigenically in various cancers, for some cancer types the findings so far are controversial. This review begins from a summarized introduction of IL-33, to its remarkable implications and molecular transduction pathway in malignant neoplasms, ends with latest inspiration for IL-33 in treatment.
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