An updated overview of experimental and computational approaches to identify non-canonical DNA/RNA structures with emphasis on G-quadruplexes and R-loops.

Multiple types of non-canonical nucleic acid structures play essential roles in DNA recombination and replication, transcription, and genomic instability and have been associated with several human diseases. Thus, an increasing number of experimental and bioinformatics methods have been developed to identify these structures. To date, most reviews have focused on the features of non-canonical DNA/RNA structure formation, experimental approaches to mapping these structures, and the association of these structures with diseases. In addition, two reviews of computational algorithms for the prediction of non-canonical nucleic acid structures have been published. One of these reviews focused only on computational approaches for G4 detection until 2020. The other mainly summarized the computational tools for predicting cruciform, H-DNA and Z-DNA, in which the algorithms discussed were published before 2012. Since then, several experimental and computational methods have been developed. However, a systematic review including the conformation, sequencing mapping methods and computational prediction strategies for these structures has not yet been published. The purpose of this review is to provide an updated overview of conformation, current sequencing technologies and computational identification methods for non-canonical nucleic acid structures, as well as their strengths and weaknesses. We expect that this review will aid in understanding how these structures are characterised and how they contribute to related biological processes and diseases.

Comprehensive evaluation of computational methods for predicting cancer driver genes.

Optimal methods could effectively improve the accuracy of predicting and identifying candidate driver genes. Various computational methods based on mutational frequency, network and function approaches have been developed to identify mutation driver genes in cancer genomes. However, a comprehensive evaluation of the performance levels of network-, function- and frequency-based methods is lacking. In the present study, we assessed and compared eight performance criteria for eight network-based, one function-based and three frequency-based algorithms using eight benchmark datasets. Under different conditions, the performance of approaches varied in terms of network, measurement and sample size. The frequency-based driverMAPS and network-based HotNet2 methods showed the best overall performance. Network-based algorithms using protein-protein interaction networks outperformed the function- and the frequency-based approaches. Precision, F1 score and Matthews correlation coefficient were low for most approaches. Thus, most of these algorithms require stringent cutoffs to correctly distinguish driver and non-driver genes. We constructed a website named Cancer Driver Catalog (http://159.226.67.237/sun/cancer_driver/), wherein we integrated the gene scores predicted by the foregoing software programs. This resource provides valuable guidance for cancer researchers and clinical oncologists prioritizing cancer driver gene candidates by using an optimal tool.

Spatial correlated vortex arrays.

Spatial correlated vortex arrays may form in the same beam when a random source contains multiple helical phase structures. We introduced two types of partially coherent sources with Cartesian and polar symmetric helical phase structure and reveal the characteristics of their radiated fields, respectively. It is demonstrated that far fields generated by these families of sources carry interesting features through the joint regulation of coherence and topological charge, being lattice-like vortex patterns with adjustable dimension and shape.

Atmospheric turbulence effects on hollow Gaussian Schell-model array beams.

Two types of hollow array beams with circular and rectangular distributions on propagating in atmospheric turbulence are investigated and analyzed comparatively with that in free space. Analytical formulas for the cross-spectral density function of two kinds of hollow array beam propagation in linear isotropic random media are derived and used to examine the behavior of the spectral densities. It is found that such beams possess stable hollow arrays with any dimension and lobes in free space, while such distributions only maintain small distances in atmospheric turbulence and ultimately tend to a Gaussian shape due to the turbulence destroying the hollow array profiles. The effects of the turbulence parameters on the behavior of the spectral density are analyzed in depth.

OncoVar: an integrated database and analysis platform for oncogenic driver variants in cancers.

