Multi-view contrastive heterogeneous graph attention network for lncRNA-disease association prediction.

MOTIVATION: Exploring the potential long noncoding RNA (lncRNA)-disease associations (LDAs) plays a critical role for understanding disease etiology and pathogenesis. Given the high cost of biological experiments, developing a computational method is a practical necessity to effectively accelerate experimental screening process of candidate LDAs. However, under the high sparsity of LDA dataset, many computational models hardly exploit enough knowledge to learn comprehensive patterns of node representations. Moreover, although the metapath-based GNN has been recently introduced into LDA prediction, it discards intermediate nodes along the meta-path and results in information loss. RESULTS: This paper presents a new multi-view contrastive heterogeneous graph attention network (GAT) for lncRNA-disease association prediction, MCHNLDA for brevity. Specifically, MCHNLDA firstly leverages rich biological data sources of lncRNA, gene and disease to construct two-view graphs, feature structural graph of feature schema view and lncRNA-gene-disease heterogeneous graph of network topology view. Then, we design a cross-contrastive learning task to collaboratively guide graph embeddings of the two views without relying on any labels. In this way, we can pull closer the nodes of similar features and network topology, and push other nodes away. Furthermore, we propose a heterogeneous contextual GAT, where long short-term memory network is incorporated into attention mechanism to effectively capture sequential structure information along the meta-path. Extensive experimental comparisons against several state-of-the-art methods show the effectiveness of proposed framework.The code and data of proposed framework is freely available at https://github.com/zhaoxs686/MCHNLDA.

miRNA-193a-mediated WT1 suppression triggers podocyte injury through activation of the EZH2/ß-catenin/NLRP3 pathway in children with diabetic nephropathy.

Diabetic nephropathy (DN), an eminent etiology of renal disease in patients with diabetes, involves intricate molecular mechanisms. Recent investigations have elucidated microRNA-193a (miR-193a) as a pivotal modulator in DN, although its precise function in podocyte impairment remains obscure. The present study investigated the role of miR-193a in podocyte injury via the WT1/EZH2/ß-catenin/NLRP3 pathway. This study employed a comprehensive experimental approach involving both in vitro and in vivo analyses. We utilized human podocyte cell lines and renal biopsy samples from pediatric patients with DN. The miR-193a expression levels in podocytes and glomeruli were quantified via qRT‒PCR. Western blotting and immunofluorescence were used to assess the expression of WT1, EZH2, ß-catenin, and NLRP3 inflammasome components. Additionally, the study used luciferase reporter assays to confirm the interaction between miR-193a and WT1. The impact of miR-193a manipulation was observed by overexpressing WT1 and inhibiting miR-193a in podocytes, followed by analysis of downstream pathway activation and inflammatory markers. We found upregulated miR-193a in podocytes and glomeruli, which directly targeted and suppressed WT1, a crucial podocyte transcription factor. WT1 suppression, in turn, activated the EZH2/ß-catenin/NLRP3 pathway, leading to inflammasome assembly and proinflammatory cytokine production. Overexpression of WT1 or inhibition of miR-193a attenuated these effects, protecting podocytes from injury. This study identified a novel mechanism by which miR-193a-mediated WT1 suppression triggers podocyte injury in DN via the EZH2/ß-catenin/NLRP3 pathway. Targeting this pathway or inhibiting miR-193a may be potential therapeutic strategies for DN.

Enantioselective [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes with Vinylazaarenes through Asymmetric Photoredox Catalysis.

Here we present a highly enantioselective [2π + 2σ] photocycloaddition of bicyclo[1.1.0]butanes (BCBs). The reaction uses a variety of vinylazaarenes as partners and is catalyzed by a polycyclic aromatic hydrocarbon (PAH)-containing chiral phosphoric acid as a bifunctional chiral photosensitizer. A wide array of pharmaceutically important bicyclo[2.1.1]hexane (BCH) derivatives have been synthesized with high yields, enantioselectivity, and diastereoselectivity. In addition to the diverse 1-ketocarbonyl-3-substituted BCBs, α/ß-substituted vinylazaarenes are compatible with such an unprecedented photoredox catalytic pathway, resulting in the successful assembly of an all-carbon quaternary stereocenter or two adjacent tertiary stereocenters on the product.

Enantioselective [2 + 2] Photocycloreversion Enables De Novo Deracemization Synthesis of Cyclobutanes.

