Time-course swRNA-seq uncovers a hierarchical gene regulatory network in controlling the response-repair-remodeling after wounding.

Wounding initiates intricate responses crucial for tissue repair and regeneration. Yet, the gene regulatory networks governing wound healing remain poorly understood. Here, employing single-worm RNA sequencing (swRNA-seq) across 12 time-points, we delineated a three-stage wound repair process in C. elegans: response, repair, and remodeling. Integrating diverse datasets, we constructed a dynamic regulatory network comprising 241 transcription regulators and their inferred targets. We identified potentially seven autoregulatory TFs and five cross-autoregulatory loops involving pqm-1 and jun-1. We revealed that TFs might interact with chromatin factors and form TF-TF combinatory modules via intrinsically disordered regions to enhance response robustness. We experimentally validated six regulators functioning in transcriptional and translocation-dependent manners. Notably, nhr-76, daf-16, nhr-84, and oef-1 are potentially required for efficient repair, while elt-2 may act as an inhibitor. These findings elucidate transcriptional responses and hierarchical regulatory networks during C. elegans wound repair, shedding light on mechanisms underlying tissue repair and regeneration.

Identification of a longevity gene through evolutionary rate covariation of insect mito-nuclear genomes.

Oxidative phosphorylation, essential for energy metabolism and linked to the regulation of longevity, involves mitochondrial and nuclear genes. The functions of these genes and their evolutionary rate covariation (ERC) have been extensively studied, but little is known about whether other nuclear genes not targeted to mitochondria evolutionarily and functionally interact with mitochondrial genes. Here we systematically examined the ERC of mitochondrial and nuclear benchmarking universal single-copy ortholog (BUSCO) genes from 472 insects, identifying 75 non-mitochondria-targeted nuclear genes. We found that the uncharacterized gene CG11837-a putative ortholog of human DIMT1-regulates insect lifespan, as its knockdown reduces median lifespan in five diverse insect species and Caenorhabditis elegans, whereas its overexpression extends median lifespans in fruit flies and C. elegans and enhances oxidative phosphorylation gene activity. Additionally, DIMT1 overexpression protects human cells from cellular senescence. Together, these data provide insights into the ERC of mito-nuclear genes and suggest that CG11837 may regulate longevity across animals.

Enhanced single RNA imaging reveals dynamic gene expression in live animals.

Imaging endogenous mRNAs in live animals is technically challenging. Here, we describe an MS2-based signal amplification with the Suntag system that enables live-cell RNA imaging of high temporal resolution and with 8xMS2 stem-loops, which overcomes the obstacle of inserting a 1300 nt 24xMS2 into the genome for the imaging of endogenous mRNAs. Using this tool, we were able to image the activation of gene expression and the dynamics of endogenous mRNAs in the epidermis of live C. elegans.

Construction of Mental Health Knowledge Service Model Based on Online Medical Community.

This paper discusses a common mental disorder prevention mode to improve residents' mental health quality and achieve the "comprehensive and fine-grained" mental health education knowledge service. The construction of mental health knowledge service model is conducive to accurately grasp the group cognition and psychological changes and take the initiative to make decisions. This paper analyzes the needs of mental health education knowledge service system and combs the research status of applying information technology and artificial intelligence to mental health education at home and abroad, the resource data of five major online medical communities at home and abroad were screened and mined, and the mental health feature tags of college students were extracted. Based on the existing mental health diagnosis experience database and multisource text, reuse and optimize ontology integration method to systematically construct mental health education ontology. Taking mental illness as an example, the rule base is constructed and the personalized recommendation service of mental health is realized. The service model can infer and output all kinds of diagnosis and treatment knowledge to provide users with intelligent mental health education knowledge services.

SOC Estimation of Lithium-Ion Battery for Electric Vehicle Based on Deep Multilayer Perceptron.

