Tryptophan (Trp) plays a critical role in the regulation of protein structure, interactions and functions through its π system and indole N–H group. A generalizable method for blocking and rescuing Trp interactions would enable the gain-of-function manipulation of various Trp-containing proteins in vivo, but generating such a platform remains challenging. Here we develop a genetically encoded N1-vinyl-caged Trp capable of rapid and bioorthogonal decaging through an optimized inverse electron-demand Diels–Alder reaction, allowing site-specific activation of Trp on a protein of interest in living cells. This chemical activation of a genetically encoded caged-tryptophan (Trp-CAGE) strategy enables precise activation of the Trp of interest underlying diverse important molecular interactions. We demonstrate the utility of Trp-CAGE across various protein families, such as catalase-peroxidases and kinases, as translation initiators and posttranslational modification readers, allowing the modulation of epigenetic signalling in a temporally controlled manner. Coupled with computer-aided prediction, our strategy paves the way for bioorthogonal Trp activation on more than 28,000 candidate proteins within their native cellular settings.
Kernel smoothing is a widely used nonparametric method in modern statistical analysis. The problem of efficiently conducting kernel smoothing for a massive dataset on a distributed system is a problem of great importance. In this work, we find that the popularly used one-shot type estimator is highly inefficient for prediction purposes. To this end, we propose a novel grid point approximation (GPA) method, which has the following advantages. First, the resulting GPA estimator is as statistically efficient as the global estimator under mild conditions. Second, it requires no communication and is extremely efficient in terms of computation for prediction. Third, it is applicable to the case where the data are not randomly distributed across different machines. To select a suitable bandwidth, two novel bandwidth selectors are further developed and theoretically supported. Extensive numerical studies are conducted to corroborate our theoretical findings. Two real data examples are also provided to demonstrate the usefulness of our GPA method.
This study assesses the health benefits of better air quality by examining the causal impact of China’s stringent “2+26” regional air pollution control policy on local air quality and population health. Employing a spatial regression discontinuity design that capitalizes on the policy’s location-specific features, we present compelling evidence that the 2+26 policy results in an average reduction of 12.2 units in the local Air Quality Index (AQI) and a 47.0% decrease in per capita medical expenditure from 2014 to 2018. A one-unit reduction in AQI corresponds to a 0.88% reduction in per capita annual medical spending, equivalent to RMB 30.2 (US$4.6). These health gains stem from reduced chronic disease prevalence and improved subjective well-being. Nationally, air quality improvement during 2014–2018 could save RMB 674billion (US$104billion) annually in national direct medical costs, constituting 11.6% of national medical expenditure in 2018. Our findings underscore the substantial health and welfare gains achievable through pollution controls in developing countries.
The heterogeneous coprecipitation of nanocrystals with metals on substrates plays a significant role in both natural and engineered systems. Due to the small dimensions and thereby the large specific surface area, nanocrystal coprecipitation with metals, which is ubiquitous in natural settings, exerts drastic effects on the biogeochemical cycling of metals on the earth’s crust. Meanwhile, the controlled synthesis of nanocrystals with metal doping to achieve tunable size/composition enables their broad applications as adsorbents and catalysts in many engineered settings. Despite their importance, complex interactions among aqueous ions/polymers, nanocrystals, substrates, and metals are far from being well-understood, leaving the controlling mechanisms for nanocrystal formation with metals on substrates uncovered.
In this Account, we discuss our systematic investigation over the past 10 years of the heterogeneous formation of representative nanocrystals with metals on typical substrates. We chose Fe(OH)3 and BaSO4 as representative nanocrystals. Mechanisms for varied metal coprecipitation were also investigated for both types of nanocrystals (i.e., Fe, Al, Cr, Cu, and Pb)(OH)3 and (Ba, Sr)(SO4, SeO4, and SeO3)). Bare SiO2 and Al2O3, as well as those coated with varied organics, were selected as geologically or synthetically representative substrates. Through the integration of state-of-the-art nanoscale interfacial characterization techniques with theoretical calculations, the complex interactions during nanocrystal formation at interfaces were probed and the controlling mechanisms were identified.
