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Hydrogen sulfide (H ₂S) is a reactive small molecule generated in the body that can be beneficial or toxic owing to its potent redox activity. In living systems, disentangling the pathways responsible for H ₂S production and their physiological and pathological consequences remains a challenge in part due to a lack of methods for monitoring changes in endogenous H ₂S fluxes. The development of fluorescent probes with appropriate selectivity and sensitivity for monitoring production of H ₂S at biologically relevant signaling levels offers opportunities to explore its roles in a variety of systems. Here we report the design, synthesis, and application of a family of azide-based fluorescent H ₂S indicators, Sulfidefluor-4, Sulfidefluor-5 acetoxymethyl ester, and Sulfidefluor-7 acetoxymethyl ester, which offer the unique capability to image H ₂S generated at physiological signaling levels. These probes are optimized for cellular imaging and feature enhanced sensitivity and cellular retention compared with our previously reported molecules. In particular, Sulfidefluor-7 acetoxymethyl ester allows for direct, real-time visualization of endogenous H ₂S produced in live human umbilical vein endothelial cells upon stimulation with vascular endothelial growth factor (VEGF). Moreover, we show that H ₂S production is dependent on NADPH oxidase–derived hydrogen peroxide (H ₂O ₂), which attenuates VEGF receptor 2 phosphorylation and establishes a link for H ₂S/H ₂O ₂ crosstalk.

Continued expansion of the chemical biology toolbox presents many new and diverse opportunities to interrogate the fundamental molecular mechanisms driving complex plant–microbe interactions. This review will examine metabolic labeling with click chemistry reagents and activity-based probes for investigating the impacts of plant-associated microbes on plant growth, metabolism, and immune responses. While the majority of the studies reviewed here used chemical biology approaches to examine the effects of pathogens on plants, chemical biology will also be invaluable in future efforts to investigate mutualistic associations between beneficial microbes and their plant hosts.

Robust and transparent election processes are needed in WHO to ensure that leaders are elected based on merit, write Kent Buse and colleagues

An informal meeting of the WHO Executive Board will discuss the selection process of regional directors in December. Reforms that would help make elections fairer for the contestants in all WHO regional election processes include: WHO revisiting criteria and competencies for nominations; regional offices publishing all nominee applications on their websites; ensuring regional directors and the Director-General are available to meet with all nominated candidates; regional committees convening public town halls in advance of elections where WHO staff and the public, including journalists, have the opportunity to submit questions to nominees; regional committees instructing regional offices to recruit human resources firms to review and verify applications and submitting reports on each candidate to the relevant regional committee; regional committees forming working groups, drawing on the EURO rules of procedure of the Regional Committee,4 to undertake preliminary evaluations and prepare a shortlist for the committee; and regional offices publicly broadcasting the candidates' job interviews. In keeping with principles of integrity in public office5 and with UN rules concerning the misuse of office, individuals involved with nominating member state candidates should be barred from nominating close relatives and friends.

Mitochondria peroxy yellow 1 (MitoPY1) is a small-molecule fluorescent probe that selectively tracks to the mitochondria of live biological specimens and responds to local fluxes of hydrogen peroxide (H 2 O 2 ) by a turn-on fluorescence enhancement. This bifunctional dye uses a triphenylphosphonium targeting group and a boronate-based molecular switch to selectively respond to H 2 O 2 over competing reactive oxygen species (ROS) within the mitochondria. MitoPY1 can be used to measure mitochondrial H 2 O 2 levels in both cell culture and tissue models. In this protocol, we describe the synthesis of MitoPY1 and how to use this chemical tool to visualize mitochondrial H 2 O 2 in live cells. The preparation of MitoPY1 is anticipated to take 7–10 d, and assays involving microscopy of cultured mammalian cells can be performed in 1–2 d.

Twelve years have now passed since the influential WHO Report on the Social Determinants of Health (SDoH) in 2008. A group of senior international public health scholars and decision-makers met in Italy in mid-2019 to review the legacy of the SDoH conceptual framework and its adequacy for the many challenges facing our field as we enter the 2020s. Four major categories of challenges were identified: emerging “exogenous” challenges to global health equity, challenges related to weak policy and practice implementation, more fundamental challenges related to SDoH theory and research, and broader issues around modern research in general. Each of these categories is discussed, and potential solutions offered. We conclude that although the SDoH framework is still a worthy core platform for public health research, policy, and practice, the time is ripe for significant evolution.

Enhancing academic publication outcomes and writing skills in postgraduates is a key goal for higher education institutions, ideally through early intervention. This study examines the challenges and support needs of early-stage Chinese postgraduates in academic writing, as well as the factors influencing their publication outcomes and writing self-efficacy. Using snowball sampling, 73 postgraduates were surveyed through questionnaires and reflective journals. Thematic analysis and linear regression were applied to analyze the data. Findings reveal primary challenges in literature review, research methods, data analysis, and topic selection. Key support needs include supervisor guidance, knowledge resources, tools, and self-assessment. Results indicate that the year of study, meeting frequency, supervisor support, teaching-research nexus, and self-efficacy do not significantly impact publication outcomes. However, supervisor support and the quality of the teaching-research nexus positively influence self-efficacy. These findings highlight the importance of providing targeted support and fostering intrinsic motivation to enhance the writing skills and self-efficacy of early-stage postgraduate students.

Cigarette smoking is associated with chronic obstructive pulmonary disease and chronic bronchitis. Acquired ion transport abnormalities, including cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, caused by cigarette smoking have been proposed as potential mechanisms for mucus obstruction in chronic bronchitis. Although e-cigarette use is popular and perceived to be safe, whether it harms the airways via mechanisms altering ion transport remains unclear. In the present study, we sought to determine if e-cigarette vapor, like cigarette smoke, has the potential to induce acquired CFTR dysfunction, and to what degree. Electrophysiological methods demonstrated reduced chloride transport caused by vaporized e-cigarette liquid or vegetable glycerin at various exposures (30 min, 57.2% and 14.4% respectively, vs. control;  < 0.0001), but not by unvaporized liquid (60 min, 17.6% vs. untreated), indicating that thermal degradation of these products is required to induce the observed defects. We also observed reduced ATP-dependent responses (-10.8 ± 3.0 vs. -18.8 ± 5.1 μA/cm control) and epithelial sodium channel activity (95.8% reduction) in primary human bronchial epithelial cells after 5 minutes, suggesting that exposures dramatically inhibit epithelial ion transport beyond CFTR, even without diminished transepithelial resistance or cytotoxicity. Vaporizing e-cigarette liquid produced reactive aldehydes, including acrolein (shown to induce acquired CFTR dysfunction), as quantified by mass spectrometry, demonstrating that respiratory toxicants in cigarette smoke can also be found in e-cigarette vapor (30 min air, 224.5 ± 15.99; unvaporized liquid, 284.8 ± 35.03; vapor, 54,468 ± 3,908 ng/ml;  < 0.0001). E-cigarettes can induce ion channel dysfunction in airway epithelial cells, partly through acrolein production. These findings indicate a heretofore unknown toxicity of e-cigarette use known to be associated with chronic bronchitis onset and progression, as well as with chronic obstructive pulmonary disease severity.

In adults with congenital adrenal hyperplasia, crinecerfont, a corticotropin-releasing factor type 1 receptor antagonist, lowered the mean glucocorticoid dose and decreased the mean androstenedione level.