Although great achievements have been made in the synthesis of giant lanthanide clusters, novel structural models are still scarce. Herein, we report a giant lanthanide cluster Dy76, constructed from ...Dy3(μ3‐OH)4 and Dy5(μ4‐O)(μ3‐OH)8 building blocks. As the largest known Dy cluster, the structure of Dy76 can be seen as arising from the fusion of two Dy48 clusters; these clusters can be isolated under various synthetic conditions and were characterized by single‐crystal X‐ray diffraction. This new, fused structural model of the pillar motif has not been found in Ln clusters. Furthermore, the successful conversion of Dy76 back into Dy48 in a retrosynthetic manner supports the proposed fusion formation mechanism of Dy76. Electrospray ionization mass spectrometry (ESI‐MS) analysis suggests that the metal cluster skeleton of Dy76 shows good stability in various solvents. This work not only reveals a new structural type of Ln clusters but also provides insight into the novel fusion assembly process.
We go together: Two dysprosium clusters with 48 and 76 metal atoms, respectively, were generated under solvothermal conditions by using 3‐furancarboxylic acid. The bi‐nanopillar Dy76 was formed by the fusion of two Dy48 nanopillars.
We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). ...Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.
Esophageal squamous dysplasia is believed to be the precursor lesion of esophageal squamous cell carcinoma (ESCC); however, the genetic evolution from dysplasia to ESCC remains poorly understood. ...Here, we applied multi-region whole-exome sequencing to samples from two cohorts, 45 ESCC patients with matched dysplasia and carcinoma samples, and 13 tumor-free patients with only dysplasia samples. Our analysis reveals that dysplasia is heavily mutated and harbors most of the driver events reported in ESCC. Moreover, dysplasia is polyclonal, and remarkable heterogeneity is often observed between tumors and their neighboring dysplasia samples. Notably, copy number alterations are prevalent in dysplasia and persist during the ESCC progression, which is distinct from the development of esophageal adenocarcinoma. The sharp contrast in the prevalence of the 'two-hit' event on TP53 between the two cohorts suggests that the complete inactivation of TP53 is essential in promoting the development of ESCC.The pathogenesis of oesophageal squamous cell carcinoma is a multi-step process but the genetic determinants behind this progression are unknown. Here the authors use multi-region exome sequencing to comprehensively investigate the genetic evolution of precursor dysplastic lesions and untransformed oesophagus.
Although great achievements have been made in the synthesis of giant lanthanide clusters, novel structural models are still scarce. Herein, we report a giant lanthanide cluster Dy
, constructed from ...Dy
(μ
-OH)
and Dy
(μ
-O)(μ
-OH)
building blocks. As the largest known Dy cluster, the structure of Dy
can be seen as arising from the fusion of two Dy
clusters; these clusters can be isolated under various synthetic conditions and were characterized by single-crystal X-ray diffraction. This new, fused structural model of the pillar motif has not been found in Ln clusters. Furthermore, the successful conversion of Dy
back into Dy
in a retrosynthetic manner supports the proposed fusion formation mechanism of Dy
. Electrospray ionization mass spectrometry (ESI-MS) analysis suggests that the metal cluster skeleton of Dy
shows good stability in various solvents. This work not only reveals a new structural type of Ln clusters but also provides insight into the novel fusion assembly process.
Abstract
Epoxy resin has been widely applied in coating preparation, due to its excellent properties. The anti‐corrosion performance improvement of epoxy‐based coatings has attracted much attention. ...The synergistic effect of the barrier function of two‐dimensional fillers and the slow release of inhibiter has been proven to be an effective way to improve the anti‐corrosion of coatings. In this work, the phytic acid (PA) intercalated hydrotalcite (HT) was fabricated by a one‐pot method. First, HT was synthesized by magnesium nitrate hexahydrate (Mg(NO
3
)
2
·6H
2
O) and aluminum nitrate nonahydrate (Al(NO
3
)
3
·9H
2
O) in the water solution. Subsequently, PA was added to the dispersion to obtain PA intercalated HT fillers (PA‐HT). The obtained PA‐HT fillers were incorporated into the epoxy resin (EP) to prepare the anti‐corrosion coating (PA‐HT/EP). The prepared PA‐HT/EP coating exhibits excellent anti‐corrosion properties at 1 wt% filler loading that the impedance modulus maintains above 10
9
Ω cm
2
after 30 days of soaking in 3.5 wt% NaCl solution. Moreover, the anti‐corrosion mechanism of the synergy of the physical barrier of two‐dimensional fillers and the release slow of inhibitors was thoroughly discussed, particularly the formation and anti‐corrosion mechanism of the passivation protection film constituted by PA.
