Asymmetric Three-Component Radical Alkene Carboazidation by Direct Activation of Aliphatic C-H Bonds.

Azide compounds are widely present in natural products and drug molecules, and their easy-to-transform characteristics make them widely used in the field of organic synthesis. The merging of transition-metal catalysis with radical chemistry offers a versatile platform for radical carboazidation of alkenes, allowing the rapid assembly of highly functionalized organic azides. However, the direct use of readily available hydrocarbon feedstocks as sp3-hybridized carbon radical precursors to participate in catalytic enantioselective carboazidation of alkenes remains a significant challenge that has yet to be addressed. Herein, we describe an iron-catalyzed asymmetric three-component radical carboazidation of electron-deficient alkenes by direct activation of aliphatic C-H bonds. This approach involves intermolecular hydrogen atom transfer between a hydrocarbon and an alkoxy/aryl carboxyl radical, leading to the formation of a carbon-centered radical. The resulting radical then reacts with electron-deficient alkenes to generate a new radical species that undergoes chiral iron-complex-mediated C-N3 bond coupling. An array of valuable chiral azides bearing a quaternary stereocenter were directly accessed from widely available chemical feedstocks, and their synthetic potential is further demonstrated through more facile transformations to give other valuable enantioenriched building blocks.

Divergent driving mechanisms of community temporal stability in China's drylands.

Climate change and anthropogenic activities are reshaping dryland ecosystems globally at an unprecedented pace, jeopardizing their stability. The stability of these ecosystems is crucial for maintaining ecological balance and supporting local communities. Yet, the mechanisms governing their stability are poorly understood, largely due to the scarcity of comprehensive field data. Here we show the patterns of community temporal stability and its determinants across an aridity spectrum by integrating a transect survey across China's drylands with remote sensing. Our results revealed a U-shaped relationship between community temporal stability and aridity, with a pivotal shift occurring around an aridity level of 0.88. In less arid areas (aridity level below 0.88), enhanced precipitation and biodiversity were associated with increased community productivity and stability. Conversely, in more arid zones (aridity level above 0.88), elevated soil organic carbon and biodiversity were linked to greater fluctuations in community productivity and reduced stability. Our study identifies a critical aridity threshold that precipitates significant changes in community stability in China's drylands, underscoring the importance of distinct mechanisms driving ecosystem stability in varying aridity contexts. These insights are pivotal for developing informed ecosystem management and policy strategies tailored to the unique challenges of dryland conservation.

Size, distribution, and vulnerability of the global soil inorganic carbon.

Global estimates of the size, distribution, and vulnerability of soil inorganic carbon (SIC) remain largely unquantified. By compiling 223,593 field-based measurements and developing machine-learning models, we report that global soils store 2305 ± 636 (±1 SD) billion tonnes of carbon as SIC over the top 2-meter depth. Under future scenarios, soil acidification associated with nitrogen additions to terrestrial ecosystems will reduce global SIC (0.3 meters) up to 23 billion tonnes of carbon over the next 30 years, with India and China being the most affected. Our synthesis of present-day land-water carbon inventories and inland-water carbonate chemistry reveals that at least 1.13 ± 0.33 billion tonnes of inorganic carbon is lost to inland-waters through soils annually, resulting in large but overlooked impacts on atmospheric and hydrospheric carbon dynamics.

Hierarchical Structure with Microcrater Covered with Nanograss Enhancing Condensation and Its Antifrosting/Anti-Icing Performance Inspired by Euphorbia helioscopia L.

Over an extended period of evolution and natural selection, a multitude of species developed a diverse array of biological interface features with specific functions. These biological structures provide a rich source of inspiration for the design of bionic structures on superhydrophobic surfaces. Understanding the functional mechanism of plant leaves is of paramount importance for the advancement of new engineering materials and the further promotion of engineering applications of bionic research. The hierarchical structure of microcrater-covered nanograss (MCNG) on the surface of E. helioscopia L. leaf provided the inspiration for the bionic MCNG surface, which was successfully prepared on a copper substrate by hybrid laser micromachining technology and chemical etching. The combined action of texture structure and surface chemistry resulted in a contact angle of 169° ± 1° for MCNG surface droplets and a rolling angle of less than 1°. Notably, the condensation-induced adhesion force does not augment with the increase of the temperature difference, which facilitated the shedding of hot droplets from the surface. The microscope observation revealed a high density of condensed droplets on the MCNG surface and the tangible jumping behavior of the droplets. The fabricated MCNG also demonstrated excellent antifrost/anti-icing abilities in low-temperature and high-humidity environments. Finally, the study confirmed the exceptional mechanical durability and reusability of the MCNG surface through various tests, including scratch damage, sandpaper wear, water flow impact and flushing, and condensation-drying cycle tests. The nanograss can be effectively protected within the microcrater structure. This research presents a promising approach for preventing and/or removing unwanted droplets in numerous engineering applications.