The state of charge (SOC) is one of the main indexes of the lithium-ion battery, which affects the practice range of new energy vehicles and the safety of the battery. Nevertheless, the value of SOC cannot be measured directly. At present, the algorithm for estimating the state of charge is not very satisfactory. The multilayer perceptron algorithm designed during this paper encompasses a sensible impact on state estimation. During this paper, the multilayer network is designed to estimate the charged state of lithium batteries from the three-layer artificial neural network to the eleven-layer artificial neural network. After preprocessing the dataset and comparing several activation functions, the ten-layer fully connected neural network is the most efficient to estimate the SOC. In order to prevent over-fitting of the multilayer perceptron algorithm, the two techniques of the BatchNormalization layer and Dropout layer work together to inhibit over-fitting. At the same time, the accuracy of extended Kalman filter, long and short memory network, and recurrent neural network are compared. The multilayer perceptron network designed during this paper has the highest accuracy. Finally, in the open dataset, both the training and test errors achieve good results. The algorithm developed in this paper has made some progress in SOC estimation.

Coupling of Thiols and Aryl Halides Mediated by Dicyclohexano-18- crown-6 and Potassium Carbonate.

AIMS: A simple, transition-metal-free C-S coupling protocol for the synthesis of aryl thioethers is reported. BACKGROUND: Sulfur-containing moieties are ubiquitous in pharmaceutical drugs and materials and therefore methods for their construction are of great importance. One approach entails the catalytic coupling of an aryl halohydrocarbon with a thiol, but the transition metal catalysts usually used are prone to poisoning by participating sulfur species and efficient catalysis is usually only achieved after complex ligand optimization. OBJECTIVE: New transition-metal-free approaches to the synthesis of C-S bonds are urgently need. METHODS: We screened the reaction conditions such as alkali, crown ether, solvent, temperature, etc., tested the compatibility of the reaction substrate, and analyzed the mechanism process. RESULTS: The optimized reaction conditions were determined to be 1.0 equiv of aryl halides and 1.2 equiv of thiols at 110 ℃ in toluene with K2CO3 (1.5 equiv) as a base, promoted by 10 mol% dicyclohexano-18-crown-6. Up to 33 examples of thioethers were synthesized under transitionmetal- free conditions in good to excellent yields. CONCLUSION: We have developed a simple and efficient method for the C-S cross-coupling of a wide variety of (hetero)aryl halides and thiols mediated by dicyclohexano-18-crown-6 and without the need for transition-metal catalyst. In addition, the preparation and gram-scale experiments of a variety of drug molecules further verify the practicability of our developed method.

Claudin 19 inhibits the malignant potential of breast cancer cells by modulating extracellular matrix-associated UBE2C/Wnt signaling.

Claudin proteins are a major component of the tight junctions between cells, which are involved in a variety of human diseases, including cancer. This study aimed to investigate the functional role of claudin 19 (CLDN19) in human breast cancer progression. Here, we firstly found that CLDN19 was downregulated in breast tumor tissues than normal control, and loss of CLDN19 predicted poor patient survival in patients with breast cancer, by utilizing the Cancer Genome Atlas Program (TCGA) dataset analysis. To further validate the tumor suppressive effects of CLDN19, we established CLDN19 overexpressed MDA-MB-231 and T47D cells. And overexpression of CLDN19 resulted in suppression of cell growth/migration in breast cancer cells cultured in 3D environment or in vivo. Mechanistically, we demonstrated that CLDN19 downregulated ubiquitin conjugating enzyme E2 C (UBE2C) expression, which further suppressed Wnt/ß-catenin pro-survival signaling pathway activation induced by extracellular matrix (ECM), in 3D environment or in vivo. Altogether, our study revealed a tumor suppressive role of CLDN19, which hindered ECM/UBE2C/Wnt signaling activation in breast cancer, and offered novel insight for tumor diagnosis and targeted therapy.

Redox-sensitive CDC-42 clustering promotes wound closure in C. elegans.

