RNA‐binding proteins can regulate nucleotide metabolism and gene expression. UPF3B regulator of nonsense mediated mRNA decay (UPF3B) exhibits dysfunction in cancers. However, its role in the ...progression of hepatocellular carcinoma (HCC) is still insufficiently understood. Here, we found that UPF3B was markedly upregulated in HCC samples and associated with adverse prognosis in patients. UPF3B dramatically promoted HCC growth both in vivo and in vitro. Mechanistically, UPF3B was found to bind to PPP2R2C, a regulatory subunit of PP2A, boosting its mRNA degradation and activating the PI3K/AKT/mTOR pathway. E2F transcription factor 6 (E2F6) directly binds to the UPF3B promoter to facilitate its transcription. Together, the E2F6/UPF3B/PPP2R2C axis promotes HCC growth through the PI3K/AKT/mTOR pathway. Hence, it could be a promising therapeutic target for treating HCC.
UPF3B is upregulated in hepatocellular carcinoma (HCC) samples and associated with adverse prognosis. UPF3B binds to PPP2R2C, boosting its mRNA degradation and activating the PI3K/AKT/mTOR pathway. E2F6 binds to the UPF3B promoter to facilitate its transcription. The E2F6/UPF3B/PPP2R2C axis could be a promising therapeutic target for treating HCC.
Iron plays an essential role in biological system. An approach for in vivo imaging of this metal ion is needed to investigate its complex contributions to physiological and pathological processes. ...Herein, we present a bioluminescent probe FP-1 as a powerful tool for targeting Fe2+ detection in vitro and in vivo. The turn-on sensing scheme is based on the caged strategy of luciferin-luciferase system. FP-1 not only can detect accumulations of exogenous Fe2+ in living animal, but also has the capability of monitoring labile endogenous Fe2+ levels in animal model of sepsis. Implementation of this technique provides a valuable opportunity for understanding underlying mechanisms of Fe2+ in biological processes and disease states.
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•A novel bioluminescent probe for visualizing Iron (II) has been developed with high sensitivity and selectivity.•This probe was successfully appied to detect exogenous Fe2+ in living animal and monitor labile endogenous Fe2+ levels in animal disease model.
It is imperative to develop novel therapeutics to overcome chemoresistance, a significant obstacle in the clinical management of prostate cancer (PCa) and other cancers.
A phenotypic screen was ...performed to identify novel inhibitors of chemoresistant PCa cells. The mechanism of action of potential candidate(s) was investigated using in silico docking, and molecular and cellular assays in chemoresistant PCa cells. The in vivo efficacy was evaluated in mouse xenograft models of chemoresistant PCa.
Nicardipine exhibited high selectivity and potency against chemoresistant PCa cells via inducing apoptosis and cell cycle arrest. Computational, molecular, and cellular studies identified nicardipine as a putative inhibitor of embryonic ectoderm development (EED) protein, and the results are consistent with a proposed mechanism of action that nicardipine destabilised enhancer of zeste homologue 2 (EZH2) and inhibited key components of noncanonical EZH2 signalling, including transducer and activator of transcription 3, S-phase kinase-associated protein 2, ATP binding cassette B1, and survivin. As a monotherapy, nicardipine effectively inhibited the skeletal growth of chemoresistant C4-2B-TaxR tumours. As a combination regimen, nicardipine synergistically enhanced the in vivo efficacy of docetaxel against C4-2 xenografts.
Our findings provided the first preclinical evidence supporting nicardipine as a novel EED inhibitor that has the potential to be promptly tested in PCa patients to overcome chemoresistance and improve clinical outcomes.
In order to solve the problem of poor dispersion and stability of mixed metal hydroxide (MMH), a kind of mixed metal hydroxide-like compound (MMHlc) gel was synthesized for use as the base mud in ...drilling fluid instead of bentonite gel. Na
CO
, Na
SiO
, and C
H
CO
Na were used as precipitants to form MMHlc with larger interlayer spacing and smaller particle size. MMHlc was synthesized by the coprecipitation method at 25 °C with a metal molar ratio of Mg:Al:Fe = 3:1:1. The performance evaluation of the treated drilling fluid showed that MMHlc (S2) synthesized using Na
SiO
as the precipitant had the characteristics of low viscosity, low filtration, and a high dynamic plastic ratio at 25 °C, which fully met the requirements of oil field application, and it maintained its excellent properties after being aged at 250 °C for 16 h. Linear expansion and rolling recovery experiments showed that the S2 sample had excellent rheological properties and good inhibition. X-ray diffraction and FT-IR experiments showed that S2 had the most complete crystal structure, its interlayer distance was large, and its ion exchange capacity was strong. The thermogravimetric experiment showed that the S2 crystal was stable and the temperature resistance of the crystal could reach 340 °C. Zeta potential, particle size analysis, SEM, and TEM results showed that S2 is a nanomaterial with a complete morphology and uniform distribution. The drilling fluid of this formula had the characteristics of low viscosity, low filtration loss, and a high dynamic plastic ratio, and it met the conditions for oil field application. Considering these results, the new MMH prepared by our research institute is a drilling fluid material that can be used at ultra-high temperatures and can provide important support for drilling ultra-deep wells.
