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New drugs for visceral leishmaniasis that are safe, low cost, and adapted to the field are urgently required. Despite concerted efforts over the last several years, the number of new chemical entities that are suitable for clinical development for the treatment of Leishmania remains low. Here, we describe the discovery and preclinical development of DNDI-6174, an inhibitor of Leishmania cytochrome bc1 complex activity that originated from a phenotypically identified pyrrolopyrimidine series. This compound fulfills all target candidate profile criteria required for progression into preclinical development. In addition to good metabolic stability and pharmacokinetic properties, DNDI-6174 demonstrates potent in vitro activity against a variety of Leishmania species and can reduce parasite burden in animal models of infection, with the potential to approach sterile cure. No major flags were identified in preliminary safety studies, including an exploratory 14-day toxicology study in the rat. DNDI-6174 is a cytochrome bc1 complex inhibitor with acceptable development properties to enter preclinical development for visceral leishmaniasis. Editor's summary: Chagas disease (CD) and visceral leishmaniasis are considered neglected tropical diseases and are responsible for ~30,000 fatalities annually. Current treatments for these vector-borne parasitic infections are inadequate, and there is a pressing need for better therapeutics. In companion articles, González et al. and Braillard et al. describe the development of closely related pyrrolopyrimidine compounds that target the cytochrome bc1 complex of the parasite electron transport chain and show promise for the treatment of both diseases. DNDI-6174 demonstrates potent activity in Leishmania models of infection and has a suitable profile for clinical development. For CD, the combination of pyrrolopyrimidine compounds with a subefficacious dose of benznidazole delivers rapid clearance of parasites in an animal model of chronic CD, offering the prospect of safer and shorter treatment regimens. Collectively, these studies represent advances in the development of potential treatments for some of the world's most neglected patient populations. —Christiana Fogg [ABSTRACT FROM AUTHOR]

Environmental protection associated with renewable energy is among the most critical challenges for translational ion‐capture based on capacitive storage of ions in electrical double layers at the interface of electrode and electrolyte. Electric double‐layer capacitance with charge induction and faradaic pseudo‐capacitance with charge transfer classifies the capacitance of the electrochemical interface. The electrochemical interface in most energy technologies involves porous and pseudocapacitive redox materials that offer varying degrees of electrolyte confinement. In this review, we discuss the factors affecting water desalination, such as the effect of nanopores for ion capture, the ion sieving effect, the effect of hydration energy, and hydration radius in the carbon sub‐nanometer pore. Moreover, the surface phenomena of electrodes, including carbon corrosion, and the potential of zero charge to control the oxidation of carbon electrodes are explained along with protection mechanisms. The various capacitive deionization (CDI) operations and the corresponding electrochemical cell technologies are briefly introduced, including the significance of double‐layer charging materials with faradaic intercalation, which suffer less from co‐ion expulsion. Finally, we revisit the effects of various nanoarchitectures and the construction of capacitive deionization electrodes for clean water technology. [ABSTRACT FROM AUTHOR]

Global climate change is anticipated to have a profound impact on drought occurrences, leading to detrimental consequences for the environment, socioeconomic relations, and ecosystem services. In order to evaluate the extent of drought impact, a comprehensive study was conducted in the Hyderabad–Karnataka region, India. Precipitation data from 31 stations spanning a 50-year period (1967–2017) were analyzed using the standardized precipitation index (SPI) based on gamma distribution. The findings reveal that approximately 15% of the assessed years of experienced drought conditions, with a range of influence between 41% and 76% under SPI_3, and between 43% and 72% under SPI_6. Examining the timescale magnitude frequency provided insights into variations in the severity of drought events across different locations and timescales. Notably, the Ballari (−8.77), Chitapur (−8.22), and Aland (−7.40) regions exhibited the most significant magnitudes of drought events for SPI_3 with a 5-year return period. The heightened risk of recurrent droughts in the study area emphasizes the necessity of integrating SPI in decision-making processes, as such integration can markedly contribute to the development of reliable and sustainable long-term water management strategies at regional and national levels. [ABSTRACT FROM AUTHOR]