For BaSO4 and Fe(OH)3 formation on substrates, the local supersaturation levels near substrates were controlled by Ba2+ adsorption and the electrostatic attraction of Fe(OH)3 monomer/polymer to substrates, respectively. Meanwhile, substrate hydrophobicity controlled the interfacial energy for the nucleation of both nanocrystals on (in)organic substrates. Metal ions’ (i.e., Cr/Al/Cu/Pb) hydrolysis constants and substrates’ dielectric constants controlled metal ion adsorption onto substrates, which altered the surface charges of substrates, thus controlling heterogeneous Fe(OH)3 nanocrystal formation on substrates by electrostatic interactions. The sizes and compositions of heterogeneous (Fe, Cr)(OH)3 and (Ba, Sr)(SO4, SeO4, SeO3) formed on substrates were found to be distinct from those of homogeneous precipitates formed in solution. The substrate (de)protonation could alter the local solution’s pH and the substrates’ surface charge; substrates could also adsorb cations, affecting local Fe/Cr/Ba/Sr ion concentrations at solid–water interfaces, thus controlling the amount/size/composition of nanocrystals by tuning their nucleation/growth/deposition on substrates. From slightly supersaturated solution, homogeneous coprecipitates of microsized (Ba, Sr)(SO4, SeO4, SeO3) formed through growth, with little Sr/Se(VI) incorporation due to higher solubilities of SrSO4 and BaSeO4 over BaSO4. While cation enrichment near substrates made the local solution highly supersaturated, nanosized coprecipitates formed on substrates through nucleation, with more Sr/Se(VI) incorporation due to lower interfacial energies of SrSO4 and BaSeO4 over BaSO4. The new insights gained advanced our understanding of the biogeochemical cycling of varied elements at solid–water interfaces and of the controlled synthesis of functional nanocrystals.
As an extremely disadvantaged group, orphans have received extensive attention from researchers. However, previous research focused on their survival status and psychological distress. The present study aims to explore the mechanism of orphans’ life satisfaction from the perspective of positive psychology. We conducted a survey among Tibetan orphans (n = 131) and compared the results with Tibetan non-orphans (n = 134). A mediation model was used to assess associations between resilience and life satisfaction, and the intermediary role of dimensions of hope (agency thinking and pathways thinking). Results indicated that, among orphans, agency thinking acted as a mediator in the mediation model, while pathways thinking did not. Moreover, hope dimensions did not play mediating roles between resilience and life satisfaction among non-orphans. The results highlighted that resilience is of vital importance for orphans’ life satisfaction. It was expected to inspire psychologists to develop specific interventions on resilience for orphans to enhance their internal resources (such as agency thinking of hope) and life satisfaction.
Microplastics are found in various human tissues and are considered harmful, raising concerns about human exposure to microplastics in the environment. Existing research has analyzed indoor and occupational scenarios, but long-term monitoring of ambient atmospheric microplastics (AMPs), especially in highly polluted urban regions, needs to be further investigated. This study estimated human environmental exposure to AMPs by considering inhalation, dust ingestion, and dermal exposure in three urban functional zones within a megacity. The annual exposure quantity was 7.37 * 104 items for children and 1.06 * 105 items for adults, comparable with the human microplastic consumption from food and water. Significant spatiotemporal differences were observed in the characteristics of AMPs that humans were exposed to, with wind speed and rainfall frequency mainly driving these changes. The annual human AMP exposure quantity in urban green land spaces, which were recognized as relatively low polluted zones, was comparable with that in public service zones and residential zones. Notably, significant positive correlations between the AMP characteristics and the pathogenicity of the airborne bacterial community were discovered. AMP size and immune-mediated disease risks brought by atmospheric microbes showed the most significant relationship, where Sphingomonas might act as the potential key mediator.