A prominent gene activation role for C-terminal binding protein in mediating PcG/trxG proteins through Hox gene regulation.

The evolutionarily conserved C-terminal binding protein (CtBP) has been well characterized as a transcriptional co-repressor. Herein, we report a previously unreported function for CtBP, showing that lowering CtBP dosage genetically suppresses Polycomb group (PcG) loss-of-function phenotypes while enhancing that of trithorax group (trxG) in Drosophila, suggesting that the role of CtBP in gene activation is more pronounced in fly development than previously thought. In fly cells, we show that CtBP is required for the derepression of the most direct PcG target genes, which are highly enriched by homeobox transcription factors, including Hox genes. Using ChIP and co-IP assays, we demonstrate that CtBP is directly required for the molecular switch between H3K27me3 and H3K27ac in the derepressed Hox loci. In addition, CtBP physically interacts with many proteins, such as UTX, CBP, Fs(1)h and RNA Pol II, that have activation roles, potentially assisting in their recruitment to promoters and Polycomb response elements that control Hox gene expression. Therefore, we reveal a prominent activation function for CtBP that confers a major role for the epigenetic program of fly segmentation and development.

AdaPPI: identification of novel protein functional modules via adaptive graph convolution networks in a protein-protein interaction network.

Identifying unknown protein functional modules, such as protein complexes and biological pathways, from protein-protein interaction (PPI) networks, provides biologists with an opportunity to efficiently understand cellular function and organization. Finding complex nonlinear relationships in underlying functional modules may involve a long-chain of PPI and pose great challenges in a PPI network with an unevenly sparse and dense node distribution. To overcome these challenges, we propose AdaPPI, an adaptive convolution graph network in PPI networks to predict protein functional modules. We first suggest an attributed graph node presentation algorithm. It can effectively integrate protein gene ontology attributes and network topology, and adaptively aggregates low- or high-order graph structural information according to the node distribution by considering graph node smoothness. Based on the obtained node representations, core cliques and expansion algorithms are applied to find functional modules in PPI networks. Comprehensive performance evaluations and case studies indicate that the framework significantly outperforms state-of-the-art methods. We also presented potential functional modules based on their confidence.

MI-MZI based distributed optical fiber sensor for location and pattern recognition.

This research addressed the drawbacks of the conventional hybrid structure and processing technique by presenting a novel distributed fiber optic sensor based on a hybrid Michelson and Mach-Zehnder interferometer. The sensor can achieve blind spot free positioning and has a wide response frequency, additionally its structure is not complex. It can obtain two phase signals from each of the two interferometers by using a demodulation method that uses a 3 × 3 optical coupler. To determine the position of the disturbance, we computed cross-correlations on the two signals following basic mathematical techniques. Markov Transition Field was used to transform the phase signals-which had been filtered by a band pass filter-into two-dimensional images. Tagged photos built a dataset, which is then fed into a neural network to identify patterns. Experiments have shown that the frequency response capacity of the structure was verified, and it was able to achieve location within 0-30 km with location errors of ±85 m. In a six-category pattern recognition, the testing set accuracy was 98.74%.

Flexible Surface-Enhanced Raman Scattering Tape Based on Ag Nanostructured Substrate for On-Site Analyte Detection.