While photochemical deracemization significantly enhances atom economy by eliminating the necessity for additional oxidants or reductants, the laborious presynthesis of substrates from feedstock chemicals is often required, thereby compromising the practicality of this method. In this study, we propose a novel approach known as de novo deracemization synthesis, which involves direct utilization of simple substrates undergoing both photochemical transformation and reversible photochemical transformation. The efficient enantiocontrol of chiral catalysts in the latter process establishes an effective platform for deracemization. This alternative and practical approach to address the challenges of asymmetric photocatalysis has been successfully demonstrated in the photosensitized de novo deracemization synthesis of azaarene-functionalized cyclobutanes featuring three stereocenters, including an all-carbon quaternary center. By exclusively employing a suitable chiral catalyst to enable kinetically controlled [2 + 2] photocycloreversion, we pave a creative path toward achieving more cost-effective photochemical deracemization.

Heterogeneous graph attention network based on meta-paths for lncRNA-disease association prediction.

MOTIVATION: Discovering long noncoding RNA (lncRNA)-disease associations is a fundamental and critical part in understanding disease etiology and pathogenesis. However, only a few lncRNA-disease associations have been identified because of the time-consuming and expensive biological experiments. As a result, an efficient computational method is of great importance and urgently needed for identifying potential lncRNA-disease associations. With the ability of exploiting node features and relationships in network, graph-based learning models have been commonly utilized by these biomolecular association predictions. However, the capability of these methods in comprehensively fusing node features, heterogeneous topological structures and semantic information is distant from optimal or even satisfactory. Moreover, there are still limitations in modeling complex associations between lncRNAs and diseases. RESULTS: In this paper, we develop a novel heterogeneous graph attention network framework based on meta-paths for predicting lncRNA-disease associations, denoted as HGATLDA. At first, we conduct a heterogeneous network by incorporating lncRNA and disease feature structural graphs, and lncRNA-disease topological structural graph. Then, for the heterogeneous graph, we conduct multiple metapath-based subgraphs and then utilize graph attention network to learn node embeddings from neighbors of these homogeneous and heterogeneous subgraphs. Next, we implement attention mechanism to adaptively assign weights to multiple metapath-based subgraphs and get more semantic information. In addition, we combine neural inductive matrix completion to reconstruct lncRNA-disease associations, which is applied for capturing complicated associations between lncRNAs and diseases. Moreover, we incorporate cost-sensitive neural network into the loss function to tackle the commonly imbalance problem in lncRNA-disease association prediction. Finally, extensive experimental results demonstrate the effectiveness of our proposed framework.

Palladium-Catalyzed Carbonylation Reaction of Indole/Pyrrole Involving HCFO-1233zd (E).

3-Indole-3-one is a key intermediate in the synthesis of many drugs and plays an important role in synthetic chemistry and biochemistry. A new method for synthesizing trifluoromethylated 3-indoleketones by Pd(0)-catalyzed carbonylation was introduced. In the absence of additives, 1-chloro-3,3,3-trifluoropropyl (an inexpensive and environmentally friendly synthetic block of trifluoromethyl) reacts with indole and carbon monoxide to generate trifluoromethylindole ketones with good yields, regioselectivity, and chemical selectivity; furthermore, the products exhibit strong resistance to basic functional groups, such as alkynes, aldehydes, and esters. In addition to the conversion of indole compounds into corresponding products, pyrrole and heteroindole may be suitable for corresponding chemical transformations. This study provides a synthetic method for the further construction of trifluoromethylated 3-indole ketones.

Visible-Light-Induced Regioselective Cascade Radical Cyclization of α-Bromocarbonyls: Access to Benzazepine Derivatives.

Visible-light-induced regioselective cascade radical cyclization of α-bromocarbonyls for the synthesis of benzazepine derivatives is described. In the presence of fac-Ir(ppy)3 (2.0 mol %) as a photocatalyst, 2,6-lutidine as a base, and dichloromethane as a solvent, the reactions proceed smoothly to afford seven-membered rings in good yields. This protocol features a broad substrate scope, excellent functional group tolerance, and mild reaction conditions. Preliminary mechanistic studies reveal that the generation of the α-carbon radical is more prone to react with the 1,1-diphenylethylene tethered acrylamide to generate the stable seven-membered heterocycle.

Hip joint rice body bursitis combined with hip dysplasia and pelvic fracture: a case report.

