Bimetallic Organic Frameworks via In Situ Solvothermal Sol-Gel-Crystal and Sol-Crystal Transformation as Durable Electrocatalysts for Oxygen Reduction Reaction.

The in situ solvothermal conversion of metal-organic gels (MOGs) to crystalline metal-organic frameworks (MOFs) represents a versatile and ingenious strategy that has been employed for the synthesis of MOF materials with specific morphologies, high yield, and improved functional properties. Herein, we have adopted an in situ solvothermal conversion of bimetallic MOGs to crystalline bimetallic MOFs with the aim of introducing a redox-active metal heterogeneity into the monometallic counterpart. The formation of bimetallic NiZn-MOF and CoZn-MOF via in situ solvothermal sol-gel-crystal and sol-crystal transformation is found to depend on the solvent systems used. The sol-to-gel-to-crystal transformation of NiZn-MOF via the formation of NiZn-MOG is found to occur through the gradual disruption of gel fibers leading to subsequent formation of microcrystals and single crystals of NiZn-MOF. These bimetallic MOFs and MOGs serve as promising electrocatalysts for oxygen reduction reaction (ORR) with an excellent methanol tolerance property, which can be attributed to the enhanced mass and charge transfer, higher oxygen vacancies, and bimetallic synergistic interactions among the heterometals. This work demonstrates a convenient strategy for producing bimetallic MOGs to MOFs through the introduction of a redox-active metal heterogeneity in the inorganic hybrid functional materials for fundamental and applied research. Our results connect MOGs and MOFs which have been regarded as having opposite physical states, that is, soft vs hard, and provide promising structural correlation between MOGs and MOFs at the molecular level.

Effect of Cooperative Redox Property and Oxygen Vacancies on Bifunctional OER and HER Activities of Solvothermally Synthesized CeO2/CuO Composites.

Herein, we report the synthesis of the CeO2/CuO composite as a bifunctional oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) electrocatalyst in a basic medium. The electrocatalyst with an optimum 1:1 CeO2/CuO shows low OER and HER overpotentials of 410 and 245 mV, respectively. The Tafel slopes of 60.2 and 108.4 mV/dec are measured for OER and HER, respectively. More importantly, the 1:1 CeO2/CuO composite electrocatalyst requires only a 1.61 V cell voltage to split water to achieve 10 mA/cm2 in a two-electrode cell. The role of oxygen vacancies and the cooperative redox activity at the interface of the CeO2 and CuO phases is explained in the light of Raman and XPS studies, which play the determining factor for the enhanced bifunctional activity of the 1:1 CeO2/CuO composite. This work provides guidance for the optimization and design of a low-cost alternative electrocatalyst to replace the expensive noble-metal-based electrocatalyst for overall water splitting.

In Situ Grown Mn(II) MOF upon Nickel Foam Acts as a Robust Self-Supporting Bifunctional Electrode for Overall Water Splitting: A Bimetallic Synergistic Collaboration Strategy.

The design of highly efficient, cost-effective non-noble metal-based electrocatalysts with superior stability for overall water splitting (OWS) reactions is of great importance as well as of immense challenge for the upcoming sustainable and green energy conversion technologies. Herein, a convenient and simple in situ solvothermal method has been adopted to fabricate a self-supported, binder-free 3D electrode (Mn-MOF/NF) by the direct growth of a newly synthesized carboxylate-based pristine Mn(II)-metal-organic framework (Mn-MOF) upon the conducting substrate nickel foam (NF). The binder-free Mn-MOF/NF electrode exhibits excellent performances toward OWS with ultralow overpotentials of 280 mV@20 mA cm-2 for the oxygen evolution reaction (OER) and 125 mV@10 mA cm-2 for the hydrogen evolution reaction (HER) with remarkable durability. Mn-MOF/NF can also attain a current density of 10 mA cm-2 with a low cell voltage of 1.68 V in a 0.1 M KOH solution in a two-electrode system for OWS. The direct growth of nonconducting electroactive Mn-MOF materials upon conducting substrate NF provides an excellent mass transport of the electrolyte with a relatively low contact resistance due to the strong catalyst-substrate contact and enhances the efficient electron transport for OWS. The redox chemical etching of the self-sacrificial substrate NF during solvothermal synthesis introduces redox-active Ni2+ in Mn-MOF/NF. Thus, the excellent OWS electrocatalytic activity can mainly be attributed to the bimetallic synergistic collaboration of the two redox active metal centers (Mn2+ and Ni2+) along with the excellent support surface of NF, which provides a high specific surface area and maximum utilization of the electroactive metal ion sites by preventing the self-aggregation of the active sites. The Mn-MOF/NF electrode also exhibits superb stability and durability for a prolonged time throughout the multiple cycles of full water splitting reactions. Therefore, this work elucidates a convenient and smart approach for constructing MOF-based bifunctional electrocatalysts for OWS.

Pembrolizumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, multi-arm, non-randomised, multicentre, phase 2 trial.

BACKGROUND: Pembrolizumab (PD-1 inhibitor) and cetuximab (EGFR inhibitor) are active as single agents and in combination with cytotoxic chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Given each drug's single agent activity and unique mechanism of action, we aimed to evaluate the anti-tumour activity of PD-1 blockade with EGFR inhibition in recurrent or metastatic HNSCC. METHODS: This study is an open-label, non-randomised, multi-arm, phase 2 trial done at four academic centres in the USA. Participants were required to have platinum-resistant or platinum-ineligible, recurrent or metastatic HNSCC, be at least 18 years old, have an Eastern Cooperative Oncology Group performance status 0-1, have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and to have received no previous immunotherapy or EGFR inhibition. All participants received pembrolizumab 200 mg intravenously every 3 weeks, combined with an initial loading dose of cetuximab 400 mg/m2 intravenously followed by 250 mg/m2 intravenously weekly (21 day cycle). The primary endpoint was overall response rate defined as the proportion of participants with a partial or complete responses (per RECIST version 1.1) by 6 months in the intention-to-treat population. The safety population included all participants who received at least one dose of pembrolizumab. Herein, the final analysis of cohort 1 (no previous PD-1, PD-L1, or EGFR inhibition for recurrent or metastatic HNSCC) is reported. Three additional cohorts (two for participants with a previous response to immunotherapy followed by relapse or progression, with or without previous cetuximab exposure, and one for cutaneous HNSCC) will be reported separately once fully accrued. This study is registered with ClinicalTrials.gov, NCT03082534, and remains open as the three additional cohorts are actively accruing participants. FINDINGS: Between March 22, 2017, and July 16, 2019, 33 participants were enrolled to cohort 1. All 33 participants received at least one dose of pembrolizumab. Median follow-up duration was 7·3 months (IQR 3·9-10·9). By 6 months, the overall response rate was 45% (95% CI 28-62), with 15 of 33 participants achieving a partial response. The most common grade 3-4 treatment-related adverse event was oral mucositis (three [9%] of 33 participants), and serious treatment-related adverse events occurred in five (15%) participants. No treatment-related deaths occurred. INTERPRETATION: Pembrolizumab combined with cetuximab shows promising clinical activity for recurrent or metastatic HNSCC, and merits further investigation. FUNDING: Merck Sharp & Dohme.

Tuning the morphology of CeO2 nanostructures using a template-free solvothermal process and their oxygen reduction reaction activity.

In fuel cells, the oxygen reduction reaction (ORR) at the cathode plays a crucial role in their performance. High cost, low abundance, catalyst poisoning, and poor durability of the pioneering ORR catalyst Pt make it less desirable for commercial fuel cells. Herein, we demonstrate a greener process to synthesize CeO2 nanostructures by varying reaction parameters in a single-step solvothermal route and provide a detailed mechanism for the formation of CeO2 nanostructures with different shapes. The shape and size of the CeO2 nanostructures such as hollow/solid spheres, triangular flakes, nanotubes, and flower-like structures result in a strong effect on their ORR activity. A normalized effect of effective surface area and oxygen vacancies in CeO2 nanostructures is found to govern the ORR activity order. Among the CeO2 nanostructures, hollow spheres exhibit the best ORR activity with a four-electron reduction pathway. Moreover, they show comparable ORR activity and outstanding stability as well as methanol fuel tolerance and are a substitute for Pt/C.

2D MOFs with Ni(II), Cu(II), and Co(II) as Efficient Oxygen Evolution Electrocatalysts: Rationalization of Catalytic Performance vs Structure of the MOFs and Potential of the Redox Couples.