Tissue damage induces immediate-early signals, activating Rho small GTPases to trigger actin polymerization essential for later wound repair. However, how tissue damage is sensed to activate Rho small GTPases locally remains elusive. Here, we found that wounding the C. elegans epidermis induces rapid relocalization of CDC-42 into plasma membrane-associated clusters, which subsequently recruits WASP/WSP-1 to trigger actin polymerization to close the wound. In addition, wounding induces a local transient increase and subsequent reduction of H2O2, which negatively regulates the clustering of CDC-42 and wound closure. CDC-42 CAAX motif-mediated prenylation and polybasic region-mediated cation-phospholipid interaction are both required for its clustering. Cysteine residues participate in intermolecular disulfide bonds to reduce membrane association and are required for negative regulation of CDC-42 clustering by H2O2. Collectively, our findings suggest that H2O2-regulated fine-tuning of CDC-42 localization can create a distinct biomolecular cluster that facilitates rapid epithelial wound repair after injury.

Visible-Light-Mediated Oxidative Cyclization of 2-Aminobenzyl Alcohols and Secondary Alcohols Enabled by an Organic Photocatalyst.

This paper describes a visible-light-mediated oxidative cyclization of 2-aminobenzyl alcohols and secondary alcohols to produce quinolines at room temperature. This photocatalytic method employed anthraquinone as an organic small-molecule catalyst and DMSO as an oxidant. According to this present procedure, a series of quinolines were prepared in satisfactory yields.

Wounding triggers MIRO-1 dependent mitochondrial fragmentation that accelerates epidermal wound closure through oxidative signaling.

Organisms respond to tissue damage through the upregulation of protective responses which restore tissue structure and metabolic function. Mitochondria are key sources of intracellular oxidative metabolic signals that maintain cellular homeostasis. Here we report that tissue and cellular wounding triggers rapid and reversible mitochondrial fragmentation. Elevated mitochondrial fragmentation either in fzo-1 fusion-defective mutants or after acute drug treatment accelerates actin-based wound closure. Wounding triggered mitochondrial fragmentation is independent of the GTPase DRP-1 but acts via the mitochondrial Rho GTPase MIRO-1 and cytosolic Ca2+. The fragmented mitochondria and accelerated wound closure of fzo-1 mutants are dependent on MIRO-1 function. Genetic and transcriptomic analyzes show that enhanced mitochondrial fragmentation accelerates wound closure via the upregulation of mtROS and Cytochrome P450. Our results reveal how mitochondrial dynamics respond to cellular and tissue injury and promote tissue repair.

Spatiotemporal expression pattern of Sjfz7 and its expression comparison with other frizzled family genes in developmental stages of Schistosoma japonicum.

Wnts are secreted signaling molecules that are implicated in a variety of growth-related processes. Frizzled proteins have been identified as receptors for Wnt ligands in vertebrates and invertebrates, but a functional role for dioecious flatworm Frizzleds has not been determined. To evaluate the endogenous role of Frizzled proteins during development, we have identified and characterized a Schistosoma japonicum frizzled gene (Sjfz7). We found that Sjfz7 encodes a 698 amino acid protein with typical characteristics of Frizzled proteins. The immunohistochemical localization pattern showed that Sjfz7 protein was extensively distributed in almost all tissues of S. japonicum, including subtegumental muscle cells, parenchymal cells, intestinal epithelial cells and male and female germ cells. This indicated that Sjfz7-mediated Wnt signaling might be associated with the development of musculature, intestinal tract and reproductive organs in schistosome. Comparing mRNA levels between frizzled family members showed that Sjfz7 mRNA was consistently higher in the developmental stages analyzed, suggesting that Sjfz7 may be responsible for more functional tasks than other frizzled family members. Comparing frizzled mRNA levels between not fully developed and normal worms suggested that Wnt signaling might be abnormal in not fully developed worms.

N-Heterocyclic carbene copper catalyzed quinoline synthesis from 2-aminobenzyl alcohols and ketones using DMSO as an oxidant at room temperature.

A facile and practical process for the synthesis of quinolines through an N-heterocyclic carbene copper catalyzed indirect Friedländer reaction from 2-aminobenzyl alcohol and aryl ketones using DMSO as an oxidant at room temperature is reported. A series of quinolines were synthesized in acceptable yields.

Characterization and expression pattern of a novel Frizzled 8 receptor gene in Schistosoma japonicum.