Surface-enhanced Raman scattering (SERS) has emerged as a powerful surface analytical technique that amplifies Raman scattering signals of molecules adsorbed onto metal nanostructured surfaces. The droplet reaction method has recently been employed to fabricate large-scale microring patterns of silver (Ag) nanostructures on rigid substrates, which enables sensitive detection within the ring area. However, these rigid substrates present limitations for direct on-site detection of analyte residues on irregular sample surfaces. There is a need to develop soft and flexible SERS substrates that can intimately conform to arbitrary surfaces. In this study, we presented a SERS substrate using flexible and adhesive tape as the supporting material. This SERS tape was fabricated by repeatedly transferring presynthesized Ag nanostructures from a rigid substrate to the tape. For a model compound adenine, our SERS tape exhibited a good linear response from 5 × 10-4 M to 5 × 10-5 M with a low limit of detection (LOD) of 5 × 10-7 M and displayed a SERS enhancement factor (EF) of 3.2 × 105. The relative standard deviation (RSD) of SERS intensity achieved was as low as 1.93%, indicating its outstanding uniformity. The as-prepared SERS tape was used for in situ detection of pesticide residue on an apple surface and dye residue on human hair. Leveraging the large surface area of Ag nanostructure patterns from the droplet reaction, the developed SERS tape demonstrates excellent performance in terms of sensitivity and uniformity. The successful detection of analyte residues on arbitrary surfaces of apple and human hair highlights the potential of this flexible SERS tape for real-world applications across various industries for enhanced diagnostic accuracy.

Characteristics of peripheral refractive errors in eyes of patients with non-amblyopic myopic anisometropia.

BACKGROUND: This study aims to investigate relative peripheral refractive (RPR) characteristics in children with non-amblyopic myopic anisometropia and explore potential associations between relative peripheral refractive errors (RPRE) and myopia. METHODS: Relative peripheral refractive errors were assessed in 64 children diagnosed with non-amblyopic myopic anisometropia utilizing multispectral refraction topography (MRT). Two eyes of each patient were divided into into the more myopia eyes group (ME) and the fellow eyes group (FE). Evaluated parameters encompassed total defocus values (TRDV), defocus values at eccentricities spanning 0 to 15 degrees (RDV-15), 0 to 30 degrees (RDV-30), 0 to 45 degrees (RDV-45), as well as superior (RDV-S), inferior (RDV-I), temporal (RDV-T), and nasal (RDV-N) positions. RESULTS: The study revealed a noteworthy contrast in TRDV values between Group ME (0.52 ± 0.36) and Group FE (0.17 ± 0.41), with a substantial significance (P < 0.0001). While no significant RDV-15 difference emerged between Group ME (0.01 ± 0.05) and Group FE (-0.01 ± 0.07) (P > 0.05), a meaningful RDV-30 difference existed between Group ME (0.11 ± 0.14) and Group FE (0.03 ± 0.19) (P = 0.0017). A significant discrepancy in RDV-45 was also observed between Group ME (0.39 ± 0.29) and Group FE (0.13 ± 0.34) (P < 0.001). Notably, RDV-I and RDV-T positions demonstrated marked differences between Group ME and Group FE (P < 0.0001), whereas no significant disparity was noted in RDV-S and RDV-N positions (P > 0.05). CONCLUSION: Eyes exhibiting greater myopia manifested more hyperopic peripheral defocus in the context of anisometropia. MRT as a novel ophthalmic evaluation technique, holds promising potential for broader clinical applications in the future.

Scope and inclination of voluntary service for urban community-living older adults provided by volunteers with nursing background: A qualitative study.

BACKGROUND: With the growing challenge of an aging population, addressing the needs of elderly individuals who face living difficulties and lack family support becomes increasingly difficult. Volunteer services are crucial in this context, yet their effectiveness is hindered by unclear service scopes and uncertain volunteer inclinations. AIM: To explore the role and specific preference of volunteers with nursing backgrounds in support of older adults living in the urban community. DESIGN, SETTING AND PARTICIPANTS: A descriptive qualitative study was conducted between September and October 2022. Twenty-three participants (hospital nurses [10], community nurses [4], nursing teachers [4] and nursing students [5]) were selected. Data analysis followed conventional content analysis. RESULTS: Nine major themes were identified based on interview data. Four themes described the service scope of nursing volunteers: (1) environment domain, (2) physiological domain, (3) psychosocial domain and (4) health-related behaviours domain. Another five themes highlighted the service inclination of these volunteers: (1) service frequency, (2) service duration per person/time, (3) service coverage, (4) service place and (5) service object. CONCLUSION: This study clarifies the service focus and scope of necessary support for volunteers, exploring the potential service capabilities of scarce volunteers to the greatest extent. Meanwhile, the results of this study also provide a foundation for stakeholders to fully exploit the synergy. The important findings of this study will help the government and relevant authorities better understand the service attributes of nursing volunteers, allowing them to develop detailed training plans and provide nursing volunteers with targeted support and assistance to meet the health expectations of urban community-living older adults in need. PATIENT OR PUBLIC CONTRIBUTION: Developing research questions, participation and conduct and provision and interpretation of evidence.