BACKGROUND: Rice body formation is an uncommon, nonspecific inflammatory process. Certain clinical features, such as chronic synovitis associated with rheumatoid arthritis, tuberculous arthritis, and osteoarthritis, can induce a non-specific response that may lead to the development of rice bodies. Currently, the etiological and prognostic significance of rice bodies remains unknown. Magnetic resonance imaging (MRI) is the preferred diagnostic imaging modality for evaluating rice body formation. CASE PRESENTATION: The patient, a 44-year-old female, presented with bursitis of the hip joint and the presence of numerous rice bodies. This case is exceptionally rare and unusual as it involves a combination of hip dysplasia and pelvic fracture. The patient underwent a one-stage resection of the rice body, internal fixation of the acetabular fracture, and two-stage total hip arthroplasty, resulting in an immediate improvement in her symptoms. We reviewed the relevant literature and observed that the majority of rice bodies were predominantly found within the capsules of the shoulder and knee joints, while instances of hip joint rice body bursitis were relatively infrequent. To our knowledge, there have been no previous reports documenting a case of hip joint rice body bursitis in conjunction with hip dysplasia and pelvic fracture. CONCLUSION: This paper presents the rare case of hip joint rice body bursitis combined with hip dysplasia and pelvic fracture, and is one of the highlights.

Improving Measurement Accuracy of Deep Hole Measurement Instruments through Perspective Transformation.

Deep hole measurement is a crucial step in both deep hole machining and deep hole maintenance. Single-camera vision presents promising prospects in deep hole measurement due to its simple structure and low-cost advantages. However, the measurement error caused by the heating of the imaging sensor makes it difficult to achieve the ideal measurement accuracy. To compensate for measurement errors induced by imaging sensor heating, this study proposes an error compensation method for laser and vision-based deep hole measurement instruments. This method predicts the pixel displacement of the entire field of view using the pixel displacement of fixed targets within the camera's field of view and compensates for measurement errors through a perspective transformation. Theoretical analysis indicates that the perspective projection matrix changes due to the heating of the imaging sensor, which causes the thermally induced measurement error of the camera. By analyzing the displacement of the fixed target point, it is possible to monitor changes in the perspective projection matrix and thus compensate for camera measurement errors. In compensation experiments, using target displacement effectively predicts pixel drift in the pixel coordinate system. After compensation, the pixel error was suppressed from 1.99 pixels to 0.393 pixels. Repetitive measurement tests of the deep hole measurement instrument validate the practicality and reliability of compensating for thermal-induced errors using perspective transformation.

Research on Point Cloud Acquisition and Calibration of Deep Hole Inner Surfaces Based on Collimated Ring Laser Beams.

In this study, a ring light point cloud calibration technique based on collimated laser beams is developed, aiming to reduce errors caused by the position and attitude changes of traditional ring light measurement devices. This article details the generation mechanism of the ring beam and the principle of deep hole measurement. It introduces the collimated beam as a reference, building on traditional ring light measurement devices, to achieve the synchronous acquisition of the ring beam and collimated spot images by an industrial camera. The Steger algorithm is employed to accurately extract the coordinates of the point cloud contours of both the ring beam and the collimated spot. By analyzing the shape and position changes of the collimated spot contour, the spatial position and attitude of the measuring device are precisely determined. This technique is applied to the 3D reconstruction of the inner surface of deep holes, ensuring the accurate restoration of the spatial positional attitude of the ring beam by incorporating the spatial positional attitude parameters of the measuring device to precisely calibrate the cross-sectional point cloud coordinates. Experimental results with ring gauges and deep hole workpieces demonstrate that this technique effectively reduces the percentage of point cloud data outside the tolerance range, and improves the accuracy of the 3D reconstruction model by 6.287%, thereby verifying the accuracy and practicality of this technique.

Synthesis and Mechanism of a Green Scale and Corrosion Inhibitor.

A new green water treatment agent, a poly(aspartic acid)-modified polymer (PASP/5-AVA), was synthesized using polysuccinimide and 5-aminovaleric acid (5-AVA) in a hybrid system. The structure was characterized, and the scale and corrosion inhibition performance were carried out with standard static scale inhibition and electrochemical methods, respectively. The mechanism was explored using XRD, XPS, SEM, and quantum chemistry calculations. The results indicated that PASP/5-AVA exhibited better scale and corrosion inhibition performance than PASP and maintained efficacy and thermal stability of the scale inhibition effect for a long time. Mechanistic studies indicated that PASP/5-AVA interferes with the normal generation of CaCO3 and CaSO4 scales through lattice distortion and dispersion, respectively; the combined effect of an alkaline environment and terminal electron-withdrawing -COOH groups can induce the stable C- ionic state formation in -CH2- of the extended side chain, thus enhancing its chelating ability for Ca2+ ions. At the same time, the extension of the side chain length also enhances the adsorption ability of the agent on the metal surface, forming a thick film and delaying the corrosion of the metal surface. This study provides the necessary theoretical reference for the design of green scale and corrosion agents.

