Twist is a critical epithelial-mesenchymal transition (EMT)-inducing transcription factor that increases expression of vimentin. How Twist1 regulates this expression remains unclear. Here, we report ...that Twist1 regulates Cullin2 (Cul2) circular RNA to increase expression of vimentin in EMT. Twist1 bound the Cul2 promoter to activate its transcription and to selectively promote expression of Cul2 circular RNA (circ-10720), but not mRNA. circ-10720 positively correlated with Twist1, tumor malignance, and poor prognosis in hepatocellular carcinoma (HCC). Twist1 promoted vimentin expression by increasing levels of circ-10720, which can absorb miRNAs that target vimentin. circ-10720 knockdown counteracted the tumor-promoting activity of Twist1
and in patient-derived xenograft and diethylnitrosamine-induced TetOn-Twist1 transgenic mouse HCC models. These data unveil a mechanism by which Twist1 regulates vimentin during EMT. They also provide potential therapeutic targets for HCC treatment and provide new insight for circular RNA (circRNA)-based diagnostic and therapeutic strategies.
A circRNA-based mechanism drives Twist1-mediated regulation of vimentin during EMT and provides potential therapeutic targets for treatment of HCC.
http://cancerres.aacrjournals.org/content/canres/78/15/4150/F1.large.jpg
.
Fabricating high-performance MXene-based polymer nanocomposites is a huge challenge because of the poor dispersion and interfacial interaction of MXene nanosheets in the polymer matrix. To address ...the issue, MXene nanosheets were successfully exfoliated and subsequently modified by long-chain cationic agents with different chain lengths, i.e., decyltrimethylammonium bromide (DTAB), octadecyltrimethylammonium bromide (OTAB), and dihexadecyldimethylammonium bromide (DDAB). With the long-chain groups on their surface, modified Ti
C
(MXene) nanosheets were well dispersed in
,
-dimethylformamide (DMF), resulting in the formation of uniform dispersion and strong interfacial adhesion within a polystyrene (PS) matrix. The thermal stability properties of cationic modified Ti
C
/PS nanocomposites were improved considerably with the temperatures at 5% weight loss increasing by 20 °C for DTAB-Ti
C
/PS, 25 °C for OTAB-Ti
C
/PS and 23 °C for DDAB-Ti
C
/PS, respectively. The modified MXene nanosheets also enhanced the flame-retardant properties of PS. Compared to neat PS, the peak heat release rate (PHRR) was reduced by approximately 26.4%, 21.5% and 20.8% for PS/OTAB-Ti
C
, PS/DDAB-Ti
C
and PS/DTAB-Ti
C
, respectively. Significant reductions in CO and CO
productions were also obtained in the cone calorimeter test and generally lower pyrolysis volatile products were recorded by PS/OTAB-Ti
C
compared to pristine PS. These property enhancements of PS nanocomposites are attributed to the superior dispersion, catalytic and barrier effects of Ti
C
nanosheets.
Over the past decades, molecular knots and links have captivated the chemical community due to their promising mimicry properties in molecular machines and biomolecules and are being realized with ...increasing frequency with small molecules. Herein, we describe how to utilize stacking interactions and hydrogen-bonding patterns to form trefoil knots, figure-eight knots and 2catenanes. A transformation can occur between the unique trefoil knot and its isomeric boat-shaped tetranuclear macrocycle by the complementary concentration effect. Remarkably, the realization and authentication of the molecular figure-eight knot with four crossings fills the blank about 4
knot in knot tables. The 2catenane topology is obtained because the selective naphthalenediimide (NDI)-based ligand, which can engender favorable aromatic donor-acceptor π interactions due to its planar, electron-deficient aromatic surface. The stacking interactions and hydrogen-bond interactions play important roles in these self-assembly processes. The advantages provide an avenue for the generation of structurally and topologically complex supramolecular architectures.
Electronic products are evolving towards miniaturization, high integration, and multi-function, which undoubtedly puts forward higher requirements for the reliability of solder joints in electronic ...packaging. Approximately 70% of failure in electronic devices originates during the packaging process, mostly due to the failure of solder joints. With the improvement of environmental protection awareness, lead-free solder joints have become a hot issue in recent years. This paper reviews the research progress on the reliability of lead-free solder joints and discusses the influence of temperature, vibration, tin whisker and electromigration on the reliability of solder joints. In addition, the measures to improve the reliability of solder joints are analyzed according to the problems of solder joints themselves, which provides a further theoretical basis for the study of the reliability of solder joints of electronic products in service.
