SALL4 is overexpressed in many cancers and is found to be involved in tumorigenesis and tumor progression. However, the function of SALL4 in cervical cancer remains unknown. Here, we showed that the ...expression of SALL4 was gradually increased from normal cervical tissue to high‐grade squamous intraepithelial lesions and then to squamous cervical carcinoma. SALL4 was upregulated or downregulated in cervical cancer cells by stably transfecting a SALL4‐expressing plasmid or a shRNA plasmid targeting SALL4, respectively. In vitro, cell growth curves and MTT (3‐(4,5‐dimethylthiazole‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assays showed that SALL4 promoted the cell proliferation of cervical cancer cells. In vivo, xenograft experiments verified that SALL4 enhanced the tumor formation of cervical cancer cells in female BALB/c Nude mice. Cell cycle analysis by fluorescence‐activated cell sorting found that SALL4 accelerates cell cycle transition from the G0/G1 phase to the S phase. TOP/FOP‐Flash reporter assay revealed that SALL4 significantly upregulates the activity of Wnt/β‐catenin pathway. Western blotting showed that the expression levels of β‐catenin and important downstream genes, including c‐Myc and cyclin D1, were increased by SALL4 in cervical cancer cells. Furthermore, dual‐luciferase reporter and chromatin immunoprecipitation assays confirmed that SALL4 transcriptionally activated CTNNB1 by physically interacting with its promoters. Taken together, The results of this study demonstrated that SALL4 may promote cell proliferation and tumor formation of cervical cancer cells by upregulating the activity of the Wnt/β‐catenin signaling pathway by directly binding to the CTNNB1 promoter and trans‐activating CTNNB1.
SALL4 promotes cell proliferation and tumor formation of cervical cancer cells. The function of SALL4 in cervical cancer is mediated by the Wnt/β‐catenin pathway. SALL4 could bind to the CTNNB1 promoter region and trans‐activate CTNNB1.
The Z-source inverter, utilizing a unique LC network and previously forbidden shoot-through states, provides unique features, such as the ability to buck and boost voltage with a simple single-stage ...structure. The analysis and control methods provided in the literature are based on an assumption that the inductor current is relatively large, continuous, and has small ripple. This assumption becomes invalid when the load power factor is low or the inductance is small in order to minimize the inductor's size and weight for some applications where volume and weight are crucial. Under these conditions, the inductor current has high ripple or even becomes discontinuous. As a result, the Z-source inverter exhibits new operation modes that have not been discussed before. This paper analyzes these new operation modes and the associated circuit characteristics.
Abstract
Copper-based materials can reliably convert carbon dioxide into multi-carbon products but they suffer from poor activity and product selectivity. The atomic structure-activity relationship ...of electrocatalysts for the selectivity is controversial due to the lacking of systemic multiple dimensions for
operando
condition study. Herein, we synthesized high-performance CO
2
RR catalyst comprising of CuO clusters supported on N-doped carbon nanosheets, which exhibited high C
2+
products Faradaic efficiency of 73% including decent ethanol selectivity of 51% with a partial current density of 14.4 mA/cm
−2
at −1.1 V vs. RHE. We evidenced catalyst restructuring and tracked the variation of the active states under reaction conditions, presenting the atomic structure-activity relationship of this catalyst.
Operando
XAS, XANES simulations and Quasi-in-situ XPS analyses identified a reversible potential-dependent transformation from dispersed CuO clusters to Cu
2
-CuN
3
clusters which are the optimal sites. This cluster can’t exist without the applied potential. The N-doping dispersed the reduced Cu
n
clusters uniformly and maintained excellent stability and high activity with adjusting the charge distribution between the Cu atoms and N-doped carbon interface. By combining
Operando
FTIR and DFT calculations, it was recognized that the Cu
2
-CuN
3
clusters displayed charge-asymmetric sites which were intensified by CH
3
*
adsorbing, beneficial to the formation of the high-efficiency asymmetric ethanol.
A recent analysis by the LHCb Collaboration suggests the existence of three narrow pentaquarklike states-the P_{c}(4312), P_{c}(4440), and P_{c}(4457)-instead of just one in the previous analysis the ...P_{c}(4450). The closeness of the P_{c}(4312) to the Dover ¯Σ_{c} threshold and the P_{c}(4440) and P_{c}(4457) to the Dover ¯^{*}Σ_{c} threshold suggests a molecular interpretation of these resonances. We show that these three pentaquarklike resonances can be naturally accommodated in a contact-range effective field theory description that incorporates heavy-quark spin symmetry. This description leads to the prediction of all the seven possible S-wave heavy antimeson-baryon molecules that is, there should be four additional molecular pentaquarks in addition to the P_{c}(4312), P_{c}(4440), and P_{c}(4457), providing the first example of a heavy-quark spin symmetry molecular multiplet that is complete. If this is confirmed, it will not only give us an impressive example of the application of heavy-quark symmetries and effective field theories in hadron physics, it will also uncover a clear and powerful ordering principle for the molecular spectrum, reminiscent of the SU(3)-flavor multiplets to which the light hadron spectrum conforms.
