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Ferroptosis is a novel cell death form against drug-resistance through bypassing apoptosis, but its therapeutic efficacy triggered by traditional iron-based nanomaterials or classic drug inducers has been far from satisfactory due to the high glutathione (GSH) level in tumor cells and insufficient lipid peroxide production. Here we reported a combinational ferroptosis/apoptosis therapy approach by depleting GSH and downregulating GPX4 to disrupt redox homeostasis and amplify ferroptosis-related oxidation effect. In this study, we developed a ROS-responsive serum-resistant nanoparticles with a thioketal-crosslinked fluorinated polyethyleneimine PEI 1.8K (TKPF) as the core and wrapped with hyaluronic acid (HA) as the shell (TKPFH NP) to co-deliver shGPX4 and shMTHFD2 plasmids for cancer treatment. The highly efficient and tumor-selective gene carrier TKPFH NPs revealed outstanding transfection efficiency (~100 %) and sustained the efficiency (~50 %) even in media containing 90 % FBS. TKPFH NPs actively targeted CD44 receptors mediated by HA to enable efficient uptake by tumor cells and experienced surface charge conversion to induce subsequently lysosomal escape. Then the TKPF NPs were effectively disintegrated by the abundant ROS in cancer cells, which facilitated release of plasmids and avoided the cytotoxicity of cationic polymers. shGPX4 plasmid induced ferroptosis by producing ROS and lipid peroxides via downregulating GPX4, while shMTHFD2 triggered apoptosis by modulating NADPH/NADP and depleting GSH of the cancer cells. Moreover, GSH consumption resulted by shMTHFD2 indirectly suppressed GPX4 and further augmented ferroptosis, showing synergistic anticancer effect against B16-F10 cells. Taken together, the rationally designed dual-gene loaded TKPFH NPs provided a safe and high-performance platform aimed for enhanced ferroptosis-apoptosis combined anticancer efficacy based on gene therapy.

China has the most abundant tea resources in the world. In oder to scrutinize superior accessions suitable for popularization and planting, the quality characteristics of distinctive tea resources were analyzed by examining their key evaluation indexes and comprehensive evaluation methods. In this study, 29 indexes of 47 tea germplasms were detected, including agronomic characters, chemical compositions, quality of green tea and stress resistance. The key evaluation indexes were selected by factor analysis and cluster analysis, whereas the weight value of the indexes was determined by analytic hierarchy process (AHP) and entropy weight method. Furthermore, the comprehensive evaluation of tea varieties was carried out by grey correlation degree and entropy weight method. Our results showed that drastic differences of character indexes existed among tea varieties, and the 29 character indexes demonstrated complex information overlapping with each other. After simplification, 12 key evaluation indexes, namely score of green tea quality, total free amino acids, growth potential, water extract, yield, epigallocatechin gallate (EGCG), epigallocatechin (EGC), one bud one leaf stage, insect resistance, germination density, bud leaf color, and gallic acid (GA) were chosen. The weight value of each index was also determined. Since the rank of some varieties in these two evaluation methods was different, based on the comprehensive evaluation results of grey correlation degree method and entropy weight method, it was more rational to combine these two evaluation methods in selecting superior varieties. Consequently, nine excellent tea varieties were selected. This study not only provides an innovative method for comprehensive evaluation of tea resources, but also an approach to promote genetic improvement of the selected excellent tea varieties.

The coverage, thickness, and crystallinity of ZnIn2S4 (ZIS) shells on SiO2 core nanoparticles (SiO2@ZIS) were systematically investigated using microwave-assisted solvothermal methods aided by the addition of acid in ethanolic medium. The surface modification of the SiO2 cores with (3-mercaptopropyl)trimethoxysilane was found to be critical to generate a homogeneous coverage of ZnIn2S4. The SiO2@ZIS core-shell nanoparticles exhibited the best coverage but poor crystallinity when synthesized in pure ethanol, whereas best crystallinity but poor coverage was observed when synthesized in an aqueous solution. The addition of selected amounts of acid (HCl) led to improved crystallinity in the ethanolic medium. The thickness of the ZIS shell could be controlled in an ethanolic solution by judiciously varying the amounts of acid and the concentration of the ZIS precursor. Increasing the concentration of the ZIS precursor to twice the standard concentration in ethanolic solution with the addition of 100 μL of HCl afforded better crystallinity, homogeneous coverage, and optimal photocatalytic hydrogen production.

Background Nitrogen (N), referred to as a “life element”, is a macronutrient essential for optimal plant growth and yield production. Amino acid (AA) permease (AAP) genes play pivotal roles in root import, long-distance translocation, remobilization of organic amide-N from source organs to sinks, and other environmental stress responses. However, few systematic analyses of AAPs have been reported in Brassica napus so far. Results In this study, we identified a total of 34 full-length AAP genes representing eight subgroups (AAP1–8) from the allotetraploid rapeseed genome (AnAnCnCn, 2n = 4x = 38). Great differences in the homolog number among the BnaAAP subgroups might indicate their significant differential roles in the growth and development of rapeseed plants. The BnaAAPs were phylogenetically divided into three evolutionary clades, and the members in the same subgroups had similar physiochemical characteristics, gene/protein structures, and conserved AA transport motifs. Darwin’s evolutionary analysis suggested that BnaAAPs were subjected to strong purifying selection pressure. Cis-element analysis showed potential differential transcriptional regulation of AAPs between the model Arabidopsis and B. napus. Differential expression of BnaAAPs under nitrate limitation, ammonium excess, phosphate shortage, boron deficiency, cadmium toxicity, and salt stress conditions indicated their potential involvement in diverse nutrient stress responses. Conclusions The genome-wide identification of BnaAAPs will provide a comprehensive insight into their family evolution and AAP-mediated AA transport under diverse abiotic stresses. The molecular characterization of core AAPs can provide elite gene resources and contribute to the genetic improvement of crop stress resistance through the modulation of AA transport.