Arsenic (As) accumulation in different genotypes of indica rice (Oryza sativa L.) and health risk assessment based on inorganic As.

To reveal differences in arsenic (As) accumulation among indica rice cultivars and assess the human health risks arising from inorganic arsenic (iAs) intake via rice consumption, a total of 320 field indica rice samples and corresponding soil samples were collected from Fujian Province in China. The results showed that available soil As (0.03 to 3.83 mg/kg) showed a statistically significant positive correlation with total soil As (0.10 to 19.45 mg/kg). The inorganic As content in brown rice was between 0.001 and 0.316 mg/kg. Among the cultivars, ten brown rice samples (3.13%) exceeded the maximum contaminant level (MCL) of iAs in food of 0.2 mg/kg in China. The estimated daily intake (EDI) and calculated individual incremental lifetime cancer risk (ILCR) ranged from 0.337 µg/day to 106.60 µg/day and from 8.18 × 10-6 to 2.59 × 10-3, respectively. Surprisingly, the average EDI and the EDIs of 258 (80.63%) brown rice samples were higher than the maximum daily intake (MDI) of 10 µg/day in drinking water as set by the National Research Council. The mean ILCR associated with iAs was 54.3 per 100,000, which exceeds the acceptable upper limit (AUL) of 10 per 100,000 set by the USEPA. Notably, the cultivars Y-Liang-You 1 and Shi-Ji 137 exhibited significantly higher mean ILCRs compared to the AUL and other cultivars, indicating that they pose more serious cancer risks to the local population. Finally, this study demonstrated that the cultivars Yi-Xiang 2292 and Quan-Zhen 10 were the optimal cultivars to mitigate risks associated with iAs to human health from rice consumption.

GmMDE genes bridge the maturity gene E1 and florigens in photoperiodic regulation of flowering in soybean.

Soybean (Glycine max) is highly sensitive to photoperiod, which affects flowering time and plant architecture and thus limits the distribution range of elite soybean cultivars. The major maturity gene E1 confers the most prominent effect on photoperiod sensitivity, but its downstream signaling pathway remains largely unknown. Here, we confirm that the encoded E1 protein is a transcriptional repressor. The expression of seven GmMDE genes (Glycine max MADS-box genes downregulated by E1) was suppressed when E1 was overexpressed and promoted when E1 was knocked out through clustered regularly-interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9)-mediated mutagenesis. These GmMDEs exhibited similar tissue specificity and expression patterns, including in response to photoperiod, E1 expression, and E1 genotype. E1 repressed GmMDE promoter activity. Results for two GmMDEs showed that E1 epigenetically silences their expression by directly binding to their promoters to increase H3K27me3 levels. The overexpression of GmMDE06 promoted flowering and post-flowering termination of stem growth. The late flowering phenotype of E1-overexpressing soybean lines was reversed by the overexpression of GmMDE06, placing GmMDE06 downstream of E1. The overexpression of GmMDE06 increased the expression of the soybean FLOWERING LOCUS T orthologs GmFT2a and GmFT5a, leading to feedback upregulation of GmMDE, indicating that GmMDE and GmFT2a/GmFT5a form a positive regulatory feedback loop promoting flowering. GmMDE06 also promoted post-flowering termination of stem growth by repressing the expression of the shoot identity gene Dt1. The E1-GmMDEs-GmFT2a/5a-Dt1 signaling pathway illustrates how soybean responds to photoperiod by modulating flowering time and post-flowering stem termination.