Converting CO2 into value-added chemical fuels and functional materials by CO2 reduction reaction (CO2RR) is conducive to achieving a carbon-neutral energy cycle. However, it is still challenging to ...efficiently navigate CO2RR toward desirable products. Herein, we report a facile strategy to extend product species in borate-containing molten electrolyte at a positively shifted cathodic potential with a high current density (e.g. 100 mA/cm2), which can selectively electro-transform CO2 into desired products (either CO or solid carbon nanofibers, respectively reaching a high selectivity of ∼90%). The borates can act as a controller of electrolyte alkalinity to buffer the concentration of sequentially generated O2− during CO2RR, positively shifting the reduction potential of the captured CO2 and concurrently extending the product species. The sustainable buffering effect is available under CO2 atmosphere. Compared with borate-free electrolyte, the CO2 conversion efficiency is over three times higher, while the electrolysis energy consumption is decreased by over 40%.
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•The product selectivity of CO2 reduction reaction was highly tunable•Extending product species via regulating electrolyte alkalinity was achieved•Borate-assisted oxygen removal was conducive to produce CO2-derived CNFs•Lower energy consumption and higher CO2 conversion efficiency were achieved
Chemical Engineering; Electrochemistry; Industrial Chemistry
The use of exergy analysis provides theoretical guidance for the cascaded latent heat storage system (CLHSS). However, the exergy analysis of the CLHSS charging–discharging processes is imperfect ...with two problems to be solved. One is the lack of exergy flow analysis, the other is the inaccurate expressions of the overall charging–discharging processes exergy efficiency. This paper aims to solve the above two problems. First, the exergy flow of the CLHSS charging–discharging processes was revealed, composed of one or more of the three exergy flow paths. Second, the overall exergy efficiency was derived by determining exergy produced and consumed. Only by satisfying the constraint that the exergy change of each PCM is equal to zero, the product of exergy efficiencies of charging and discharging processes can represent the overall exergy efficiency. On this basis, previous models that used the product of exergy efficiencies were modified by adding constraints. Compared to models without constraints, the model with constraints has more accurate and complete optimization results, which is conducive to the CLHSS stable operation. Finally, the model with constraints was adopted to guide the application of the CLHSS in the solar power tower.
•Cascaded latent heat storage system (CLHSS) charge–discharge exergy flow is revealed.•The overall exergy efficiency and product of exergy efficiencies are distinguished.•The model that used product of exergy efficiencies was revised by adding constraints.•The revised model has more accurate optimization results and is recommended.•Application guidance of the CLHSS in the solar power tower system was provided.
The regenerative treatment of infectious vertical bone defects remains difficult and challenging today. Current clinical treatments are limited in their ability to control bacteria and infection, ...which is unfavorable for new bone formation and calls for a new type of material with excellent osteogenic and antibacterial properties. Here a multifunctional scaffold is synthesized that mimics natural bone nanostructures by incorporating silver nanowires into a hierarchical, intrafibrillar mineralized collagen matrix (IMC/AgNWs), to achieve the therapeutic goals of inhibiting bacterial activity and promoting infectious alveolar bone augmentation in rats and beagle dogs. An appropriate concentration of 0.5 mg mL−1 AgNWs is selected to balance biocompatibility and antibacterial properties. The achieved IMC/AgNWs exhibit a broad spectrum of antimicrobial properties against Gram‐negative Porphyromonas gingivalis and Gram‐positive Streptococcus mutans. When the IMC/AgNWs are cocultured with periodontal ligament stem cells, it possesses excellent osteoinductive activities under both non‐inflammatory and inflammatory conditions. By constructing a rat mandibular infected periodontal defect model, the IMC/AgNWs achieve a near‐complete healing through the canonical BMP/Smad signaling. Moreover, the IMC/AgNWs enhance vertical bone height and osseointegration in peri‐implantitis in beagle dogs, indicating the clinical translational potential of IMC/AgNWs for infectious vertical bone augmentation.
This study introduces a multifunctional scaffold (IMC/AgNWs) that mimics natural bone nanostructures by incorporating silver nanowires into a hierarchical, intrafibrillar mineralized collagen matrix, to achieve the therapeutic goals of inhibiting bacterial activity and promoting infectious alveolar bone augmentation in rats and beagle dogs.
Objective
Fluorine‐18‐fluorodeoxyglucose–positron emission tomography (FDG‐PET) is routinely used for presurgical evaluation in many epilepsy centers. Hypometabolic characteristics have been ...extensively examined in prior studies, but the metabolic patterns associated with specific pathological types of drug‐resistant epilepsy remain to be fully defined. This study was developed to explore the relationship between metabolic patterns or characteristics and surgical outcomes in type I and II focal cortical dysplasia (FCD) patients based on results from a large cohort.
