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Abstract Background Increasing evidence shows the pivotal significance of miRNAs in the pathogenesis of osteoporosis. miR-381-3p has been identified as an inhibitor of osteogenesis. This study explored the role and mechanism of miR-381-3p in postmenopausal osteoporosis (PMOP), the most common type of osteoporosis. Methods Bilateral ovariectomy (OVX) rat model was established and miR-381-3p antagomir was administrated through the tail vein in vivo. The pathological changes in rats were assessed through the evaluation of serum bone turnover markers (BALP, PINP, and CTX-1), hematoxylin and eosin (H&E) staining, as well as the expression of osteoblast differentiation biomarkers. Moreover, isolated bone marrow mesenchymal stem cells from OVX-induced rats (OVX-BMMSCs) were utilized to explore the impact of miR-381-3p on osteoblast differentiation. In addition, the target gene and downstream pathway of miR-381-3p were further investigated both in vivo and in vitro. Results miR-381-3p expression was elevated, whereas KLF5 was suppressed in OVX rats. miR-381-3p antagomir decreased serum levels of bone turnover markers, improved trabecular separation, promoted osteoblast differentiation biomarker expression in OVX rats. ALP activity and mineralization were suppressed, and levels of osteoblast differentiation biomarkers were impeded after miR-381-3p overexpression during osteoblast differentiation of OVX-BMMSCs. While contrasting results were found after inhibition of miR-381-3p. miR-381-3p targets KLF5, negatively affecting its expression as well as its downstream Wnt/β-catenin pathway, both in vivo and in vitro. Silencing of KLF5 restored Wnt/β-catenin activation induced by miR-381-3p antagomir. Conclusion miR-381-3p aggravates PMOP by inhibiting osteogenic differentiation through targeting KLF5/Wnt/β-catenin pathway. miR-381-3p appears to be a promising candidate for therapeutic intervention in PMOP.

The goal of precision oncology is to select more effective treatments or beneficial drugs for patients. The transcription of ‘‘hidden responders’’ which precision oncology often fails to identify for patients is important for revealing responsive molecular states. Recently, a RAS pathway activation detection method based on machine learning and a nature-inspired deep RAS activation pan-cancer has been proposed. However, we note that the activating gene variations found in KRAS, HRAS and NRAS vary substantially across cancers. Besides, the ability of a machine learning classifier to detect which KRAS, HRAS and NRAS gain of function mutations or copy number alterations causes the RAS pathway activation is not clear. Here, we proposed a deep neural network framework for deciphering and identifying pan-cancer RAS pathway activation (DIPRAS). DIPRAS brings a new insight into deciphering and identifying the pan-cancer RAS pathway activation from a deeper perspective. In addition, we further revealed the identification and characterization of RAS aberrant pathway activity through gene ontological enrichment and pathological analysis. The source code is available by the URL https://github.com/zhaoyw456/DIPRAS.

Golden 2-Like (GLK) transcription factors play a crucial role in chloroplast development and chlorophyll synthesis in many plant taxa. To date, no systematic analysis of GLK transcription factors in tree species has been conducted. In this study, 40 EgrGLK genes in the Eucalyptus grandis genome were identified and divided into seven groups based on the gene structure and motif composition. The EgrGLK genes were mapped to 11 chromosomes and the distribution of genes on chromosome was uneven. Phylogenetic analysis of GLK proteins between E. grandis and other species provided information for the high evolutionary conservation of GLK genes among different species. Prediction of cis-regulatory elements indicated that the EgrGLK genes were involved in development, light response, and hormone response. Based on the finding that the content of chlorophyll in mature leaves was the highest, and leaf chlorophyll content of triploid Eucalyptus urophylla was higher than that of the diploid control, EgrGLK expression pattern in leaves of triploid and diploid E. urophylla was examined by means of transcriptome analysis. Differential expression of EgrGLK genes in leaves of E. urophylla of different ploidies was consistent with the trend in chlorophyll content. To further explore the relationship between EgrGLK expression and chlorophyll synthesis, co-expression networks were generated, which indicated that EgrGLK genes may have a positive regulatory relationship with chlorophyll synthesis. In addition, three EgrGLK genes that may play an important role in chlorophyll synthesis were identified in the co-expression networks. And the prediction of miRNAs targeting EgrGLK genes showed that miRNAs might play an important role in the regulation of EgrGLK gene expression. This research provides valuable information for further functional characterization of GLK genes in Eucalyptus.