Comparative proteomics study of exosomes in Vibrio harveyi and Vibrio anguillarum.

Exosomes are a class of extracellular vesicles released by bacteria and contain diverse biomolecules. In this study, we isolated exosomes from Vibrio harveyi and Vibrio anguillarum, which are both serious pathogens in mariculture, using a supercentrifugation method, and the proteins in the exosomes of these two vibrios were analyzed by LC-MS/MS proteomics. Exosome proteins released by V. harveyi and V. anguillarum were different; they not only contained virulence factors (such as lipase and phospholipase in V. harveyi, metalloprotease and hemolysin in V. anguillarum), but also participated in the important life activities of bacteria (such as fatty acid biosynthesis, biosynthesis of antibiotics, carbon metabolism). Subsequently, to verify whether the exosomes participated in bacterial toxicity, after Ruditapes philippinarum was challenged with V. harveyi and V. anguillarum, the corresponding genes of virulence factors from exosomes screened by proteomics were tested by quantitative real-time PCR. All the genes detected were upregulated which suggested that exosomes were involved in vibrio toxicity. The results could provide an effective proteome database for decoding the pathogenic mechanism of vibrios from the exosome perspective.

Gene delivery to breast cancer by incorporated EpCAM targeted DARPins into AAV2.

OBJECTIVE: The aim of this study is to evaluate an AAV vector that can selectively target breast cancer cells and to investigate its specificity and anti-tumor effects on breast cancer cells both in vitro and in vivo, offering a new therapeutic approach for the treatment of EpCAM-positive breast cancer. METHODS: In this study, a modified AAV2 viral vector was used, in which EpCAM-specific DARPin EC1 was fused to the VP2 protein of AAV2, creating a viral vector that can target breast cancer cells. The targeting ability and anti-tumor effects of this viral vector were evaluated through in vitro and in vivo experiments. RESULTS: The experimental results showed that the AAV2MEC1 virus could specifically infect EpCAM-positive breast cancer cells and accurately deliver the suicide gene HSV-TK to tumor tissue in mice, significantly inhibiting tumor growth. Compared to the traditional AAV2 viral vector, the AAV2MEC1 virus exhibited reduced accumulation in liver tissue and had no impact on tumor growth. CONCLUSION: This study demonstrates that AAV2MEC1 is a gene delivery vector capable of targeting breast cancer cells and achieving selective targeting in mice. The findings offer a potential gene delivery system and strategies for gene therapy targeting EpCAM-positive breast cancer and other tumor types.

Kidney-type glutaminase is a biomarker for the diagnosis and prognosis of hepatocellular carcinoma: a prospective study.

PURPOSE: The pathological diagnosis and prognosis prediction of hepatocellular carcinoma (HCC) is challenging due to the lack of specific biomarkers. This study aimed to validate the diagnostic and prognostic efficiency of Kidney-type glutaminase (GLS1) for HCC in prospective cohorts with a large sample size. METHODS: A total of 1140 HCC patients were enrolled in our prospective clinical trials. Control cases included 114 nontumour tissues. The registered clinical trial (ChiCTR-DDT-14,005,102, chictr.org.cn) was referred to for the exact protocol. GLS1 immunohistochemistry was performed on the whole tumour section. The diagnostic and prognostic performances of GLS1 was evaluated by the receiver operating characteristic curve and Cox regression model. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and area under the curve of GLS1 for the diagnosis of HCC were 0.746, 0.842, 0.979, 0.249, 0.588, and 0.814, respectively, which could be increased to 0.846, 0.886, 0.987,0.366, 0.732, and 0.921 when combined with glypican 3 (GPC3) and alpha-fetoprotein (AFP), indicating better diagnostic performance. Further, we developed a nomogram with GPC3 and GLS1 for identifying HCC which showed good discrimination and calibration. GLS1 expression was also related with age, T stage, TNM stage, Edmondson-Steiner grade, microvascular invasion, Ki67, VEGFR2, GPC3, and AFP expression in HCC. GLS1 expression was negatively correlated with disease-free survival (P < 0.001) probability of patients with HCC. CONCLUSIONS: It was validated that GLS1 was a sensitive and specific biomarker for pathological diagnosis of HCC and had prognostic value, thus having practical value for clinical application.