The prevalence of neutral mutations in cancer cell population impedes the distinguishing of cancer-causing driver mutations from passenger mutations. To systematically prioritize the oncogenic ability of somatic mutations and cancer genes, we constructed a useful platform, OncoVar (https://oncovar.org/), which employed published bioinformatics algorithms and incorporated known driver events to identify driver mutations and driver genes. We identified 20 162 cancer driver mutations, 814 driver genes and 2360 pathogenic pathways with high-confidence by reanalyzing 10 769 exomes from 33 cancer types in The Cancer Genome Atlas (TCGA) and 1942 genomes from 18 cancer types in International Cancer Genome Consortium (ICGC). OncoVar provides four points of view, 'Mutation', 'Gene', 'Pathway' and 'Cancer', to help researchers to visualize the relationships between cancers and driver variants. Importantly, identification of actionable driver alterations provides promising druggable targets and repurposing opportunities of combinational therapies. OncoVar provides a user-friendly interface for browsing, searching and downloading somatic driver mutations, driver genes and pathogenic pathways in various cancer types. This platform will facilitate the identification of cancer drivers across individual cancer cohorts and helps to rank mutations or genes for better decision-making among clinical oncologists, cancer researchers and the broad scientific community interested in cancer precision medicine.

High-Temperature Mechanical Properties of NbTaHfTiZrV0.5 Refractory High-Entropy Alloys.

The NbTaHfTiZrV0.5 is a refractory multi-principal-element alloy with high strength and good ductility at room temperature. It is important for possible high-temperature applications to investigate the deformation mechanism of the NbTaHfTiZrV0.5 alloy at different temperatures using tensile tests. In this investigation, the tensile tests were conducted at room temperature to 1273 K on sheet materials fabricated by cold rolling combined with annealing treatments. At 473 K, the NbTaHfTiZrV0.5 alloy exhibited a high tensile ductility (12%). At a testing temperature range of 673~873 K, the ductility was reduced, but the yield strength remained above 800 MPa, which is rare in most other alloys. The TEM investigations revealed that a dislocation slip controlled the plastic deformation, and the degree of deformation was closely related to the dislocation density. The true stress-strain curves of the alloy under different deformation conditions were obtained by tensile deformation at different deformation temperatures (673~873 K) and strain rates (0.001~0.0005 s-1). Experimental results were utilized to construct the parameters of a constitutive model based on a traditional mathematical model to predict the flow behavior at high temperatures. The excellent high-temperature mechanical properties of the NbTaHfTiZrV0.5 alloy will enable it to be used in several engineering applications.

Prevalence and architecture of posttranscriptionally impaired synonymous mutations in 8,320 genomes across 22 cancer types.

Somatic synonymous mutations are one of the most frequent genetic variants occurring in the coding region of cancer genomes, while their contributions to cancer development remain largely unknown. To assess whether synonymous mutations involved in post-transcriptional regulation contribute to the genetic etiology of cancers, we collected whole exome data from 8,320 patients across 22 cancer types. By employing our developed algorithm, PIVar, we identified a total of 22,948 posttranscriptionally impaired synonymous SNVs (pisSNVs) spanning 2,042 genes. In addition, 35 RNA binding proteins impacted by these identified pisSNVs were significantly enriched. Remarkably, we discovered markedly elevated ratio of somatic pisSNVs across all 22 cancer types, and a high pisSNV ratio was associated with worse patient survival in five cancer types. Intriguing, several well-established cancer genes, including PTEN, RB1 and PIK3CA, appeared to contribute to tumorigenesis at both protein function and posttranscriptional regulation levels, whereas some pisSNV-hosted genes, including UBR4, EP400 and INTS1, exerted their function during carcinogenesis mainly via posttranscriptional mechanisms. Moreover, we predicted three drugs associated with two pisSNVs, and numerous compounds associated with expression signature of pisSNV-hosted genes. Our study reveals the prevalence and clinical relevance of pisSNVs in cancers, and emphasizes the importance of considering posttranscriptional impaired synonymous mutations in cancer biology.

Long-lasting photocatalytic activity of trace phosphorus-doped g-C3N4/SMSO and its application in antibacterial ceramics.