A novel visible-light-driven Cu/rGO/MoS2 (CRM) ternary nanostructure as a photocatalyst with high catalytic activity towards environmental purification using solar energy was successfully synthesized through a facile solvothermal method. It was found that the nanoflower structure of MoS2 increased the number of its exposed edges. Meanwhile rGO as a catalytic substrate played a role of charge-carrier channel to improve the separation of holes and electrons, which originated from the band gap absorption of MoS2. The content of Cu in photocatalyst affected photocatalytic performance obviously. And the optimal 30% Cu/rGO/MoS2 possessed the highest photocatalytic performance, which could be attributed to the improved separation of charges and synergistic effects among Cu, rGO and MoS2. The removal efficiency of Rhodamine B (RhB) over CRM was up to 100% in 5 min. CRM as a photocatalyst maintained good reproducibility and stability during 3 times of the recycle experiments. These results indicate CRM is a promising photocatalyst for degrading organic pollutants in wastewater.

Enhancers and promoters predominantly interact within large-scale topologically associating domains (TADs), which are formed by loop extrusion mediated by cohesin and CTCF. However, it is unclear whether complex chromatin structures exist at sub-kilobase-scale and to what extent fine-scale regulatory interactions depend on loop extrusion. To address these questions, we present an MNase-based chromosome conformation capture (3C) approach, which has enabled us to generate the most detailed local interaction data to date (20 bp resolution) and precisely investigate the effects of cohesin and CTCF depletion on chromatin architecture. Our data reveal that cis-regulatory elements have distinct internal nano-scale structures, within which local insulation is dependent on CTCF, but which are independent of cohesin. In contrast, we find that depletion of cohesin causes a subtle reduction in longer-range enhancer-promoter interactions and that CTCF depletion can cause rewiring of regulatory contacts. Together, our data show that loop extrusion is not essential for enhancer-promoter interactions, but contributes to their robustness and specificity and to precise regulation of gene expression.

BackgroundOilseed rape (B. napusL.) has great potential for phytoremediation of cadmium (Cd)-polluted soils due to its large plant biomass production and strong metal accumulation. Soil properties and the presence of other soluble compounds or ions, cause a heterogeneous distribution of Cd.ResultsThe aim of our study was to reveal the differential responses ofB. napusto different Cd abundances. Herein, we found that high Cd (50 μM) severely inhibited the growth ofB. napus, which was not repressed by low Cd (0.50 μM) under hydroponic culture system. ICP-MS assays showed that the Cd2+concentrations in both shoots and roots under 50 μM Cd were over 10 times higher than those under 0.50 μM Cd. Under low Cd, the concentrations of only shoot Ca2+/Mn2+and root Mn2+were obviously changed (both reduced); under high Cd, the concentrations of most cations assayed were significantly altered in both shoots and roots except root Ca2+and Mg2+. High-throughput transcriptomic profiling revealed a total of 18,021 and 1408 differentially expressed genes under high Cd and low Cd conditions, respectively. The biological categories related to the biosynthesis of plant cell wall components and response to external stimulus were over-accumulated under low Cd, whereas the terms involving photosynthesis, nitrogen transport and response, and cellular metal ion homeostasis were highly enriched under high Cd. Differential expression of the transporters responsible for Cd uptake (NRAMPs), transport (IRTsandZIPs), sequestration (HMAs,ABCs, andCAXs), and detoxification (MTPs,PCR,MTs, andPCSs), and some other essential nutrient transporters were investigated, and gene co-expression network analysis revealed the core members of these Cd transporters. Some Cd transporter genes, especiallyNRAMPsandIRTs, showed opposite responsive patterns between high Cd and low Cd conditions.ConclusionsOur findings would enrich our understanding of the interaction between essential nutrients and Cd, and might also provide suitable gene resources and important implications for the genetic improvement of plant Cd accumulation and resistance through molecular engineering of these core genes under varying Cd abundances in soils.

BackgroundCadmium (Cd) is a heavy metal with high toxicity that severely inhibits wheat growth and development. Cd easily accumulates in wheat kernels and enters the human food chain. Genetic variation in the resistance to Cd toxicity found in wheat genotypes emphasizes the complex response architecture. Understanding the Cd resistance mechanisms is crucial for combating Cd phytotoxicity and meeting the increasing daily food demand.ResultsUsing two wheat genotypes (Cd resistant and sensitive genotypes T207 and S276, respectively) with differing root growth responses to Cd, we conducted comparative physiological and transcriptomic analyses and exogenous application tests to evaluate Cd detoxification mechanisms. S276 accumulated more H2O2, O2−, and MDA than T207 under Cd toxicity. Catalase activity and levels of ascorbic acid (AsA) and glutathione (GSH) were greater, whereas superoxide dismutase (SOD) and peroxidase (POD) activities were lower in T207 than in S276. Transcriptomic analysis showed that the expression ofRBOHA,RBOHC, andRBOHEwas significantly increased under Cd toxicity, and two-thirds (22 genes) of the differentially expressedRBOHgenes had higher expression levels in S276 than inT207. Cd toxicity reshaped the transcriptional profiling of the genes involving the AsA-GSH cycle, and a larger proportion (74.25%) of the corresponding differentially expressed genes showed higher expression in T207 than S276. The combined exogenous application of AsA and GSH alleviated Cd toxicity by scavenging excess ROS and coordinately promoting root length and branching, especially in S276.ConclusionsThe results indicated that the ROS homeostasis plays a key role in differential Cd resistance in wheat genotypes, and the AsA-GSH cycle fundamentally and vigorously influences wheat defense against Cd toxicity, providing insight into the physiological and transcriptional mechanisms underlying Cd detoxification.

Objective To investigate the predictive value of hyperhomocysteinaemia (HHcy) for obstructive coronary artery disease (CAD) in an Asian population in northern China. Methods This retrospective study enrolled patients at their first cardiac assessment and assigned them to an obstructive CAD group or a non-obstructive CAD group according to the coronary angiography results. HHcy was defined as a homocysteine (Hcy) level > 15 µmol/l. Results This study enrolled 2987 participants: 1172 in the non-obstructive CAD group and 1815 in the obstructive CAD group. Hcy level in the obstructive CAD group was significantly higher than in the non-obstructive CAD group. The proportion of patients with HHcy in the obstructive CAD group was significantly greater than in the non-obstructive CAD group. Multivariate logistic regression analysis demonstrated that HHcy was independently correlated with obstructive CAD in both young (aged ≤ 55 years) and old patients (aged > 55 years). HHcy showed a higher sensitivity (93.1%), specificity (86.1%) and accuracy (90.0%) for obstructive CAD. The odds ratio for HHcy was 84.2. The Kappa value (0.8) showed substantial agreement between obstructive CAD and HHcy. Conclusions HHcy was associated with obstructive CAD and may be a potentially independent risk factor for obstructive CAD with good predictive value.