Asymmetric Synthesis of Hydrodibenzofurans from Norcaradienes: Kinetic Resolution via [3 + 2] Cycloaddition with Quinones.

The catalytic asymmetric [3 + 2] cycloaddition of racemic norcaradienes with quinones to construct multicyclic hydrodibenzofurans was achieved by the use of chiral N,N'-dioxide/metal complex catalysts. Kinetic resolution of norcaradienes accompanied by partial racemization occurred, and one enantiomer in prior acted as the C2 synthon to participate in diastereoselective cycloaddition. An enantiodivergent synthesis via a switch of metal ions was observed when naphthoquinone was used as the partner. DFT calculations revealed the profiles of the cycloaddition processes.

Asymmetric Synthesis of Hydroindoles via Desymmetrizing [3+2] Annulation of p-Quinamines and Arylalkylketenes.

The asymmetric desymmetrizing [3+2] annulation reaction of p-quinamines and arylalkylketenes to synthesize hydroindoles was realized. Catalyzed by chiral bisguanidinium hemisalt via multiple hydrogen bond interactions, enantiomerically enriched products with reversal of diastereoselectivity in comparison with the racemic version were afforded in good yields under mild reaction conditions. Diaryl-substituted hydroindoles could also perform the Friedel-Crafts type of addition to give more complicated multicycles. Density functional theory calculations revealed that the enantio- and diastereoselectivity stem from varied hydrogen-bonding manners.

IronIII-catalyzed asymmetric inverse-electron-demand hetero-Diels-Alder reaction of dioxopyrrolidines with simple olefins.

The asymmetric catalytic inverse-electron-demand hetero-Diels-Alder reaction of dioxopyrrolidines with a variety of simple olefins has been accomplished, significantly expanding the applicability of this cyclization to both cyclic hetero-dienes and dienophiles. A new type of strong Lewis acid catalyst of ferric salt enables the LUMO activation of dioxopyrrolidines via formation of cationic species, this method yields a range of bicyclic dihydropyran derivatives with exceptional outcomes, including high yields (up to 99%), diastereoselectivity (up to 99 : 1) and enantioselectivity (up to 99% ee) under mild conditions. This facile protocol was available for the late-stage modification of several bioactive molecules and transformation into macrocycle molecules as well. The origins of enantioselectivity were elucidated based on control experiments.

Superhydrophobic Surfaces with Excellent Ice Prevention and Drag Reduction Properties Inspired by Iridaceae Leaf.

The anti-icing and drag-reduction properties of diverse microstructured surfaces have undergone extensive study over the past decade. Nonetheless, tough environments enforce stringent demands on the composite characteristics of superhydrophobic surfaces (SHS). In this study, fresh composite structures were fabricated on a metal substrate by nanosecond laser machining technology, drawing inspiration from the hardy plant Iridaceae. The prepared sample surface mainly consists of a periodic microrhombus array and irregular nanosheets. To comprehensively investigate the effect of its special structure on surface properties, three surfaces with different sizes of rhombic structures were used for comparative analysis, and the results show that the SH-S2 sample is optimal. This can significantly delay the freezing time by an impressive 1404 s at -10 °C while revealing the sample surface anti-icing strategy. In addition, the rheological experiments determined over 300 µm of slip length for the SH-S2 sample, and the drag reduction rate of the surface reaches nearly 40%, which is well aligned with the results of the delayed icing experiments. Finally, the mechanical durability of the SH-S2 surface was investigated through scratch damage, sandpaper abrasion, reparability trials, and icing and melting cycle tests. This research presents a new approach and methodology for the application of SHS on polar ship surfaces.

Enantioselective sulfonylation to construct 3-sulfonylated oxindoles.

Asymmetric synthesis of 3-sulfonylated 3-substituted oxindoles through the addition of sodium sulfinate salts to 3-bromo-3-substituted oxindoles has been achieved using chiral nickel complexes of N,N'-dioxides. This method facilitates the creation of diverse chiral sulfonyl oxindoles, several of which display promising anticancer properties. Notably, the catalyst demonstrates remarkable tolerance to water, crucial for maintaining enantioselectivity. Furthermore, the utilization of topographic steric maps of the catalysts offers valuable insights into the mechanism underlying enantioselection reversal.

