Lack of K-Dependent Oxidative Stress in Cotton Roots Following Coronatine-Induced ROS Accumulation

Coronatine [COR] is a novel type of plant growth regulator with similarities in structure and property to jasmonate. The objective of this study was to examine the relationship between increased root vitality induced by 10nM COR and reactive oxygen species scavenging under potassium (K)-replete (2.5mM) and K-deficient (0.05mM) conditions in hydroponic cultured cotton seedlings. K-replete and K-deficient conditions increased root vitality by 2.7- and 3.5-fold, respectively. COR treatment significantly decreased lipid peroxidation in cotton seedlings determined by reduction in MDA levels. These results suggest that COR improves the functioning of both enzymatic and non-enzymatic antioxidant systems. Under K-replete and K-deficient conditions, COR significantly increased the activities of antioxidant enzymes SOD (only for K-repletion), CAT, GPX, and APX comparing; COR also significantly increased DPPH-radical scavenging activity. However, COR led to 1.6- and 1.7-fold increases in superoxide anion (O2•-) concentrations, and 5.7- and 2.1-fold increases in hydrogen peroxide (H2O2) levels, respectively. Additionally, COR intensified the DAB staining of H2O2 and the NBT staining of O2•-. Therefore, our results reveal that COR-induced ROS accumulation stimulates the activities of most antioxidant enzymes but does not induce oxidative stress in cotton roots

Prognostic value of programmed death ligand 1, p53, and Ki-67 in patients with advanced stage colorectal cancer

Current prognostic indicators are ineffective for identifying advanced stage colorectal cancer (CRC) patients with high risk of recurrence after surgical resection. We investigated the prognostic value of p53, Ki-67, and programmed death ligand 1 (PD-L1) in 254 patients with stage II and III CRC. The expression of p53 was positive in 63% of cases. Up-regulation of p53 was associated with smaller tumor size (P = .001) and higher Ki-67 labeling index (LI) (P = .031). The tumor Ki-67 LI was high (≥ 20%) in 197 (78%) of the patients. High Ki-67 LI was associated with higher TNM stage (P = .031), positive p53 expression (P = .031), and negative PD-L1 expression (P = .003). The five-year relapse-free survivals (RFS) were 53% and 89%, respectively, for the p53-positive and Ki-67 LI-high patients and the p53-negative and Ki-67 LI-low patients (P < .001). In univariate analysis, negative p53 (P = .001), low Ki-67 LI (P = .006), low PD-L1 expression (P = .044), low TNM stage (P < .001), recto-sigmoid location (P = .026), and small size (P = .013) were significantly related to RFS. In multivariate Cox regression analysis, positive p53 expression (hazard ratio [HR]: 2.48; 95% confidence interval: 1.34–4.59, P = .004), high Ki-67 LI (HR: 2.62; 95% CI: 1.12–6.14, P = .027) and high TNM stage (HR: 2.598, 95% CI: 1.55–4.37, P < .001,) were independent predictors of unfavorable prognosis. In summary, PD-L1, Ki-67, and p53 staining individually had significant prognostic value for patients with stage II and III CRC. Moreover, combining p53 H-score ≥ 35 and Ki-67 LI ≥ 20% identifies patients with poor clinical outcome

Frequent copy number variations of PI3K/AKT pathway and aberrant protein expressions of PI3K subunits are associated with inferior survival in diffuse large B cell lymphoma

BACKGROUND: It has been reported that the PI3K/AKT signaling pathway is activated in diffuse large B-cell lymphoma (DLBCL), PI3K constitutive activation plays a crucial role in PI3K/AKT pathway. However, the copy number variations (CNVs) of PI3K subunits on gene level remain unknown in DLBCL. Therefore, the aim of the study is to investigate the CNV of PI3K subunits and their relationship with clinicopathological features exploring the possible mechanism underlying of PI3K activation in DLBCL. METHODS: CNV of 12 genes in the PI3K/AKT pathway was detected by NanoString nCounter in 60 de novo DLBCLs and 10 reactive hyperplasia specimens as controls. Meanwhile, immunohistochemistry (IHC) was performed to examine the expression of p110α, p110β, p110γ, p110δ, and pAKT on DLBCL tissue microarrays. RESULTS: All PI3K and AKT subunits, except for PIK3R1, had various CNVs in the form of copy number amplifications and copy number losses. Their rates were in the range of 8.3–20.0%. Of them PIK3CA and PIK3CB gene CNVs were significantly associated with decreased overall survival (P = 0.029 and P = 0.019, respectively). IHC showed that the frequency of strong positive expression of p110α, p110β, p110γ, and p110δ were 26.7%, 25.0%, 18.3%, and 25.0% respectively, and they were found to be associated with decreased survival (P = 0.022, P = 0.015, P = 0.015, and P = 0.008, respectively). Expression of p110α was not only significantly associated with CNVs of PIK3CA (P = 0.002) but also positively correlated with strong positive expression of pAKT (P = 0.026). CONCLUSIONS: CNV of PIK3CA is highly associated with aberrant p110α protein expression and subsequent activation of PI3K/AKT pathway. CNVs of PIK3CA and PIK3CB, and aberrant protein expression of p110 isoforms are of great important value for predicting inferior prognosis in DLBCL. Frequent CNVs of PI3K/AKT subunits may play an important role in the tumorigenesis of DLBCL