Photoredox Catalytic Deracemization Enabled Enantioselective and Modular Access to Axially Chiral N-Arylquinazolinones.

Visible light-driven photocatalytic deracemization is highly esteemed as an ideal tool for organic synthesis due to its exceptional atom economy and synthetic efficiency. Consequently, successful instances of deracemization of allenes have been established, where the activated energy of photosensitizer should surpass that of the substrates, representing an intrinsic requirement. Accordingly, this method is not applicable for axially chiral molecules with significantly high triplet energies. In this study, we present a photoredox catalytic deracemization approach that enables the efficient synthesis of valuable yet challenging-to-access axially chiral 2-azaarene-functionalized quinazolinones. The substrate scope is extensive, allowing for both 3-axis and unmet 1-axis assembly through facile oxidation of diverse central chiral 2,3-dihydroquinazolin-4(1H)-ones that can be easily prepared and achieve enantiomer enrichment via deracemization. Mechanistic studies reveal the importance of photosensitizer selection in attaining excellent chemoselectivity and highlight the indispensability of a chiral Brønsted acid in enabling highly enantioselective protonation to accomplish efficient deracemization.

Catalytic Asymmetric Redox-Neutral [3+2] Photocycloadditions of Cyclopropyl Ketones with Vinylazaarenes Enabled by Consecutive Photoinduced Electron Transfer.

Consecutive photoinduced electron transfer (ConPET) is a powerful and atom-economical protocol to overcome the limitations of the intrinsic redox potential of visible light-absorbing photosensitizers, thereby considerably improving the substrate and reaction types. Likely because such an exothermic single-electron transfer (SET) process usually does not require the aid of chiral catalysts, resulting in an inevitable racemic background reaction, notably, no enantioselective manifolds have been reported. Herein, we report on the viability of cooperative ConPET and chiral hydrogen-bonding catalysis for the [3+2] photocycloaddition of cyclopropyl ketones with vinylazaarenes. In addition to enabling the first use of olefins that preferentially interact with chiral catalysts, this catalysis platform paves the way for the efficient synthesis of pharmaceutically and synthetically important cyclopentyl ketones functionalized by azaarenes with high yields, ees and dr. The robust capacity of the method can be further highlighted by the low loading of the chiral catalyst (1.0 mol %), the good compatibility of both 2-azaarene and 3-pyridine-based olefins, and the successful concurrent construction of three stereocenters on cyclopentane rings involving an elusive but important all-carbon quaternary.

Asymmetric Olefin Isomerization via Photoredox Catalytic Hydrogen Atom Transfer and Enantioselective Protonation.

Asymmetric olefin isomerization can be appreciated as an ideal synthetic approach to access valuable enantioenriched C═C-containing molecules due to the excellent atom economy. Nonetheless, its occurrence usually requires a thermodynamic advantage, namely, a higher stability of the product to the substrate. It has thus led to rather limited examples of success. Herein, we report a photoredox catalytic hydrogen atom transfer (HAT) and enantioselective protonation strategy for the challenging asymmetric olefin isomerization. As a paradigm, by establishing a dual catalyst system involving a visible light photosensitizer DPZ and a chiral phosphoric acid, with the assistance of N-hydroxyimide to perform HAT, a wide array of allylic azaarene derivatives, featuring α-tertiary carbon stereocenters and ß-C═C bonds, was synthesized with high yields, ees, and E/Z ratios starting from the conjugated α-substituted alkenylazaarene E/Z-mixtures. The good compatibility of assembling deuterium on stereocenters by using inexpensive D2O as a deuterium source further underscores the broad applicability and promising utility of this strategy. Moreover, mechanistic studies have provided clear insights into its challenges in terms of reactivity and enantioselectivity. The exploration will robustly inspire the development of thermodynamically unfavorable asymmetric olefin isomerizations.

Enantioselective Chemodivergent Three-Component Radical Tandem Reactions through Asymmetric Photoredox Catalysis.

Chemodivergent synthesis has been achieved in asymmetric photocatalysis. Under a dual catalyst system consisting of a chiral phosphoric acid and DPZ as a photosensitizer, different inorganic bases enabled the formation of two sets of valuable products from the three-component radical tandem transformations of 2-bromo-1-arylenthan-1-ones, styrenes, and quinoxalin-2(1H)-ones. The key to success was the distinct pKa environment, in which the radicals that formed on the quinoxalin-2(1H)-one rings after two radical addition processes underwent either single-electron oxidation or single-electron reduction. In addition, this work represents the first use of quinoxalin-2(1H)-ones in asymmetric photoredox catalysis.

Metal-Free Construction of Multisubstituted Indolizines via Intramolecular Amination of Allylic Alcohols.

