Single-nucleus transcriptome unveils the role of ferroptosis in ischemic stroke.

Multiple cell death pathways are involved in neuronal death in ischemic stroke (IS). However, the role of different cell death pathways in different cell types has not been elucidated. By analyzing three single-nucleus RNA sequencing (snRNA-seq) data of IS, we first found that a variety of programmed cell death (PCD) -related genes were significantly changed in different cell types. Based on machine learning and virtual gene knockout, we found that ferroptosis related genes, ferritin heavy chain 1 (Fth1) and ferritin light chain (Ftl1), play a key role in IS. Ftl1 and Fth1 can promote microglia activation, as well as the production of inflammatory factors and chemokines. Cell communication analysis showed that activated microglia could enhance chemotactic peripheral leukocyte infiltration, such as macrophages and neutrophils, through Spp1-Cd44 and App-Cd74 signaling, thereby aggravating brain tissue damage. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) showed that P2ry12 and Mef2c were significantly decreased in oxygen-glucose deprivation (OGD) group, while Ftl1, Fth1, Apoe, Ctsb, Cd44 and Cd74 were significantly increased in OGD group. Collectively, our findings suggested targeted therapy against microglia Ftl1 and Fth1 might improve the state of microglia, reduce the infiltration of peripheral immune cells and tissue inflammation, and then improve the ischemic brain injury in mouse.

Discovery of new N-Phenylamide Isoxazoline derivatives with high insecticidal activity and reduced honeybee toxicity.

Isoxazoline is a novel structure with strong potential for controlling agricultural insect pests, but its high toxicity to honeybees limits its development in agriculture. Herein, a series of N-phenylamide isoxazoline derivatives with low honeybee toxicity were designed and synthesized using the intermediate derivatization method. Bioassay results showed that these compounds exhibited good insecticidal activity. Compounds 3b and 3f showed significant insecticidal effects against Plutella xylostella (P. xylostella) with median lethal concentrations (LC50) of 0.06 and 0.07 mg/L, respectively, comparable to that of fluralaner (LC50 = 0.02 mg/L) and exceeding that of commercial insecticide fluxametamide (LC50 = 0.52 mg/L). It is noteworthy that the acute honeybee toxicities of compounds 3b and 3f (LD50 = 1.43 and 1.63 µg/adult, respectively) were significantly reduced to 1/10 of that of fluralaner (LD50 = 0.14 µg/adult), and were adequate or lower than that of fluxametamide (LD50 = 1.14 µg/adult). Theoretical simulation using molecular docking indicates that compound 3b has similar binding modes with fluralaner and a similar optimal docking pose with fluxametamide when binding to the GABA receptor, which may contribute to its potent insecticidal activity and relatively low toxicity to honey bees. This study provides compounds 3b and 3f as potential new insecticide candidates and provides insights into the development of new isoxazoline insecticides exhibiting both high efficacy and environmental safety.

Hydrochlorothiazide-induced glucose metabolism disorder is mediated by the gut microbiota via LPS-TLR4-related macrophage polarization.

Hydrochlorothiazide (HCTZ) is reported to impair glucose tolerance and may induce new onset of diabetes, but the pharmacomicrobiomics of the adverse effect for HCTZ remains unknown. Mice-fed HCTZ exhibited insulin resistance and impaired glucose tolerance. By using FMT and antibiotic cocktail models, we found that HCTZ-induced metabolic disorder was mediated by commensal microbiota. HCTZ consumption disturbed the structure of the intestinal microbiota, causing abnormal elevation of Gram-negative Enterobacteriaceae and lipopolysaccharide (LPS) then leading to intestinal barrier dysfunction. Additionally, HCTZ activated TLR4 signaling and induced macrophage polarization and inflammation in the liver. Furthermore, HCTZ-induced macrophage polarization and metabolic disorder were abrogated by blocking TLR4 signaling. HCTZ consumption caused a significant increase in Gram-negative Enterobacteriaceae, which elevated the levels of LPS, thereby activating LPS/TLR4 pathway, promoting inflammation and macrophage polarization, and resulting in metabolic disorders. These findings revealed that the gut microbiome is the key medium underlying HCTZ-induced metabolic disorder.

Hydraulic constraints determine the distribution of heteromorphic leaves along plant vertical height.