Conventional photocatalysts generate numerous active species-primarily hydroxyl radicals (•OH)-under solar light excitation to exert photocatalytic activity for especially antibacterial effects. However, the light dependence limits their competitiveness against other antimicrobial materials since they do not work at night. Herein, a P-g-C3N4/Sr2MgSi2O7:Eu2+,Dy3+ (P-g-C3N4/SMSO) composite day-night photocatalyst is synthesized, using a model methyl orange (MO) substrate, and the impacts of trace P doping and the SMSO composite on the activity of the photocatalyst in MO degradation is investigated; Its antibacterial effect against Escherichia coli and Staphylococcus aureus on ceramic surfaces is further examined. The morphology, structure, and composition of the photocatalyst are characterized by SEM, TEM, XRD, FT-IR, and UV-vis DRS. Finally, the photocatalytic mechanism is elucidated through active species capture experiments and ESR testing. P doping and the SMSO heterojunction structure reduce the width of the forbidden band of g-C3N4 and broaden its visible-light-response range. Moreover, SMSO acts as a light source to realize long-lasting photocatalytic performance of the composite, even in the dark. The photocatalytic process produces •O2-, 1O2, and h+ active species, with •O2- and 1O2 playing the dominant role-instead of •OH as previously thought.

A Decision-Making Strategy for Car Following Based on Naturalist Driving Data via Deep Reinforcement Learning.

To improve the satisfaction and acceptance of automatic driving, we propose a deep reinforcement learning (DRL)-based autonomous car-following (CF) decision-making strategy using naturalist driving data (NDD). This study examines the traits of CF behavior using 1341 pairs of CF events taken from the Next Generation Simulation (NGSIM) data. Furthermore, in order to improve the random exploration of the agent's action, the dynamic characteristics of the speed-acceleration distribution are established in accordance with NDD. The action's varying constraints are achieved via a normal distribution 3σ boundary point-to-fit curve. A multiobjective reward function is designed considering safety, efficiency, and comfort, according to the time headway (THW) probability density distribution. The introduction of a penalty reward in mechanical energy allows the agent to internalize negative experiences. Next, a model of agent-environment interaction for CF decision-making control is built using the deep deterministic policy gradient (DDPG) method, which can explore complicated environments. Finally, extensive simulation experiments validate the effectiveness and accuracy of our proposal, and the driving strategy is learned through real-world driving data, which is better than human data.

Lightweight Multiprincipal Element Alloys with Excellent Mechanical Properties at Room and Cryogenic Temperatures.

Lightweight multiprincipal element alloys (MPEAs) are promising candidates for potential application as engineering materials due to their high strength and low density. In this work, lightweight Ti70Al15V15 and Ti80Al10V10 MPEAs were fabricated via vacuum arc melting. The phases of the Ti70Al15V15 alloys consisted of a BCC phase and a small amount of B2 phase while the Ti80Al10V10 alloys displayed a dual-phase structure with BCC and HCP phases. The different phase compositions led to differences in their mechanical properties. When the temperature changed from 298 K to 77 K, the strength of the alloys further increased and maintained a certain plasticity. This is attributed to the increasing lattice friction stress at cryogenic temperature. TEM observation demonstrated that dislocation played a crucial role in plastic deformation for both the Ti70Al15V15 and Ti80Al10V10 alloys. In addition, Ti80Al10V10 exhibited significant work-hardening capabilities. By analyzing the strengthening mechanism of the alloys, the theoretical yield strength was calculated, and the results agreed with the experimental values. The present results provide new insight into developing lightweight MPEAs containing Ti and Al.

OncoBase: a platform for decoding regulatory somatic mutations in human cancers.

Whole-exome and whole-genome sequencing have revealed millions of somatic mutations associated with different human cancers, and the vast majority of them are located outside of coding sequences, making it challenging to directly interpret their functional effects. With the rapid advances in high-throughput sequencing technologies, genome-scale long-range chromatin interactions were detected, and distal target genes of regulatory elements were determined using three-dimensional (3D) chromatin looping. Herein, we present OncoBase (http://www.oncobase.biols.ac.cn/), an integrated database for annotating 81 385 242 somatic mutations in 68 cancer types from more than 120 cancer projects by exploring their roles in distal interactions between target genes and regulatory elements. OncoBase integrates local chromatin signatures, 3D chromatin interactions in different cell types and reconstruction of enhancer-target networks using state-of-the-art algorithms. It employs informative visualization tools to display the integrated local and 3D chromatin signatures and effects of somatic mutations on regulatory elements. Enhancer-promoter interactions estimated from chromatin interactions are integrated into a network diffusion system that quantitatively prioritizes somatic mutations and target genes from a large pool. Thus, OncoBase is a useful resource for the functional annotation of regulatory noncoding regions and systematically benchmarking the regulatory effects of embedded noncoding somatic mutations in human carcinogenesis.

