Near-Field Probing of Microwave Oscillators with Josephson Microscopy.

Voltage-controlled oscillators, serving as fundamental components in semiconductor chips, find extensive applications in diverse modules such as phase-locked loops, clock generators, and frequency synthesizers within high-frequency integrated circuits. This study marks the first implementation of superconducting Josephson probe microscopy for near-field microwave detection on multiple voltage-controlled oscillators. Focusing on spectrum tracking, various phenomena, such as stray spectra and frequency drifts, were found under nonsteady operating states. Parasitic electromagnetic fields, originating from power supply lines and frequency divider circuits, were identified as sources of interference between units. The investigation further determined optimal working states by analyzing features of the microwave distributions. Our research not only provides insights into the optimization of circuit design and performance enhancement in oscillators but also emphasizes the significance of nondestructive near-field microwave microscopy as a pivotal tool in characterizing integrated millimeter-wave chips.

USP33 enhances cell survival and stemness by deubiquitinating CTNNB1 in BXPC-3 and SW1990 cells.

Ubiquitin-specific protease 33 (USP33) has been implicated in various cancers, but its biological function and mechanism of action remain unknown in pancreatic cancer (PCa) as a deubiquitinating enzyme. Herein, we report that USP33 silencing inhibits PCa cell survival and self-renewal. USPs highly expressed in spherical PCa cells were screened by comparing the levels of ubiquitin-specific proteases in spherical PCa cells and adherent PCa cells. After silencing USP, the effect of USP on the proliferation of PCa cells was detected by CCK-8 and colony formation assay, and the effect of USP on cell stemness was detected by tumor sphere formation assay, flow analysis, and western blot analysis. The interaction of USP with CTNNB1 and the effect of USP on the ubiquitination of CTNNB1 were verified by coimmunoprecipitation assay. After replenishing CTNNB1, cell proliferation and cell stemness were examined. USP33 is upregulated in spheric BXPC-3, PCNA-1, and SW1990, compared with adherent BXPC-3, PCNA-1, and SW1990. USP33 interacts with CTNNB1, and stabilizes CTNNB1 by suppressing its degradation. Furthermore, cell proliferation, colony-forming, and self-renewal abilities of PCa cells in vitro, and the expression of stem cell markers EpCAM and CD44, C-myc, Nanog, and SOX2, were suppressed when USP33 was knocked down, which was reversed when CTNNB1 was ectopically expressed in PCa cells. Thus, USP33 promotes PCa cell proliferation and self-renewal by inhibiting the degradation of CTNNB1. USP33 inhibition may be a new treatment option for PCa patients.

Advanced oxidation protein products induce hepatocyte epithelial-mesenchymal transition via a ROS-dependent, TGF-ß/Smad signaling pathway.

Epithelial-mesenchymal transition (EMT) occurs during the progression of liver fibrosis in response to chronic liver injury. However, the molecular mechanism underlying the regulation of hepatocyte EMT remains unclear. The aim of this study was to determine whether advanced oxidation protein products (AOPP) had an effect on hepatocyte EMT. The human L02 hepatocyte cell line and hepatocytes from normal Sprague-Dawley rats were challenged with AOPP treatment in both in vitro and in vivo studies. The expression of cell and molecular markers of EMT in L02 hepatocytes were studied using Western blotting, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays. Hepatocyte migratory potential was analyzed using a wound healing assay. Intracellular reactive oxygen species (ROS) were detected using the dichlorofluorescein (DCF) assay. In liver tissue sections, expression of EMT markers was evaluated using immunohistochemistry, and collagen was assessed using histochemical staining with Masson's trichrome. The findings were that AOPP treatment resulted in EMT in hepatocytes, which was associated with reduced expression of E-cadherin, increased expression of vimentin, increased deposition of collagen protein, and enhanced cell migration in vivo and in vitro. AOPP was also found to promote migration in L02 cells, and to promote the production of ROS and the activation of TGF-ßR and Smad signaling. Inhibition of the generation of intracellular ROS and TGF-ß receptor blocking could reverse AOPP-induced EMT in hepatocytes. This study has identified a novel mechanism in the regulation of hepatocyte EMT, and the findings may have implications for the control of liver fibrosis.

