Despite improvements in the diagnosis and treatment of hepatocellular carcinoma (HCC), the prognosis is still poor. Pioneering work has demonstrated a potential role for tumour cell-derived exosomes ...(TEXs) in HCC. TEXs can mediate immune responses, antigen presentation and intracellular communication by serving as vehicles for the transfer of proteins, viruses, lipids and RNA between cells. An improved understanding of the roles played by exosomes could lead to a powerful new strategy for preventing and treating HCC. In this review, we summarise current understanding on the topic. The literature points to two faces of TEXs in HCC: 1) They can promote invasion, metastasis, immune evasion and modulation and 2) they can act as diagnostic and prognostic biomarkers, and can be used in anti-cancer drug resistance and immunotherapy in the future.
The converter transformer is the most important piece of equipment in ultrahigh voltage direct current (UHVDC) transmission systems. The rectifying valve side of the converter transformer is dealing ...with composite voltages, containing both ac and dc components. Therefore, the characteristics of the partial discharge (PD) in oil-paper insulation of such rectifying valves are different from those of rectifying valves subjected to pure ac or dc voltage. In this study, theories of hydrodynamic drift-diffusion and bipolar charge transfer were used to build the needle-plate electrode model with a paperboard depression, and experiments were used to verify the feasibility of the simulation method. The electric field and net charge distribution that can reflect the PD were analyzed. Besides, the effects of instantaneous voltage, the proportion of ac-dc components, and depression parameters on the development characteristics of PD were also discussed. Simulation results show that applied voltage, interface charge density, and model parameters can all affect the electric field strength, which in turn influences the development of PD in the depression. This research reveals the process and influencing factors of PD during the electrical aging process, which not only helps to optimize the oil-paper insulation at the rectifying valve side of the converter transformer but also provides a basis for further explaining the PD mechanism.
Recurrence after atrial fibrillation (AF) ablation is still common.
This study aimed to evaluate the predictive abilities of AF duration and early recurrence (ER) to discriminate high-risk patients ...for recurrence.
We enrolled 1,763 consecutive patients with AF who were scheduled to receive the index radiofrequency catheter ablation (RFCA) from January 2016 to August 2021 in Dalian, China. Long AF duration (LAFD) was considered if the course of AF lasted for ≥ 12 months. ER was defined as any atrial tachycardia (AT) or AF event longer than 30 s occurring within a 3-month post-RFCA.
Late recurrence occurred in 643 (36.5%) of the 1,763 patients at a median of 35 months after RFCA. Multivariate analysis identified LAFD (hazard ratio (HR): 1.80, 95% confidence interval (CI): 1.38-2.35,
< 0.001) and ER (HR: 2.34, 95% CI: 1.82-3.01,
< 0.001) as strong independent predictors of late recurrence in non-paroxysmal AF. Similarly, LAFD (HR: 1.48, 95% CI: 1.20-1.84,
< 0.001) and ER (HR: 3.40, 95% CI: 2.68-4.30,
< 0.001) were significantly associated with late recurrence in paroxysmal AF. Receiver operating curve analyses revealed that the CAAP-AF (CAD, Atrial diameter, Age, Persistent or longstanding AF, Antiarrhythmic drugs failed, Female) had the highest predict power area under ROC curve (AUC) 0.586. The addition of ER and LAFD to the CAAP-AF score significantly improved risk discrimination for late recurrence after AF ablation from 0.586 to 0.686.
Long AF duration and ER were independently associated with late recurrence. The prediction performance of the CAAP-AF model for recurrence was improved by the addition of LAFD and ER.
