Genome editing of a rice CDP-DAG synthase confers multipathogen resistance.

The discovery and application of genome editing introduced a new era of plant breeding by giving researchers efficient tools for the precise engineering of crop genomes1. Here we demonstrate the power of genome editing for engineering broad-spectrum disease resistance in rice (Oryza sativa). We first isolated a lesion mimic mutant (LMM) from a mutagenized rice population. We then demonstrated that a 29-base-pair deletion in a gene we named RESISTANCE TO BLAST1 (RBL1) caused broad-spectrum disease resistance and showed that this mutation caused an approximately 20-fold reduction in yield. RBL1 encodes a cytidine diphosphate diacylglycerol synthase that is required for phospholipid biosynthesis2. Mutation of RBL1 results in reduced levels of phosphatidylinositol and its derivative phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). In rice, PtdIns(4,5)P2 is enriched in cellular structures that are specifically associated with effector secretion and fungal infection, suggesting that it has a role as a disease-susceptibility factor3. By using targeted genome editing, we obtained an allele of RBL1, named RBL1Δ12, which confers broad-spectrum disease resistance but does not decrease yield in a model rice variety, as assessed in small-scale field trials. Our study has demonstrated the benefits of editing an LMM gene, a strategy relevant to diverse LMM genes and crops.

Non-canonical regulation of the reactivation of an oncogenic herpesvirus by the OTUD4-USP7 deubiquitinases.

Deubiquitinases (DUBs) remove ubiquitin from substrates and play crucial roles in diverse biological processes. However, our understanding of deubiquitination in viral replication remains limited. Employing an oncogenic human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) to probe the role of protein deubiquitination, we found that Ovarian tumor family deubiquitinase 4 (OTUD4) promotes KSHV reactivation. OTUD4 interacts with the replication and transcription activator (K-RTA), a key transcription factor that controls KSHV reactivation, and enhances K-RTA stability by promoting its deubiquitination. Notably, the DUB activity of OTUD4 is not required for K-RTA stabilization; instead, OTUD4 functions as an adaptor protein to recruit another DUB, USP7, to deubiquitinate K-RTA and facilitate KSHV lytic reactivation. Our study has revealed a novel mechanism whereby KSHV hijacks OTUD4-USP7 deubiquitinases to promote lytic reactivation, which could be potentially harnessed for the development of new antiviral therapies.

Palmitoylation of KSHV pORF55 is required for Golgi localization and efficient progeny virion production.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus etiologically associated with multiple malignancies. Both latency and sporadic lytic reactivation contribute to KSHV-associated malignancies, however, the specific roles of many KSHV lytic gene products in KSHV replication remain elusive. In this study, we report that ablation of ORF55, a late gene encoding a tegument protein, does not impact KSHV lytic reactivation but significantly reduces the production of progeny virions. We found that cysteine 10 and 11 (C10 and C11) of pORF55 are palmitoylated, and the palmytoilation is essential for its Golgi localization and secondary envelope formation. Palmitoylation-defective pORF55 mutants are unstable and undergo proteasomal degradation. Notably, introduction of a putative Golgi localization sequence to these palmitoylation-defective pORF55 mutants restores Golgi localization and fully reinstates KSHV progeny virion production. Together, our study provides new insight into the critical role of pORF55 palmitoylation in KSHV progeny virion production and offers potential therapeutic targets for the treatment of related malignancies.

Inhibitor of cardiolipin biosynthesis-related enzyme MoGep4 confers broad-spectrum anti-fungal activity.

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

Pituitary-related immune adverse events induced by programmed death Protein-1 inhibitors differ clinically from hypophysitis.