High-performance bismuth vanadate photoanodes cocatalyzed with nitrogen, sulphur co-doped ferrocobalt-metal organic frameworks thin layer for photoelectrochemical water splitting.

In this study, we prepare a highly efficient BiVO4 photoanode co-catalyzed with an ultrathin layer of N, S co-doped FeCo-Metal Organic Frameworks (MOFs) for photoelectrochemical water splitting. The introduction of N and S into FeCo-MOFs enhances electron and mass transfer, exposing more catalytic active sites and significantly improving the catalytic performance of N, S co-doped FeCo-based MOFs in water oxidation. The optimized BiVO4/NS-FeCo-MOFs photoanode exhibits impressive results, with a photocurrent density of 5.23 mA cm-2 at 1.23 V vs. Reversible Hydrogen Electrode (RHE) and an incident photon-to-charge conversion efficiency (IPCE) of 74.4 % at 450 nm in a 0.1 M phosphate buffered solution (pH = 7). These values are 4.84 times and 6.2 times higher than those of the original BiVO4 photoanode, respectively. Furthermore, the optimized BiVO4/NS-FeCo-MOFs photoanode demonstrates exceptional long-term stability, maintaining 96 % of the initial current after five hours.

IL-1ß-pretreated bone mesenchymal stem cell-derived exosomes alleviate septic endoplasmic reticulum stress via regulating SIRT1/ERK pathway.

Background: Endoplasmic reticulum (ER) plays a crucial role in the development of organ injury caused by sepsis. Therefore, it is highly important to devise strategies that specially target ER stress for the treatment of sepsis. Previous research has shown that priming chemokines can enhance the therapeutic effects of mesenchymal stem cells (MSCs). In this study, we aimed to investigate the function and mechanism of exosomes derived from MSCs that were pretreated with IL-1ß (IB-exos) in the context of septic ER stress. Methods: Mouse bone MSCs were preconditioned with or without IL-1ß and the supernatant was used for exosome extraction. In vitro sepsis cell mode was induced by treating HUVECs with LPS, while in vivo sepsis model was established through cecal ligation and puncture (CLP) operation in mice. Cell viability, apoptosis, motility, and tube formation were assessed using the EDU proliferation assay, flow cytometry analysis, migration assay, and tube formation assay, respectively. The molecular mechanism was investigated using ELISA, qRT-PCR, Western blot, and immunofluorescence staining. Results: Pretreatment with IL-1ß enhanced the positive impact of MSC-exos on the viability, apoptosis, motility, and tube formation ability of HUVECs. The administration of LPS or CLP increased ER stress response, but this effect was blocked by the treatment of IB-exos. Additionally, IB-exos reversed the inhibitory effects of LPS or CLP on the expression levels of SIRT1 and ERK phosphorylation. Knockdown of SIRT1 counteracted the effects of IB-exos on HUVEC cellular function and ER stress. In a mouse model, the injection of IB-exos mitigated sepsis-induced lung injury by inhibiting ER stress response through the activation of SIRT1. Conclusion: IB-exos have been found to alleviate sepsis-induced lung injury via inhibiting ER stress through the SIRT1/ERK pathway. These findings indicated that IB-exos could potentially be used as a strategy to mitigate lung injury caused by sepsis.

Evaluation of Beta-Cyfluthrin Resistance of Cigarette Beetle (Coleoptera: Anobiidae) from Cigarette Manufacturing Factories of China and Underlying Metabolic Mechanisms Responsible for Resistance.

