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The study and application of transition metal hydrides (TMHs) has been an active area of chemical research since the early 1960s 1 , for energy storage, through the reduction of protons to generate hydrogen 2 , 3 , and for organic synthesis, for the functionalization of unsaturated C–C, C–O and C–N bonds 4 , 5 . In the former instance, electrochemical means for driving such reactivity has been common place since the 1950s 6 but the use of stoichiometric exogenous organic- and metal-based reductants to harness the power of TMHs in synthetic chemistry remains the norm. In particular, cobalt-based TMHs have found widespread use for the derivatization of olefins and alkynes in complex molecule construction, often by a net hydrogen atom transfer (HAT) 7 . Here we show how an electrocatalytic approach inspired by decades of energy storage research can be made use of in the context of modern organic synthesis. This strategy not only offers benefits in terms of sustainability and efficiency but also enables enhanced chemoselectivity and distinct, tunable reactivity. Ten different reaction manifolds across dozens of substrates are exemplified, along with detailed mechanistic insights into this scalable electrochemical entry into Co–H generation that takes place through a low-valent intermediate. A perspective is given on how an electrocatalytic approach, inspired by decades of energy storage studies, can be used in the context of efficient cobalt-hydride generation with a variety of applications in modern organic synthesis.

Electrochemical research often requires stringent combinations of experimental parameters that are demanding to manually locate. Recent advances in automated instrumentation and machine-learning algorithms unlock the possibility for accelerated studies of electrochemical fundamentals via high-throughput, online decision-making. Here we report an autonomous electrochemical platform that implements an adaptive, closed-loop workflow for mechanistic investigation of molecular electrochemistry. As a proof-of-concept, this platform autonomously identifies and investigates an EC mechanism, an interfacial electron transfer ( E step) followed by a solution reaction ( C step), for cobalt tetraphenylporphyrin exposed to a library of organohalide electrophiles. The generally applicable workflow accurately discerns the EC mechanism’s presence amid negative controls and outliers, adaptively designs desired experimental conditions, and quantitatively extracts kinetic information of the C step spanning over 7 orders of magnitude, from which mechanistic insights into oxidative addition pathways are gained. This work opens opportunities for autonomous mechanistic discoveries in self-driving electrochemistry laboratories without manual intervention. Electrochemical research often requires stringent combinations of experimental parameters that are demanding to manually locate. Here the authors report an autonomous electrochemical platform that implements an adaptive, closed-loop workflow for mechanistic investigation of molecular electrochemistry.

Oxidative addition is a fundamental step in organometallic chemistry and plays a crucial role in catalytic processes, leading to various organic transformations. Despite significant advances in its synthetic applications, the mechanistic understanding of this step remains limited especially for first row transition metals. In this dissertation, comprehensive mechanistic studies of oxidative addition reactions for four different organometallic systems were conducted. A combination of electroanalytical and statistical modeling techniques was employed to investigate key mechanistic features such as substrate/ligand effects and transition state geometry. The dissertation is divided into six chapters, with the first chapter providing an overview of the oxidative addition mechanisms and the techniques used in the studies. The following chapters focus on the mechanistic development of four specific oxidative addition processes, including redox catalysis of benzyl bromides by a bis-ligated cobalt(I) complex (Chapter 2), oxidative addition of benzyl halides by low-valent manganese, iron, cobalt, and nickel complexes (Chapter 3), oxidative addition of allyl electrophiles by cobalt(I) and nickel(I) complexes (Chapter 4), and oxidative addition of aryl iodides by nickel(I) complexes (Chapter 5). The results presented in this dissertation reveal the complexity of oxidative addition mechanisms, which are metal, ligand, and substrate-dependent, and hence require sophisticated analysis. The studies provide a better understanding of this fundamental organometallic process. In the final chapter, potential future directions for research were discussed.

Background: COVID-19 is a global pandemic that is affecting more than 200 countries worldwide. Efficient diagnosis and treatment are crucial to combat the disease. Computer-interpretable guidelines (CIGs) can aid the broad global adoption of evidence-based diagnosis and treatment knowledge. However, currently, no internationally shareable CIG exists. Objective: The aim of this study was to establish a rapid CIG development and dissemination approach and apply it to develop a shareable CIG for COVID-19. Methods: A 6-step rapid CIG development and dissemination approach was designed and applied. Processes, roles, and deliverable artifacts were specified in this approach to eliminate ambiguities during development of the CIG. The Guideline Definition Language (GDL) was used to capture the clinical rules. A CIG for COVID-19 was developed by translating, interpreting, annotating, extracting, and formalizing the Chinese COVID-19 diagnosis and treatment guideline. A prototype application was implemented to validate the CIG. Results: We used 27 archetypes for the COVID-19 guideline. We developed 18 GDL rules to cover the diagnosis and treatment suggestion algorithms in the narrative guideline. The CIG was further translated to object data model and Drools rules to facilitate its use by people who do not employ the non-openEHR archetype. The prototype application validated the correctness of the CIG with a public data set. Both the GDL rules and Drools rules have been disseminated on GitHub. Conclusions: Our rapid CIG development and dissemination approach accelerated the pace of COVID-19 CIG development. A validated COVID-19 CIG is now available to the public.