OBJECTIVE: We aimed to elucidate the clinical features of pituitary immune-related adverse events (irAEs) induced by PD-1 inhibitors in a Chinese cohort and the previous literatures. PATIENTS AND DESIGN AND MEASUREMENTS: We retrospectively analysed the clinical manifestations, laboratory examination findings, imaging features and treatments of 14 patients with pituitary irAEs caused by PD-1 inhibitors in our cohort. In addition, we searched PubMed for all English articles on pituitary irAEs induced by PD-1 inhibitors published from 1950 to 2023. A total of 47 articles were included, and the clinical characteristics of 94 patients with pituitary irAEs induced by PD-1 inhibitors in these literatures were compared to the characteristics of our cohort. RESULTS: Among the 14 patients in our cohort with pituitary irAEs induced by PD-1 inhibitors, 12 patients (85.71%, 12/14) exhibited isolated ACTH deficiency (IAD), 100.0% (14/14) of the central adrenocortical insufficiency, and 2 patients showed more than one hypothalamic-pituitary axis injury (14.29%, 2/14). Pituitary magnetic resonance imaging in all the 14 patients showed no pituitary enlargement. In previous studies we reviewed, 82.98% of the total (78/94) presented with pituitary irAEs as IAD, 100.0% (94/94) of the central adrenocortical insufficiency, and 78.33% of the patients showed no abnormality of the pituitary gland (47/60). The pituitary irAEs caused by PD-1 inhibitors did not involve typical manifestations of hypophysitis, such as pituitary enlargement, headache, visual field defects, and multiple pituitary function impairments in our cohort and the previous literatures. CONCLUSION: In our study, pituitary immune-related adverse reactions induced by PD-1 inhibitors mainly manifested isolated ACTH deficiency rather than hypophysitis.

Fine Mapping of Candidate Gene Controlling Anthocyanin Biosynthesis for Purple Peel in Solanum melongena L.

Fruit color is an intuitive quality of horticultural crops that can be used as an evaluation criterion for fruit ripening and is an important factor affecting consumers' purchase choices. In this study, a genetic population from the cross of green peel 'Qidong' and purple peel '8 guo' revealed that the purple to green color of eggplant peel is dominant and controlled by a pair of alleles. Bulked segregant analysis (BSA), SNP haplotyping, and fine genetic mapping delimited candidate genes to a 350 kb region of eggplant chromosome 10 flanked by markers KA2381 and CA8828. One ANS gene (EGP22363) was predicted to be a candidate gene based on gene annotation and sequence alignment of the 350-kb region. Sequence analysis revealed that a single base mutation of 'T' to 'C' on the exon green peel, which caused hydrophobicity to become hydrophilic serine, led to a change in the three-level spatial structure. Additionally, EGP22363 was more highly expressed in purple peels than in green peels. Collectively, EGP22363 is a strong candidate gene for anthocyanin biosynthesis in purple eggplant peels. These results provide important information for molecular marker-assisted selection in eggplants, and a basis for analyzing the regulatory pathways responsible for anthocyanin biosynthesis in eggplants.

Doxorubicin inhibits phosphatidylserine decarboxylase and confers broad-spectrum antifungal activity.

As phospholipids of cell membranes, phosphatidylethanolamine (PE) and phosphatidylserine (PS) play crucial roles in glycerophospholipid metabolism. Broadly, some phospholipid biosynthesis enzymes serve as potential fungicide targets. Therefore, revealing the functions and mechanism of PE biosynthesis in plant pathogens would provide potential targets for crop disease control. We performed analyses including phenotypic characterizations, lipidomics, enzyme activity, site-directed mutagenesis, and chemical inhibition assays to study the function of PS decarboxylase-encoding gene MoPSD2 in rice blast fungus Magnaporthe oryzae. The Mopsd2 mutant was defective in development, lipid metabolism, and plant infection. The PS level increased while PE decreased in Mopsd2, consistent with the enzyme activity. Furthermore, chemical doxorubicin inhibited the enzyme activity of MoPsd2 and showed antifungal activity against 10 phytopathogenic fungi including M. oryzae and reduced disease severity of two crop diseases in the field. Three predicted doxorubicin-interacting residues are important for MoPsd2 functions. Our study demonstrates that MoPsd2 is involved in de novo PE biosynthesis and contributes to the development and plant infection of M. oryzae and that doxorubicin shows broad-spectrum antifungal activity as a fungicide candidate. The study also implicates that bacterium Streptomyces peucetius, which biosynthesizes doxorubicin, could be potentially used as an eco-friendly biocontrol agent.

Melatonin targets MoIcl1 and works synergistically with fungicide isoprothiolane in rice blast control.

