The fragmentomic property of plasma cell-free DNA enables the non-invasive detection of diabetic nephropathy in patients with diabetes mellitus

BackgroundDiabetic nephropathy (DN) is one of the most prevalent complications of diabetes mellitus (DM). However, there is still a lack of effective methods for non-invasive diagnosis of DN in clinical practice. We aimed to explore biomarkers from plasma cell-free DNA as a surrogate of renal biopsy for the differentiation of DN patients from patients with DM.Materials and methodsThe plasma cell-free DNA (cfDNA) was sequenced from 53 healthy individuals, 53 patients with DM but without DN, and 71 patients with both DM and DN. Multidimensional features of plasma DNA were analyzed to dissect the cfDNA profile in the DM and DN patients and identify DN-specific cfDNA features. Finally, a classification model was constructed by integrating all informative cfDNA features to demonstrate the clinical utility in DN detection.ResultsIn comparison with the DM patients, the DN individuals exhibited significantly increased cfDNA concentration in plasma. The cfDNA from the DN patients showed a distinct fragmentation pattern with an altered size profile and preferred motifs that start with “CC” in the cfDNA ending sites, which were associated with deoxyribonuclease 1 like 3 (DNASE1L3) expression in the kidney. Moreover, patients with DM or DN were found to carry more alterations in whole-genome cfDNA coverage when compared with healthy individuals. We integrated DN-specific cfDNA features (cfDNA concentration, size, and motif) into a classification model, which achieved an area under the receiver operating characteristic curve (AUC) of 0.928 for the differentiation of DN patients from DM patients.ConclusionOur findings showed plasma cfDNA as a reliable non-invasive biomarker for differentiating DN patients from DM patients. The utility of cfDNA in clinical practice in large prospective cohorts is warranted

GhCalS5 is involved in cotton response to aphid attack through mediating callose formation

Callose synthase plays an essential role in plant growth and development and in response to all sorts of stresses through regulating callose formation. However, few research about the function and mechanism of the insect resistance of callose synthase genes have been reported in cotton. In this study, a cotton callose synthase gene GhCalS5 was cloned, and its function and mechanism of resistance to cotton aphids were analyzed. The expression of GhCalS5 was significantly upregulated in both, leaves and stems of cotton plants at 48 h after cotton aphid infestation and in the leaves of cotton plants at 24 h after salicylic acid treatment. The overexpression of GhCalS5 enhanced cotton resistance to cotton aphids. Expectedly silencing of GhCalS5 reduced cotton resistance to cotton aphids. Overexpression of GhCalS5 enhanced callose formation in cotton leaves. Our results suggest that GhCalS5 is involved in cotton resistance against cotton aphids by influencing callose formation

Construction of Spinel/Perovskite Heterojunction for Boosting Photocatalytic Performance for Polyacrylamide

The use of photocatalytic technology to degrade polyacrylamide in crude oil extraction wastewater is a promising approach, but there have been few reports so far. In this study, ZnFe2O4/Ba0.7Sr0.3TiO3 heterogeneous composite materials of a spinel/perovskite type with different proportions were synthesized. The composite materials with 31% ZnFe2O4 content exhibited a maximum polyacrylamide degradation efficiency of 46.54%, which demonstrated the unique role of the spinel/perovskite heterogeneous structure. When Ag nanoparticles were grown in situ on the surface of ZnFe2O4/Ba0.7Sr0.3TiO3, the photocatalytic degradation efficiency reached 81.28%. The main reason was that the introduction of Ag nanoparticles not only increased the active sites and enhanced light absorption capacity but also accelerated the separation of photo-generated charges. This work provides new ideas for the construction of spinel/perovskite heterogeneous composite materials and has reference significance for the application of photocatalytic degradation in the treatment of wastewater-containing polymers

William Roxburgh, Botanic Garden, near Calcutta, [India], to James Edward Smith

In addition to other items he is sending by Mr Brown also sending seeds, and box of insects gathered by Mr Le Beck, they both wish to become members of the Linnean Society; Le Beck will be a valuable correspondent as he intends to spend his life in India. Recently drew and described a new species of 'Dolphinus'; as large as common dolphin but without dorsal fin, 60 teeth in each jaw, and chiefly inhabits the Ganges river, calls it 'D. gangetica'. [Francis] Buchanan is visiting them; he will send Smith plants

[3,3]-Sigmatropic Rearrangement versus Carbene Formation in Gold-Catalyzed Transformations of Alkynyl Aryl Sulfoxides: Mechanistic Studies and Expanded Reaction Scope

Gold-catalyzed intramolecular oxidation of terminal alkynes with an arenesulfinyl group as the tethered oxidant is a reaction of high impact in gold chemistry, as it introduced to the field the highly valued concept of gold carbene generation via alkyne oxidation. The proposed intermediacy of α-oxo gold carbenes in these reactions, however, has never been substantiated. Detailed experimental studies suggest that the involvement of such reactive intermediates in the formation of dihydro­benzo­thiepinones is highly unlikely. Instead, a [3,3]-sigmatropic rearrangement of the initial cyclization intermediate offers a reaction path that can readily explain the high reaction efficiency and the lack of sulfonium formation. With internal alkyne substrates, however, the generation of a gold carbene species becomes competitive with the [3,3]-sigmatropic rearrangement. This reactive intermediate, nevertheless, does not proceed to afford the Friedel–Crafts-type cyclization product. Extensive density functional theory studies support the mechanistic conclusion that the cyclized product is formed via an intramolecular [3,3]-sigmatropic rearrangement instead of the previously proposed Friedel–Crafts-type cyclization. With the new mechanistic insight, the product scope of this versatile formation of mid-sized sulfur-containing cyclo­alkenones has been expanded readily to various dihydro­benzo­thiocinones, a tetrahydro­benzo­cyclo­nonenone, and even those without the entanglement of a fused benzene ring. Besides gold, Hg­(OTf)₂ can be an effective catalyst, thereby offering a cheap alternative for this intramolecular redox reaction