A novel 7-base pair deletion at a splice site in MS-2 impairs male fertility via premature tapetum degradation in common bean (Phaseolis vulgaris L.).

KEY MESSAGE: A novel splice-site mutation in the P. vulgarisgene for TETRAKETIDE α-PYRONE REDUCTASE 2 impairs male fertility, and parthenocarpic pod development can be improved by external application of IAA. Snap bean (Phaseolus vulgaris L.) is an important vegetable crop in many parts of the world, and the main edible part is the fresh pod. Here, we report the characterization of the genic male sterility (ms-2) mutant in common bean. Loss of function of MS-2 accelerates degradation of the tapetum, resulting in a complete male sterility. Through fine-mapping, co-segregation, and re-sequencing analysis, we identified Phvul.003G032100, which encodes the TETRAKETIDE α-PYRONE REDUCTASE 2 (PvTKPR2) protein in common bean, as the causal gene for MS-2. PvTKPR2 is predominantly expressed at the early stages of flower development. A novel 7-bp (+ 6028 bp to + 6034 bp) deletion mutation spans the splice site between the fourth intron and fifth exon, leading to a 9-bp deletion in transcribed mRNA and a 3-amino acid (G210M211V212) deletion in the protein coding sequence of the PvTKPR2ms-2 gene. The 3-D structural changes in the protein due to the mutation may impair the activities of NAD-dependent epimerase/dehydratase and the NAD(P)-binding domains of PvTKPR2ms-2 protein. The ms-2 mutant plants produce many small parthenocarpic pods, and the size of the pods can be doubled by external application of 2 mM indole-3-acetic acid (IAA). Our results demonstrate that a novel mutation in PvTKPR2 impairs male fertility through premature degradation of the tapetum.

A review of current antibiotic resistance and promising antibiotics with novel modes of action to combat antibiotic resistance.

The emergence and transmission of antibiotic resistance is a global public health crisis with significant burden on healthcare systems, resulting in high mortality and economic costs. In 2019, almost five million deaths were associated with drug-resistant infections, and if left unchecked, the global economy could lose $100 trillion by 2050. To effectively combat this crisis, it is essential for all countries to understand the current situation of antibiotic resistance. In this review, we examine the current driving factors leading to the crisis, impact of critical superbugs in three regions, and identify novel mechanisms of antibiotic resistance. It is crucial to monitor the phenotypic characteristics of drug-resistant pathogens and describe the mechanisms involved in preventing the emergence of cross-resistance to novel antimicrobials. Additionally, maintaining an active pipeline of new antibiotics is essential for fighting against diverse antibiotic-resistant pathogens. Developing antibacterial agents with novel mechanisms of action is a promising way to combat increasing antibiotic-resistant pathogens.

Evolution of Morphology and Distribution of Salt Crystals on a Photothermal Layer during Solar Interfacial Evaporation.

Solar interfacial evaporation (SIE) by leveraging photothermal conversion could be a clean and sustainable solution to the scarcity of fresh water, decontamination of wastewater, and steam sterilization. However, the process of salt crystallization on photothermal materials used in SIE, especially from saltwater evaporation, has not been completely understood. We report the temporal and spatial evolution of salt crystals on the photothermal layer during SIE. By using a typical oil lamp evaporator, we found that salt crystallization always initiates from the edge of the evaporation surface of the photothermal layer due to the local fast flux of the vapor to the surroundings. Interestingly, the salt crystals exhibit either compact or loose morphology, depending on the location and evaporation duration. By employing a suite of complementary analytical techniques of Raman and infrared spectroscopy and temperature mapping, we followed the evolution and spatial distribution of salt crystals, interfacial water, and surface temperature during evaporation. Our results suggested that the compact crystal structure may emerge from the recrystallization of salt in an initially porous structure, driven by continuous water evaporation from the porous and loose crystals. The holistic view provided in this study may lay the foundation for effective strategies for mitigation of the negative impact of salt crystallization in solar evaporation.