Visfatin is considered a pro-inflammatory adipocytokine, and it is commonly increased in obesity-related diseases. This study aimed to evaluate the levels of serum visfatin in patients with ...hepatocellular carcinoma (HCC) and its diagnostic and predictive value in detecting HCC. Fasting serum levels of visfatin of 135 HCC patients, 115 chronic hepatitis B (CHB) patients, 129 liver cirrhosis (LC) patients, and 149 healthy controls were determined via enzyme-linked immunosorbent assay. Meanwhile, serum alpha fetal protein (AFP) and interleukin-6 (IL-6) were also assayed. The median serum visfatin concentration in HCC patients was 1.113 ng/mL (range: 0.823-2.214 ng/mL), which was significant higher than those of healthy controls, CHB patients, and LC patients (P<0.05). The serum visfatin concentration in HCC patients was positively correlated with AFP (r=0.595, P<0.001) and IL-6 (r=0.261, P<0.015) and was also associated with tumor size and tumor node metastasis stage. Moreover, elevated levels of serum visfatin were associated with a higher HCC risk for CHB and LC patients. Multivariate Cox regression analysis had shown that HCC patients with high levels of serum visfatin had significantly shorter overall survival times than those with low serum visfatin levels (P<0.001). Using a cutoff visfatin level of 1.403 ng/mL, the receiver operating characteristic curve analysis showed unappealing sensitivity and specificity values (45.76% and 74.79%, respectively; AUC=0.626) regarding visfatin's use as a diagnostic marker for HCC. Our results indicate that increased serum visfatin levels are associated with poor prognosis of HCC. Visfatin may be a potential therapeutic target of HCC.
•FGF21 attenuates the inflammatory response and renal interstitial fibrosis in LN mice.•FGF21 ameliorates inflammation and fibrosis induced by LN serum in vitro.•FGF21 attenuates the progression of ...LN by up-regulating Irgm1 and through its inhibiting effect on NLRP3 inflammasome.•This study suggests that FGF21 is a potential therapeutic option for the treatment of LN.
As an endocrine cytokine, fibroblast growth factor 21 (FGF21) exhibits anti-inflammatory properties. With the development of lupus nephritis (LN), which is tightly related to pathogenic factors, including inflammation and immune cell dysregulation, we explored the impact of Fibroblast Growth Factor 21 (FGF21) as well as its underlying mechanism. We induced an in vivo LN model using pristane in both wild-type C57BL/6 and FGF21 knockout (FGF21–/–) mice. LN serum obtained from 32-week-old wild-type LN mice was used to stimulate RAW264.7 and human renal tubular epithelial (HK-2) cells to mimic an in vitro LN model. Moreover, our findings revealed that FGF21–/– mice showed more severe kidney injury compared to wild-type mice, as evidenced by increased levels of renal function markers, inflammatory factors, and fibrosis markers. Notably, exogenous administration of FGF21 to wild-type LN mice markedly mitigated these adverse effects. Additionally, we used tandem mass tag (TMT)-based quantitative proteomics to detect differentially expressed proteins following FGF21 treatment. Results indicated that 121 differentially expressed proteins influenced by FGF21 were involved in biological processes such as immune response and complement activation. Significantly upregulated protein Irgm 1, coupled with modulated inflammatory response, appeared to contribute to the beneficial effects of FGF21. Furthermore, Western blot analysis demonstrated that FGF21 upregulated Irgm 1 while inhibiting nucleotide-binding oligomerization domain-like receptors family pyrin domain including 3 (NLRP3) inflammasome expression. Silencing Irgm 1, in turn, reversed FGF21′s inhibitory effect on NLRP3 inflammasome. In summary, FGF21 can potentially alleviate pristane-induced lupus nephritis in mice, possibly through the FGF21/Irgm 1/NLRP3 inflammasome pathway.
Electronic waste is the fastest growing waste stream and one of the most significant constituents is electronic plastics. In this study, the combustion kinetic of typical electronic plastic ...waste-television set (TV) plastic shell-was investigated using two basic kinetic methods. The reaction mechanism and kinetic compensation effect were probed as well. The thermogravimetric analysis (TGA) revealed that its degradation process can be divided into four stages, namely, reaction initiation stage (20-300 °C), major reaction stage (300-450 °C), minor reaction stage (450-600 °C), and reaction cessation stage (600-1,000 °C). The activation energy (E) were calculated and indicated that, the kinetic parameters from six model-free methods gradually decreased with α increasing from 0.1 to 0.35, and then slightly increased. The Flynn--Wall--Ozawa (FWO) method was more reliable and E values decreased from 155.0 to 147.51 kJ/mol with α range of 0.1-0.35, then gradually increased to 165.21 kJ/mol. Within the Coats--Redfern method, the first-order (F1) model had higher coefficient of determination (R
2
) and comparable E values with that from FWO method. The result of kinetic compensation effect confirmed that the compensation effect existed between E and A during the plastic waste combustion. A linear relationship lnA = 0.183E-3.11 (R
2
= 0.991) was obtained. The pre-exponential factors (A) were also determined as 7.67 × 10
10
min
−1
based on the F1 reaction model and FWO method.