In higher eukaryotes, many genes are regulated by enhancers that are 104–106 base pairs (bp) away from the promoter. Enhancers contain transcription-factor-binding sites (which are typically around 7–22 bp), and physical contact between the promoters and enhancers is thought to be required to modulate gene expression. Although chromatin architecture has been mapped extensively at resolutions of 1 kilobase and above; it has not been possible to define physical contacts at the scale of the proteins that determine gene expression. Here we define these interactions in detail using a chromosome conformation capture method (Micro-Capture-C) that enables the physical contacts between different classes of regulatory elements to be determined at base-pair resolution. We find that highly punctate contacts occur between enhancers, promoters and CCCTC-binding factor (CTCF) sites and we show that transcription factors have an important role in the maintenance of the contacts between enhancers and promoters. Our data show that interactions between CTCF sites are increased when active promoters and enhancers are located within the intervening chromatin. This supports a model in which chromatin loop extrusion1 is dependent on cohesin loading at active promoters and enhancers, which explains the formation of tissue-specific chromatin domains without changes in CTCF binding. Micro Capture-C allows physical contacts to be determined at base-pair resolution, revealing that transcription factors have an important role in the maintenance of the contacts between enhancers and promoters.

Straw sizes were found to affect the methylmercury (MeHg) accumulation in rice grains induced by straw incorporation. The mechanism behind, however, still remains unclear. Here, we incorporated rice straw in different sizes (powder, 2 cm and 5 cm) into a Hg-contaminated paddy soil. Our results showed that straw sizes regulated the release of different fractions of organic matter (OM) in straw residues and further Hg methylation in paddy soil. The easily degradable OM (EDOM) was a key driving factor that facilitated net Hg methylation, though it only occupied a small fraction (1.12–3.12%) of the soil OM. Powdered straw reduced the duration of net Hg methylation by 74.39% compared to 5 cm straw, resulting in a strong and rapid net Hg methylation in paddy soil before the rice flowering. After the release of EDOM, the humified OM dominated in paddy soil and bound to MeHg, leading to less MeHg being transported to rice grains during the grain filling. Powdered straw decreased MeHg accumulation by 25.32% in the mature rice grains compared with 5 cm straw. Our study suggests that straw powdering before incorporation provides a feasible pathway for reducing MeHg accumulation in rice grains induced by straw incorporation.

Lin28a has been found to enhance glucose uptake and insulin sensitivity. Lin28a alleviates cardiac dysfunction under various pathological conditions. However, the effects and underlying mechanisms of Lin28a on diabetic cardiomyopathy (DCM) are not well-understood. The aim of this study was to determine whether Lin28a protects against DCM and the potential mechanisms. Two to three days old mouse neonatal primary cardiomyocytes were randomized for treatment with adenoviruses harboring Lin28a and mammalian sterile 20-like kinase 1 (Mst1) short hairpin RNA, 48 hr before culturing in normal or high glucose medium. Cardiomyocyte apoptosis, autophagy, mitochondrial morphology, adenosine triphosphate content, and cytokine levels in the high glucose or normal conditions were observed between all groups. Either Lin28a overexpression or Mst1 knockdown alleviated mitochondrial ultrastructure impairment, decreased cytokine levels, inhibited apoptosis, and enhanced autophagy in primary neonatal mouse cardiomyocytes treated with high glucose. Importantly, the protective effects of Lin28a and Mst1 disappeared after treatment with 3-methyladenine, an autophagy inhibitor. Interestingly, in Mst1 knockdown cardiomyocytes, Lin28a overexpression failed to further enhance autophagy and alleviate high glucose-induced cardiomyocyte injury, which implies the protective roles of Lin28a counteracting high glucose-induced cardiomyocyte injury are dependent on Mst1 inhibition. Furthermore, co-immunoprecipitation and immunofluorescence double staining suggested that there were no direct interactions between Mst1 and Lin28a. Lin28a increased the expression of Akt, which inhibited the activation of Mst1-mediated apoptotic pathways.

Nitrogen is essential for plant growth and crop productivity; however, nitrogen use efficiency (NUE) decreases with increasing N supply, resulting in a waste of resources. Molecular mechanisms underlying low-nitrogen (LN)-mediated enhancement of NUE are not clear. We used high-NUE Brassica napus genotype H (Xiangyou 15), low-NUE B. napus genotype L (814), and Arabidopsis mutant aux1 to elucidate the mechanism underlying the changes in NUE under different rates of N fertilizer application. NUE of B. napus increased under LN, which enhanced N uptake ability by regulating root system architecture and plasma membrane H+-ATPase activity; AUX1 was involved in this process. Additionally, BnNRT1.5 was upregulated and BnNRT1.8 was downregulated under LN, whereby more N was transferred to the shoot through enhanced N transport. Observed changes in photosynthesis under LN were associated with N assimilation efficiency. Our study provides new insights into the mechanisms of plant adaptation to the environment.

A multiomics approach encompassing morphophysiology, ionomic profiling, whole-genome resequencing, transcriptomics, and high-resolution metabolomics reveals that differences in cadmium resistance between two rapeseed cultivars is determined by subcellular reallocation., Oilseed rape (Brassica napus) has great potential for phytoremediation of cadmium (Cd)-polluted soils due to its large plant biomass production and strong metal accumulation. Enhanced plant Cd resistance (PCR) is a crucial prerequisite for phytoremediation through hyper-accumulation of excess Cd. However, the complexity of the allotetraploid genome of rapeseed hinders our understanding of PCR. To explore rapeseed Cd-resistance mechanisms, we examined two genotypes, ‘ZS11’ (Cd-resistant) and ‘W10’ (Cd-sensitive), that exhibit contrasting PCR while having similar tissue Cd concentrations, and characterized their different fingerprints in terms of plant morphophysiology (electron microscopy), ion abundance (inductively coupled plasma mass spectrometry), DNA variation (whole-genome resequencing), transcriptomics (high-throughput mRNA sequencing), and metabolomics (ultra-high performance liquid chromatography-mass spectrometry). Fine isolation of cell components combined with ionomics revealed that more Cd accumulated in the shoot vacuoles and root pectins of the resistant genotype than in the sensitive one. Genome and transcriptome sequencing identified numerous DNA variants and differentially expressed genes involved in pectin modification, ion binding, and compartmentalization. Transcriptomics-assisted gene co-expression networks characterized BnaCn.ABCC3 and BnaA8.PME3 as the central members involved in the determination of rapeseed PCR. High-resolution metabolic profiles revealed greater accumulation of shoot Cd chelates, and stronger biosynthesis and higher demethylation of root pectins in the resistant genotype than in the sensitive one. Our comprehensive examination using a multiomics approach has greatly improved our understanding of the role of subcellular reallocation of Cd in the determination of PCR.