Earth-abundant transition-metal-based metal-organic frameworks (MOFs) are of immense interest for the development of efficient and durable heterogeneous water splitting electrocatalysts. This repot explores the design of two-dimensional (2D) MOFs with redox-active metal centers (Ni(II), Co(II), and Cu(II)) containing two types of electron-rich linkers such as bis(5-azabenzimidazole), linear L1 and angular L2, and aromatic dicarboxylates. The electron-rich linkers are considered to stabilize the higher oxidation state of the redox-active metal centers in the course of the electrocatalytic oxygen evolution reaction (OER) process. The 2D MOFs of L1 and L2 with Co(II) (1 and 3) and Ni(II) (2 and 4) have been produced via the conventional hydrothermal synthesis, while the MOFs of Cu(II) (Cu@1 and Cu@3) are obtained by the postsynthetic transmetallation reaction of MOFs 1 and 3. The electrocatalytic OER activities of the six MOFs have been studied to explore the influence of the redox potential of the transition-metal quasi-reversible couples and the coordination environment around the redox-active metal centers in the electrocatalytic activity. The lowest overpotential of 370 mV exhibited by MOF 2 with the highest current density and TOF value indicates the importance of the presence of coordinated water molecules and the lowest redox potential value of the most favorable quasi-reversible couple Ni+2/Ni+3. These catalysts exhibit a remarkable stability up to 1000 OER cycles. These studies pave the way for the design of MOF materials toward the development of a promising heterogeneous OER electrocatalyst.

Isostructural NiII Metal-Organic Frameworks (MOFs) for Efficient Electrocatalysis of Oxygen Evolution Reaction and for Gas Sorption Properties.

Design and synthesis of stable, active and cost-effective electrocatalyst for water splitting applications is an emerging area of research, given the depletion of fossil fuels. Herein, two isostructural NiII redox-active metal-organic frameworks (MOFs) containing flexible tripodal trispyridyl ligand (L) and linear dicarboxylates such as terephthalate (TA) and 2-aminoterphthalate (H2 NTA) are studied for their catalytic activity in oxygen evaluation reaction (OER). The 2D-layered MOFs form 3D hydrogen bonded frameworks containing one-dimensional hydrophilic channels that are filled with water molecules. The electrochemical studies reveal that MOFs display an efficient catalytic activity towards oxygen evolution reaction in alkaline conditions with an overpotential as low as 356 mV. Further, these 2D-MOFs exhibit excellent ability to adsorb water vapor (180-230 cc g-1 at 273 K) and CO2 (33 cc g-1 at 273 K). The presence of hydrophilic functionality in the frameworks was found to significantly enhance the electrocatalytic activity as well as H2 O sorption.

Cardiovascular Risk Factor Reduction in First Responders Resulting From an Individualized Lifestyle and Blood Test Program: A Randomized Controlled Trial.

OBJECTIVE: We tested the hypothesis that a lifestyle program would improve risk factors linked to cardiovascular disease (CVD) in first responders. METHODS: A 1-year cluster-randomized controlled clinical trial in 10 cities. Participants were 175 first responders, with increased waist circumference and/or low levels of large (α1) high-density lipoprotein (HDL) particles. The intervention group received personalized online tools and access to telephonic coaching sessions. RESULTS: At 1 year the intervention significantly reduced body weight (P = 0.004) and waist circumference (P = 0.002), increased α1 HDL (P = 0.01), and decreased triglyceride (P = 0.005) and insulin concentrations (P = 0.03). Program adherence was associated with weight loss (P = 0.0005) and increases in α1 HDL (P = 0.03). CONCLUSIONS: In first responders, a personalized lifestyle intervention significantly improved CVD risk factors in proportion to program adherence. Changes in large HDL particles were more sensitive indicators of lifestyle changes than HDL-cholesterol measurement. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT03322046.

Probing the role of ortho-dihydroxy groups on lysozyme fibrillation.

Changes in the microenvironment of Trp in lysozyme are one of the key factors in the fibrillation process. Gallic acid through the oxidation of o-dhydroxy moiety into quinone was shown to inhibit lysozyme fibrillation by stabilizing the Trp microregions [Konar et al., Int. J. Biol. Macromol. 103 (2017) 1224-1231]. In this article we compare the inhibitory effects of several gallic acid-based phenolic compounds. The results show that pyrogallol, and 3,4-dihydroxy benzoic acid, each containing the o-dihydroxy moiety exhibited a significant inhibitory effect on lysozyme fibrillation which is further supported by docking studies. Interestingly, the inhibitory effect of pyrogallol is almost similar to that observed for gallic acid. The lower inhibitory effect of 3,5-dihydroxy benzoic acid and 4-hydroxy benzoic acid corroborates this finding as neither of the compounds can be transformed into quinone intermediates. The ineffectiveness of benzoic acid towards fibrillation questions the role of the COOH group in the inhibition. The IC20 values determined show the similar trends. Results of the Thioflavin T binding assay and parameters from the docking studies reveal a strong correlation based on which a relation has been obtained that could be used to identify potential polyphenol based inhibitors by considering docking studies alone.