GSNOR overexpression enhances CAR-T cell stemness and anti-tumor function by enforcing mitochondrial fitness.

Chimeric antigen receptor-T (CAR-T) cell has been developed as a promising agent for patients with refractory or relapsed lymphoma and leukemia, but not all the recipients could achieve a long-lasting remission. The limited capacity of in vivo expansion and memory differentiation post activation is one of the major reasons for suboptimal CAR-T therapeutic efficiency. Nitric oxide (NO) plays multifaceted roles in mitochondrial dynamics and T cell activation, but its function on CAR-T cell persistence and anti-tumor efficacy remains unknown. Herein, we found the continuous signaling from CAR not only promotes excessive NO production, but also suppressed S-nitrosoglutathione reductase (GSNOR) expression in T cells, which collectively led to increased protein S-nitrosylation, resulting in impaired mitochondrial fitness and deficiency of T cell stemness. Intriguingly, enforced expression of GSNOR promoted memory differentiation of CAR-T cell after immune activation, rendered CAR-T better resistance to mitochondrial dysfunction, further enhanced CAR-T cell expansion and anti-tumor capacity in vitro and in a mouse tumor model. Thus, we revealed a critical role of NO in restricting CAR-T cell persistence and functionality, and defined that GSNOR overexpression may provide a solution to combat NO stress and render patients with more durable protection from CAR-T therapy.

Development of Solid Waste-Based Composite Calcium Ferrite Flux and Its Application in Hot Metal Pre-Dephosphorization.

To enhance the slagging efficiency of the lime-based slag system during the pre-treatment stage of hot metal, a composite calcium ferrite flux based on aluminum industry solid waste was developed in this study. The melting characteristics of the flux and its application in the pre-treatment of hot metal were investigated. The results indicated that the main phases of the composite calcium ferrite were CaFe2O4, Ca2Fe2O5, and Ca2(Fe,Al)2O4. It exhibited high oxidation, high alkalinity, and a low melting point, thereby achieving excellent melting performance. Simulations of various dephosphorization fluxes in the pre-treatment of high-phosphorus hot metal, ordinary hot metal, and kilogram-scale dephosphorization experiment processes were conducted. Under the same experimental conditions, the composite calcium ferrite flux was able to achieve a dephosphorization rate of over 90% and a final phosphorus content of less than 0.02 wt% under high carbon content ([%C] = 3.2 wt%). In the application of hot metal pre-dephosphorization, this flux was able to achieve efficient melting and rapid slagging of lime at a lower temperature, and its slagging time was 50% faster than that of calcium ferrite flux. In addition, this flux enhanced the utilization efficiency of lime during the steelmaking process, effectively prevented the agglomeration of slag, and achieved efficient slag-metal separation. These characteristics were significantly better than the application effect of calcium ferrite flux. This flux has significant implications for the industrial application of deep dephosphorization in the pre-treatment stage of hot metal or the early stage of converter steelmaking.

A Wind Bell Inspired Triboelectric Nanogenerator for Extremely Low­Speed and Omnidirectional Wind Energy Harvesting.

As one of the most promising renewable energies, wind energy is abundant in the natural environment. However, it is still challenging to effectively collect wind energy because of its variable wind speed and unpredictable direction. Here, a triboelectric nanogenerator, which is inspired by ancient Chinese wind bells, has been developed to collect energy from variable-speed and multi-directional wind. The wind-bell-inspired triboelectric nanogenerator (W-TENG) has the capability to generate electricity even at a very low wind speed of 0.5 m s-1. Furthermore, it is able to harvest wind energy effectively from all directions (0-360 degrees). The parameter-optimized W-TENG achieves a maximum output voltage of 9.3 V and a maximum current of 0.63 µA. Electronic devices including a digital watch and 40 light-emitting diodes (LEDs) are successfully powered by the designed W-TENG, demonstrating its applicability. In this study, it is believed that a novel and effective strategy is provided to harvest energy from variable-speed and multi-directional wind.

Water-enabling strategies for asymmetric catalysis.

