Potentials of neuron-specific enolase as a biomarker for gastric cancer

Purpose: To investigate the potentials of neuron-specific enolase (NSE) as a biomarker for gastric cancer (GC). Methods: Gastric cancer (GC) patients (n = 412) who underwent gastrectomy were recruited over a 3- year period for this study. Their clinicopathological data such as age, sex, histological type, depth, tumor invasion, lymph node metastasis, and distant metastasis were analyzed. The patients were followed up for four years and the outcomes were also assessed. Histological changes in biopsies and levels of expression of NSE in biopsies and serum of patients were determined using immunohistochemical staining, western blotting and enzyme-linked immunosorbent assay (ELISA), respectively. Results: Immunohistochemical staining showed that NSE was differentially expressed in the cytoplasm of GC cells. Histological changes in biopsies of patients in the overexpression group were not significantly different from those of patients in under-expression group (p > 0.05). In NSE overexpression group, the number of patients in early stage GC subgroup (n = 186, 86.10 %, T1) were significantly higher than that in advanced GC subgroup (n = 124, 62.20 % T2–T4) (p < 0.05). However, in NSE under-expression group, there were more patients in advanced GC subgroup (n = 72, 37.70 %) than in early GC subgroup (n = 30, 13.80 %) (p < 0.05). Patients in NSE overexpression group survived longer than those in NSE under-expression group (p < 0.05). The level of expression of NSE significantly decreased with increase in TNM stage (p < 0.05). There was no significant difference in serum NSE level between GC patients and healthy control (p > 0.05). The results of the correlation analysis indicated that NSE levels were positively associated with GC. Conclusion: The results obtained in this study suggest that NSE could serve as a potential biomarker for GC. Keywords: Biomarker, Gastric cancer, Neuron-specific enolase, Overexpression, TNM stagin

Transcriptional Repressor NIR Functions in the Ribosome RNA Processing of Both 40S and 60S Subunits

BACKGROUND: NIR was identified as an inhibitor of histone acetyltransferase and it represses transcriptional activation of p53. NIR is predominantly localized in the nucleolus and known as Noc2p, which is involved in the maturation of the 60S ribosomal subunit. However, how NIR functions in the nucleolus remains undetermined. In the nucleolus, a 47S ribosomal RNA precursor (pre-rRNA) is transcribed and processed to produce 18S, 5.8S and 28S rRNAs. The 18S rRNA is incorporated into the 40S ribosomal subunit, whereas the 28S and 5.8S rRNAs are incorporated into the 60S subunit. U3 small nucleolar RNA (snoRNA) directs 18S rRNA processing and U8 snoRNA mediates processing of 28S and 5.8 S rRNAs. Functional disruption of nucleolus often causes p53 activation to inhibit cell proliferation. METHODOLOGY/PRINCIPAL FINDINGS: Western blotting showed that NIR is ubiquitously expressed in different human cell lines. Knock-down of NIR by siRNA led to inhibition of the 18S, 28S and 5.8S rRNAs evaluated by pulse-chase experiment. Pre-rRNA particles (pre-rRNPs) were fractionated from the nucleus by sucrose gradient centrifugation and analysis of the pre-RNPs components showed that NIR existed in the pre-RNPs of both the 60S and 40S subunits and co-fractionated with 32S and 12S pre-rRNAs in the 60S pre-rRNP. Protein-RNA binding experiments demonstrated that NIR is associated with the 32S pre-rRNA and U8 snoRNA. In addition, NIR bound U3 snoRNA. It is a novel finding that depletion of NIR did not affect p53 protein level but de-repressed acetylation of p53 and activated p21. CONCLUSIONS: We provide the first evidence for a transcriptional repressor to function in the rRNA biogenesis of both the 40S and 60S subunits. Our findings also suggested that a nucleolar protein may alternatively signal to p53 by affecting the p53 modification rather than affecting p53 protein level

Cathode–Electrolyte Interface Modification by Binder Engineering for High-Performance Aqueous Zinc-Ion Batteries

A stable cathode-electrolyte interface (CEI) is crucial for aqueous zinc-ion batteries (AZIBs), but it is less investigated. Commercial binder poly(vinylidene fluoride) (PVDF) is widely used without scrutinizing its suitability and cathode-electrolyte interface (CEI) in AZIBs. A water-soluble binder is developed that facilitated the in situ formation of a CEI protecting layer tuning the interfacial morphology. By combining a polysaccharide sodium alginate (SA) with a hydrophobic polytetrafluoroethylene (PTFE), the surface morphology, and charge storage kinetics can be confined from diffusion-dominated to capacitance-controlled processes. The underpinning mechanism investigates experimentally in both kinetic and thermodynamic perspectives demonstrate that the COO- from SA acts as an anionic polyelectrolyte facilitating the adsorption of Zn2+ ; meanwhile fluoride atoms on PTFE backbone provide hydrophobicity to break desolvation penalty. The hybrid binder is beneficial in providing a higher areal flux of Zn2+ at the CEI, where the Zn-Birnessite MnO2 battery with the hybrid binder exhibits an average specific capacity 45.6% higher than that with conventional PVDF binders; moreover, a reduced interface activation energy attained fosters a superior rate capability and a capacity retention of 99.1% in 1000 cycles. The hybrid binder also reduces the cost compared to the PVDF/NMP, which is a universal strategy to modify interface morphology