A Cu(I)-catalyzed [3 + 2] intramolecular cycloaddition reaction of N-indole-tethered cyclopropenes is presented in this paper. This reaction starts from the formation of π-allyl cationic intermediate or its resonance-stabilized metal carbenoid intermediate upon activation of cyclopropene with Cu(I) catalyst and a Friedel-Crafts-type cyclization to give functionalized hydrogenated diazabenzo[ a]cyclopenta[ cd]azulenes in good to excellent yields along with moderate to good dr values. The asymmetric variant of this cycloaddition reaction can be realized, giving the desired products with moderate ee values.

Two new Dy2 compounds, namely, [Dy2(dbm)4(H2L)(CH3O)(CH3OH)] (1) and [Dy2(dbm)5(H2L)] (2) (dbm = dibenzoylmethane, H3L = (2E,N′E)-2-(hydroxyimino)-N′-(pyridin-2-ylmethylene)propanehydrazide, based a polydentate Schiff base ligand have been synthesized, structurally and magnetically characterized. The single-crystal X-ray diffraction research show that both compounds 1 and 2 are binuclear structures. The only difference is that two methanol molecules coordinated to Dy(III) ion in 1 instead of a dbm− coordinated to Dy(III) ion in 2. Magnetic property measurements indicate that they exhibit distinct slow magnetic relaxation behaviors (ΔE/kB = 0.87 K for 1 and ΔE/kB = 18.68 K for 2). This work revealed that the different solvent induced slight disparate structural and magnetic behaviors of two Dy2 compounds, which may provide an effective approach for tuning slow magnetization relaxation behaviors in polynuclear Ln-clusters.

In search of simple approaches to rationally modulate the single-molecule magnet behaviors in polynuclear lanthanide clusters, a new system containing two structurally closely related rhombus-shaped Dy4 clusters, Dy4(tmhd)4L6(μ3-OH)2·5CH3CN (1) and Dy4(acac)4L6(μ3-OH)2 (2) (HL = 5-(4-ethyoxylbenzylidene)-8-hydroxylquinoline, Htmhd = 2,2,6,6-tetramethyl-3,5-heptanedione and Hacac = acetylacetonate), have been obtained by employing two dysprosium β-diketonate salts to react with a bidentate Schiff base ligand (HL). The two Dy4 clusters have similar structures and possess a structure in which four Dy3+ ions remain in a perfect plane with a rhombus-shaped geometric construction. Dynamic magnetic analysis revealed different single-molecule magnet (SMM) behaviors occurs in 1 and 2. Under zero direct-current (dc) field, 1 displays typical SMMs behavior with ΔE/kB = 39.6 K and τ0 = 2.1 × 10−6 s. However, for 2, a peculiar feature of the χ″ versus temperature curves is that more than two peaks that are frequency-dependent are revealed, indicating the occurrence of multifold relaxation processes that lead to two ΔE/kB (31.3 K and 81.6 K) and pre-exponential factors (τ0 = 3.1 × 10−6 s, τ0 = 2.2 × 10−7 s).

Brazing is an effective technique for joining tungsten and steel. However, the high residual stresses are produced due to the different coefficients of thermal expansions between tungsten and steel. Compared with the direct brazing with BNi-2 foil filler, BNi-2/Cu/ BNi-2 multiple interlayer was used as filler to minimize the residual stresses between tungsten and 316L steel. The brazing experiments were conducted at 1050 °C for 25 min using Cu foils with different thickness. The results show that tungsten and 316L steel have been successfully joined by brazing. The intermetallic compound of NiW formed at the W/BNi-2 interface, which was detrimental to the strength of the joint. The microhardness of different diffusion zones is higher than that of the substrates owing to the formation of intermetallic compound and solid solution. All specimens of shear testing fractured at the W/BNi-2 interface close to W substrate, and the average strength of joints was 197, 275 and 268 MPa with multiple interlayer thickness of 0.2 , 0.1 and 0.05 mm copper foil, respectively, while the average strength of joints was 143 MPa with BNi-2 foil filler. The significant increase in the joint shear strength can be ascribed to the Cu foil in the multiple interlayer because of with excellent plasticity and toughness. Accepted version This work is supported by National Magnetic Confinement Fusion Program (Grant Nos. 2014GB121001 and 2014GB121001B) and The Foundation of Laboratory of Nonferrous Metal material and Processing Engineering of Anhui Province (15CZS08031).

Enhancers are DNA sequences that enable complex temporal and tissue-specific regulation of genes in higher eukaryotes. Although it is not entirely clear how enhancer-promoter interactions can increase gene expression, this proximity has been observed in multiple systems at multiple loci and is thought to be essential for the maintenance of gene expression. Bromodomain and Extra-Terminal domain (BET) and Mediator proteins have been shown capable of forming phase condensates and are thought to be essential for super-enhancer function. Here, we show that targeting of cells with inhibitors of BET proteins or pharmacological degradation of BET protein Bromodomain-containing protein 4 (BRD4) has a strong impact on transcription but very little impact on enhancer-promoter interactions. Dissolving phase condensates reduces BRD4 and Mediator binding at enhancers and can also strongly affect gene transcription, without disrupting enhancer-promoter interactions. These results suggest that activation of transcription and maintenance of enhancer-promoter interactions are separable events. Our findings further indicate that enhancer-promoter interactions are not dependent on high levels of BRD4 and Mediator, and are likely maintained by a complex set of factors including additional activator complexes and, at some sites, CTCF and cohesin., The role of BRD4 and Mediator in regulating enhancer-promoter interactions is poorly understood. Here the authors find that treatment with BET inhibitors or pharmacological degradation of BRD4 disrupts transcription while having very little effect on enhancer-promoter interactions.