Beta-cyfluthrin, as a synthetic pyrethroid, has been widely used in cigarette manufacturing factories in China to control Lasioderma serricorne (F.) (Coleoptera: Anobiidae). In this study, spray toxicity bioassays and filter paper residual contact toxicity bioassays were conducted to investigate the beta-cyfluthrin sensitivity level of five field strains of L. serricorne collected from cigarette manufacturing factories in China. Bioassay results indicated that five field strains had developed different levels of resistance to beta-cyfluthrin with RR50 of 3.51-10.20 at 2 hr after application and 4.05-49.50 at 24 hr after application in spray toxicity bioassays, and RR50 of 4.74-14.47 at 2 hr exposure in filter paper residual contact bioassays. In addition, we examined CarE, GST, and CYP450 enzyme activity and content of L. serricorne adults and larvae. Enzyme-linked immunosorbent assay results suggested that there was no significant difference in GST, CYP450, and CarE content of L. serricorne adults between field strains and reference sensitive strain. Biochemical assay results indicated that CYP450 activity of L. serricorne adults and larvae of five field strains was significantly higher than that of reference sensitive strain, with increased CYP450 activity of 1.08-1.82-fold in adults and 1.08-2.12-fold in larvae. The results implied that elevated CYP450 activity may contribute to metabolic resistance of L. serricorne to pyrethroid. Our study indicated that there was no clear evidence that the enhanced CarE and GST activity was associated with pyrethroid resistance of L. serricorne.

Studies on interactions between plant secondary metabolites and glutathione transferase using fluorescence quenching method.

The interactions between plant secondary metabolites (tannic acid, rutin, cinnamic acid and catechin) and glutathione transferase (GST) were investigated by fluorescence and UV-Vis absorption spectroscopy. Intrinsic fluorescence of GST was measured by selectively exciting their tryptophan (Trp) residues and quenching constants were determined using the Stern-Volmer equation. The binding affinity was found to be strongest for tannic acid and ranked in the order tannic acid>rutin>cinnamic acid>catechin. The pH values in the range of 6.7-7.9, except for tannic acid, did not affect significantly the affinity of rutin, cinnamic acid and catechin with GST. Results showed that the fluorescence quenching of GST was a static_quenching. Fluorescence quenching and UV-Vis absorption spectroscopy suggested that only the tannic acid changed the microenvironment of the Trp residues. Furthermore, the number of binding sites and binding constants at different pH values showed that tannic acid had strongest affinity towards GST and hydrogen bonding played an important role in the affinity between GST and the metabolites.

Efficient high-performance liquid chromatography with liquid-liquid partition cleanup method for the determination of pymetrozine in tobacco.

For the first time, a novel, simple and reliable method for analysis of pymetrozine residues in flue-cured tobacco leaves has been developed utilizing HPLC-UV with liquid-liquid partition cleanup. Pre-treatment with ultrasonic extraction and liquid-liquid partition procedures gave preferable baseline separation and clean chromatograms by removing water-soluble and fat-soluble components which interfere with pymetrozine in the test. The performance of the method was evaluated and validated: the detection limit (LOD) was 0.005 microg x mL(-1), the relative standard deviation (RSD) was 1.2% (n = 5), and the overall recovery was above 90% at fortification levels of 0.200, 0.500, 1.000, and 5.000 mg x kg(-1). The proposed method was successfully employed for the determination of pymetrozine residues in twelve flue-cured tobacco samples collected from different regions of China.

[Fluorescence spectra and analysis of chicken liver GST].

Glutathione transferases (GST; EC2. 5. 1. 18) is an important detoxification enzyme which catalyze the conjugation of glutathione to a large variety of endogenous and exogenous electrophilic compounds to protect the functions of body. In the present paper, three dimensional fluorescence spectra were obtained, through which the authors could identify the fluorescence spectra of peptide bond, Tyr and Trp residue. The authors compared aromatic amino-acid residue fluorescence spectra in GST with dissociative to know red or blue shift of the fluorescence peak. The authors also studied the peptide bond and Trp residue fluorescence spectra at various pH, which suggested the change in GST surface and surface hydrophobicity, and the microenviroment change of aromatic amino-acid residue in enzyme.