On the noise effect of test mass surface roughness in spaceborne gravitational wave detectors

Spaceborne gravitational wave detection mission has a demanding requirement for the precision of displacement sensing, which is conducted by the interaction between the laser field and test mass. However, due to the roughness of the reflecting surface of the test mass, the displacement measurement along the sensitive axis suffers a coupling error caused by the residue motion of other degrees of freedom. In this article, we model the coupling of the test mass residue random motion to the displacement sensing along the sensitive axis and derived an analytical formula of the required precision of the surface error for the spaceborne gravitational wave detectors. Our result shows that this coupling error will not contaminate the picometer displacement sensing for the test masses in the LISA pathfinder.Comment: 8 page

Distilling determination of water content in hydraulic oil with a ZnO/glass surface acoustic wave device

Detection of water content in hydraulic oil is critical to identify abnormal wear conditions for purpose of predicting possible machinery failure in hydraulic systems. The paper reports a feasibility study of measuring the water content in the hydraulic oil using a ZnO thin film surface acoustic wave (SAW) device combined with the standard distillation method. The shift of resonant frequency of the SAW device increases with the increase of water content in hydraulic oil, and reaches 919 kHz for 0.80 wt% water content in oil samples. The results indicate that the ZnO SAW sensor can detect water content in hydraulic oil with high sensitivity

Association between metabolically healthy obesity and risk of atrial fibrillation:taking physical activity into consideration

The modification of physical activity (PA) on the metabolic status in relation to atrial fibrillation (AF) in obesity remains unknown. We aimed to investigate the independent and joint associations of metabolic status and PA with the risk of AF in obese population. Based on the data from UK Biobank study, we used Cox proportional hazards models for analyses. Metabolic status was categorized into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). PA was categorized into four groups according to the level of moderate-to-vigorous PA (MVPA): none, low, medium, and high. A total of 119,424 obese participants were included for analyses. MHO was significantly associated with a 35% reduced AF risk compared with MUO (HR = 0.65, 95% CI: 0.57–0.73). No significant modification of PA on AF risk among individuals with MHO was found. Among the MUO participants, individuals with medium and high PA had significantly lower AF risk compared with no MVPA (HR = 0.84, 95% CI: 0.74–0.95, and HR = 0.87, 95% CI: 0.78–0.96 for medium and high PA, respectively). As the severity of MUO increased, the modification of PA on AF risk was elevated accordingly. To conclude, MHO was significantly associated with a reduced risk of AF when compared with MUO in obese participants. PA could significantly modify the relationship between metabolic status and risk of AF among MUO participants, with particular benefits of PA associated with the reduced AF risk as the MUO severity elevated. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-022-01644-z

Association Between Remnant Cholesterol and Risk of Incident Atrial Fibrillation: Population-Based Evidence From a Large-Scale Prospective Cohort Study