A copper(I)-catalyzed three-component addition–cycloisomerization difunctionalization reaction of 1,3-enyne-ACPs with Togni I reagent and TMSCN under mild reaction conditions has been developed, affording 3-trifluoroethylcyclopenta[b]naphthalene-4-carbonitrile derivatives. The reaction proceeded through a copper(I)-catalyzed 1,4-addition of conjugated 1,3-enynes via a radical relay process and aromatic cycloisomerization of allene–ACP intermediates.

Background Salinity severely inhibit crop growth, yield, and quality worldwide. Allotetraploid rapeseed (Brassica napus L.), a major glycophyte oil crop, is susceptible to salinity. Understanding the physiological and molecular strategies of rapeseed salinity resistance is a promising and cost-effective strategy for developing highly resistant cultivars. Results First, early leaf senescence was identified and root system growth was inhibited in rapeseed plants under severe salinity conditions. Electron microscopic analysis revealed that 200 mM NaCl induced fewer leaf trichomes and stoma, cell plasmolysis, and chloroplast degradation. Primary and secondary metabolite assays showed that salinity led to an obviously increased anthocyanin, osmoregulatory substances, abscisic acid, jasmonic acid, pectin, cellulose, reactive oxygen species, and antioxidant activity, and resulted in markedly decreased photosynthetic pigments, indoleacetic acid, cytokinin, gibberellin, and lignin. ICP-MS assisted ionomics showed that salinity significantly constrained the absorption of essential elements, including the nitrogen, phosphorus, potassium, calcium, magnesium, iron, mangnese, copper, zinc, and boron nutrients, and induced the increase in the sodium/potassium ratio. Genome-wide transcriptomics revealed that the differentially expressed genes were involved mainly in photosynthesis, stimulus response, hormone signal biosynthesis/transduction, and nutrient transport under salinity. Conclusions The high-resolution salt-responsive gene expression profiling helped the efficient characterization of central members regulating plant salinity resistance. These findings might enhance integrated comprehensive understanding of the morpho-physiologic and molecular responses to salinity and provide elite genetic resources for the genetic modification of salinity-resistant crop species.

Background: Epilepsy is a chronic, complex, unprovoked, and recurrent disorder of the nervous system that affected several people worldwide. Phyllanthus amarus (PA) has been documented to have neuroprotective potential. Aim: To evaluate the potential of standardized extract of PA and its possible mechanism of action against the Pentylenetetrazol (PTZ)-induced convulsion and kindling associated post-ictal depression in experimental mice. Materials and Methods: Phyllathin was isolated from methanolic extract of PA and well-characterized using HPTLC, ESI-MS/MS, and LC/MS. Phyllathin containing a standardized extract of PA (50, 100, and 200 mg/kg) was administered in convulsed and kindled mice, followed by an assessment of various parameters. Results: The spectral analysis confirmed the molecular formula and weight of phyllanthin as C24H34O6 and 418.2342 Da. PA (100 and 200 mg/kg) significantly ameliorated PTZ-induced ( p < 0.05) duration, onset of tonic-clonic convulsion, and mortality in mice. It also significantly attenuated ( p < 0.05) PTZ-induced kindling in mice. Alteration in brain GABA, dopamine, and glutamate, Na+K+ATPase, Ca+2-ATPase activities, and oxido-nitrosative stress in kindled mice was significantly restored ( p < 0.05) by PA treatment. It also significantly ( p < 0.05) down-regulated brain mRNA expressions of NF-κB, TNF-α, IL-1β, COX-2, and TLR-4. Histological aberrations induced by PTZ in the brain of a kindled rat was significantly ( p < 0.05) ameliorated by PA. Conclusion: Phyllanthin containing a standardized extract of PA exerts its antiepileptic potential via balancing excitatory (glutamate) and inhibitory (GABA) brain monoamines, voltage-gated ion channels (Na+K+/Ca+2-ATPase) and inhibition of NF-κB/TLR-4 pathway to ameliorate neuroinflammation (TNF-α, IL-1β, and COX-2) in experimental mice.

Two types of polymer latexes and one expansive agent were employed to investigate their effects on the resistance of cement asphalt (CA) pastes to sulfuric acid. Mercury intrusion porosimet...

The transformations of cyclopropenes have attracted the attention of organic chemists for decades. As readily accessible strained carbocycles, cyclopropenes show a diverse range of reactivities. This feature article focuses on the developments of cyclopropenes from 2016 until the end of 2019, including reactions through vinylmetal carbenes, reactions through metal complex insertion, addition reactions with 1,3-dipole, radical reactions of cyclopropenes, and reactions of highly reactive in situ generated cyclopropenes. In addition, several new synthetic methods and applications of cyclopropenes are also disclosed in this paper.

Nitrogen (N) is essential for plant growth and crop productivity. Organic N is a major form of remobilized N in plants&rsquo, response to N limitation. It is necessary to understand the regulatory role of N limitation adaption (NLA) in organic N remobilization for this adaptive response. Transcriptional and proteomic analyses were integrated to investigate differential responses of wild-type (WT) and nla mutant plants to N limitation and to identify the core organic N transporters targeted by NLA. Under N limitation, the nla mutant presented an early senescence with faster chlorophyll loss and less anthocyanin accumulation than the WT, and more N was transported out of the aging leaves in the form of amino acids. High-throughput transcriptomic and proteomic analyses revealed that N limitation repressed genes involved in photosynthesis and protein synthesis, and promoted proteolysis, these changes were higher in the nla mutant than in the WT. Both transcriptional and proteomic profiling demonstrated that LHT1, responsible for amino acid remobilization, were only significantly upregulated in the nla mutant under N limitation. These findings indicate that NLA might target LHT1 and regulate organic N remobilization, thereby improving our understanding of the regulatory role of NLA on N remobilization under N limitation.

Four new acyloxy bridged LnIII2 compounds [Ln2(L)2(acac)2(EtOH)2] (Ln(III) = Gd (1), Tb (2), Dy (3), and Ho (4), Hacac = acetylacetone, and H2L = pyridine-2-carboxylic acid (3-ethoxy-2-hydroxy-benzylidene)-hydrazide) have been prepared by a polydentate Schiff base ligand under solvothermal condition. The single-crystal X-ray structure study reveals that 1-4 are isostructural and contain a parallelogram Ln2O2 core. Magnetic study reveals that antiferromagnetic interaction exists in compound 1. More importantly, compound 1 displays well cryogenic magnetic refrigeration property (−ΔSm = 28.2 J kg−1 K−1, T = 2.0 K and ΔH =70 kOe); while compound 3 exhibits evident single-molecule magnet behavior under zero-field condition (ΔE/kB = 26.8 K, τ0 = 1.05 × 10−7 s).