Melatonina natural harmless molecule-displays versatile roles in human health and crop disease control such as for rice blast. Rice blast, caused by the filamentous fungus Magnaporthe oryzae, is one devastating disease of rice. Application of fungicides is one of the major measures in the control of various crop diseases. However, fungicide resistance in the pathogen and relevant environmental pollution are becoming serious problems. By screening for possible synergistic combinations, here, we discovered an eco-friendly combination for rice blast control, melatonin, and the fungicide isoprothiolane. These compounds together exhibited significant synergistic inhibitory effects on vegetative growth, conidial germination, appressorium formation, penetration, and plant infection by M. oryzae. The combination of melatonin and isoprothiolane reduced the effective concentration of isoprothiolane by over 10-fold as well as residual levels of isoprothiolane. Transcriptomics and lipidomics revealed that melatonin and isoprothiolane synergistically interfered with lipid metabolism by regulating many common targets, including the predicted isocitrate lyase-encoding gene MoICL1. Furthermore, using different techniques, we show that melatonin and isoprothiolane interact with MoIcl1. This study demonstrates that melatonin and isoprothiolane function synergistically and can be used to reduce the dosage and residual level of isoprothiolane, potentially contributing to the environment-friendly and sustainable control of crop diseases.

Melatonin functions as a broad-spectrum antifungal by targeting a conserved pathogen protein kinase.

Melatonin is a low-cost natural small indole molecule with versatile biological functions. However, melatonin's fungicidal potential has not been fully exploited, and the mechanism remains elusive. Here, we report that melatonin broadly inhibited 13 plant pathogens. In the rice blast fungal pathogen Magnaporthe oryzae, melatonin inhibited fungal growth, formation of infection-specific structures named appressoria, and plant infection, reducing disease severity. Melatonin entered fungal cells efficiently and colocalized with the critical mitogen-activated protein kinase named Mps1, suppressing phosphorylation of Mps1. Melatonin's affinity for Mps1 via two hydrogen bonds was demonstrated using surface plasmon resonance and chemical modifications. To improve melatonin's efficiency, we obtained 20 melatonin derivatives. Tert-butyloxycarbonyl melatonin showed a 25-fold increase in fungicidal activities, demonstrating the feasibility of chemical modifications in melatonin modification. Our study demonstrated the broad-spectrum fungicidal effect of melatonin by suppressing Mps1 as one of the targets. Through further systematic modifications, developing an eco-friendly melatonin derivative of commercial values for agricultural applications appears promising.

Angptl7 promotes insulin resistance and type 2 diabetes mellitus by multiple mechanisms including SOCS3-mediated IRS1 degradation.

Angptl7 is a secreted and circulating cytokine that belongs to Angiopoietin-like family. The current knowledge about the function of Angptl7 is still limited, and its biological role is only marginally known, such as in the promotion of angiogenesis and inflammation. Here, we demonstrated that Angptl7 promotes insulin resistance and type 2 diabetes mellitus (T2DM). We found that the circulating Angptl7 levels in T2DM patient and mouse models were significantly elevated. Artificial overexpression of Angptl7 in hepatic cells inhibited glucose uptake and impaired insulin signaling pathway. Furthermore, in vivo overexpression of Angptl7 in experimental healthy mice also caused insulin resistance-like characteristics. Mechanistic studies revealed that Angptl7 can upregulate SOCS3 expression, leading to the IRS1 degradation in proteasome. Furthermore, over-expressed Angptl7 inhibited the phosphorylation of Akt and promoted the phosphorylation of ERK1/2, which was known to be associated with insulin resistance. Taken together, our study provided strong evidence that Angptl7 promotes insulin resistance and T2DM by multiple mechanisms, which made Angptl7 a new potential therapeutic target for treatment of insulin resistance and T2DM.

Hypobaric hypoxia regulates iron metabolism in rats.

Intermittent hypobaric hypoxia can produce a protective effect on both the nervous system and non-nervous system tissues. Intermittent hypobaric hypoxia preconditioning has been shown to protect rats from cardiac ischemia-reperfusion injury by decreasing cardiac iron levels and reactive oxygen species (ROS) production, thereby decreasing oxidative stress to achieve protection. However, the specific mechanism underlying the protective effect of hypobaric hypoxia is unclear. To shed light on this phenomenon, we subjected Sprague-Dawley rats to hypobaric hypoxic preconditioning (8 hours/day). The treatment was continued for 4 weeks. We then measured the iron content in the heart, liver, spleen, and kidney. The iron levels in all of the assessed tissues decreased significantly after hypobaric hypoxia treatment, corroborating previous results that hypobaric hypoxia may produce its protective effect by decreasing ROS production by limiting the levels of catalytic iron in the tissue. We next assessed the expression levels of several proteins involved in iron metabolism (transferrin receptor, L-ferritin, and ferroportin1 [FPN1]). The increased transferrin receptor and decreased L-ferritin levels after hypobaric hypoxia were indicative of a low-iron phenotype, while FPN1 levels remained unchanged. We also examined hepcidin, transmembrane serine proteases 6 (TMPRSS6), erythroferrone (ERFE), and erythropoietin (EPO) levels, all of which play a role in the regulation of systemic iron metabolism. The expression of hepcidin decreased significantly after hypobaric hypoxia treatment, whereas the expression of TMPRSS6 and ERFE and EPO increased sharply. Finally, we measured serum iron and total iron binding capacity in the serum, as well as red blood cell count, mean corpuscular volume, hematocrit, red blood cell distribution width SD, and red blood cell distribution width CV. As expected, all of these values increased after the hypobaric hypoxia treatment. Taken together, our results show that hypobaric hypoxia can stimulate erythropoiesis, which systemically draws iron away from nonhematopoietic tissue through decreased hepcidin levels.