Water possesses unique advantages, including abundance, environmental friendliness and mild effects. Undoubtedly, it is an ideal solvent or reagent in chemical syntheses. Water also shows unique abilities in catalytic asymmetric synthesis. It can accelerate reaction rates, improve diastereo- or enantioselectivities, initiate reactions, diversify chemo, diastereo- or enantioselectivities through various effects (hydrophobic, hydrogen bonding, protonation). Several reviews have demonstrated the positive effects of water in asymmetric synthesis. In this review, we summarize water-enabling strategies in the last decade, and focus on advances which reveal how water affects a reaction.

Myeloid leukemia-derived galectin-1 downregulates CAR expression to hinder cytotoxicity of CAR T cells.

BACKGROUND: Chimeric antigen receptor (CAR) T cells have shown significant activity in B-lineage malignancies. However, their efficacy in myeloid leukemia has not been successful due to unclear molecular mechanisms. METHODS: We conducted in vitro and in vivo experiments to investigate whether myeloid leukemia cells directly induce CAR down-regulation. Furthermore, we designed a CD33 CARKR in which all lysines in the cytoplasmic domain of CAR were mutated to arginine and verified through in vitro experiments that it could reduce the down-regulation of surface CARs and enhance the killing ability. Transcriptome sequencing was performed on various AML and ALL cell lines and primary samples, and the galectin-1-specific inhibitory peptide (anginex) successfully rescued the killing defect and T-cell activation in in vitro assays. RESULTS: CAR down-regulation induced by myeloid leukemia cells under conditions of low effector-to-tumor ratio, which in turn impairs the cytotoxicity of CAR T cells. In contrast, lysosomal degradation or actin polymerization inhibitors can effectively alleviate CAR down-regulation and restore CAR T cell-mediated anti-tumor functions. In addition, this study identified galectin-1 as a critical factor used by myeloid leukemia cells to induce CAR down-regulation, resulting in impaired T-cell activation. CONCLUSION: The discovery of the role of galectin-1 in cell surface CAR down-regulation provides important insights for developing strategies to restore anti-tumor functions.

Imbalance in lake variability but not embodying driving factors on the Qinghai-Tibetan Plateau calls on heterogeneous lake management.

Comprehensive regional remote analysis tends to neglect lakes in exorheic basins on the Qinghai-Tibetan Plateau (QTP), and a concurrent lack of discussions on whether there exist imbalanced explanations for the driving forces of both internal and external lakes is also present. We integrate multisourced lake datasets, high-resolution information, and available altimetry datasets to establish multiple mathematical models to meta-simulate lake volume changes, extend current lake variation datasets, and quantify the imbalance of variations and factors driving the water mass budget. The results showed that the primary cause of lake variations in QTP is net precipitation (57.75 ± 31.46%), followed by glacier runoff (33.53 ± 31.42%), and permafrost (8.34 ± 7.87%). Even though glacier runoff is currently considered as a weak factor of lake variation, heterogeneous results call for remaining attention in glacier-induced lake basins. Imbalance embodying in lake variability but not in contributions of driving factors, which calls for special lake management ways in different watersheds.

The feedback of greening on local hydrothermal conditions in Northern China.

Northern China has experienced a significant increase in vegetation cover over the past few decades. It lacks a comprehensive understanding of how greening impacts local hydrothermal conditions. To address this issue, in our study, the RegCM-CLM45 model was used to conduct a thorough assessment of the impacts of greening on temperature, vapor pressure deficit (VPD), precipitation, and soil moisture. The findings revealed that the local climatic effects of greening varied across different drought gradients based on the aridity index (AI). In drier regions with AI<0.3, the increased energy induced by greening tended to dissipate as sensible heat, exacerbating both warming and drought conditions. Conversely, in wetter regions with AI>0.3, a greater proportion of energy was lost through evapotranspiration, attenuating warming. Additionally, greening enhanced precipitation and soil moisture in drier regions and moderated their decline in wetter regions. Significantly, our research emphasized the effectiveness of grassland expansion and conservation as prime strategies for ecological restoration, particularly in drylands, where they could effectively alleviate soil drought. Given the diverse responses of different land cover transformations to local hydrothermal conditions in drylands, there is an urgent need to address potential adverse effects arising from inappropriate ecological restoration strategies and to develop an optimal restoration framework for the future.

Exosomal secreted SCIMP regulates communication between macrophages and neutrophils in pneumonia.