As an interesting and important trait of some drought-tolerant species, heteromorphic leaves are distributed differentially along plant vertical heights. However, the underpinning mechanism for the formation of heteromorphic leaves remains unclear. We hypothesize that heteromorphic leaves are caused by the hydraulic constraints possibly due to the compensation of the changes in functional traits in response to water transport capacity or the reduction of ineffective water loss. In this study, differences in water transport capacity, morphological traits, anatomical structures, and cellular water relations among three typical types of heteromorphic leaves (i.e., lanceolate, ovate, and broad-ovate) of Populus euphratica Oliv. (a dominant species of desert riparian forest in Central and West Asia) and their relationships were analyzed in order to explore the forming mechanism of heteromorphic leaves. The results showed that the lanceolate, ovate, and broad-ovate leaves were growing in the lower, intermediate, and higher positions from the ground, respectively. Morphological traits, anatomical structures, cellular water relations, and water transport capacity significantly varied among the three types of heteromorphic leaves (P< 0.01). Drought stress in broad-ovate leaves was significantly higher than that in ovate and lanceolate leaves (P< 0.01). Water transport capacity has significant correlations with morphological traits, anatomical structures, and cellular water relations (R 2 ≥ 0.30; P< 0.01). Our results indicated that heteromorphic leaves were used as an important adaptive strategy for P. euphratica to alleviate the increase of hydraulic constraints along vertical heights.

Genetic association of hypoxia inducible factor 1-alpha (HIF1A) Pro582Ser polymorphism with risk of diabetes and diabetic complications.

Diabetes is an age-related chronic disease associated with a number of complications, emerging as one of the major causes of morbidity and mortality worldwide. Several studies indicated that hypoxia-inducible factor 1-alpha (HIF1A) genetic polymorphisms may be associated with diabetes and diabetic complications. However, this association remains ambiguous. Thus, we performed a meta-analysis to provide more precise conclusion on this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CI) were applied to assess the strength of the relationships. There was a protective association between HIF1A Pro582Ser polymorphism and diabetes under the heterozygous genetic model (OR = 0.70, 95% CI = 0.55-0.91; P = 0.007). Similar associations were observed in diabetic complications risk under the allelic (OR = 0.69, 95% CI = 0.57-0.83; P < 0.001), homozygous (OR = 0.51, 95% CI = 0.30-0.87; P = 0.014), recessive (OR = 0.73, 95% CI = 0.59-0.90; P = 0.004) and dominant (OR = 0.40, 95% CI = 0.25-0.65; P < 0.001) genetic models. No effects of the HIF1A Ala588Thr polymorphism were found in risk of diabetes and diabetic complications. Taken together, these findings revealed the protective effect of HIF1A Pro582Ser polymorphism against diabetes and diabetic complications.

Iodine-promoted radical alkyl sulfuration of imidazopyridines with dialkyl azo compounds and elemental sulfur.

Dialkyl azo compounds were found to be effective alkyl radical sources for direct alkyl sulfuration with imidazopyridines using elemental sulfur under metal-free conditions. Iodine, an inexpensive and mild reagent, could promote alkyl sulfuration. A variety of quaternary cyanoalkyl radicals were successfully coupled with elemental sulfur. A subsequent C-H sulfuration of imidazopyridines afforded a diverse array of imidazopyridine derivatives bearing cyanoalkylthio groups. The cyano group could be modified and further underwent condensation with 2-aminothiazole to afford an interesting heterocyclic amide. Control experiments showed that iodine could greatly suppress the self-coupling of cyanoalkyl radicals, thus making the sulfuration proceed smoothly.

Sulfite-Promoted Synthesis of N-Difluoromethylthioureas via the Reaction of Azoles with Bromodifluoroacetate and Elemental Sulfur.

A sulfite-promoted transformation of azoles into N-difluoromethylthioureas through N-difluoromethylation and sulfuration has been developed. In this reaction, inexpensive ethyl bromodifluoroacetate and nontoxic elemental sulfur were used as the difluoromethylation and sulfuration reagents, respectively. A variety of azoles, including benzimidazoles, imidazoles, and triazoles, performed well to afford a broad range of azole thioureas in moderate to good yields.

Novel Bacillus cereus strain from electrokinetically remediated saline soil towards the remediation of crude oil.

A new strain SWH-15 was successfully isolated after initial electrokinetic remediation experiment using the same saline soil sampled from Shengli Oilfield, China. Four methods (morphological and biochemical characteristics, whole-cell fatty acid methyl esters (FAMEs) analysis, 16S rRNA sequence analysis and DNA G + C content and DNA-DNA hybridization analysis) were used to identify the taxonomic status of SWH-15 and confirmed that SWH-15 was a novel species of the Bacillus (B.) cereus group. Then, we assessed the degrading ability of the novel strain SWH-15 to crude oil through a microcosm experiment with four treatments, including control (CK), bioremediation using SWH-15 (Bio), electrokinetic remediation (EK), and combined bioremediation and electrokinetic remediation (Bio + EK). The results showed that the Bio + EK combined remediation treatment was more effective than the CK, Bio, and EK treatments in degrading crude oil contaminants. Bioaugmentation, by addition of the strain SWH-15 had synergistic effect with EK in Bio + EK treatment. Bacterial community analysis showed that electrokinetic remediation alone significantly altered the bacterial community of the saline soil. The addition of the strain SWH-15 alone had a weak effect on the bacterial community. However, the strain SWH-15 boosted the growth of other bacterial species in the metabolic network and weakened the impact of electrical field on the whole bacterial community structure in the Bio + EK treatment.