Iron regulatory protein 2 deficiency may correlate with insulin resistance.

Iron is known to be a crucial regulator of glucose, and several studies have demonstrated that iron overload is one of the risk factors for insulin resistance and diabetes; however, the mechanism has not yet been clarified. To investigate the effect of iron overload on glucose metabolism and the underlying mechanism, Irp2 knockout (Irp2-/-) mice (endogenous iron overload model) were used. We found that Irp2-/- mice exhibited hyperglycemia and iron overload in the liver and skeletal muscle. Increased MDA, decreased SOD levels, and increased cell apoptosis were also found in the liver and muscle of Irp2-/- mice. Glucose concentrations were significantly higher in Irp2-/- mice in insulin tolerance tests. However, early-phase insulin secretion was not altered in Irp2-/- mice. The expression of hepatic IRS2 and muscle GLUT4 was declined in Irp2-/- mice at both mRNA and protein levels when compared with those of wild-type control. In conclusions, Irp2-/- mice showed hyperglycemia, which might due to insulin resistance rather than due to impaired insulin secretion.

Irp2 Knockout Causes Osteoporosis by Inhibition of Bone Remodeling.

It has been found that iron disorder may lead to osteoporosis. However, the mechanism has been little explored. In the present study, we try to investigate the effects of iron disorder on bone metabolism using Irp2 knockout (Irp2-/-) mice. Female Irp2-/- mice were used in this study. Bone mineral density (BMD) was measured by Micro-CT. Serum markers for bone turnover were measured by enzyme-linked immunosorbent assay. Content of iron was measured in bone and liver tissue, and Vitamin D 25-hydroxylase (CYP2R1) content was measured in liver tissue. Relative gene expression involved in iron export and uptake, and some genes involved in activities of osteoblast and osteoclast were all measured by real-time PCR and western blot. Compared to wild-type mice, Irp2-/- mice exhibited reduced BMD, bone iron deficiency, and hepatic iron overload. Serum levels of 25(OH)D3 and markers for bone formation such as bone alkaline phosphatase (Balp), bone-gla-protein (BGP), and type I collagen alpha1 chain (Col I α1) were decreased, while markers for bone resorption including cathepsin K (Ctsk) and tartrate-resistant acid phosphatase (Trap) were all significantly increased. Hepatic CYP2R1 level was decreased in Irp2-/- mice compared with wild-type control mice. Compared to wild-type C57BL6 control mice, the expression of genes involved in osteoblast activity such as Balp, BGP, and Col I α1 were all significantly decreased in bone tissue, while genes for osteoclast activity such as Ctsk and Trap were all markedly increased in Irp2-/- mice at mRNA level. Genes involved in iron storage, uptake, and exporting were also measured in bone tissue. Posttranscriptionally decreased ferritin (FTL), ferroportin 1 (FPN1), and increased transferrin receptor 1 (TfR1) gene expressions have been unexpectedly found in bone tissue of Irp2-/- mice. Irp2-/- mice exhibit reduced bone iron content and osteoporosis. Decreased circulating 25(OH)D3 levels promoted activity of osteoclast, while impaired activity of osteoblast may contribute to pathogenesis of osteoporosis. And, reduced bone iron content may not be totally caused by TfR1-dependent pathways.

Bimetallic plasmonic Au@Ag nanocuboids for rapid and sensitive detection of phthalate plasticizers with label-free surface-enhanced Raman spectroscopy.