The investigation of a solid surface structure is an important field of research in science. To understand chemical adsorption or catalytic processes on the surface, more detailed investigations of the properties of solid surfaces are needed. This dissertation addresses the theory and applications of an important surface analysis technique: x-ray photoelectron diffraction (XPD) (126). A full multiple-scattering scheme for the calculations of x-ray electron diffraction spectra from a surface cluster is described. This strategy forms the basis of the concentric-shell algorithm. In that scheme, the calculations are rendered tractable by the division of the cluster into concentric shells centered on the photoemitter (45). X-ray photoelectron diffraction will he used to firmly establish the adsorption geometry of CH$\\sb3$S/Ni(111) and CH$\\sb3$S/Ni(001) by comparing the experimentally measured photoelectron angular distribution with theoretically calculated distribution for various trial structures. The key to success for this strategy is to have effective methods for accurately calculating the structures of the adsorbed species from the angular distributions of the photoelectrons. This method is called a full multiple-scattering (FMS) algorithm which was proposed by D. K. Saidin et al. (45). We also address the structural analysis of S on Ni(111) and Ni(001) by computer simulating the angle-resolved photoemission process. The theoretical photoemission angular dependent spectrum was compared with the experimental photoemission angular dependent spectrum from atomic S which is known to adsorb in the FCC hollow site on Ni(111) and in the four fold hollow site on Ni(001) (131). This work was initially motivated by the desire to determine the geometrical structure of these species and also to compare the spectrum obtained by experiment and theory to test our theory and program. Photoelectron diffraction from S 2p core levels has been used to determine the adsorption site and orientation of sulfur and methyl thiolate (CH$\\sb3$S) on Ni(111) and Ni(001) (8). The purpose of study S/Ni(111) is to determine the perpendicular distance of sulfur to the substrate. At 150K, CH$\\sb3$S adsorbs in the FCC hollow site on Ni(111) and in the four fold site in Ni(001). The C-S bond is tilted from the surface normal on Ni(111) and is normal to the surface on Ni(001). Therefore, the purpose for studying these species is to determine the bond length of carbon and sulfur, the perpendicular distance of sulfur to the substrate as well as to determine the orientation of them. Upon annealing to 250K, CH$\\sb3$S changes adsorptional orientation on Ni(111). The C-S bond becomes orientated along the surface normal. The purpose of studying this species is, therefore, to determine the bond length of carbon and sulfur as well as the perpendicular distance of sulfur to the substrate. In recent studies, the CH$\\sb3$S/Ni(111) is considered to be a reconstructed surface (139). The investigation of these suggested models are also addressed in the dissertation. As is the case with low energy electrons employed in other surface probes, photoelectrons scatter strongly form atoms within the sample. Consequently, the accurate computer simulation of photoelectron diffraction pattern is a challenge of multiple-scattering theory. The excellent agreement between the experimental data and theoretical data calculated in this work suggests that the calculation of the angular distribution can adequately describe the experiment and offers a powerful tool for establishing the nature of adsorbed species on chemically heterogeneous surface.

Obesity is the most common nutritional disorder worldwide and is associated with dyslipidemia and atherosclerotic cardiovascular disease. The hallmark of dyslipidemia in obesity is low high density lipoprotein (HDL) cholesterol (HDL-C) levels. Moreover, the quality of HDL is also changed in the obese setting. However, there are still some disputes on the explanations for this phenomenon. There is increasing evidence that adipose tissue, as an energy storage tissue, participates in several metabolism activities, such as hormone secretion and cholesterol efflux. It can influence overall reverse cholesterol transport and plasma HDL-C level. In obesity individuals, the changes in morphology and function of adipose tissue affect plasma HDL-C levels and HDL function, thus, adipose tissue should be the main target for the treatment of HDL metabolism in obesity. In this review, we will summarize the cross-talk between adipocytes and HDL related to cardiovascular disease and focus on the new insights of the potential mechanism underlying obesity and HDL dysfunction.

