mirAct: a web tool for evaluating microRNA activity based on gene expression data

MicroRNAs (miRNAs) are critical regulators in the complex cellular networks. The mirAct web server (http://sysbio.ustc.edu.cn/software/mirAct) is a tool designed to investigate miRNA activity based on gene-expression data by using the negative regulation relationship between miRNAs and their target genes. mirAct supports multiple-class data and enables clustering analysis based on computationally determined miRNA activity. Here, we describe the framework of mirAct, demonstrate its performance by comparing with other similar programs and exemplify its applications using case studies

The emerging role of lncRNAs in osteoarthritis development and potential therapy

Osteoarthritis impairs the functions of various joints, such as knees, hips, hands and spine, which causes pain, swelling, stiffness and reduced mobility in joints. Multiple factors, including age, joint injuries, obesity, and mechanical stress, could contribute to osteoarthritis development and progression. Evidence has demonstrated that genetics and epigenetics play a critical role in osteoarthritis initiation and progression. Noncoding RNAs (ncRNAs) have been revealed to participate in osteoarthritis development. In this review, we describe the pivotal functions and molecular mechanisms of numerous lncRNAs in osteoarthritis progression. We mention that long noncoding RNAs (lncRNAs) could be biomarkers for osteoarthritis diagnosis, prognosis and therapeutic targets. Moreover, we highlight the several compounds that alleviate osteoarthritis progression in part via targeting lncRNAs. Furthermore, we provide the future perspectives regarding the potential application of lncRNAs in diagnosis, treatment and prognosis of osteoarthritis

Taxonomic and functional dynamics of nirS denitrifiers along a salinity gradient in the Pearl River Estuary

Understanding the factors that shape the diversity, distribution, and function of denitrifying microbes is vital for managing nitrogen cycling in these ecosystems. This study explores the diversity, biogeographic distribution, assembly processes, interaction, and denitrification potential of the nirS-encoding microbial community (nirS denitrifier) in the Pearl River Estuary based on high-throughput and metagenomics sequencing dataset. The results of this study show that salinity is a crucial regulatory environmental factor that determines the spatial distribution, phylogenetic turnover, and co-occurrence patterns of nirS denitrifiers. Additionally, the dissolved organic carbon (DOC), suspended sediment concentration (SSC), and dissolved oxygen (DO) in water also significantly impact the biodiversity and abundance of nirS denitrifiers. Furthermore, our findings demonstrate that, in comparison to environmental factors, the ecological and evolutionary characteristics of nirS denitrifiers play a more prominent role in regulating their denitrification potential, suggesting that alterations in the microbial community within dynamic changes in estuarine water can profoundly affect its denitrification function. Our results indicate the significant roles of denitrification microbial structure and phylogenetic characteristics in maintaining their ecological functions. Future studies should continue to explore the interactions between microbial communities and environmental factors to further elucidate the denitrification process in estuaries and its implications for ecosystem health and water quality

Interface cracking damage of W/Cu monoblocks as divertor target after high-cyclic plasma discharges in EAST

W/Cu monoblocks will be employed in ITER as divertor targets for high heat loads. Experimental results of W/Cu monoblocks in high heat flux (HHF) tests have demonstrated their endurance on 5000 cycles at 10 MW/m2 and occasionally 300 cycles at 20 MW/m2. However, plasma-facing units (PFUs) serve in a harsh and complex environment in tokamaks and whether W/Cu monoblocks can show the same excellent properties in tokamaks needs to be further tested. Experimentally evaluating the evolution of ITER-like PFUs is one of the main missions for the EAST tokamak. The ITER-like actively cooled W/Cu monoblocks installed in the EAST lower divertor in 2021 exhibited abnormal behavior after 13,346 plasma discharges. The abnormal temperature evolution of the component was observed via infrared cameras (IR). Subsequent non-destructive testing (NDT) indicated that it might primarily arise from interface damage and scanning electron microscopy (SEM) confirmed that there were obvious cracks at the interface. The cracking center was also found above the interface. Simulation of the structural characteristics of W/Cu monoblocks under heat load in EAST can obtain temperature distribution and stress–strain distribution, which can be used to analyze the causes of material interface cracks. These findings unveil the phenomenon and mechanism of interface damage in W/Cu monoblocks after enduring over 10,000 plasma discharges in EAST, providing valuable insights for the future long-term application of W/Cu monoblocks in ITER and fusion reactors