Phthalate plasticizers (PAEs) are posing a serious threat to human health, so it is urgent to develop effective and reliable ways to detect the food additives PAEs sensitively. In this study, we have reported plasmonic bimetallic Au@Ag core-shell nanocuboids for the rapid and sensitive detection of PAEs in liquor samples with a label-free Surface-enhanced Raman Spectroscopy (SERS) strategy. Compared with single-element nanostructures, the bimetallic SERS platform can integrate two distinct functions into a single entity with unprecedented properties. Consequently, we synthesized Au@Ag nanocuboids (Au@Ag NCs) composed of a Au nanorod (Au NR) core and a Ag cuboid shell, which could produce richer and broader plasmonic resonance modes than Au NRs. It is obvious that the SERS signals of crystal violet (CV) and butyl benzyl phthalate (BBP) reached a maximum as the thickness of the Ag coating shell was in a certain threshold and there was a strong dependence of the Raman enhancement on the Ag cuboid shell-thickness. Based on the optimized size, the sensitivity and repeatability of Au@Ag NCs were evaluated with limits of detection (LODs) at around 10-9 M both for BBP and diethylhexyl phthalate (DEHP). In addition, the SERS active substrate core-shell Au@Ag NCs can be used to detect BBP as low as 1.3 mg kg-1 spiked into the liquor samples. Thereby, the unique bimetallic Au@Ag NCs showed a huge potential for the rapid and sensitive detection of PAEs in liquor samples.

HS-ß-cyclodextrin-functionalized Ag@Fe3O4@Ag nanoparticles as a surface-enhanced Raman spectroscopy substrate for the sensitive detection of butyl benzyl phthalate.

In recent years, there have been incidents involving the illegal addition of phthalic acid esters (PAEs) to liquors. It is well known that PAEs such as butyl benzyl phthalate (BBP) have estrogen-like effects, so high PAE levels in the body can lead to a decreased sperm count in males and altered sexual organ development in children, for example. The rapid detection of PAEs in liquor is therefore an important task. Compared with traditional methods of testing for PAEs, surface-enhanced Raman spectroscopy (SERS) offers higher sensitivity and the ability to search for chemical fingerprints, allowing the rapid detection of particular PAEs. In the present work, we synthesized Ag@Fe3O4@Ag/ß-cyclodextrin (CD) nanoparticles for use as a SERS-active substrate. Fe3O4 aggregates quickly under the influence of an external magnetic field, making it possible to magnetically separate out the NPs, which simplifies sample processing. The detection limit of the system for PAEs is also improved because the ß-CD acts as a functional group with a cavity structure that is capable of adsorbing BBP to form a host (ß-CD)-guest (BBP) complex. This substrate was shown to possess good repeatability and sensitivity when using malachite green (MG) as a probe molecule. Furthermore, the nanoparticle-based SERS substrate permitted the detection of BBP down to a level of 1.3 mg/kg in liquor, which is low enough to be able to detect BBP in real-world liquor samples. We expect that this method will prove useful for the rapid detection of PAEs in food. Graphical abstract.

Biological function of a gC1qR homolog (EcgC1qR) of Exopalaemon carinicauda in defending bacteria challenge.

The gC1qR is a ubiquitously expressed cell protein that interacts with the globular heads of C1q (gC1q) and many other ligands. In this study, one gC1qR homolog gene was obtained from Exopalaemon carinicauda and named EcgC1qR. The complete nucleotide sequence of EcgC1qR contained a 774 bp open reading frame (ORF) encoding EcgC1qR precursor of 257 amino acids. The deduced amino acid sequence of EcgC1qR revealed a 55-amino-acid-long mitochondrial targeting sequence at the N-terminal and a mitochondrial acidic matrix protein of 33 kDa (MAM33) domain. The genomic organization of EcgC1qR gene showed that EcgC1qR gene contained five exons and four introns. EcgC1qR could express in all of the detected tissues and its expression was much higher in hepatopancreas and hemocytes. The expression of EcgC1qR in the hepatopancreas of prawns challenged with Vibrio parahaemolyticus and Aeromonas hydrophila changed in a time-dependent manner. The expression of EcgC1qR in prawns challenged with V. parahaemolyticus was up-regulated at 6 h (p < 0.05), and significantly up-regulated at 12 h and 24 h (p < 0.01), and then returned to the control levels at 48 h post-challenge (p > 0.05). At the same time, the expression in Aeromonas-challenged group was significantly up-regulated at 6, 12 and 24 h. The recombinant EcgC1qR could inhibit the growth of two tested bacteria. In addition, we successfully deleted EcgC1qR gene through CRISPR/Cas9 technology and it was the first time to obtain the mutant of gC1qR homolog gene in crustacean. It's a great progress to study the biological function of gC1qR in crustacean in future.