Methods
Data from individuals who underwent epilepsy surgery from 2014 to 2019 with a follow‐up duration of over 3 years and a pathological classification of type I or II FCD in our hospital were retrospectively analyzed. Hypometabolic patterns were quantitatively identified via statistical parametric mapping (SPM) and qualitatively analyzed via visual examination of PET‐MRI co‐registration images. Univariate analyses were used to explore the relationship between metabolic patterns and surgical outcomes.
Results
In total, this study included data from 210 patients. Following SPM calculations, four hypometabolic patterns were defined including unilobar, multi‐lobar, and remote patterns as well as cases where no pattern was evident. In type II FCD patients, the unilobar pattern was associated with the best surgical outcomes (p = 0.014). In visual analysis, single gyrus (p = 0.032) and Clear‐cut hypometabolism edge (p = 0.040) patterns exhibited better surgery outcomes in the type II FCD group.
Conclusions
PET metabolic patterns are well‐correlated with the prognosis of type II FCD patients. However, similar correlations were not observed in type I FCD, potentially owing to the complex distribution of the epileptogenic region.
Plain Language Summary
In this study, we demonstrated that FDG‐PET was a crucial examination for patients with FCD, which was a common cause of epilepsy. We compared the surgical prognosis for patients with different hypometabolism distribution patterns and found that clear and focal abnormal region in PET was correlated with good surgical outcome in type II FCD patients.
Trefoil Factor 1 (TFF1, also named pS2), which serves as the gastrointestinal mucosal protector, is known as gastric‐specific tumor suppressor gene. However, the genetic variants of TFF1 are still ...not well studied. In our study, we aim to explore the effects of tagging single nucleotide polymorphisms (tagSNPs) of TFF1 on risk and prognosis of gastric cancer. Seven tagSNPs of TFF1 gene were first analyzed in the discovery set, which was consisted of 753 cases and 950 cancer‐free controls. Then, the validation set (940 cases and 1,042 controls) was used for further evaluation. Moreover, we also tested the relation between these tagSNPs and prognosis of gastric cancer (GC). A series of experiments were performed to investigate the underlying mechanisms. We found that rs3761376 AA in the promoter region of TFF1, could reduce the expression of TFF1 by affecting the binding affinity of estrogen receptor 1 (ESR1, ERα), and thereby increased the risk of GC (1.29, 1.08–1.53). Moreover, the rs3761376 AA genotype was also found associated with worse prognosis among patients receiving 5‐FU based chemotherapy after surgery (1.71, 1.18–2.48). Further functional assays demonstrated that TFF1 could increase the chemosensitivity of 5‐FU by modulating NF‐κB targeted genes. These results identified the effect of rs3761376 on TFF1 expression, which accounted for the correlation with susceptibility and prognosis of GC; and this genetic variant may be a potential biomarker to predict the risk and survival of GC.
What's new?
TFF1 is a well‐established gastric‐specific tumor suppressor gene, but the mechanisms underlying its expression and role in gastric tumorigenesis remain unclear. This study shows that rs3761376 AA in the promoter region of TFF1 can reduce TFF1 expression by affecting the binding affinity of estrogen receptor 1, thereby increasing the risk of gastric cancer. Moreover, rs3761376 AA was associated with worse prognosis among patients receiving 5‐FU based chemotherapy after surgery, with TFF1 increasing the chemosensitivity of 5‐FU by modulating NF‐κB targeted genes. The findings suggest that TFF1 rs3761376 may be used as a potential biomarker for gastric cancer diagnosis and prognosis.
Oxidative stress and inflammation contribute importantly to the pathogenesis of chronic kidney disease (CKD). Epigallocatechin‐3‐gallate (EGCG), which is the most abundant and most active catechin ...polyphenol extracted from green tea, has been proved to have many bioactivities. In this study, the renoprotective effect of EGCG was evaluated in a widely used kidney disease model, the unilateral ureteral obstruction (UUO) mice model. After 14 days of EGCG administration, mean arterial blood pressure, body‐weight and obstructed kidney weight were measured. Levels of blood urea nitrogen (BUN) and creatinine (CR) and activities of glutamic–pyruvic transaminase (GPT) and lactate dehydrogenase (LDH) in serum were estimated as indicators of renal function. Periodic acid–Schiff (PAS) staining was performed to observe the pathological changes of the obstructed kidney. Antioxidant enzymes and pro‐inflammatory cytokine production were estimated to reflect the oxidative stress and inflammatory state in the obstructed kidney. Finally, the main proteins in the NF‐κB and Nrf2 signalling pathway and DNA binding activity of NF‐κB and Nrf2 were measured to investigate the effect of EGCG on these two pathways. The results demonstrated that EGCG could restore UUO‐induced kidney weight loss and renal dysfunction. In addition, UUO‐induced oxidative stress and inflammatory responses in the obstructed kidney were also prevented by EGCG. Furthermore, EGCG could induce both NF‐κB and Nrf2 nuclear translocation in the UUO kidney and promote heme oxygenase‐1 (HO‐1) production. These results indicated that the renoprotective effect of EGCG might be through its NF‐κB and Nrf2 signalling pathway regulations.
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