As a biodegradable and renewable material, polylactic acid is considered a major environmentally friendly alternative to petrochemical plastics. Microbial fermentation is the traditional method for ...lactic acid production, but it is still too expensive to compete with the petrochemical industry. Agro-industrial wastes are generated from the food and agricultural industries and agricultural practices. The utilization of agro-industrial wastes is an important way to reduce costs, save energy and achieve sustainable development. The present study aimed to develop a method for the valorization of Zizania latifolia waste and cane molasses as carbon sources for L-lactic acid fermentation using Rhizopus oryzae LA-UN-1. The results showed that xylose derived from the acid hydrolysis of Z. latifolia waste was beneficial for cell growth, while glucose from the acid hydrolysis of Z. latifolia waste and mixed sugars (glucose and fructose) from the acid hydrolysis of cane molasses were suitable for the accumulation of lactic acid. Thus, a three-stage carbon source utilization strategy was developed, which markedly improved lactic acid production and productivity, respectively reaching 129.47 g/L and 1.51 g/L·h after 86 h of fermentation. This work demonstrates that inexpensive Z. latifolia waste and cane molasses can be suitable carbon sources for lactic acid production, offering an efficient utilization strategy for agro-industrial wastes.
Dual‐frequency (DF) dual‐antenna inductively coupled plasma (ICP) sources have been proposed as one of the methods to produce large‐area uniform plasma. In this study, a hybrid model, consisting of a ...fluid module and an electron Monte Carlo (eMC) module, is used to further investigate the modulation of the plasma characteristics (i.e., induced electric field, electron energy distribution, electron heating mechanism, electron temperature, and plasma density) by the low‐frequency (LF) and high‐frequency (HF) currents in a DF argon discharge. When the inner LF current increases from 12 to 22 A at a fixed outer HF current of 10 A, the induced electric field is strengthened near the LF coil and weakened near the HF coil. The fraction of high‐energy electrons at different spatial positions increases with the increase of LF current, which is caused by the sufficient collision heating in the skin layer of LF source, leading to an increase in electron temperature. When the outer HF current rises from 7 to 13 A with the inner LF current fixed at 17 A, the induced electric field is enhanced near the HF coil and weakened near the LF coil. The fraction of low‐energy electrons at different positions increases with the increase of HF current since the energetic electrons from the skin layer of HF source are cooled due to the ionization, excitation, and stepwise ionization collisions between electrons and neutral particles, as well as the weakened induced electric field near the LF coil. As a result, the electron temperature drops with the increase of HF current. Moreover, when the LF and HF currents increase, the plasma density increases, and the distribution of plasma density is also significantly modulated.
The second near-infrared (NIR-II) window is a fundamental modality for deep-tissue in vivo imaging. However, it is challenging to synthesize NIR-II probes with high quantum yields (QYs), good ...biocompatibility, satisfactory pharmacokinetics, and tunable biological properties. Conventional long-wavelength probes, such as inorganic probes (which often contain heavy metal atoms in their scaffolds) and organic dyes (which contain large π-conjugated groups), exhibit poor biosafety, low QYs, and/or uncontrollable pharmacokinetic properties. Herein, we present a bioengineering strategy that can replace the conventional chemical synthesis methods for generating NIR-II contrast agents. We use a genetic engineering technique to obtain a series of albumin fragments and recombinant proteins containing one or multiple domains that form covalent bonds with chloro-containing cyanine dyes. These albumin variants protect the inserted dyes and remarkably enhance their brightness. The albumin variants can also be genetically edited to develop size-tunable complexes with precisely tailored pharmacokinetics. The proteins can also be conjugated to biofunctional molecules without impacting the complexed dyes. This combination of albumin mutants and clinically-used cyanine dyes can help widen the clinical application prospects of NIR-II fluorophores.
Currently, only a few studies have been conducted on the mental status recovery in elderly aortic stenosis (AS) patients after treatment. How transcatheter aortic valve replacement (TAVR) and ...surgical aortic valve replacement (SAVR) differentially impinge on the mental status of elderly AS patients is completely unknown. The present prospective study aims to investigate this question by comparing the post-treatment levels of depression and anxiety, quality of life and frailty.