Transcriptional activation of PD-L1 by Sox2 contributes to the proliferation of hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies in the world. Sox2 is a potential oncogene in the pathogenesis of HCC, however, the actual mechanisms of Sox2 functions in HCC has not emerged yet. In this study, we explored the expression, function and the relationship between Sox2 and PD-L1 in HCC. We found that both Sox2 and PD-L1 were expressed at a markedly higher level in HCC tissues in comparison to adjacent non-tumor tissues. Moreover, the expression levels of both genes were correlated with each other. Knockdown of Sox2 reduced the cell proliferation ability and induces apoptosis of HCC cells, suggesting the function of Sox2 in regulating both the cell proliferation and apoptosis. Noteworthy, the depletion of Sox2 also reduced the expression of PD-L1. Further analysis showed that there is a consensus Sox2 binding site in the promoter region of PD-L1. Through in vitro EMSA assay and in vivo chromatin immunoprecipitation assays, we demonstrated that Sox2 directly bound to the PD-L1 promoter through the consensus Sox2 motif. Further evidence by luciferase reporter assays revealed that Sox2 promoted the transcription activity of PD-L1 promoter region through the Sox2 motif. Collectively, our data provide a novel insight into the function and the interplay of Sox2 and PD-L1 in HCC.

EHHM, a novel phenolic natural product from Livistona chinensis, induces autophagy-related apoptosis in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) ranks the second cause of cancer-associated mortality worldwide. In the present study, the effects and mechanisms of a new phenolic natural product E-[6'-(5'-hydroxypentyl)tricosyl]-4-hydroxy-3-methoxycinnamate (EHHM) isolated from Livistona chinensis on the growth of HCC cells were investigated. It was observed that EHHM treatment significantly suppressed cell proliferation and colony formation, and induced cell apoptosis via a mitochondria-dependent caspase pathway in HepG2 cells in a time- and dose-dependent manner. Meanwhile, EHHM treatment also led to upregulated expression of autophagy protein 5 (Atg5), Beclin 1 and light chain 3 (LC3)-II proteins, and accumulation of green fluorescent protein-LC3 punctate florescent foci in HCC cells, suggesting that EHHM-induced apoptosis is accompanied by autophagy induction. Western blotting revealed that EHHM-induced autophagy is related to the inhibition of the Akt/mechanistic target of rapamycin/p70 ribosomal protein S6 kinase signaling pathway. Furthermore, treatment with Atg5 small interfering RNA or autophagy inhibitors significantly enhanced EHHM-mediated growth inhibition and apoptotic cell death, indicating that autophagy serves as a self-protective mechanism in EHHM-treated HCC cells, and that combined treatment with EHHM and autophagy inhibitors may be an effective therapeutic strategy for HCC.

Knockdown of Histone Methyltransferase hSETD1A Inhibits Progression, Migration, and Invasion in Human Hepatocellular Carcinoma.

Our aim was to study the expression of human SET domain containing protein 1A (hSETD1A) in hepatocellular carcinoma patients and its relationship with human hepatocellular carcinoma cell function. A total of 30 patients with hepatocellular carcinoma were enrolled in this study. The expression of hSETD1A was detected by real-time polymerase chain reaction (PCR) and Western blotting. The immortalized normal human liver cell line including SMMC-7721 was subjected to real-time PCR for hSETD1A mRNA. Furthermore, hSETD1A-small hairpin RNA (shRNA) was used to knock down hSETD1A expression in SMMC-7721 cells. Cell proliferation, cell apoptosis, and cell migration were determined by CCK8, flow cytometry, and Transwell assays. The positive expression rate level of hSETD1A mRNA and protein in liver carcinoma tissues was 73.33%. hSETD1A knockdown using a specific hSETD1A-shRNA inhibited cell proliferation and promoted cell apoptosis in SMMC-7721 cells. It was also found that downregulation of hSETD1A inhibited cell migration ability but did not affect cell invasion. In conclusion, the expression of hSETD1A occurs at a high rate in hepatocellular carcinoma patients. The expression state of hSETD1A may be a prognostic factor in hepatocellular carcinoma.

Treatment outcomes of spontaneous rupture of hepatocellular carcinoma with hemorrhagic shock: a multicenter study.