The poor mechanical strength of graphene oxide (GO) membranes, caused by the weak interlamellar interactions, poses a critical challenge for any practical application. In addition, intrinsic but ...large‐sized 2D channels of stacked GO membranes lead to low selectivity for small molecules. To address the mechanical strength and 2D channel size control, thiourea covalent‐linked graphene oxide framework (TU‐GOF) membranes on porous ceramics are developed through a facile hydrothermal self‐assembly synthesis. With this strategy, thiourea‐bridged GO laminates periodically through the dehydration condensation reactions via NH2 and/or SH with OCOH as well as the nucleophilic addition reactions of NH2 to COC, leading to narrowed and structurally well‐defined 2D channels due to the small dimension of the covalent TU‐link and the deoxygenated processes. The resultant TU‐GOF/ceramic composite membranes feature excellent sieving capabilities for small species, leading to high hydrogen permselectivities and nearly complete rejections for methanol and small ions in gas, solvent, and saline water separations. Moreover, the covalent bonding formed at the GO/support and GO/GO interfaces endows the composite membrane with significantly enhanced stability.
A thiourea bridging graphene oxide framework membrane, which is defect‐free, and robust, and has narrowed and structurally well‐defined 2D channels, is prepared facilely by self‐assembly. This membrane exhibits excellent hydrogen permselectivity and complete rejection for the smallest alcohol.
Poor tumor penetration is a major challenge for the use of nanoparticles in anticancer therapy. Moreover, the inability to reach hypoxic tumor cells that are distant from blood vessels results in ...inadequate exposure to antitumor therapeutics and contributes to development of chemoresistance and increased metastasis. In the present study, we developed iRGD-modified nanoparticles for simultaneous tumor delivery of a photosensitizer indocyanine green (ICG) and hypoxia-activated prodrug tirapazamine (TPZ). The iRGD-modified nanoparticles loaded with ICG and TPZ showed significantly improved penetration in both 3D tumor spheroids in vitro and orthotopic breast tumors in vivo. ICG-mediated photodynamic therapy upon irradiation with a near-IR laser induced hypoxia, which activated antitumor activity of the codelivered TPZ for synergistic cell-killing effect. In vivo studies demonstrated that the nanoparticles could efficiently deliver the drug combination in 4T1 orthotopic tumors. Primary tumor growth and metastasis were effectively inhibited by the iRGD-modified combination nanoparticles with minimal side effects. The results also showed the anticancer benefits of codelivering ICG and TPZ in a single nanoparticle formulation in contrast to a mixture of nanoparticles containing individual drugs. The study demonstrates the benefits of combining tumor-penetrating nanoparticles with hypoxia-activated drug treatment and establishes a delivery platform for PDT and hypoxia-activated chemotherapy.
Abstract
Human respiratory syncytial viruses (RSVs) are classified into two major groups (A and B) based on antigenic differences in the G glycoprotein. To investigate circulating characteristics and ...phylodynamic history of RSV, we analyzed the genetic variability and evolutionary pattern of RSVs from 1977 to 2019 in this study. The results revealed that there was no recombination event of intergroup. Single nucleotide polymorphisms (SNPs) were observed through the genome with the highest occurrence rate in the G gene. Five and six sites in G protein of RSV-A and RSV-B, respectively, were further identified with a strong positive selection. The mean evolutionary rates for RSV-A and -B were estimated to be 1.48 × 10
–3
and 1.92 × 10
–3
nucleotide substitutions/site/year, respectively. The Bayesian skyline plot showed a constant population size of RSV-A and a sharp expansion of population size of RSV-B since 2005, and an obvious decrease 5 years later, then became stable again. The total population size of RSVs showed a similar tendency to that of RSV-B. Time-scaled phylogeny suggested a temporal specificity of the RSV-genotypes. Monitoring nucleotide changes and analyzing evolution pattern for RSVs could give valuable insights for vaccine and therapy strategies against RSV infection.
SARS-CoV-2 has been spreading around the world for the past year. Recently, several variants such as B.1.1.7 (alpha), B.1.351 (beta), and P.1 (gamma), which share a key mutation N501Y on the ...receptor-binding domain (RBD), appear to be more infectious to humans. To understand the underlying mechanism, we used a cell surface-binding assay, a kinetics study, a single-molecule technique, and a computational method to investigate the interaction between these RBD (mutations) and ACE2. Remarkably, RBD with the N501Y mutation exhibited a considerably stronger interaction, with a faster association rate and a slower dissociation rate. Atomic force microscopy (AFM)-based single-molecule force microscopy (SMFS) consistently quantified the interaction strength of RBD with the mutation as having increased binding probability and requiring increased unbinding force. Molecular dynamics simulations of RBD-ACE2 complexes indicated that the N501Y mutation introduced additional π-π and π-cation interactions that could explain the changes observed by force microscopy. Taken together, these results suggest that the reinforced RBD-ACE2 interaction that results from the N501Y mutation in the RBD should play an essential role in the higher rate of transmission of SARS-CoV-2 variants, and that future mutations in the RBD of the virus should be under surveillance.
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