Performance Evaluation and Formation Mechanism of Viscoelastic Surfactant Fracturing Fluids with Moderate Interfacial Activity Enhanced by Janus-SiO2 Nanoparticles.

Nanoparticles (NPs) exhibit great potential to improve various properties of viscoelastic surfactant (VES) fracturing fluids in the development of low-permeability reservoirs. In the present study, the amphiphilic Janus NPs (JANPs) were fabricated via the Pickering emulsion method and employed to construct the novel JA12C (JANPs with dodecyl hydrophobic carbon chains)-assisted VES fracturing fluid (JAVES). The successful fabrication of JANPs was confirmed via Fourier transform infrared spectroscopy (FTIR) measurements and water contact angle tests. The rheology behavior of the VES fracturing fluid incorporating various SiO2 NPs including hydrophilic SiO2 NPs (HLNPs), JA8C (JANPs with octyl hydrophobic carbon chains), and JA12C was systematically investigated. It was revealed that the additional JA12C significantly improved the tolerance and proppant suspension properties. To explore the subsequent oil recovery performance of various gel breaking liquids, the formation wettability and the oil-water interfacial tension (IFT) were studied after the evaluation of breaking properties and formation damage properties of various fracturing fluids. The results suggested that the JAVES gel breaking liquid showed remarkable wettability alternation capability and moderate oil-water IFT reduction ability, which can partially reduce the impact on reservoir permeability. Moreover, the formation mechanism of the JAVES was proposed by molecular dynamics simulations at the molecular level, which was further visually verified via the cryo-TEM images. The improved viscoelasticity of developed the JAVES with moderate interfacial activity is advantageous to enhance subsequent oil recovery.

Co-expression of recombinant human collagen α1(III) chain with viral prolyl 4-hydroxylase in Pichia pastoris GS115.

The Collagen α1(Ш) chain (COL3A1) is an important structural protein on the surface of human skin. The activity of prolyl 4-hydroxylase (P4H) is crucial to maintaining the stable triple-helix structure and function of human COL3A1. To obtain hydroxylated human COL3A1, virus-derived P4H A085R was co-expressed with human COL3A1 in Pichia pastoris GS115. Colony PCR analysis and sequencing after transfection confirmed that the target gene was successfully inserted. Quantitative reverse transcription PCR (RT-qPCR) indicated that human COL3A1 and P4H A085R were expressed at mRNA levels in the clones. SDS-PAGE and Western blot analysis of supernatant from the recombinant methylotrophic yeast culture showed that recombinant human COL3A1 (rhCOL3A1) was secreted into the culture medium with an apparent molecular mass of approximately 130 kDa. It was observed that the amount of secreted rhCOL3A1 was highest at 120 h after induction. Furthermore, mass spectrometry analysis demonstrated that rhCOL3A1 was successfully expressed in P. pastoris. The His-tagged rhCOL3A1 protein was purified by Ni-affinity column chromatography.

Genetic inconsistency at the D6S1043 locus caused by microdeletion at 6q15.

In the practice of parentage testing, short tandem repeat (STR) genetic inconsistencies occasionally occur and are usually treated as genetic mutations. However, they arise for various reasons. To elucidate the reasons for their occurrence, this study investigates a typical trio. For the D6S1043 locus, the genotype of the biological mother comprised the heterozygous alleles "7,20"; that of the child, allele 20; and that of the alleged father, a heterozygous allele "11,13," revealing a 7-step mutation. Different kits were first used to verify the data. The locus map, primers, and core sequences were then analyzed. Ultimately, the STR and single nucleotide polymorphisms of 6q were tested to determine the microdeletion range. The results revealed that this was indeed a true trio, and the underlying cause of the genetic inconsistency at this locus was a microdeletion of approximately 0.74-1.78 Mb in 6q15. Overall, genetic inconsistencies detected during practical work, and particularly rare multi-step mutations, cannot be directly identified as STR mutations. Different tools should be used to examine the causes of genetic inconsistencies from various perspectives and improve the effectiveness of genetic evidence.