An intramolecular amination of allylic alcohols is developed as an efficient and general access to biologically important multisubstituted indolizines and their variants. Two metal-free synthetic platforms including using aqueous hydrochloric acid solution as the solvent and p-toluenesulfonic acid as the catalyst have been established, enabling the divergent synthesis of these valuable compounds in high yields.

NHC-Catalyzed Tandem Reaction: A Strategy for the Synthesis of 2-Pyrrolidinone-Functionalized Phenanthridines.

Herein, an N-heterocyclic carbene (NHC)-catalyzed tandem cyclization/addition/cyclization reaction of 2-isocyanobiaryls and α-bromo-N-cinnamylamides for the synthesis of 2-pyrrolidinone-functionalized phenanthridines is developed. This protocol features a radical cascade process, broad substrate scope, and good functional group compatibility under metal- and oxidant-free reaction conditions.

LysP53 activity against Salmonella and its application in decontamination of Salmonella on fresh romaine lettuce.

Salmonella is a zoonotic pathogen that is commonly associated with foodborne disease outbreaks. This study found that a newly identified Gram-negative lysin LysP53 had good activity against a wide range of Salmonella, including Salmonella Newington, Salmonella Typhimurium, and Salmonella Dublin. Without the help of an outer membrane permeabilizer, 4 µM LysP53 could reduce 97.6% of planktonic Salmonella Enteritidis and 90% of the bacteria in biofilms. Moreover, LysP53 was highly thermostable because it maintained >90% activity even after exposure to temperatures up to 95 °C. Although high concentrations of salts could reduce the activity, LysP53 was found safe for oral gavage of mice without affecting body weights and cytokines in sera and able to reduce 90% of Salmonella Enteritidis loads on fresh romaine lettuce after 30 min of treatment. Because of its good activity against a wide range of bacteria, thermal stability, safe for oral administration, LysP53 could be used as a biocontrol agent for reducing bacterial loads in fresh vegetable food. KEY POINTS: • Lysin LysP53 has high bactericidal activity against Salmonella. • LysP53 is thermostable even at high temperature of up to 95 °C. • LysP53 can be used for topical decontamination of Salmonella on vegetables.

Transcriptome analysis of differentially expressed genes involved in the inflammageing status of gingiva in aged mice.

OBJECTIVE: To identify immune-inflammation-related genes related to susceptibility to periodontitis in the gingiva of aged mice with RNA sequencing. METHODS: Gingival samples from 18-month-old, 8-week-old healthy mice and 8-week-old mice with periodontitis were taken for RNA-seq. The differentially expressed genes (DEGs) were validated with qRT-PCR using mouse and human gingival samples. RESULTS: 977 (upregulated) and 1824 (downregulated) genes were identified in the old compared with the young mice. 14.2% were related to immune-inflammatory responses. This proportion of overlap (ageing and periodontitis)-DEGs was higher (48.4%). Enrichment analysis of overlap (ageing and periodontitis)-DEGs showed that the top five GO and KEGG terms were related to the immune-inflammatory responses, and disease analysis was more specific to periodontitis. The candidate genes of overlap (ageing and periodontitis)-DEGs selected by protein-protein interaction (PPI) network showed the higher match with clinical data sets. By qRT-PCR, nine candidate genes were identified as hub genes that are associated with susceptibility to periodontitis in the elderly, including CXCL3, CXCL5, CSF3, CSF3R, FPR1, IL1B, OSM, SERPINE1 and SELP. CONCLUSION: Our studies provide insights into the mechanisms by which ageing affects the immune-inflammatory status of gingival tissues, thereby increasing the risk of periodontitis. It may become targets for future prevention of periodontitis.

Kinetic Resolution of Azaarylethynyl Tertiary Alcohols by Chiral Brønsted Acid Catalysed Phosphine-Mediated Deoxygenation.

A chiral Brønsted acid catalysed phosphine-mediated deoxygenation protocol is reported. This metal-free method provides a precise kinetic resolution platform for azaarylethynyl tertiary alcohols, which are a broad category of biologically and synthetically important azaarene derivatives. In addition to providing an efficient method for the first asymmetric preparation of these tertiary alcohols, the strategy facilitates the construction of azaaryl-functionalized allenes with good to excellent enantioselectivities. The high selectivity factors (s up to 235), broad substrate scope, and ability to convert azaaryl compounds into both chiral tertiary alcohols and allenes robustly underscore the efficiency and promising utility of this method. The practicability is further validated by the successful synthesis of deuterated allenes with high ee values and substantial incorporation of deuterium using inexpensive D2 O as the deuterium source.