Implications: Municipal solid waste (MSW) is a complex mixture of different components and the plastic takes up a significant portion in total MSW. Understanding the combustion process of typical electronic plastic waste and further probing its combustion kinetic are significant. Through this study, it will be significant for the reactor designing and optimizing in practice.
Background
Histone deacetylases (HDACs) engage in the regulation of various cellular processes by controlling global gene expression. The dysregulation of HDACs leads to carcinogenesis, making HDACs ...ideal targets for cancer therapy. However, the use of HDAC inhibitors (HDACi) as single agents has been shown to have limited success in treating solid tumors in clinical studies. This study aimed to identify a novel downstream effector of HDACs to provide a potential target for combination therapy.
Methods
Transcriptome sequencing and bioinformatics analysis were performed to screen for genes responsive to HDACi in breast cancer cells. The effects of HDACi on cell viability were detected using the MTT assay. The mRNA and protein levels of genes were determined by quantitative reverse transcription‐PCR (qRT‐PCR) and Western blotting. Cell cycle distribution and apoptosis were analyzed by flow cytometry. The binding of CREB1 (cAMP‐response element binding protein 1) to the promoter of the KDELR (The KDEL (Lys‐Asp‐Glu‐Leu) receptor) gene was validated by the ChIP (chromatin immunoprecipitation assay). The association between KDELR2 and protein of centriole 5 (POC5) was detected by immunoprecipitation. A breast cancer‐bearing mouse model was employed to analyze the effect of the HDAC3‐KDELR2 axis on tumor growth.
Results
KDELR2 was identified as a novel target of HDAC3, and its aberrant expression indicated the poor prognosis of breast cancer patients. We found a strong correlation between the protein expression patterns of HADC3 and KDELR2 in tumor tissues from breast cancer patients. The results of the ChIP assay and qRT‐PCR analysis validated that HDAC3 transactivated KDELR2 via CREB1. The HDAC3‐KDELR2 axis accelerated the cell cycle progression of cancer cells by protecting the centrosomal protein POC5 from proteasomal degradation. Moreover, the HDAC3‐KDELR2 axis promoted breast cancer cell proliferation and tumorigenesis in vitro and in vivo.
Conclusion
Our results uncovered a previously unappreciated function of KDELR2 in tumorigenesis, linking a critical Golgi‐the endoplasmic reticulum traffic transport protein to HDAC‐controlled cell cycle progression on the path of cancer development and thus revealing a potential therapeutical target for breast cancer.
•Microwave dielectric and optical properties of YAG ceramic are concurrently studied.•Dielectric and optical properties of YAG ceramic can be effectively coordinated.•Sintering parameters affect both ...microwave dielectric and optical properties.•Change trends of dielectric and optical properties are not exactly the same.
Current studies on yttrium aluminum garnet (Y3Al5O12, YAG) ceramic are mainly focused on its optical properties and hardly pay attention to its microwave dielectric properties. This work systematically studies the coordination of the microwave dielectric and optical properties of YAG ceramics by exploring the effects of heating rate, sintering temperature, and holding time on the microstructure, dielectric properties, and transmittance of YAG ceramics fabricated by spark plasma sintering. Results show that the sintering parameters affect the microstructure of YAG ceramics, thereby affecting their microwave dielectric properties and transmittance. However, the change trends of the microwave dielectric and optical properties with the changes in sintering parameters are not exactly the same. The microwave dielectric and optical properties of YAG ceramics can be effectively coordinated by regulating the sintering parameters. The tunable ranges of the satisfactory transmittance, Q × f, εr, and τf are 80.1%–82.0% at 1064 nm wavelengths, 88,587–105,934 GHz, 10.5–10.7, and −53.5–−54.6 ppm/°C, respectively.
