Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19

IntroductionTocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in tocilizumab efficacy may stem from the different immune responses of critical COVID-19 patients. In this study, we described two groups of immunologically distinct COVID-19 patients, based on their IL-6 response.MethodsWe prospectively enrolled critical COVID-19 patients, requiring oxygen support with a high flow nasal cannula or a mechanical ventilator, and analyzed their serial samples. An enzyme-linked immunosorbent assay and flow cytometry were used to evaluate the cytokine kinetics and cellular immune responses, respectively.ResultsA total of nine patients with critical COVID-19 were included. The high (n = 5) and low IL-6 (n = 4) groups were distinguished by their peak serum IL-6 levels, using 400 pg/mL as the cut-off value. Although the difference of flow cytometric data did not reach the level of statistical significance, the levels of pro-inflammatory cytokines and the frequencies of intermediate monocytes (CD14+CD16+), IFN-γ+ CD4+ or CD8+ T cells, and HLA-DR+PD-1+ CD4+ T cells were higher in the high IL-6 group than in the low IL-6 group.ConclusionThere were distinctive two groups of critical COVID-19 according to serum IL-6 levels having different degrees of cytokinemia and T-cell responses. Our results indicate that the use of immune modulators should be more tailored in patients with critical COVID-19

Interstitial Cystitis-Associated Urinary Metabolites Identified by Mass-Spectrometry Based Metabolomics Analysis

This study on interstitial cystitis (IC) aims to identify a unique urine metabolomic profile associated with IC, which can be defined as an unpleasant sensation including pain and discomfort related to the urinary bladder, without infection or other identifiable causes. Although the burden of IC on the American public is immense in both human and financial terms, there is no clear diagnostic test for IC, but rather it is a disease of exclusion. Very little is known about the clinically useful urinary biomarkers of IC, which are desperately needed. Untargeted comprehensive metabolomic profiling was performed using gas-chromatography/mass-spectrometry to compare urine specimens of IC patients or health donors. The study profiled 200 known and 290 unknown metabolites. The majority of the thirty significantly changed metabolites before false discovery rate correction were unknown compounds. Partial least square discriminant analysis clearly separated IC patients from controls. The high number of unknown compounds hinders useful biological interpretation of such predictive models. Given that urine analyses have great potential to be adapted in clinical practice, research has to be focused on the identification of unknown compounds to uncover important clues about underlying disease mechanisms

Printable Solid Electrolyte Interphase Mimic for Antioxidative Lithium Metal Electrodes

Despite the ever-growing demand for Li metals as next-generation Li battery electrodes, little attention has been paid to their oxidation stability, which must be achieved for practical applications. Here, a new class of printable solid electrolyte interphase mimic (pSEI) for antioxidative Li metal electrodes is presented. The pSEI (approximate to 1 mu m) is directly fabricated on a thin Li metal electrode (25 mu m) by processing solvent-free, UV polymerization-assisted printing, exhibiting its manufacturing simplicity and scalability. The pSEI is rationally designed to mimic a typical SEI comprising organic and inorganic components, in which ethoxylated trimethylolpropane triacrylate and diallyldimethylammonium bis(trifluoromethanesulfonyl)imide are introduced as an organic mimic (acting as a moisture-repellent structural framework) and inorganic mimic (allowing facile Li-ion transport/high Li+ transference number), respectively. Driven by the chemical/architectural uniqueness, the pSEI enables the thin Li metal electrode to show exceptional antioxidation stability and reliable full cell performance after exposure to humid environments

Critical role of elemental copper for enhancing conversion kinetics of sulphur cathodes in rechargeable magnesium batteries

Despite recent remarkable progress associated with the electrolyte, understanding of the reaction mechanism of magnesium-sulphur batteries is not yet mature. In particular, the lethargic redox reactions involved in the electrochemical conversion of sulphur and MgS in the cathode need to be overcome. Here, we unveil the reaction mechanism involving copper (Cu) metal, a common current collector for electrodes in rechargeable batteries. Specifically, Cu can undergo chemical reactions with polysulphides produced from the reaction of sulphur or MgS with Mg2+. Throughout the conversion reaction, these Cu-polysulphide reactions play a critical role to improve reaction kinetics markedly. The present investigation opens new avenues to the emerging Mg-S battery technology, that is, the incorporation of various metals that can speed up the conversion reaction between sulphur and Mg.

Epidermal growth factor expression as a predictor of chemotherapeutic resistance in muscle-invasive bladder cancer

Abstract Background Epidermal growth factor receptor (EGFR) overexpression is believed to be associated with bladder cancer (BC) progression and poor clinical outcomes. In vivo studies have linked EGFR subcellular trafficking and chemo-resistance to cisplatin-based chemotherapies. This has not been studied in the clinical adjuvant setting. We aimed to investigate the prognostic significance of EGFR expression in patients receiving cisplatin-based adjuvant chemotherapy following radical cystectomy for advanced BC. Methods The database from the Urology and Nephrology Center at Mansoura University was reviewed. BC patients who were treated with radical cystectomy and adjuvant chemotherapy for adverse pathological features or node positive disease were identified. Patients who underwent palliative cystectomy, had histological diagnoses other than pure urothelial carcinoma, or received adjuvant radiotherapy were excluded from the study. Immunohistochemical staining for EGFR expression was performed on archived bladder specimens. The following in vitro functional analyses were performed to study the relationship of EGFR expression and chemoresponse. Results The study included 58 patients, among which the mean age was 57 years old. Majority of patients had node positive disease (n = 53, 91%). Mean follow up was 26.61 months. EGFR was overexpressed in 25 cystectomy specimens (43%). Kaplan-Meier analysis revealed that EGFR over-expression significantly correlated with disease recurrence (p = 0.021). Cox proportional hazard modeling identified EGFR overexpression as an independent predictor for disease recurrence (p = 0.04). Furthermore, in vitro experiments demonstrated that inhibition of EGFR may sensitize cellular responses to cisplatin. Conclusions Our findings suggest that EGFR overexpression is associated with disease recurrence following adjuvant chemotherapy for advanced BC. This may aid in patient prognostication and selection prior to chemotherapeutic treatment for BC

Magnesium Anode Pretreatment Using a Titanium Complex for Magnesium Battery

Although magnesium batteries have received a great deal of attention as a promising power source, the native oxide layer on the Mg surface significantly impedes practical applications, because of the sluggish kinetic behavior of Mg-ion deposition and dissolution. Here, a new approach to improve electrochemical reactivity of Mg anode is proposed, based on chemical pretreatment of the Mg anode using a titanium complex, Ti­(TFSI)₂Cl₂, that effectively removes the native oxide layer on the Mg anode surface. The pretreatment of the Mg anode by Ti­(TFSI)₂Cl₂ remarkably decreases the binding affinity between Mg and O via the formation of a multicoordinate complex (Mg–O–Ti). Thereafter, a series of chemical reactions cleave the Mg–O bonds, resulting in a fresh Mg surface. This creates a cell comprised of the Ti­(TFSI)₂Cl₂-pretreated Mg anode, glyme-based electrolytes, and cathode material that exhibits reversible electrochemical behavior at the electrode/electrolyte interface, resulting in practical applicability and good electrochemical performance