Liquid-liquid interfacial self-assembled Au NP arrays for the rapid and sensitive detection of butyl benzyl phthalate (BBP) by surface-enhanced Raman spectroscopy.

Recent years have seen a large number of incidents involving the contamination of liquor with phthalate plasticizers (PAEs). There is therefore an urgent need to develop novel analytical strategies for the rapid and sensitive detection of PAEs. The PAE butyl benzyl phthalate (BBP) is very harmful to the human body, so we developed a surface-enhanced Raman spectroscopy (SERS) platform for the rapid detection of BBP in liquor based on liquid-liquid extraction and the simultaneous self-assembly of arrays of Au nanoparticles (Au NPs) at an organic/aqueous interface. The self-assembly of Au NPs occurs under the influence of the surface tension at the interface between the immiscible solvents. In the first step of the strategy, cyclohexane (CYH) is mixed with BBP-containing liquor to extract the BBP. Then the self-assembly of Au NPs at an organic/aqueous interface is induced using the CYH supernatant as the organic phase, a colloid of Au NPs as the aqueous phase, and ethanol as the inducer. During this process, the BBP molecules extracted from the liquor participate directly in the Au NP self-assembly process, which causes the analytes to be loaded into SERS-active nanogaps in the Au NP arrays, thus permitting the sensitive detection of BBP. BBP levels as low as 1.3 mg/kg in the liquor were detected using this method. Fifteen batches of the assembled SERS platform produced a relative standard deviation of 10.58% in the SERS intensity of the peak at 1178 cm-1 generated in the presence of 0.08 ppm crystal violet, indicating that this strategy possesses good reproducibility. Furthermore, interfacial assembly allowed the dual-analyte detection of BBP in the organic phase and an edible pigment (sunset yellow) in the aqueous phase to be achieved with high sensitivity and credible reproducibility using the SERS platform. Interfacial self-assembled SERS-active arrays therefore show great potential for the rapid and sensitive in situ detection of BBP in liquor samples. Graphical abstract ᅟ.

Directed assembly of functionalized nanoparticles with amphiphilic diblock copolymers.

The ability to design and fabricate highly ordered superstructures from nanoscale particles remains a major scientific and technological challenge. Patchy nanoparticles have recently emerged as a novel class of building units to construct functional materials. Using simulations of coarse-grained molecular dynamics, we propose a simple approach to achieve soft nanoparticles with a self-patchiness nature through self-assembly of tethered copolymers with a sequence of inner solvophilic and outer solvophobic blocks. As building units, the patch-like nanoparticles are directed to further assemble into a rich variety of highly ordered superstructures via condensation-coalescence mechanisms. The growth kinetics of the superstructures obeys the kinetic model of the step-growth polymerization process. Our simulations also demonstrate that the intermediate patch-like nanoparticles and the final assembled superstructures can be rationally tuned by changing the number and the composition of the tethered copolymer chains. This strategy of copolymer functionalization conceptually enables the design and fabrication of highly ordered superstructures of nanoparticle ensembles with new horizons for promising applications in soft nanotechnology and biotechnology.

A mixed solvent system for preparation of spherically agglomerated crystals of ascorbic acid.

The objective of this research was to develop a novel solvent system to prepare spherically agglomerated crystals (SAC) of ascorbic acid with improved flowability for direct compression. A spherical agglomeration method was developed by selecting the mixed solvents (n-butyl and ethyl acetate) as a poor solvent and the process was further optimized by using triangular phase diagram and particle vision measurement. Physiochemical properties of SAC were characterized and compared with original drug crystals. It showed that amount of poor solvent, ratio of solvent mixture, and drug concentration are critical for preparation of SAC with desirable properties. The solid state of SAC was same as original crystals according to DSC, XRD, and FT-IR results. There was no significant difference in solubility and dissolution rate of drug between SAC and original crystals. The flowability and packability of SAC as well as the tensile strength and elastic recovery of tablets made from SAC were all significantly improved when compared with original crystals and tablets from crystals. It is concluded that the present method was suitable to prepare SAC of ascorbic acid for direct compression.