•C. butyricum can alleviate the coprophagy prevention induced intestine inflammation.•C. butyricum can reshape intestinal microflora and improve intestinal immune microenvironment.•C. butyricum ...inhibits apoptosis and promotes mucosal repair by inhibiting Flagellin-TLR5 signaling pathway.
As bacteria synthesize nutrients primarily in the cecum, coprophagy is indispensable for supplying rabbits with essential nutrients. Recent research has demonstrated its pivotal role in maintaining intestinal microbiota homeostasis and immune regulation in rabbits, although the specific mechanism remains unknown. Here, we used coprophagy prevention (CP) to investigate the effects of coprophagy on the cecum homeostasis and microbiota in New Zealand white rabbits. Furthermore, whether supplementation of Clostridium butyricum (C. butyricum) may alleviate the cecum inflammation and apoptosis caused by CP was also explored. Four groups were randomly assigned: control (Con), sham-coprophagy prevention (SCP), coprophagy prevention (CP), and CP and C. butyricum addition (CPCB). Compared to Con and SCP, CP augmented cecum inflammation and apoptosis, as well as bacterial adhesion to the cecal epithelial mucosa, while decreasing the expression of tight junction proteins (ZO-1, occluding, and claudin-1). The relative abundance of short-chain fatty acids (SCFAs)-producing bacteria was significantly decreased in the CP group. Inversely, there was an increase in the Firmicutes/Bacteroidetes ratio and the relative abundance of Christensenellaceae_R-7_group. Additionally, CP increased the levels of Flagellin, IFN-γ, TNF-a, and IL-1β in cecum contents and promoted the expression of TLR5/MyD88/NF-κB pathway in cecum tissues. However, the CPCB group showed significant improvements in all parameters compared to the CP group. Dietary C. butyricum supplementation significantly increased the production of SCFAs, particularly butyric acid, triggering anti-inflammatory, tissue repairing, and barrier-protective responses. Notably, CPCB effectively mitigated CP-induced apoptosis and inflammation. In summary, CP disrupts the cecum epithelial barrier and induces inflammation in New Zealand white rabbits, but these effects can be alleviated by C. butyricum supplementation. This process appears to be largely associated with the TLR5/MyD88/NF-κB signaling pathway.
The average share of nuclear energy in electricity production is expected to increase under the background of the global pursuit towards carbon neutrality. Conjugating with its rapid development, the ...wave of decommissioning and dismantling (D&D) of nuclear facilities is coming. The surface decontamination is a prerequisite to D&D, which will make it easier and reduce the volume of radioactive wastes. However, there are no comprehensive studies on the decontamination methods, which is not helpful for the sustainable development of nuclear energy and environment protection. Therefore, in this work, the current status and future trends of global energy and nuclear energy are first analyzed. Then, various decontamination approaches are comparatively studied, including cleaning mechanisms, application subjects, and intrinsic advantages and disadvantages. Finally, the criteria and factors for selecting a decontamination process, the challenges, and future studies are directed. Among the mechanical methods, laser-based cleaning is high-speed, having automation ability, and thus is promising, although it creates a dust and airborne contaminant hazard. In further studies, factors such as selecting a proper laser facility, optimizing operating parameters, and designing a high-efficiency dust collection system could be studied. Regarding the chemical method, chemical gels are good for decontaminating complex shapes and vertical and overhead surfaces. In addition, they can enhance other decon agents’ efficiency by improving contact time. However, the formulation of colloidal gels is complex and no gel type is useful for all contaminants. Therefore, novel and versatile gels need be developed to enlarge their application field. Combining various decontamination methods will often have better results and thus a reasonable and effective combination of these decontamination methods has become the main direction.
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