Effects of different remediation treatments on crude oil contaminated saline soil.

Remediation of the petroleum contaminated soil is essential to maintain the sustainable development of soil ecosystem. Bioremediation using microorganisms and plants is a promising method for the degradation of crude oil contaminants. The effects of different remediation treatments, including nitrogen addition, Suaeda salsa planting, and arbuscular mycorrhiza (AM) fungi inoculation individually or combined, on crude oil contaminated saline soil were assessed using a microcosm experiment. The results showed that different remediation treatments significantly affected the physicochemical properties, oil contaminant degradation and bacterial community structure of the oil contaminated saline soil. Nitrogen addition stimulated the degradation of total petroleum hydrocarbon significantly at the initial 30d of remediation. Coupling of different remediation techniques was more effective in degrading crude oil contaminants. Applications of nitrogen, AM fungi and their combination enhanced the phytoremediation efficiency of S. salsa significantly. The main bacterial community composition in the crude oil contaminated saline soil shifted with the remediation processes. γ-Proteobacteria, ß-Proteobacteria, and Actinobacteria were the pioneer oil-degraders at the initial stage, and Firmicutes were considered to be able to degrade the recalcitrant components at the later stage.

Mixing effects of understory plant litter on decomposition and nutrient release of tree litter in two plantations in Northeast China.

Understory vegetation plays a crucial role in carbon and nutrient cycling in forest ecosystems; however, it is not clear how understory species affect tree litter decomposition and nutrient dynamics. In this study, we examined the impacts of understory litter on the decomposition and nutrient release of tree litter both in a pine (Pinus sylvestris var. mongolica) and a poplar (Populus × xiaozhuanica) plantation in Northeast China. Leaf litter of tree species, and senesced aboveground materials from two dominant understory species, Artemisia scoparia and Setaria viridis in the pine stand and Elymus villifer and A. sieversiana in the poplar stand, were collected. Mass loss and N and P fluxes of single-species litter and three-species mixtures in each of the two forests were quantified. Data from single-species litterbags were used to generate predicted mass loss and N and P fluxes for the mixed-species litterbags. In the mixture from the pine stand, the observed mass loss and N release did not differ from the predicted value, whereas the observed P release was greater than the predicted value. However, the presence of understory litter decelerated the mass loss and did not affect N and P releases from the pine litter. In the poplar stand, litter mixture presented a positive non-additive effect on litter mass loss and P release, but an addition effect on N release. The presence of understory species accelerated only N release of poplar litter. Moreover, the responses of mass loss and N and P releases of understory litter in the mixtures varied with species in both pine and poplar plantations. Our results suggest that the effects of understory species on tree litter decomposition vary with tree species, and also highlight the importance of understory species in litter decomposition and nutrient cycles in forest ecosystems.

A first-principles study on the intrinsic asymmetric ferroelectricity of the SrTiO3-BaTiO3-CaTiO3 tricolor superlattice at the nanoscale.

We report a systematic theoretical study on the ferroelectric behavior of ultrathin three-component ferroelectric films, e.g., CaTiO3-BaTiO3-SrTiO3, sandwiched between electrodes. Using first-principles calculations we demonstrate that such structures have intrinsic asymmetric ferroelectricity which is robust even at the nanoscale. In addition, there exists a certain relationship between the polarization directions and geometric stacking sequences of the superlattices. Specifically, the lowest energy states always have polarizations pointing from CaTiO3 via BaTiO3 to SrTiO3, while the sequence in the metastable states is SrTiO3-BaTiO3-CaTiO3. Therefore we were able to distinguish one ferroelectric state from its opposite state by means of their geometric stackings along the polarization directions. Besides this, band alignment analysis reveals that such structures are well behaved at the metal/ferroelectric interface, confirming the credibility and reliability of our first-principles calculation. Our finding may suggest a controllable and unambiguous way to build ferroelectric and multiferroic tunnel junctions.

Epitaxial strain induced magnetic transitions and phonon instabilities in tetragonal SrRuO3.

Using density-functional theory calculations, we investigate the magnetic as well as the dynamical properties of tetragonal SrRuO3 (SRO) under the influence of epitaxial strain. It is found that both tensile and compressive strain in the xy-plane can induce an abrupt change in the magnetic moment of the Ru atom. In particular, under an in-plane compressive strain of ~4%, a ferromagnetic to nonmagnetic transition is induced, whereas for a tensile strain larger than 3%, the magnetic moment of Ru drops gradually with increase of the strain, exhibiting a weak ferromagnetic state. We find that these magnetic transitions can be qualitatively explained by the Stoner model. In addition, frozen-phonon calculations at the Γ point and phonon dispersion calculations reveal that structural instabilities can occur under both compressive and tensile strain. These instabilities are very similar to those of the ferroelectric perovskite oxides, even though SRO remains metallic in the range we studied. This might have an influence on the physical properties of oxide supercells having SRO as a constituent.