BACKGROUND: Spontaneous rupture is one of the most fatal complications of HCC. The incidence of HCC still remains a significant health problem in Eastern Asia. Many studies have shown that the in-hospital or 30-day mortality rates are as high as 25-100 %. It is often difficult to stratify these patients based on clinical manifestations and biochemical data, for deciding on an appropriate treatment strategy, especially when the patient's hemodynamic status is unstable. This study aimed to explore the clinical outcomes of treatment of spontaneously ruptured hepatocellular carcinoma with hemorrhagic shock. METHODS: One hundred and sixty two patients with hemorrhagic shock secondary to spontaneous rupture of hepatocellular carcinoma were included in this retrospective study. The therapeutic methods included conservative treatment, transcatheter arterial embolization (TAE) and hepatectomy. The outcomes in terms of 30 day and 1 year survival were analyzed. RESULTS: Thirty five (21.6 %) received only conservative management, TAE was performed in 48 (29.6 %) and partial hepatectomy (emergency and staged) in 106 (65.4 %) patients. The 30-day survival rate was lower in patients receiving conservative treatment (8.6 %) than in those receiving either hepatectomy or TAE (88.2 %; P < 0.001). Conservative treatment was associated with poorer long-term survival (0 % at 1 year) when compared to those receiving either hepatectomy or TAE (54.3 % at 1 year; P < 0.001). The survival rates at 30 days and 1 year were 92.5 % and 59.4 % for the patients who underwent hepatectomy, which were significantly higher (66.7 and 28.6 % respectively) than those receiving TAE alone (P = 0.003 and P = 0.009, respectively). Multivariate Cox-regression analysis showed that hepatectomy and TAE were significant protective factors for survival as compared with conservative treatment (all P < 0.01). CONCLUSIONS: Partial hepatectomy, tended to provide better survival than transcatheter arterial embolization alone or conservative treatment in the management of patients with hemorrhagic shock secondary to spontaneous rupture of hepatocellular carcinoma.

Beta-Aminobutyric acid-mediated enhancement of resistance in tobacco against TMV and consideration of its capability in wounded tobacco plants.

Systemic acquired resistance (SAR) is an important component of disease-resistance arsenal of plants, and is associated with enhanced potency of activating local and systemic defense-related responses upon pathogen attack. In this report, we demonstrated that pre-treatment with beta-aminobutyric acid (BABA), a new elicitor of SAR in the plants, enhanced resistance against tobacco mosaic virus (TMV) in a temperately-sensitive tobacco (Nicotiana tabacum L.) cultivar Yunyan 85. The resistance is based on the elicitation of defense-related responses induced by BABA that brings the TMV-susceptible tobacco plants to a defense-ready state, even before exposure to the pathogen. The induced resistance was strongly associated with potentiated activation of defense-related enzymes [phenylalanine ammonia lyase (PAL) and polyphenol oxidase (PPO)] activities, proportional to the concentration of the BABA sprayed. Interestingly, simultaneous clipping, an important agricultural practice in tobacco production, attenuated BABA-mediated enhancement of TMV resistance in tobacco. The changes in the defense-related enzymes activities indicated that the interaction between BABA and wounding was reciprocally antagonistic. Moreover, such a negative interaction regulated the expression of defense-related enzymes. depending on the time of induction.

MicroRNA301 is a potential diagnostic biomarker for hepatocellular cancer.

We explored microRNA301 diagnosis value in hepatocellular cancer (HCC), attempting to provide novel insights for early detection, effective prevention, and timely treatment. 42 patients with HCC and 38 controls composed of 9 liver cirrhosis (LC), 9 chronic hepatitis B (CHB) and 20 healthy individuals were investigated in the study. Serum microRNA301 expression levels were detected using fluorescent quantitative polymerase chain reaction (FQ-PCR) technology. ROC curve was performed to evaluate diagnosis value of microRNA301. Meanwhile, the correlations of microRNA301 levels with clinical characteristics were also analyzed. Significantly up-regulated expression of serum microRNA301 was seen in HCC patients compared with the controls (P<0.05). We also noted that level changes of microRNA301 were associated with differentiation, alpha fetoprotein (AFP), portal vein-emboli and HasAg (P<0.05), rather than age, gender and tumor size. Based on the area under ROC curve of 0.880, the critical value of microRNA301 was 2.3530 and the sensitivity and specificity were 88.1% and 70.3%, respectively. The results of this study revealed that microRNA301 might function as a potential diagnostic biomarker for HCC.