A Multimodal Deep Learning Framework for Predicting PPI-Modulator Interactions.

Protein-protein interactions (PPIs) are essential for various biological processes and diseases. However, most existing computational methods for identifying PPI modulators require either target structure or reference modulators, which restricts their applicability to novel PPI targets. To address this challenge, we propose MultiPPIMI, a sequence-based deep learning framework that predicts the interaction between any given PPI target and modulator. MultiPPIMI integrates multimodal representations of PPI targets and modulators and uses a bilinear attention network to capture intermolecular interactions. Experimental results on our curated benchmark data set show that MultiPPIMI achieves an average AUROC of 0.837 in three cold-start scenarios and an AUROC of 0.994 in the random-split scenario. Furthermore, the case study shows that MultiPPIMI can assist molecular docking simulations in screening inhibitors of Keap1/Nrf2 PPI interactions. We believe that the proposed method provides a promising way to screen PPI-targeted modulators.

Deep6mAPred: A CNN and Bi-LSTM-based deep learning method for predicting DNA N6-methyladenosine sites across plant species.

DNA N6-methyladenine (6mA) is a key DNA modification, which plays versatile roles in the cellular processes, including regulation of gene expression, DNA repair, and DNA replication. DNA 6mA is closely associated with many diseases in the mammals and with growth as well as development of plants. Precisely detecting DNA 6mA sites is of great importance to exploration of 6mA functions. Although many computational methods have been presented for DNA 6mA prediction, there is still a wide gap in the practical application. We presented a convolution neural network (CNN) and bi-directional long-short term memory (Bi-LSTM)-based deep learning method (Deep6mAPred) for predicting DNA 6mA sites across plant species. The Deep6mAPred stacked the CNNs and the Bi-LSTMs in a paralleling manner instead of a series-connection manner. The Deep6mAPred also employed the attention mechanism for improving the representations of sequences. The Deep6mAPred reached an accuracy of 0.9556 over the independent rice dataset, far outperforming the state-of-the-art methods. The tests across plant species showed that the Deep6mAPred is of a remarkable advantage over the state of the art methods. We developed a user-friendly web application for DNA 6mA prediction, which is freely available at http://106.13.196.152:7001/ for all the scientific researchers. The Deep6mAPred would enrich tools to predict DNA 6mA sites and speed up the exploration of DNA modification.

Salvianolic acid B, a new type I IRE1 kinase inhibitor, abrogates AngII-induced angiogenesis by interacting with IRE1 in its active conformation.

Angiotensin II (AngII)-mediated pathological angiogenesis is one of the important factors promoting the progression of atherosclerosis, tumour metastasis, and diabetic retinopathy. Here, we first demonstrate that salvianolic acid B (Sal B) attenuated AngII-induced angiogenesis by downregulating the IRE1/ASK1/JNK/p38MAPK signalling pathway and protected vascular endothelial cells from hypoxia-induced damage. These pharmacological consequences could be ascribed to the unique interactions between Sal B and the ATP-binding cavity of IREIα, leading to bi-directional roles of IRE1 kinase and endonuclease activity; this may possibly be one of the essential mechanisms of the bi-directional regulation of angiogenesis in different conditions. Moreover, our results indicated that IRE1 was a novel anti-angiogenesis target and type I IRE1 kinase inhibitor (e.g., Sal B, APY29) and might be a potentially eligible low-toxicity drug for treating AngII-mediated pathological angiogenesis.