A Cu(I)-catalyzed coupling and cycloisomerization of diazo compounds with terminal yne-alkylidenecyclopropanes (ACPs) has been presented. This reaction starts from the formation of an allenic intermediate in the Cu(I)-catalyzed cross-coupling reaction of a diazo compound with terminal alkyne in yne-tethered ACP and then undergoes a domino cycloisomerization of a 6π-electrocyclization and cyclopropane ring-opening rearrangement to give functionalized cyclopenta[ b]naphthalene derivatives in moderate to excellent yields under mild conditions.

Lamb-dips of the ro-vibrational lines of 12C2H2 near 789 nm were recorded using cavity ring-down saturation spectroscopy. Calibrated by an optical frequency comb, frequencies of 45 acetylene lines were determined with an accuracy of 1.1 × 10 − 7 cm − 1 ( δ ν / ν = 8 × 10 − 12 ), which is over two orders of magnitude more accurate than previous Doppler-limited studies. An averaged shift of about 0.01 cm − 1 were found by comparing the upper energies obtained in this work to those recently presented by Chubb et al. from a MARVEL analysis.

Intercropping Persian walnut (Juglans regia L.) and wheat (Triticum aestivum L.) have been widely applied in the Xinjiang Uygur Autonomous Region in Northwest China as a means of reducing soil and water losses and improving both land-use efficiency and economic returns. To understand how changes in soil conditions and nematode community structure can contribute to the evaluation of wheat–walnut intercropping systems from the view of soil fauna, we studied the soil nematode community in wheat rhizosphere soil under both monoculture and intercropping systems for 2 years. The results showed that the pH and total nitrogen and organic matter contents in intercropping systems with walnut trees were decreased compared with those of system with wheat alone. The nematode communities differed significantly between intercropping and monoculture plots, e.g., Rhabditis and Dorylaimus were dominant only in monocultures, whereas Tylenchus was dominant only in intercropping systems. Moreover, intercropping systems resulted in decreased nematode abundance, increased proportions of plant-feeding nematodes, and decreased omnivores/predators, particularly in the second year (2012). The decrease in diversity indices (H′) and ecological indices (WI, EI, and SI) of the nematode communities indicated high disturbance and low soil fertility in intercropping systems. Overall, wheat intercropping with walnut had a significant negative effect on wheat rhizosphere soil conditions.

Ammonium (NH4+) toxicity has become a serious ecological and agricultural issue owing to increasing soil nitrogen inputs and atmospheric nitrogen deposition. There is accumulating evidence for the mechanisms underlying NH4+-tolerance in rice and Arabidopsis, but similar knowledge for dryland crops is currently limited. We investigated the responses of a natural population of allotetraploid rapeseed to NH4+ and nitrate (NO3-) and screened one NH4+-tolerant genotype (T5) and one NH4+-sensitive genotype (S211). Determination of the shoot and root NH4+ concentrations showed that levels were higher in S211 than in T5. 15NH4+ uptake assays, glutamine synthetase (GS) activity quantification, and relative gene transcriptional analysis indicated that the significantly higher GS activity observed in T5 roots than that in S211 was the main reason for its NH4+-tolerance. In-depth metabolomic analysis verified that Gln metabolism plays an important role in rapeseed NH4+-tolerance. Furthermore, adaptive changes in carbon metabolism were much more active in T5 shoots than in S211. Interestingly, we found that N-glycosylation pathway was significantly induced by NH4+, especially the mannose metabolism, which concentration was 2.75-fold higher in T5 shoots than in S211 with NH4+ treatment, indicating that mannose may be a metabolomic marker which also confers physiological adaptations for NH4+ tolerance in rapeseed. The corresponding amino acid and soluble sugar concentrations and gene expression in T5 and S211 were consistent with these results. Genomic sequencing identified variations in the GLN (encoding GS) and GMP1 (encoding the enzyme that provides GDP-mannose) gene families between the T5 and S211 lines. These genes will be utilized as candidate genes for future investigations of the molecular mechanisms underlying NH4+ tolerance in rapeseed.

Designing theranostic agents that are responsive to weakly acidic tumor microenvironments for optimized imaging and therapeutic effects is of great interest in nanomedicine. In the current study, we constructed a pH-triggered smart theranostic system based on pH-responsive Prussian blue, which shows good performance in the photoacoustic imaging (PAI)-guided photothermal therapy (PTT) of tumors. Precursors to Prussian blue, namely ferrous and ferricyanide ions, were separately encapsulated into pH-responsive hydrogels that only degraded under acidic conditions. In vitro results showed that the encapsulated ions were gradually released in acidic buffer, accompanied by hydrogel degradation. After the resultant hydrogel was mixed and intratumorally injected into tumor-bearing mice, the encapsulated ferrous ions and ferricyanide ions were successfully released in the acidic tumor environment, allowing the in situ formation of Prussian blue in the tumor area. This provided an efficient theranostic agent for PAI-guided PTT of cancer. Our research highlights the potential of Prussian blue-based theranostic agents for the precise diagnosis and treatment of cancer.