A total of 120 elderly patients (age above 70) with symptomatic AS were included, where 78 of them were treated with TAVR and 42 of them were treated with SAVR. Levels of depression and anxiety, quality of life and frailty were assessed by the Chinese version of Hospital Anxiety and Depression Scale (HADS), World Health Organization Quality of Life Instrument-Older Adults Module (WHOQOL-OLD) and clinical frailty scale, respectively. Scores were recorded and compared at admission, 1 month, 4 months and 8 months after treatment.
Before treatment, both patient groups had similar baseline characteristics and all mental parameters. During the follow-up period, patients in the TAVR group demonstrated significant improvement in all assessed mental parameters to certain extent compared to the SAVR group. Specifically, frailty was significantly improved in the TAVR-treated patients at all three follow-up time points. Levels of depression and anxiety were significantly improved 8 months after treatment, although the remaining patient number is limited. Quality of life was only significantly improved 1 month after treatment.
TAVR may provide a better mental recovery outcome in elderly AS patients.
Dysregulation of the neddylation pathway is related to various cancers. However, the specific role of the neddylation pathway in human hepatocellular carcinoma (HCC) remains largely unclear. In this ...study, the neddylation pathway in HCC and adjacent noncancerous liver (ANL) tissues was evaluated by immunohistochemistry (IHC), Western blotting, and qRT‐PCR (quantitative real‐time polymerase chain reaction). The results showed that the entire neddylation pathway, including NEDD8 (the IHC staining of NEDD8 represents the global‐protein neddylation), E1 NEDD8‐activating enzymes (NAE1 and UBA3), E2 NEDD8‐conjugating enzymes (UBE2F and UBE2M), E3 NEDD8‐ligases (MDM2, RBX1 and RNF7), and deneddylation enzymes (COPS5, UCHL1 and USP21), was overactivated in HCC. Furthermore, the upregulation of NEDD8 in HCC was correlated with aggressive characteristics and was an independent risk factor for overall survival (OS) and recurrence‐free survival (RFS) in patients with HCC after hepatectomy. The upregulation of NAE1, UBE2M, and UCHL1 in HCC was associated with aggressive characteristics and poor OS and RFS in patients with HCC after hepatectomy. In conclusion, our research reveals that the entire neddylation pathway is overactivated in HCC and associated with clinical characteristics and prognosis of patients with HCC.
The entire neddylation pathway is overactivated in human HCC tissues. The overactivation of neddylation pathway is associated with poor prognosis and aggressive characteristics.
The gut microbiota plays a critical role in obesity and lipid metabolism disorder. Chokeberry (
L
) are rich in polyphenols with various physiological and pharmacological activities. We determined ...serum physiological parameters and fecal microbial components by using related kits, liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA gene sequencing every 10 days. Real-time PCR analysis was used to measure gene expression of bile acids (BAs) and lipid metabolism in liver and adipose tissues. We analyzed the effects of different Chokeberry polyphenol (CBPs) treatment time on obesity and lipid metabolism in high fat diet (HFD)-fed rats. The results indicated that CBPs treatment prevents obesity, liver steatosis and improves dyslipidemia in HFD-fed rats. CBPs modulated the composition of the gut microbiota with the extended treatment time, reducing the
/
ratio (F/B ratio) and increasing the relative abundance of
,
,
and other bacterial species associated with anti-obesity properties. We found that CBPs treatment gradually decreased the total BAs pool and particularly reduced the relative content of cholic acid (CA), deoxycholic acid (DCA) and enhanced the relative content of chenodeoxycholic acid (CDCA). These changes were positively correlated
,
and negatively correlated with
,
,
. In liver and white adipose tissues, the gene expression of lipogenesis, lipolysis and BAs metabolism were regulated after CBPs treatment in HFD-fed rats, which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism. In addition, the mRNA expression of PPARγ, UCP1 and PGC-1α were upregulated markedly in interscapular brown adipose tissue (iBAT) after CBPs treatment. We confirmed that CBPs could reduce the body weight of HFD-fed rats by accelerating energy homeostasis and thermogenesis in iBAT. Finally, the fecal microbiota transplantation (FMT) experiment results demonstrated that FMT from CBPs-treated rats failed to reduce the weight of HFD-fed rats. However, FMT from CBPs-treated rats improved dyslipidemia and reshaped gut microbiota in HFD-fed rats. In conclusion, CBPs treatment improved obesity and complications by regulating gut microbiota in HFD-fed rats. The gut microbiota plays an important role in BAs metabolism after CBPs treatment, and BAs have therefore emerged as major effectors in microbe-host signaling events that influence host lipid metabolism, energy metabolism and thermogenesis.