Mental distress and influencing factors in nurses caring for patients with COVID-19.

BACKGROUND: Nurses are experiencing tremendous stress during the new coronavirus disease 2019 (COVID-19) pandemic, especially intensive care nurses. The pandemic of the disease is a tragedy, which may leave a catastrophic psychological imprint on nurses. Understanding nurses' mental distress can help when implementing interventions to mitigate psychological injuries to nurses. AIMS AND OBJECTIVES: To quantify the severity of nurses' post-traumatic stress disorder (PTSD) symptoms and stress and explore the influencing factors of their psychological health when caring for patients with COVID-19. DESIGN: A cross-sectional survey. METHODS: The PTSD Checklist-Civilian and the Perceived Stress Scale were administered from 11 to 18 March 2020, to 90 nurses selected from another city to go and help an intensive care unit (ICU) in Wuhan, China. These nurses were selected because of their high levels of clinical performance and resilience status. RESULTS: Nurses' average PTSD score was 24.62 ± 6.68, and five (5.6%) of the nurses reported a clinically significant level of PTSD symptoms (>38 points). Nurses' perceived stress averaged 19.33 ± 7, and 20 nurses (22.22%) scored positively >25 points. Nurses' stress and PTSD symptoms were positively correlated (P < .01). Major stress sources included working in an isolated environment, concerns about personal protective equipment shortage and usage, physical and emotional exhaustion, intensive workload, fear of being infected, and insufficient work experiences with COVID-19. CONCLUSIONS: This study showed that even relatively highly resilient nurses experienced some degree of mental distress, including PTSD symptoms and perceived stress. Our findings highlight the importance of helping nurses cultivate resilience and reduce stress. RELEVANCE TO CLINICAL PRACTICE: Recommendations for practice include providing adequate training and orientation before assigning nurses to ICU to help, offering disaster-emergency-preparedness training to keep nurses prepared, providing caring and authentic nursing leadership, offering ongoing psychological support to frontline nurses.

The oxygenated products of cryptotanshinone by biotransformation with Cunninghamella elegans exerting anti-neuroinflammatory effects by inhibiting TLR 4-mediated MAPK signaling pathway.

Cryptotanshinone (1), a major bioactive constituent in the traditional Chinese medicinal herb Dan-Shen Salvia miltiorrhiza Bunge, has been reported to possess remarkable pharmacological activities. To improve its bioactivities and physicochemical properties, in the present study, cryptotanshinone (1) was biotransformed with the fungus Cunninghamella elegans AS3.2028. Three oxygenated products (2-4) at C-3 of cryptotanshinone (1) were obtained, among them 2 was a new compound. Their structures were elucidated by comprehensive spectroscopic analysis including HRESIMS, NMR and ECD data. All of the biotransformation products (2-4) were found to inhibit significantly lipopolysaccharide-induced nitric oxide production in BV2 microglia cells with the IC50 values of 0.16-1.16 µM, approximately 2-20 folds stronger than the substrate (1). These biotransformation products also displayed remarkably improved inhibitory effects on the production of inflammatory cytokines (IL-1ß, IL-6, TNF-α, COX-2 and iNOS) in BV-2 cells via targeting TLR4 compared to substrate (1). The underlying mechanism of 2 was elucidated by comparative transcriptome analysis, which suggested that it reduced neuroinflammatory mainly through mitogen-activated protein kinase (MAPK) signaling pathway. Western blotting results revealed that 2 downregulated LPS-induced phosphorylation of JNK, ERK, and p38 in MAPK signaling pathway. These findings provide a basal material for the discovery of candidates in treating Alzheimer's disease.

Annular oxygenation and rearrangement products of cryptotanshinone by biotransformation with marine-derived fungi Cochliobolus lunatus and Aspergillus terreus.