The present study assessed the effects of microRNA‑1 (miR‑1) on the development of osteoarthritis using human tissues and a Col2a1‑Cre‑ERT2/GFPfl/fl‑RFP‑miR‑1 mouse model of osteoarthritis. Human cartilage tissues (n=20) were collected for reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), histological analysis and immunohistochemistry experiments. A transgenic mouse model of osteoarthritis was established by subjecting Col2a1‑Cre‑ERT2/GFPfl/fl‑RFP‑miR‑1 transgenic mice to anterior cruciate ligament transection (ACLT). Mice were subjected to radiography and in vivo fluorescence molecular tomography (FMT), while mouse tissues were collected for histological analysis, RT‑qPCR and Safranin O staining. It was found that the miR‑1 level was downregulated, whereas the levels of Indian hedgehog (Ihh), as well as those of its downstream genes were upregulated in human osteoarthritic cartilage. In the transgenic mice, treatment with tamoxifen induced miR‑1, as well as collagen, type II (Col2a1) and Aggrecan (Acan) expression; however, it decreased Ihh, glioma‑associated oncogene homolog (Gli)1, Gli2, Gli3, smoothened homolog (Smo), matrix metalloproteinase (MMP)‑13 and collagen type X (Col10) expression. Safranin O staining revealed cartilage surface damage in the non‑tamoxifen + ACLT group, compared with that in the tamoxifen + ACLT group. Histologically, an intact cartilage surface and less fibrosis were observed in the tamoxifen + ACLT group. Immunohistochemistry revealed that the protein expression of Ihh, Col10, and MMP‑13 was significantly higher in the joint tissues of the non‑tamoxifen + ACLT group than in those of the tamoxifen + ACLT group. However, Col2a1 expression was lower in the joint tissues of the non‑tamoxifen + ACLT group than in those of the tamoxifen + ACLT group. The results of RT‑qPCR and FMT further confirmed these findings. On the whole, the findings of the present study demonstrate that miR‑1 expression protects against osteoarthritis‑induced cartilage damage and gene expression by inhibiting Ihh signaling.

Although WRKY transcription factors (TFs) are known to be involved in the regulation of plant root development, the mechanisms by which these TFs regulate plant tolerance to ammonium (NH4+) toxicity remain unclear. To identify the molecular mechanisms underlying NH4+-induced repression of primary root growth and NH4+ sensitivity in Arabidopsis, wild-type (Col-0) and mutant (wrky23) plants were treated with 10 mM KNO3 (control) or 5 mM (NH4)2SO4 (NH4+ toxicity) for 7 days. Under NH4+ toxicity, the fresh weight of wrky23 mutant was significantly lower than that of Col-0 plants, and the NH4+ concentration in wrky23 roots was significantly higher than that in Col-0 roots. However, we observed no significant differences between the two genotypes under the control treatment. Ammonium transporter AMT1;2 expression was induced in wrky23 roots but not in Col-0 roots. The transcript levels of cytosolic glutamine synthetase-encoding genes and activity of glutamine synthetase did not differ significantly between wrky23 and Col-0. Furthermore, the fluorescence and staining patterns of DR5::GFP and DR5::GUS, respectively, were more pronounced under NH4+ toxicity than under the control treatment. Collectively, our results indicate that AMT1;2 expression was induced in the wrky23 mutant in response to NH4+ toxicity, leading to NH4+ accumulation in the roots and primary root growth repression. Under NH4+ toxicity, both auxin transport and distribution were affected, and auxin accumulation in the root tips inhibited primary root growth in the wrky23 mutant. Our study provides important insights into the molecular mechanisms by which WRKY23 TF regulates plant responses to NH4+ toxicity.

As an erosional landform, the formation processes of Danxia landform are controlled by internal and external forces as well as lithologic properties. Using field data, we studied the role of lithologic properties on the formation of Danxia landform in Kongtongshan National Geopark, northwest China, through a series of experiments, including uniaxial compressive strength, identification analysis under polarizing microscope, X-ray diffraction analysis, inductively coupled plasma-mass spectrometry analysis, and scanning electron microscopy. The results show that the diagenesis degree, mineral composition, cement composition, degree of cementation, geochemical composition and element contents, and micro-structure influenced the structure and anti-weathering and anti-erosion abilities of the Danxia rock mass. Differential weathering of rock in different environments was an important force shaping the different types of Danxia landform. Weathering failure of the Danxia rock mass was the result of multiple combined factors; as well as lithology, other factors, such as those induced during tectonic uplift (i.e., faulting, jointing, and fracturing) and climate, cannot be neglected. Therefore, lithology played an important role in the structural development of Danxia landform, and different lithologies influenced its weathering rate and formation processes. Our findings can provide a reference for revealing the microscopic development of Danxia landform in arid and semi-arid areas.

Priming haematopoietic stem/progenitor cells (HSPCs)in vitrowith specific chromatin modifying agents and cytokines under serum-free-conditions significantly enhances engraftable HSC numbers. We extend these studies by culturing human CD133+ HSPCs on nanofibre scaffolds to mimic the niche for 5-days with the HDAC inhibitor Scriptaid and cytokines. Scriptaid increases absolute Lin−CD34+CD38−CD45RA−CD90+CD49f+ HSPC numbers, while concomitantly decreasing the Lin−CD38−CD34+CD45RA−CD90− subset. Hypothesising that Scriptaid plus cytokines expands the CD90+ subset without differentiation and upregulates CD90 on CD90− cells, we sorted, then cultured Lin−CD34+CD38−CD45RA−CD90− cells with Scriptaid and cytokines. Within 2-days and for at least 5-days, most CD90− cells became CD90+. There was no significant difference in the transcriptomic profile, by RNAsequencing, between cytokine-expanded and purified Lin−CD34+CD38−CD45RA−CD49f+CD90+ cells in the presence or absence of Scriptaid, suggesting that Scriptaid maintains stem cell gene expression programs despite expansion in HSC numbers. Supporting this, 50 genes were significantly differentially expressed between CD90+ and CD90− Lin−CD34+CD38−CD45RA−CD49f+ subsets in Scriptaid-cytokine- and cytokine only-expansion conditions. Thus, Scriptaid treatment of CD133+ cells may be a useful approach to expanding the absolute number of CD90+ HSC, without losing their stem cell characteristics, both through direct effects on HSC and potentially also conversion of their immediate CD90− progeny into CD90+ HSC.

Diffusion bonding is an effective technique for joining dissimilar metals. In this paper, tungsten and MA956 steel were diffusion-bonded by Spark Plasma Sintering (SPS) technique with titanium (Ti) foil as an interlayer. The bonded joints were evaluated by metallographic analysis and mechanical tests, and the results reveal that all W/Ti/MA956 joints were well bonded by efficient SPS technique. Microstructure analysis showed that W-Ti solid solution formed at W/Ti interface; reaction phases at Ti/MA956 steel interface varied with the joining temperature, e.g. intermetallics phases FeTi for 850 °C, FeTi, Fe2Ti and Cr2Ti for 900 °C and 950 °C joining temperature. The peak value of microhardness occurred at the interfaces of Ti/MA956 steel owing to the formation of intermetallic compound. All specimens of shear testing fractured at the Ti/MA956 steel interface close to MA956, and the average shear strength of joints was 182 MPa, 228 MPa and 164 MPa bonded at 850 °C, 900 °C and 950 °C respectively. Accepted version This work was supported by National Magnetic Confinement Fusion Program [2014GB121001 and 2014GB121001B].