Monolayer molybdenum disulfide (MoS2) has attracted great interest due to its potential applications in electronics and optoelectronics. Ideally, single-crystal growth over a large area is necessary ...to preserve its intrinsic figure of merit but is very challenging to achieve. Here, we report an oxygen-assisted chemical vapor deposition method for growth of single-crystal monolayer MoS2. We found that the growth of MoS2 domains can be greatly improved by introducing a small amount of oxygen into the growth environment. Triangular monolayer MoS2 domains can be achieved with sizes up to ∼350 μm and a room-temperature mobility up to ∼90 cm2/(V·s) on SiO2. The role of oxygen is not only to effectively prevent the poisoning of precursors but also to eliminate defects during the growth. Our work provides an advanced method for high-quality single-crystal monolayer MoS2 growth.
As an important oncogenic miRNA, microRNA-21 (miR-21) is associated with various malignant diseases. However, the precise biological function of miR-21 and its molecular mechanism in hypertrophic ...scar fibroblast cells has not been fully elucidated.
Quantitative Real-Time PCR (qRT-PCR) analysis revealed significant upregulation of miR-21 in hypertrophic scar fibroblast cells compared with that in normal skin fibroblast cells. The effects of miR-21 were then assessed in MTT and apoptosis assays through in vitro transfection with a miR-21 mimic or inhibitor. Next, PTEN (phosphatase and tensin homologue deleted on chromosome ten) was identified as a target gene of miR-21 in hypertrophic scar fibroblast cells. Furthermore, Western-blot and qRT-PCR analyses revealed that miR-21 increased the expression of human telomerase reverse transcriptase (hTERT) via the PTEN/PI3K/AKT pathway. Introduction of PTEN cDNA led to a remarkable depletion of hTERT and PI3K/AKT at the protein level as well as inhibition of miR-21-induced proliferation. In addition, Western-blot and qRT-PCR analyses confirmed that hTERT was the downstream target of PTEN. Finally, miR-21 and PTEN RNA expression levels in hypertrophic scar tissue samples were examined. Immunohistochemistry assays revealed an inverse correlation between PTEN and hTERT levels in high miR-21 RNA expressing-hypertrophic scar tissues.
These data indicate that miR-21 regulates hTERT expression via the PTEN/PI3K/AKT signaling pathway by directly targeting PTEN, therefore controlling hypertrophic scar fibroblast cell growth. MiR-21 may be a potential novel molecular target for the treatment of hypertrophic scarring.
Breast cancer resistance to the monoclonal erbB2/HER2 antibody trastuzumab (or herceptin) has become a significant obstacle in clinical targeted therapy of HER2-positive breast cancer. Previous ...research demonstrated that such drug resistance may be related to dysregulation of miRNA expression. Here, we found that knockdown of the long non-coding RNA, urothelial cancer associated 1 (UCA1), can promote the sensitivity of human breast cancer cells to trastuzumab. Mechanistically, UCA1 knockdown upregulated miR-18a and promoted miR-18a repression of Yes-associated protein 1 (YAP1). A luciferase reporter assay confirmed the association of miR-18a with wild-type UCA1 but not with UCA1 mutated at the predicted miR-18a-binding site. The direct targeting of YAP1 by miR-18a was verified by the observation that miR-18a mimic suppressed luciferase expression from a construct containing the YAP1 3′ untranslated region. Meanwhile, reciprocal repression of UCA1 and miR-18a were found to be Argonaute 2-dependent. Knockdown of YAP1 recapitulated the effect of UCA1 silencing by reducing the viability of trastuzumab-treated breast cancer cells, whereas inhibition of miR-18a abrogated UCA1 knockdown-induced improvement of trastuzumab sensitivity in breast cancer cells. These findings demonstrate that the UCA1/miR-18a/YAP1 axis plays an important role in regulating the sensitivity of breast cancer cells to trastuzumab, which has implications for the development of novel approaches to improving breast cancer responses to targeted therapy.