ZmRop1 participates in maize defense response to the damage of Spodoptera frugiperda larvae through mediating ROS and soluble phenol production

Abstract As plant‐specific molecular switches, Rho‐like GTPases (Rops) are vital for plant survival in response to biotic and abiotic stresses. However, their roles in plant defense response to phytophagous insect's damage are largely unknown. In this study, the expression levels of nine maize RAC family genes were analyzed after fall armyworm (FAW) larvae infestation. Among the analyzed genes, ZmRop1 was specifically and highly expressed, and its role in maize response to FAW larvae damage was studied. The results showed that upon FAW larvae infestation, salicylic acid and methyl jasmonate treatment ZmRop1 gene transcripts were all down‐regulated. However, upon mechanical injury, the expression level of ZmRop1 was up‐regulated. Overexpression of ZmRop1 gene in maize plants could improve maize plant resistance to FAW larvae damage. Conversely, silencing of ZmRop1 increased maize plant susceptibility to FAW larvae damage. The analysis of the potential anti‐herbivore metabolites, showed that ZmRop1 promoted the enzyme activities of catalase, peroxidase and the expression levels of ZmCAT, ZmPOD, ZmRBOHA and ZmRBOHB, thereby enhancing the reactive oxygen species (ROS) production, including the content of O2− and H2O2. In addition, overexpression or silencing of ZmRop1 could have influence on the content of the total soluble phenol through mediating the activity of polyphenol oxidase. In summary, the results illuminated our understanding of how ZmRop1 participate in maize defense response to FAW larvae damage as a positive regulator through mediating ROS production and can be used as a reference for the green prevention and control of FAW larvae

Amniotic membrane extract ameliorates benzalkonium chloride-induced dry eye in a murine model

National Basic Research Program of China (Project 973) [2011CB504606]; National Natural Science Foundation of China, Beijing, China [81270978]; Cross-strait Program of the National Foundation [U1205025]Human amniotic membrane (AM) is avascular but contains various beneficial bioactive factors, its extract (AE) is also effective in treating many ocular surface disorders. In this study, we for the first time evaluated the therapeutic effects of AE on dry eye induced by benzalkonium chloride in a BALB/c mouse model. Topical application of AE (1.5 and 3 mu g/eye/day) resulted in significantly longer tear break-up time on Day 3 and 6, lower fluorescein staining scores on Day 3, and lower inflammatory index on Day 6. AE reduced corneal epithelial K10 expression, inflammatory infiltration, and levels of TNF-alpha, IL-1 beta and IL-6 in BAC treated mice than that in the control mice. Moreover, decreased TUNEL positive cells in cornea and increased goblet cells in conjunctiva were also observed in AE treated corneas. Finally, AE induced more Ki-67 positive cells in corneal epithelium of dry eye mouse. Taken together, our data provide further support for BAC induced dry eye model as a valuable for dry eye study and suggest a great potential for AE as a therapeutic agent in the clinical treatment of dry eye. (C) 2013 Elsevier Ltd. All rights reserved

Polymer-mesoporous silica nanoparticle core-shell nanofibers as a dual-drug-delivery system for guided tissue regeneration

Bioactive membranes with growth factors that mimic the physiological microenvironment of periodontal tissues have shown great potential for guided tissue regeneration (GTR). However, the loss of bioactivity and the uncontrolled drug release in conventional membranes limit their efficacy. In addition, membranes with local infection control ability would provide additional benefits to regeneration. In this work, nanoengineered membranes with growth factor and antibiotic delivery capabilities were developed to achieve dual functions for efficient GTR. Mesoporous silica nanoparticles (MSNs) with large pores with the ability to encapsulate and preserve the bioactivity of growth factors were used as the core, and antibiotics were loaded in shell nanofibers with coaxial electrospinning. A sustained release behavior of the growth factor was observed, and the nanoparticle-encapsulated core-shell nanofibers show better ontogenetic regeneration abilities toward bone marrow stromal cells, compared to current commercial Bio-Gide membranes. In addition, the drug-loaded nanocomposite core-shell nanofibers showed excellent antibacterial properties toward Gram-positive, Gram-negative, and multispecies oral bacteria. The MSNs-embedded core-shell nanofiber system provides an attractive strategy to deliver dual drugs for GTR with better performance

Additional file 4 of TSLP promoting B cell proliferation and polarizing follicular helper T cell as a therapeutic target in IgG4-related disease

Additional file 4: Supplementary Methods

Additional file 3 of TSLP promoting B cell proliferation and polarizing follicular helper T cell as a therapeutic target in IgG4-related disease

Additional file 3: Table S2. List of differential expression genes of TSLP activated B cells and B cells from IgG4-RD