BACKGROUND: Evidence for the relationship between remnant cholesterol (RC) and incident atrial fibrillation (AF) risk remains sparse and limited.METHODS AND RESULTS: Participants were enrolled between 2006 and 2010 and followed up to 2021. The multivariable Cox proportional hazards model was used to examine the relationship between RC quartiles and risk of incident AF. Subgroup analyses and sensitivity analyses were performed to explore the potential modification of the association and the robustness of the main findings. A total of 422 316 participants (mean age, 56 years; 54% women) were included for analyses. During a median follow-up of 11.9 years (first quartile-third quartile, 11.6-13.2 years), there were 24 774 AF events documented with an incidence of 4.92 events per 1000 person-years (95% CI, 4.86-4.98). Participants in higher RC quartiles had a lower risk of incident AF than those in the lowest quartile (first quartile): hazard ratio (HR)=0.96 (95% CI, 0.91-1.00) for second quartile; HR=0.92 (95% CI, 0.88-0.96) for third quartile; and HR=0.85 (95% CI, 0.81-0.89) for fourth quartile (P for trend &lt;0.001). The association between RC quartiles and risk of incident AF was stronger in participants aged ≥65 years, in men, and in participants without history of diabetes when compared with control groups (P&lt;0.001 for interaction).CONCLUSIONS: On the basis of data from this large-scale prospective cohort study, elevated RC was associated with a lower risk of incident AF.</p

Activation of MET signaling by HDAC6 offers a rationale for a novel ricolinostat and crizotinib combinatorial therapeutic strategy in diffuse large B‐cell lymphoma

Some histone deacetylases (HDACs) promote tumor cell growth and pan‐ or selective HDAC inhibitors are active in some cancers; however, the pivotal HDAC enzyme and its functions in human diffuse large B‐cell lymphoma (DLBCL) remain largely unknown. Using NanoString nCounter assays, we profiled HDAC mRNA expression and identified HDAC6 as an upregulated HDAC family member in DLBCL tissue samples. We then found that HDAC6 plays an oncogenic role in DLBCL, as evidenced by its promotion of cell proliferation in vitro and tumor xenograft growth in vivo. Mechanistically, the interaction between HDAC6 and HR23B downregulated HR23B expression, thereby reducing the levels of casitas B‐lineage lymphoma (c‐Cbl), an E3 ubiquitin ligase for hepatocyte growth factor receptor (MET), which resulted in the inhibition of MET ubiquitination‐dependent degradation. In addition, enhanced HDAC6 expression and decreased HR23B expression were correlated with poor overall survival rates among patients with DLBCL. Taken together, these results establish an HDAC6–HR23B–MET axis and indicate that HDAC6 is a potent promoter of lymphomagenesis in DLBCL. Thus, a therapeutic strategy based on HDAC6 inhibitors in combination with MET inhibitors is promising. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146400/1/path5108_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146400/2/path5108.pd

Doping High-Mobility Donor : Acceptor Copolymer Semiconductors with an Organic Salt for High-Performance Thermoelectric Materials

Organic semiconductors (OSCs) are attractive for fabrication of thermoelectric devices with low cost, large area, low toxicity, and high flexibility. In order to achieve high-performance organic thermoelectric devices (OTEs), it is essential to develop OSCs with high conductivity (σ), large Seebeck coefficient (S), and low thermal conductivity (κ). It is equally important to explore efficient dopants matching the need of thermoelectric devices. The thermoelectric performance of a high-mobility donor–acceptor (D–A) polymer semiconductor, which is doped by an organic salt, is studied. Both a high p-type electrical conductivity approaching 4 S cm−1 and an excellent power factor (PF) of 7 µW K−2 m−1 are obtained, which are among the highest reported values for polymer semiconductors. Temperature-dependent conductivity, Seebeck coefficient and power factor of the doped materials are systematically investigated. Detailed analysis on the results of thermoelectric measurements has revealed a hopping transport in the materials, which verifies the empirical relationship: S ∝ σ−1/4 and PF ∝ σ1/2. The results demonstrate that D–A copolymer semiconductors with proper combination of dopants have great potential for fabricating high-performance thermoelectric devices. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Cannabinoid Receptor Subtype 2 (Cb2R) Agonist Gw405833 Reduces Agonist-Induced Ca2+ Oscillations In Mouse Pancreatic Acinar Cells

Emerging evidence demonstrates that the blockade of intracellular Ca 2+ signals may protect pancreatic acinar cells against Ca 2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB 2 R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB 2 Rs modulate intracellular Ca 2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB 2 R agonist, GW405833 (GW) in agonist-induced Ca 2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB 1 R-knockout (KO), and CB 2 R-KO mice. Immunohistochemical labeling revealed that CB 2 R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB 2 Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca 2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB 2 R antagonist, AM630, or was absent in CB 2 R-KO but not CB 1 R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca 2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB 2 Rs eliminates ACh-induced Ca 2+ oscillations and L-arginine-induced enhancement of Ca 2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB 2 R-mediated protection in acute pancreatitis