Wnt signaling as mediated by the Frizzled family receptors plays a vital role in the early development of animal embryos, organ formation, tissue regeneration and other physiological processes. In the present study, a novel Frizzled member, SjFz8, was isolated and characterized in Schistosoma japonicum. SjFz8 encodes an 1162-amino-acid protein with typical characteristics of Frizzled proteins. Quantitative real-time polymerase chain reaction analysis indicated that SjFz8 transcript level was highest in 7-day-old schistosomula. In adult stages, SjFz8 mRNA expression remained at a low level after male-female pairing. The immunohistochemical localization of the Fz8 protein revealed that it existed in almost all tissues of S. japonicum, including subtegumental muscle, parenchyma, oral suckers, ventral suckers, testes of the male and ovaries of the female. We speculated that the Wnt signaling pathway that was mediated by Fz8 might take part in regulating histogenesis and organogenesis during the schistosomulum period, and play an important role in regulating further growth and development of male and female worms.

Dietary Selenium Status Regulates the Transcriptions of Selenoproteome and Activities of Selenoenzymes in Chicken Kidney at Low or Super-nutritional Levels.

To determine dietary selenium (Se) status regulates the transcriptions of selenoproteome and activities of selenoenzymes in chicken kidney, 1-day-old chickens received low Se (0.028 mg Se per kg of diet) or super-nutritional Se (3.0 or 5.0 mg Se per kg of diet) in their diets for 8 weeks. It was observed that dietary low or super-nutritional Se did not make renal appearance pathological changes in chicken. Low Se significantly reduced total antioxidant capability (T-AOC), glutathione (GSH) content, but malondialdehyde (MDA) content in the kidney increased and decreased glutathione peroxidase (Gpx) and thioredoxin reductase (TrxR) activity with changes in their mRNA levels. Super-nutritional Se (3.0 mg/kg) increased T-AOC and GSH contents then made them reduce, but it reduced MDA content significantly, elevated then reduced Gpx activity, and decreased TrxR activity with changes in their mRNA levels. Dietary low Se downregulated the mRNA expressions of Gpx1-4, Txnrd3, Sepn1, Selw, Sepx1, Selh, and SEPSECS. At super-nutritional Se, most selenoproteins were upregulated in chicken kidney, but Sepp2 and Sep15 was only upregulated in Se excess (5.0 mg/kg) bird. These results indicated that dietary Se status stabilizes normal renal physiology function via regulation of the selenoprotemic transcriptions and selenoenzyme activities in avian.

Effects on liver hydrogen peroxide metabolism induced by dietary selenium deficiency or excess in chickens.

To determine the relationship between dietary selenium (Se) deficiency or excess and liver hydrogen peroxide (H2O2) metabolism in chickens, 1-day-old chickens received insufficient Se (0.028 mg Se per kg of diet) or excess Se (3.0 or 5.0 mg Se per kg of diet) in their diets for 8 weeks. Body and liver weight changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, H2O2 content, and activities and mRNA levels of enzymes associated with H2O2 metabolism (catalase (CAT) and superoxide dismutase (SOD) 1-3) were determined in the liver. This study showed that Se deficiency or excess Se intake elicited relative severe changes. Se deficiency decreased growth, while Se excess promoted growth in chickens. Both diets vastly altered the liver function, but no obvious histopathological changes were observed in the liver. Se deficiency significantly lowered SOD and CAT activities, and the H2O2 content in the liver and serum increased. Se excess (3.0 mg/kg) decreased SOD and CAT activities with changes in their mRNA levels, and the H2O2 content increased. The larger Se excess (5.0 mg/kg) showed more serious effects but was not fatal. These results indicated that the H2O2 metabolism played a destructive role in the changes in bird liver function induced by Se deficiency or excess.

(Z)-5-Benzyl-idene-3-butyl-4-phenyl-1,3-oxazolidin-2-one.

In the title compound, C(20)H(21)NO(2), the benzyl group and the oxazolidin-2-one unit are each essentially planar, with maximum deviations of 0.026 (2) and 0.031 (2) Å, respectively. The dihedral angle between the phenyl ring and the oxazolidin-2-one unit is 69.25 (2)°. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O and C-H⋯π inter-actions.