No abstract

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis, several of which are currently in clinical trials. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis.

Formamidinium-lead-iodide (FAPbI3)-based perovskites with bandgap below 1.55 eV are of interest for photovoltaics in view of their close-to-ideal bandgap. Record-performance FAPbI3-based solar cells have relied on fabrication via the sequential-deposition method; however, these devices exhibit unstable output under illumination due to the difficulty of incorporating cesium cations (stabilizer) in sequentially deposited films. Here we devise a perovskite seeding method that efficiently incorporates cesium and beneficially modulates perovskite crystallization. First, perovskite seed crystals are embedded in the PbI2 film. The perovskite seeds serve as cesium sources and act as nuclei to facilitate crystallization during the formation of perovskite. Perovskite films with perovskite seeding growth exhibit a lowered trap density, and the resulting planar solar cells achieve stabilized efficiency of 21.5% with a high open-circuit voltage of 1.13 V and a fill factor that exceeds 80%. The Cs-containing FAPbI3-based devices show a striking improvement in operational stability and retain 60% of their initial efficiency after 140 h operation under one sun illumination.

The past two decades of vigorous interdisciplinary approaches has seen tremendous breakthroughs in both scientific and technological developments of bulk-heterojunction organic solar cells (OSCs) based on nanocomposites of π-conjugated organic semiconductors. Because of their unique functionalities, the OSC field is expected to enable innovative photovoltaic applications that can be difficult to achieve using traditional inorganic solar cells: OSCs are printable, portable, wearable, disposable, biocompatible, and attachable to curved surfaces. The ultimate objective of this field is to develop cost-effective, stable, and high-performance photovoltaic modules fabricated on large-area flexible plastic substrates via high-volume/throughput roll-to-roll printing processing and thus achieve the practical implementation of OSCs. Recently, intensive research efforts into the development of organic materials, processing techniques, interface engineering, and device architectures have led to a remarkable improvement in power conversion efficiencies, exceeding 11%, which has finally brought OSCs close to commercialization. Current research interests are expanding from academic to industrial viewpoints to improve device stability and compatibility with large-scale printing processes, which must be addressed to realize viable applications. Here, both academic and industrial issues are reviewed by highlighting historically monumental research results and recent state-of-the-art progress in OSCs. Moreover, perspectives on five core technologies that affect the realization of the practical use of OSCs are presented, including device efficiency, device stability, flexible and transparent electrodes, module designs, and printing techniques.

Control over carrier type and doping levels in semiconductor materials is key for optoelectronic applications. In colloidal quantum dots (CQDs), these properties can be tuned by surface chemistry modification, but this has so far been accomplished at the expense of reduced surface passivation and compromised colloidal solubility; this has precluded the realization of advanced architectures such as CQD bulk homojunction solids. Here we introduce a cascade surface modification scheme that overcomes these limitations. This strategy provides control over doping and solubility and enables n-type and p-type CQD inks that are fully miscible in the same solvent with complete surface passivation. This enables the realization of homogeneous CQD bulk homojunction films that exhibit a 1.5 times increase in carrier diffusion length compared with the previous best CQD films. As a result, we demonstrate the highest power conversion efficiency (13.3%) reported among CQD solar cells.

The electrochemical carbon dioxide reduction reaction (CORR) produces diverse chemical species. Cu clusters with a judiciously controlled surface coordination number (CN) provide active sites that simultaneously optimize selectivity, activity, and efficiency for CORR. Here we report a strategy involving metal-organic framework (MOF)-regulated Cu cluster formation that shifts CO electroreduction toward multiple-carbon product generation. Specifically, we promoted undercoordinated sites during the formation of Cu clusters by controlling the structure of the Cu dimer, the precursor for Cu clusters. We distorted the symmetric paddle-wheel Cu dimer secondary building block of HKUST-1 to an asymmetric motif by separating adjacent benzene tricarboxylate moieties using thermal treatment. By varying materials processing conditions, we modulated the asymmetric local atomic structure, oxidation state and bonding strain of Cu dimers. Using electron paramagnetic resonance (EPR) and in situ X-ray absorption spectroscopy (XAS) experiments, we observed the formation of Cu clusters with low CN from distorted Cu dimers in HKUST-1 during CO electroreduction. These exhibited 45% CH faradaic efficiency (FE), a record for MOF-derived Cu cluster catalysts. A structure-activity relationship was established wherein the tuning of the Cu-Cu CN in Cu clusters determines the CORR selectivity.

Background: HNF4␣ is a key factor regulating hepatocyte differentiation and liver-specific functions. Results: Acute disruption of HNF4␣ in the adult liver causes rapid hepatocyte proliferation through direct and indirect control of multiple pathways. Conclusion: HNF4␣ is necessary to maintain the differentiated state of hepatocytes in adult liver. Significance: HNF4␣ expression maintains normal liver function, and its loss stimulates hepatocytes proliferation, possibly leading to cancer.

The molecular ordering of aqueous conducting polymers is controlled using a rational method. By introducing various ionic liquids, which have designed electrostatic interactions to PEDOT:PSS solutions, the evolution of the molecular ordering of the PEDOT is manipulated. Consequently, highly ordered nanostructures are achieved with a reduced π-π stacking distance of ≈3.38 Å and, thus, a maximum σ of ≈2100 S cm .