Fabrication and applications of van der Waals heterostructures

Van der Waals heterostructures (vdWHs) are showing considerable potential in both fundamental exploration and practical applications. Built upon the synthetic successes of (two-dimensional) 2D materials, several synthetic strategies of vdWHs have been developed, allowing the convenient fabrication of diverse vdWHs with decent controllability, quality, and scalability. This review first summarizes the current state of the art in synthetic strategies of vdWHs, including physical combination, deposition, solvothermal synthesis, and synchronous evolution. Then three major applications and their representative vdWH devices have been reviewed, including electronics (tunneling field effect transistors and 2D contact), optoelectronics (photodetector), and energy conversion (electrocatalysts and metal ion batteries), to unveil the potentials of vdWHs in practical applications and provide the general design principles of functional vdWHs for different applications. Besides, moiré superlattices based on vdWHs are discussed to showcase the importance of vdWHs as a platform for novel condensed matter physics. Finally, the crucial challenges towards ideal vdWHs with high performance are discussed, and the outlook for future development is presented. By the systematical integration of synthetic strategies and applications, we hope this review can further light up the rational designs of vdWHs for emerging applications

A Rare Variant Nonparametric Linkage Method for Nuclear and Extended Pedigrees with Application to Late-Onset Alzheimer Disease via WGS Data

To analyze family-based whole-genome sequence (WGS) data for complex traits, we developed a rare variant (RV) non-parametric linkage (NPL) analysis method, which has advantages over association methods. The RV-NPL differs from the NPL in that RVs are analyzed, and allele sharing among affected relative-pairs is estimated only for minor alleles. Analyzing families can increase power because causal variants with familial aggregation usually have larger effect sizes than those underlying sporadic diseases. Differing from association analysis, for NPL only affected individuals are analyzed, which can increase power, since unaffected family members can be susceptibility variant carriers. RV-NPL is robust to population substructure and admixture, inclusion of nonpathogenic variants, as well as allelic and locus heterogeneity and can readily be applied outside of coding regions. In contrast to analyzing common variants using NPL, where loci localize to large genomic regions (e.g., >50 Mb), mapped regions are well defined for RV-NPL. Using simulation studies, we demonstrate that RV-NPL is substantially more powerful than applying traditional NPL methods to analyze RVs. The RV-NPL was applied to analyze 107 late-onset Alzheimer disease (LOAD) pedigrees of Caribbean Hispanic and European ancestry with WGS data, and statistically significant linkage (LOD >= 3.8) was found with RVs in PSMF1 and PTPN21 which have been shown to be involved in LOAD etiology. Additionally, nominally significant linkage was observed with RVs in ABCA7, ACE, EPHA1, and SORL1, genes that were previously reported to be associated with LOAD. RV-NPL is an ideal method to elucidate the genetic etiology of complex familial diseases

De novo mutations in NALCN cause a syndrome characterized by congenital contractures of the limbs and face, hypotonia, and developmental delay

Freeman-Sheldon syndrome, or distal arthrogryposis type 2A (DA2A), is an autosomal-dominant condition caused by mutations in MYH3 and characterized by multiple congenital contractures of the face and limbs and normal cognitive development. We identified a subset of five individuals who had been putatively diagnosed with “DA2A with severe neurological abnormalities” and for whom congenital contractures of the limbs and face, hypotonia, and global developmental delay had resulted in early death in three cases; this is a unique condition that we now refer to as CLIFAHDD syndrome. Exome sequencing identified missense mutations in the sodium leak channel, non-selective (NALCN) in four families affected by CLIFAHDD syndrome. We used molecular-inversion probes to screen for NALCN in a cohort of 202 distal arthrogryposis (DA)-affected individuals as well as concurrent exome sequencing of six other DA-affected individuals, thus revealing NALCN mutations in ten additional families with “atypical” forms of DA. All 14 mutations were missense variants predicted to alter amino acid residues in or near the S5 and S6 pore-forming segments of NALCN, highlighting the functional importance of these segments. In vitro functional studies demonstrated that NALCN alterations nearly abolished the expression of wild-type NALCN, suggesting that alterations that cause CLIFAHDD syndrome have a dominant-negative effect. In contrast, homozygosity for mutations in other regions of NALCN has been reported in three families affected by an autosomal-recessive condition characterized mainly by hypotonia and severe intellectual disability. Accordingly, mutations in NALCN can cause either a recessive or dominant condition characterized by varied though overlapping phenotypic features, perhaps based on the type of mutation and affected protein domain(s