•Knockdown of UCA1 expression restored sensitivity of breast cancer cells to trastuzumab.•UCA1 knockdown upregulated miR-18a and downregulated YAP1 in breast cancer cells.•YAP1 is a direct target of miR-18a in breast cancer cells.•The UCA1/miR-18a/YAP1 feedback axis regulated the sensitivity of breast cancer cells to trastuzumab.
Resistance to trastuzumab and concomitantly distal metastasis are leading causes of mortality in HER2‐positive breast cancers, the molecular basis of which remains largely unknown. Here, we generated ...trastuzumab‐resistant breast cancer cells with increased tumorigenicity and invasiveness compared with parental cells, and observed robust epithelial–mesenchymal transition (EMT) and consistently elevated TGF‐β signaling in these cells. MiR‐200c, which was the most significantly downregulated miRNA in trastuzumab‐resistant cells, restored trastuzumab sensitivity and suppressed invasion of breast cancer cells by concurrently targeting ZNF217, a transcriptional activator of TGF‐β, and ZEB1, a known mediator of TGF‐β signaling. Given the reported backward inhibition of miR‐200c by ZEB1, ZNF217 also exerts a feedback suppression of miR‐200c via TGF‐β/ZEB1 signaling. Restoration of miR‐200c, silencing of ZEB1 or ZNF217 or blockade of TGF‐β signaling increased trastuzumab sensitivity and suppressed invasiveness of breast cancer cells. Therefore, our study unraveled nested regulatory circuits of miR‐200c/ZEB1 and miR‐200c/ZNF217/TGF‐β/ZEB1 in synergistically promoting trastuzumab resistance and metastasis of breast cancer cells. These findings provide novel insights into the common role of EMT and related molecular machinery in mediating the malignant phenotypes of breast cancers.
What's new?
Epithelial‐mesenchymal transition (EMT) enables invasion and metastasis by malignant cells. A family of microRNAs (miRNAs) called miR‐200 is known to suppress tumor progression by targeting genes involved in EMT, including TGF‐β. In this study, the authors found that miR‐200c deregulation can cause both resistance to trastuzumab (Herceptin) and metastasis in HER2‐positive breast cancers. They also identified several molecular factors that regulate TGF‐β activity and form nested, synergistic regulatory circuits involving miR‐200c. These findings provide novel insights into the role of EMT and related molecular machinery in mediating the malignant phenotypes of breast cancers.
Pancreatic cancer is currently one of the deadliest of the solid malignancies, whose incidence and death rates are increasing consistently during the past 30 years. Ribonucleotide reductase (RR) is a ...rate-limiting enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides, which are essential for DNA synthesis and replication. In this study, 23 small interfering RNAs (siRNAs) against RRM2, the second subunit of RR, were designed and screened, and one of them (termed siRRM2), with high potency and good RNase-resistant capability, was selected. Transfection of siRRM2 into PANC-1, a pancreatic cell line, dramatically repressed the formation of cell colonies by inducing remarkable cell-cycle arrest at S-phase. When combining with doxorubicin (DOX), siRRM2 improved the efficacy 4 times more than applying DOX alone, suggesting a synergistic effect of siRRM2 and DOX. Moreover, the combined application of siRRM2-loaded lipid nanoparticle and DOX significantly suppressed the tumor growth on the PANC-1 xenografted murine model. The inhibition efficiency revealed by tumor weight at the endpoint of the treatment reached more than 40%. Hence, siRRM2 effectively suppressed pancreatic tumor growth alone or synergistically with DOX. This study provides a feasible target gene, a drug-viable siRNA, and a promising therapeutic potential for the treatment of pancreatic cancer.
Display omitted
PDF