Structural modification of natural products by biotransformation with fungi is an attractive tool to obtain novel bioactive derivatives. In the present study, cryptotanshinone (1), a quinoid abietane diterpene from traditional Chinese medicine Salvia miltiorrhiza (Danshen), was transformed by two marine-derived fungi. By using Cochliobolus lunatus TA26-46, one new oxygenated and rearranged product (2), containing a 5,6-dihydropyrano[4,3-b]chromene moiety, together with one known metabolite (10), were obtained from the converted broth of cryptotanshinone (1) with the isolated yields of 1.0% and 2.1%, respectively. While, under the action of Aspergillus terreus RA2905, seven new transformation products (3-9) as well as 10 with the fragments of 2-methylpropan-1-ol and oxygenated p-benzoquinone were produced and obtained with the isolated yields of 0.1%-1.3%. The structures of the new compounds were elucidated by comprehensive spectroscopic analysis including High Resolution Electrospray Ionization Mass Spectroscopy (HRESIMS), Nuclear Magnetic Resonance (NMR) and Electronic Circular Dichroism (ECD). The metabolic pathways of cryptotanshinone by these two fungi were presumed to be the opening and rearrangement of furan ring, and/or oxygenation of cyclohexane ring. Cryptotanshinone (1) and its metabolites displayed anti-inflammatory activities against NO production in LPS-stimulated BV-2 cells and antibacterial activities towards methicillin-resistant Staphylococcus aureus. These findings revealed the potential of marine fungi to transform the structures of natural products by biotransformation.

New Thiodiketopiperazine and 3,4-Dihydroisocoumarin Derivatives from the Marine-Derived Fungus Aspergillus terreus.

Aspergillus terreus has been reported to produce many secondary metabolites that exhibit potential bioactivities, such as antibiotic, hypoglycemic, and lipid-lowering activities. In the present study, two new thiodiketopiperazines, emestrins L (1) and M (2), together with five known analogues (3-7), and five known dihydroisocoumarins (8-12), were obtained from the marine-derived fungus Aspergillus terreus RA2905. The structures of the new compounds were elucidated by analysis of the comprehensive spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HRESIMS), one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) data. This is the first time that the spectroscopic data of compounds 3, 8, and 9 have been reported. Compound 3 displayed antibacterial activity against Pseudomonas aeruginosa (minimum inhibitory concentration (MIC) = 32 µg/mL) and antifungal activity against Candida albicans (MIC = 32 µg/mL). In addition, compound 3 exhibited an inhibitory effect on protein tyrosine phosphatase 1 B (PTP1B), an important hypoglycemic target, with an inhibitory concentration (IC)50 value of 12.25 µM.

Benzyl Furanones and Pyrones from the Marine-Derived Fungus Aspergillus terreus Induced by Chemical Epigenetic Modification.

Chemical epigenetic modification on a marine-derived fungus Aspergillus terreus RA2905 using a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), resulted in a significantly changed metabolic profile. A chemical investigation of its ethyl acetate (EtOAc) extract led to the isolation of a racemate of benzyl furanone racemate (±)-1, which further separated chirally as a pair of new enantiomers, (+)- and (-)-asperfuranone (1), together with two new benzyl pyrones, asperpyranones A (2) and B (3). Their structures were elucidated by analysis of the comprehensive spectroscopic data, including one-dimensional (1D) and two-dimensional (2D) NMR, and HRESIMS. The absolute configurations were determined by electronic circular dichroism (ECD) calculation and single-crystal X-ray crystallographic experiment. The structures with benzyl furanone or benzyl pyrone skeletons were discovered from natural products for the first time. Compounds (±)-1, (+)-1, (-)-1, and 2 displayed the antifungal activities against Candida albicans with MIC values of 32, 16, 64, and 64 µg/mL and PTP1B inhibitory activities with the IC50 values of 45.79, 17.32, 35.50, and 42.32 µM, respectively. Compound 2 exhibited antibacterial activity against Pseudomonas aeruginosa with the MIC value of 32 µg/mL.

Investigation on the behavior of a laser propagating through a random environment induced by wind.