Pathological Tau From Alzheimer’s Brain Induces Site-Specific Hyperphosphorylation and SDS- and Reducing Agent-Resistant Aggregation of Tau in vivo

Neurofibrillary tangles (NFTs) made up of hyperphosphorylated tau are a histopathological hallmark of Alzheimer’s disease (AD) and related tauopathies. Hyperphosphorylation of tau is responsible for its loss of normal physiological function, gain of toxicity and its aggregation to form NFTs. Injection of misfolded tau seeds into mouse brain induces tau aggregation, but the nature of tau phosphorylation in pathologic tau seeded pathology is unclear. In the present study, we injected hyperphosphorylated and oligomeric tau isolated from AD brain (AD P-tau) into hippocampus of human tau transgenic mice and found that in addition to tau aggregation/pathology, tau was hyperphosphorylated at Ser202/Thr205, Thr212, Ser214, Thr217, Ser262, and Ser422 in AD P-tau injected hippocampus and at Ser422 in the contralateral hippocampus and in the ipsilateral cortex. AD P-tau-induced AD-like high molecular weight aggregation of tau that was SDS- and reducing agent-resistant and site-specifically hyperphosphorylated in the ipsilateral hippocampus. There were no detectable alterations in levels of tau phosphatases or tau kinases in AD P-tau-injected brains. Furthermore, we found that hyperphosphorylated tau was easier to be captured by AD P-tau and that aggregated tau was more difficult to be dephosphorylated than the non-aggregated tau by protein phosphatase 2A (PP2A). Based on these findings, we speculate that AD P-tau seeds hyperphosphorylated tau to form aggregates, which resist to the dephosphorylation by PP2A, resulting in hyperphosphorylation and pathology of tau

Adaptive optimal output regulation for wheel-legged robot Ollie: A data-driven approach

The dynamics of a robot may vary during operation due to both internal and external factors, such as non-ideal motor characteristics and unmodeled loads, which would lead to control performance deterioration and even instability. In this paper, the adaptive optimal output regulation (AOOR)-based controller is designed for the wheel-legged robot Ollie to deal with the possible model uncertainties and disturbances in a data-driven approach. We test the AOOR-based controller by forcing the robot to stand still, which is a conventional index to judge the balance controller for two-wheel robots. By online training with small data, the resultant AOOR achieves the optimality of the control performance and stabilizes the robot within a small displacement in rich experiments with different working conditions. Finally, the robot further balances a rolling cylindrical bottle on its top with the balance control using the AOOR, but it fails with the initial controller. Experimental results demonstrate that the AOOR-based controller shows the effectiveness and high robustness with model uncertainties and external disturbances

Incidence, clinical characteristics and prognosis of tumor lysis syndrome following B-cell maturation antigen-targeted chimeric antigen receptor-T cell therapy in relapsed/refractory multiple myeloma

Background aimsB-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T cell (CAR-T) therapy is used for refractory or relapsed multiple myeloma (r/r MM). However, CAR-T-related tumor lysis syndrome (TLS) has been observed. We aimed to elucidate the incidence, clinical and laboratory characteristics, and prognosis of CAR-T cell-related TLS.MethodsPatients (n=105) with r/r MM treated with BCMA-targeted CAR-T cell therapy were included. Patient characteristics, laboratory parameters, and clinical outcomes were assessed.ResultsEighteen (17.1%) patients developed TLS after BCMA-targeted CAR-T cell therapy. The median time till TLS onset was 8 days. Patients with TLS had steep rise in uric acid (UA), creatinine, and lactate dehydrogenase (LDH) within 6 days following CAR-T cell infusion and presented earlier and persistent escalation of cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-γ [IFN-γ], and ferritin levels). All 18 patients had cytokine release syndrome (CRS), of which 13 (72.2%) developed grade 3–4 CRS. Three of 18 patients (16.7%) developed immune effector cell-associated neurotoxicity syndrome (ICANS): two patients with grade 1 ICANS and one with grade 2 ICANS. TLS development had a negative effect on the objective response rate (77.8% in the TLS group vs. 95.4% in the non-TLS group, p<0.01). During the median follow-up of 15.1 months, the median PFS was poorer of patients with TLS (median: 3.4 months in the TLS group vs. 14.7 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.5 [95% confidence interval [CI] 1.5–8.5]). Also, TLS development exhibited significant effects on OS (median: 5.0 months in the TLS group vs. 39.8 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.7 [95% CI 1.3–10.3]). TLS was associated with a higher tumor burden, elevated baseline creatinine and UA levels, severe CRS, pronounced CAR-T cell expansion, and corticosteroid use.ConclusionTLS is a frequently observed CAR-T therapy complication and negatively influences clinical response and prognosis. Close monitoring for TLS should be implemented during CAR-T cell therapy, especially for those at high TLS risk