Alternative carbene precursors for metal-catalyzed cross coupling may expand the portfolio of methods for C-C bond construction. Here, the authors report a Suzuki−Miyaura coupling of Pd−carbene complexes formed by desulfurization of thioureas or thioamides and affording a broad array of amidinium salts and diaryl ketones.

This paper investigates the attitude estimation errors caused by the deflections of vertical (DOV) in the case of a rotational inertial navigation system (INS) integrated with a global satellite navigation system (GNSS). It has been proved theoretically and experimentally that the DOV can introduce a tilt error to the INS/GNSS integration, whereas less attention has been given to its effect to the heading estimation. In fact, due to the intercoupling characteristic of attitude errors, the heading estimation of an INS/GNSS integrated navigation system can also be affected. In this paper, first, the attitude estimation errors caused by DOV were deduced based on the INS’s error propagation functions. Then, the corresponding simulations were conducted and the results were well consistent with the theoretical analysis. Finally, a real shipborne marine test was organized with the aimed to verify the effect of DOV on attitude estimation in the rotational INS/GNSS integration, whereas the global gravity model was used for DOV compensation. The results with DOV compensation were compared with the corresponding results where the compensation was not used and showed that the heading estimation errors caused by DOV could exceed 20 arcsecs, which must be considered in high-precision application cases.

Paper mulberry is a high-quality woody feed resource plant with high crude protein content. It is widely distributed in China and has excellent characteristics of salt and alkali tolerance. Paper mulberry has ecological and economic importance. Salt stress has become a critical factor with the increasing degree of soil salinity that restricts plant growth. In the saline-alkali environments, transcriptome expression is altered leading to phenotypic defects in most plants. However, the regulatory mechanism related to paper mulberry's salt-stress (SS) response is not clearly understood. In the present study de novo transcriptomic assembly was performed, and gene expression levels were measured between different SS and natural conditions (25°C) as a control for paper mulberry plants. According to the results of our study, under NaCl stress conditions, the differential gene expression was observed in the leaves of paper mulberry compared with the control. A total of 2126 differentially expressed unigenes were observed. Among these unigenes the expression of 812 DEGs was up-regulated and the expression of 1,314 DEGs was down-regulated. Additionally, The GO and KEGG analyses regarding differentially expressed unigenes (DEUs) revealed that the observed critical transcriptomic alterations under salt stress (SS) conditions were associated with primary and secondary metabolism, photosynthesis, and plant hormone signaling pathways. Further investigations such as gene function studies regarding the unigenes depicting altered expression under salt stress conditions in paper mulberry will help understand the mechanism of salt tolerance, and this information can be utilized in paper mulberry breeding and improvement programs. [ABSTRACT FROM AUTHOR]

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is highly abundant in the brain and confers protection against numerous neurological diseases, yet the fundamental mechanisms regulating the enrichment of DHA in the brain remain unknown. Here, we have discovered that a member of the long-chain acyl-CoA synthetase family, Acsl6, is required for the enrichment of DHA in the brain by generating an Acsl6-deficient mouse (Acsl6-/-). Acsl6 is highly enriched in the brain and lipid profiling of Acsl6-/- tissues reveals consistent reductions in DHA-containing lipids in tissues highly abundant with Acsl6. Acsl6-/- mice demonstrate motor impairments, altered glutamate metabolism, and increased astrogliosis and microglia activation. In response to a neuroinflammatory lipopolysaccharide injection, Acsl6-/- brains show similar increases in molecular and pathological indices of astrogliosis compared with controls. These data demonstrate that Acsl6 is a key mediator of neuroprotective DHA enrichment in the brain. [ABSTRACT FROM AUTHOR]

A palladium-catalyzed dual ortho C-H bond activation of aryl thiocarbamates is developed. This tandem reaction initiates by thiocarbamate-directed ortho C-H palladation, which leads to favorable olefin insertion rather than reductive elimination. The oxidative Heck reaction followed by another C-H activation and sulfuration affords the dual-functionalized products. This reaction provides a concise route to the S,O,C multisubstituted benzene skeleton which could be successfully applied for the synthesis of a COX-2 inhibitor. [ABSTRACT FROM AUTHOR]

A Rh-catalyzedannulation of aryl thiocarbamates with internalalkynes via C–H bond activation has been developed. This protocolprovides a new route to 3,4-disubstituted coumarins. [ABSTRACT FROM AUTHOR]