Wind is an important factor in environment disturbance, and the inhomogeneous distribution of wind velocity leads to random airflow, which severely affects beam propagation. In this paper, numerical and experimental studies have been performed to investigate the behavior of a laser propagating through a random environment induced by wind, and the main focus is the beam deflection evolution under the effect of the wind velocity. The experiment is performed with the wind tunnel, and the beam deviates from the center during propagation, a process in which the average beam deflection presents an increasing trend for the larger wind velocity and the airflow interval. The simulation model of beam propagation through this kind of environment is proposed, and the numerical simulation agrees with the experimental results. With the model, the average beam deflection results are extended into the high-speed region, and the comparison between the airflow and turbulence environment is also presented. The results can find potential applications in optical propagation and communication between two moving platforms with high speed.

Cistrome Data Browser: a data portal for ChIP-Seq and chromatin accessibility data in human and mouse.

Chromatin immunoprecipitation, DNase I hypersensitivity and transposase-accessibility assays combined with high-throughput sequencing enable the genome-wide study of chromatin dynamics, transcription factor binding and gene regulation. Although rapidly accumulating publicly available ChIP-seq, DNase-seq and ATAC-seq data are a valuable resource for the systematic investigation of gene regulation processes, a lack of standardized curation, quality control and analysis procedures have hindered extensive reuse of these data. To overcome this challenge, we built the Cistrome database, a collection of ChIP-seq and chromatin accessibility data (DNase-seq and ATAC-seq) published before January 1, 2016, including 13 366 human and 9953 mouse samples. All the data have been carefully curated and processed with a streamlined analysis pipeline and evaluated with comprehensive quality control metrics. We have also created a user-friendly web server for data query, exploration and visualization. The resulting Cistrome DB (Cistrome Data Browser), available online at http://cistrome.org/db, is expected to become a valuable resource for transcriptional and epigenetic regulation studies.

Average intensity and beam quality of optical coherence lattices in oceanic turbulence with anisotropy.

Based on the extended Huygens-Fresnel principle, we have derived the analytical expression of the average intensity of optical coherence lattices (OCLs) in oceanic turbulence with anisotropy, and then the beam quality parameters including the Strehl ratio (SR) and the power-in-the-bucket (PIB) are obtained. One can find that the OCLs will eventually evolve into Gaussian shape with the periodicity reciprocity gradually breaking down when propagating through the anisotropic ocean water, and that the trend of evolving into Gaussian can be accelerated for increasing the ratio of temperature and salinity contributions to the refractive index spectrum ω, the lattice constant a and the rate of dissipation of mean square temperature χT or decreasing the anisotropic factor ξ and the rate of dissipation of turbulent kinetic energy per unit mass of fluid ε. Further, the SR and PIB in the target plane under the effects of oceanic parameters are discussed in detail, and the SR and PIB can be increased for the larger ξ and ε or the smaller χT and ω, namely, the beam quality becomes better. Our results can find potential application in the future optical communication system in an oceanic environment.

Two-photon imaging of the endoplasmic reticulum thiol flux in the brains of mice with depression phenotypes.

Depression is a common mental illness with high morbidity and mortality. Mounting evidence suggests that an imbalance of the oxidant-antioxidant defence system is strongly correlated with depression and the dysfunction of the endoplasmic reticulum (ER) is strongly related to the oxidative stress. Therefore, as vital and abundant antioxidants in the ER, biothiols may contribute to the etiology of depression. However, ideal two-photon (TP) fluorescent probes for in vivo imaging of ER-associated thiols in the brains of mice with depression phenotypes are still lacking. Hence, we describe a fluorescent probe (ER-SH) to visualize thiols in living systems. ER-SH displays high sensitivity, excellent ER-targeting ability, outstanding TP properties and low cytotoxicity. Using this ER-SH probe, we succeeded in revealing an increase in the endogenous thiol levels under ER stress induced by DTT. Significantly, TP in vivo imaging showed for the first time that the thiol levels are reduced in brains of mice with depression phenotypes. Collectively, this work can assist in further understanding the molecular mechanism of depression and offers a crucial dimension for diagnosis and anti-depression treatments.