In pneumonia, the deficient or delayed pathogen clearance can lead to pathogen proliferation and subsequent overactive immune responses, inducing acute lung injury (ALI). While screening human genome coding genes using our peripheral blood cell chemotactic platform, we unexpectedly find SLP adaptor and CSK interacting membrane protein (SCIMP), a protein with neutrophil chemotactic activity secreted during ALI. However, the specific role of SCIMP in ALI remains unclear. In this study, we investigate the secretion of SCIMP in exosomes (SCIMPexo) by macrophages after bacterial stimulation, both in vitro and in vivo. We observe a significant increase in the levels of SCIMPexo in bronchoalveolar lavage fluid and serum of pneumonia patients. We also find that bronchial perfusion with SCIMPexo or SCIMP N-terminal peptides increases the survival rate of the ALI model. This occurs due to the chemoattraction and activation of peripheral neutrophils dependent on formyl peptide receptor 1/2 (FPR1/2). Conversely, exosome suppressors and FPR1/2 antagonists decrease the survival rate in the lethal ALI model. Scimp-deficient and Fpr1/2-deficient mice also have lower survival rates and shorter survival times than wild-type mice. However, bronchial perfusion of SCIMP rescues Scimp-deficient mice but not Fpr1/2-deficient mice. Collectively, our findings suggest that the macrophage-SCIMP-FPRs-neutrophil axis plays a vital role in the innate immune process underlying ALI.

Iron-Catalyzed Asymmetric α-Alkylation of 2-Acylimidazoles via Dehydrogenative Radical Cross-Coupling with Alkanes.

The direct α-alkylation of acyclic carbonyls with nonactivated hydrocarbons through C(sp3 )-H functionalization is both extremely promising and notably challenging, especially when attempting to achieve enantioselectivity using iron-based catalysts. We have identified a robust chiral iron complex for the oxidative cross-coupling of 2-acylimidazoles with benzylic and allylic hydrocarbons, as well as nonactivated alkanes. The readily available and tunable N,N'-dioxide catalysts of iron in connection with oxidants exhibit precise asymmetric induction (up to 99 % ee) with good compatibility in moderate to good yields (up to 88 % yield). This protocol provides an elegant and straightforward access to optically active acyclic carbonyl derivatives starting from simple alkanes without prefunctionalization. Density functional theory (DFT) calculations and control experiments were made to gain insight into the nature of C-C bond formation and the origin of enantioselectivity. We propose a radical-radical cross-coupling process enabled by the immediate interconversion between chiral ferric species and ferrous species.

Chiral cobalt(ii) complex-promoted asymmetric para-Claisen rearrangement of allyl α-naphthol ethers.

Due to experiencing a challenging dearomatization process, the aromatic sigmatropic rearrangement of allyl naphthyl ethers is a difficult yet efficient method to build useful naphthalenone skeletons. Here, we report a para-Claisen rearrangement-based asymmetric dearomatization of allyl α-naphthol ethers enabled by a N,N'-dioxide/CoII complex. A variety of naphthalenones were obtained in moderate to good yields with good to excellent ee values. Interestingly, by exchanging the allyl group on the ether and that at the para-position of the benzene ring, enantiodivergent synthesis can be achieved. Experimental studies and DFT calculations revealed that aryl allyl ethers tend to transform via a stepwise allyl π-complex migration pathway, while, alkyl allyl ethers transformed through a concerted ortho-Claisen rearrangement/Cope rearrangement sequence.

Catalytic Enantioselective Nucleophilic Addition to Arynes by a New Quaternary Guanidinium Salt-Based Phase-Transfer Catalyst.

Owing to the mild generation methods, arynes have been widely used in synthetic chemistry. However, achieving asymmetric organocatalytic reactions with arynes remains a formidable and infrequent challenge, primarily because these neutral and transient species tend to spontaneously quench. To address this issue, a solid-liquid phase-transfer strategy is devised in which the generation speed of arynes could be controlled by the in situ generated fluoride-based chiral phase-transfer catalyst. In this study, we present a catalytic enantioselective nucleophilic addition reaction involving arynes, utilizing an amino amide-based guanidinium salt QG•X. Furthermore, we demonstrate the broad compatibility of this reaction with various arynes and cyclic/acyclic ß-keto amides, leading to the creation of diverse α-aryl quaternary stereocenters with good stereoselectivity. Mechanistic investigations have uncovered the potential involvement of a chiral intramolecular cationic-anionic pair and HF during the ion exchange between QG•X and CsF for nucleophile activation and aryne generation. Additionally, DFT calculations suggested that the observed high levels of enantioselectivity can be attributed to steric repulsion and the cumulative noncovalent interactions between the catalysts and substrates.