Progress at elimination of malaria is limited by the challenges of reaching large rural population and ensuring patient adherence to adequate pharmacologic treatment. In the present study, a novel material (octadecylamine modified chondroitin sulfate) was synthesized, to fabricate a long acting release meshy gel system as an efficient weapon for protracted warfare to malaria. Ivermectin loaded meshy gels (IVM-MG) composed of different amount of phospholipids, triglyceride and modified chondroitin sulfate were formulated. They were in aqueous state with low viscosity before injection, but rapidly turned into gel state with significantly increased viscosity upon exposure to an aqueous environment after injection. In vitro study proved a sustained released effect in different releasing media. In vivo study showed no irritation at injection site and slowly drug release over a 30-day release period in rat model. Among the three IVM-MG formulations, IVM-MG-3 with the highest amount of octadecylamine modified chondroitin sulfate presented the highest viscosity increase after solution-gel transition, the least initial burst release, and the longest sustained release effect over 30 days in rat model. Furthermore, by using mathematical models, IVM-MG system could boost the efficacy of mass drug administration toward malaria elimination goals. Meshy gel systems for long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases of which treatment adherence is essential for their efficacy.

Diabetic cardiomyopathy (DCM) is a form of idiopathic heart disease, with signs including hypertrophy of myocardial cells, hypertension-independent fibrosis and coronary artery disease. Considering the involvement of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in diabetes, it was hypothesized that DDAH2 may be beneficial to cardiac function and myocardial fibrosis during the progression of DCM with involvement of the DDAH/asymmetric NG, NGdimethyl-L-arginine (ADMA)/nitric oxide synthase (NOS)/nitric oxide (NO) signaling pathway. Following establishment of diabetic rat models, diabetes-related blood biochemical indices and cardiac function were measured in diabetic rats treated with lentivirus expressing DDAH2, short hairpin RNA against DDAH2, or L-NNA (inhibitor of NOS) to identify the roles of DDAH2 in DCM. The functional roles of DDAH2 in DCM were further determined through detection of the levels of collagen I, matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2 (TIMP2). The H9C2 myocardial cell line was selected for in vitro experiments. The effects of DDAH2 on the migration of myocardial cells under high glucose conditions were also examined. To further investigate the underlying regulatory mechanism of DDAH2 in DCM, the contents of ADMA and NO, and the activities of DDAH and NOS were observed. The DCM model rats treated with DDAH2 exhibited reduced left ventricular end-diastolic pressure, and decreased blood glucose, total cholesterol, triglyceride, fasting blood glucose, and fasting insulin levels, but exhibited increased left ventricular systolic pressure and maximum rate of left ventricular pressure rise/fall levels in myocardial tissues. Myocardial cells under high glucose conditions treated with DDAH2 showed reductions in collagen I, MMP2 and TIMP2, indicating that DDAH2 reduced cell migration. Decreased levels of ADMA and NO but increased levels of DDAH and NOS were observed following treatment with DDAH2, indicating that the DDAH/ADMA/NOS/NO pathway was activated. These results reveal that the overexpression of DDAH2 attenuates myocardial fibrosis and protects against DCM through activation of the DDAH/ADMA/NOS/NO pathway in DCM rats. These results indicate that DDAH2 is a potential therapeutic candidate for the treatment of DCM.

The NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER FAMILY (NPF) genes, initially characterized as nitrate or peptide transporters in plants, are involved in the transport of a large variety of substrates, including amino acids, nitrate, auxin (IAA), jasmonates (JAs), abscisic acid (ABA) and gibberellins (GAs) and glucosinolates. A total of 169 potential functional NPF genes were excavated in Brassica napus, and they showed diversified expression patterns in 90 different organs or tissues based on transcriptome profile data. The complex time-serial expression changes were found for most functional NPF genes in the development process of leaves, silique walls and seeds, which indicated that the expression of Brassica napus NPF (BnaNPF) genes may respond to altered phytohormone and secondary metabolite content through combining with promoter element enrichment analysis. Furthermore, many BnaNPF genes were detected to respond to vernalization with two different patterns, and 20 BnaNPF genes responded to nitrate deficiency. These results will provide useful information for further investigation of the biological function of BnaNPF genes for growth and development in rapeseed.

Porous carbon (PC) has been widely regarded as one of the most promising absorbents for methane storage. Studies show that its uptake capacity and selectivity highly depend on textural structures. Although much effort has been made, unveiling their detailed structure-performance relationship remains a challenge. Here, we propose an innovative study where, with the assistance of machine learning, the hidden relationship of the textural structures of PC with the methane uptake and separation can be derived from existing data in material literature. Machine learning models were trained by the data, including specific surface area, micropore volume, mesopore volume, temperature, and pressure as the input variables and methane uptake as the output variable for prediction. Among the tested models, the multilayer perceptron (MLP) shows the highest accuracy in predicting the methane uptake. In addition, the model enables to automatically construct a uptake performance map in terms of micropore volume and mesopore volume. The obtained MLP model was also extended to explore the CO2/CH4 selectivity by retraining it with the data collected from literature of PC for the CO2 uptake. The constructed 2D selectivity map shows that the high selectivity can be achieved in the low CH4 uptake region.

Two new Ln(III)-based clusters, namely [Dy2(acac)2(HL)2(H2O)2] (1) and [Tb4(L)4(CH3OH)4]•3CH3OH•H2O (2) (H3L = 2-hydroxy-N'-[(1E)-(8-hydroxyquinolin-2-yl)methylidene]benzohydrazide, and Hacac = acetylacetone), were successfully synthesized by employing a polydentate Schiff base ligand (H3L) under solvothermal conditions. The structures and magnetic properties of clusters 1 and 2 have been systematacially investigated. Single crystal X-ray diffraction indicates that cluster 1 is a dinuclear structure, whereas cluster 2 displays a novel Tb4 tetrahedral arrangement. Magnetic studies reveal that cluster 1 exhibits single-molecule magnets (SMMs) behavior under zero dc filed (ΔE/kB = 48.1 K, and τ0 = 3.63 × 10−7 s), while no SMM behavior was observed in cluster 2.