In the field of high-altitude operations, the frequent occurrence of fall accidents is usually closely related to safety measures such as the incorrect use of safety locks and the wrong installation of safety belts. At present, the manual inspection method cannot achieve real-time monitoring of the safety status of the operators and is prone to serious consequences due to human negligence. This paper designs a new type of high-altitude operation safety device based on the STM32F103 microcontroller. This device integrates ultra-wideband (UWB) ranging technology, thin-film piezoresistive stress sensors, Beidou positioning, intelligent voice alarm, and intelligent safety lock. By fusing five modes, it realizes the functions of safety status detection and precise positioning. It can provide precise geographical coordinate positioning and vertical ground distance for the workers, ensuring the safety and standardization of the operation process. This safety device adopts multi-modal fusion high-altitude operation safety monitoring technology. The UWB module adopts a bidirectional ranging algorithm to achieve centimeter-level ranging accuracy. It can accurately determine dangerous heights of 2 m or more even in non-line-of-sight environments. The vertical ranging upper limit can reach 50 m, which can meet the maintenance height requirements of most transmission and distribution line towers. It uses a silicon carbide MEMS piezoresistive sensor innovatively, which is sensitive to stress detection and resistant to high temperatures and radiation. It builds a Beidou and Bluetooth cooperative positioning system, which can achieve centimeter-level positioning accuracy and an identification accuracy rate of over 99%. It can maintain meter-level positioning accuracy of geographical coordinates in complex environments. The development of this safety device can build a comprehensive and intelligent safety protection barrier for workers engaged in high-altitude operations.

The large energy loss (Eloss) is one of the main obstacles to further improve the photovoltaic performance of organic solar cells (OSCs), which is closely related to the charge transfer (CT) state. Herein, ternary donor alloy strategy is used to precisely tune the energy of CT state (ECT) and thus the Eloss for boosting the efficiency of OSCs. The elevated ECT in the ternary OSCs reduce the energy loss for charge generation (ΔECT), and promote the hybridization between localized excitation state and CT state to reduce the nonradiative energy loss (ΔEnonrad). Together with the optimal morphology, the ternary OSCs afford an impressive power conversion efficiency of 19.22% with a significantly improved open‐circuit voltage (Voc) of 0.910 V without sacrificing short‐cicuit density (Jsc) and fill factor (FF) in comparison to the binary ones. This contribution reveals that precisely tuning the ECT via donor alloy strategy is an efficient way to minimize Eloss and improve the photovoltaic performance of OSCs. Donor alloy strategy is proposed to tune chare transfer (CT) state erergy and thus Eloss for boosting organic solar cells (OSCs) efficiency. Together with optimal morphology, ternary OSCs deliver an outstanding efficiency of 19.22% with significantly improved open‐circuit voltage (Voc) of 0.910 V, the highest value for over 19% efficiency OSCs.

Pancreatic beta cells are of great interest for biomedical research and regenerative medicine. Here we show the conversion of human fibroblasts towards an endodermal cell fate by employing non-integrative episomal reprogramming factors in combination with specific growth factors and chemical compounds. On initial culture, converted definitive endodermal progenitor cells (cDE cells) are specified into posterior foregut-like progenitor cells (cPF cells). The cPF cells and their derivatives, pancreatic endodermal progenitor cells (cPE cells), can be greatly expanded. A screening approach identified chemical compounds that promote the differentiation and maturation of cPE cells into functional pancreatic beta-like cells (cPB cells) in vitro . Transplanted cPB cells exhibit glucose-stimulated insulin secretion in vivo and protect mice from chemically induced diabetes. In summary, our study has important implications for future strategies aimed at generating high numbers of functional beta cells, which may help restoring normoglycemia in patients suffering from diabetes. Insulin-producing pancreatic beta cells, generated in vitro , could lead to new anti-diabetic therapies. Here, Zhu et al . convert human fibroblasts into endodermal progenitors that differentiate in vitro into glucose-responsive beta-like cells that, following transplantation in mice, protect from diabetes.

Autophagy receptor p62/SQSTM1 promotes the assembly and removal of ubiquitylated proteins by forming p62 bodies and mediating their encapsulation in autophagosomes. Here we show that under nutrient-deficient conditions, cellular p62 specifically undergoes acetylation, which is required for the formation and subsequent autophagic clearance of p62 bodies. We identify K420 and K435 in the UBA domain as the main acetylation sites, and TIP60 and HDAC6 as the acetyltransferase and deacetylase. Mechanically, acetylation at both K420 and K435 sites enhances p62 binding to ubiquitin by disrupting UBA dimerization, while K435 acetylation also directly increases the UBA-ubiquitin affinity. Furthermore, we show that acetylation of p62 facilitates polyubiquitin chain-induced p62 phase separation. Our results suggest an essential role of p62 acetylation in the selective degradation of ubiquitylated proteins in cells under nutrient stress, by specifically regulating the assembly of p62 bodies. The autophagy receptor p62 mediates the assembly and removal of ubiquitylated protein aggregates by forming p62 bodies. Here, the authors identify an acetylation-dependent mechanism that regulates formation and autophagic clearance of p62 bodies under nutrient-deficient conditions.