Transcriptional repression of MdMa1 by MdMYB21 in Ma locus decreases malic acid content in apple fruit.

Malic acid is a major organic acid component of apples and a crucial determinant of fruit organoleptic quality. A candidate gene for malic acid content, designated MdMa1, was previously identified in the Ma locus, which is a major quantitative trait locus (QTL) for apple fruit acidity located on the linkage group 16. Region-based association mapping to detect candidate genes in the Ma locus identified MdMa1 and an additional MdMYB21 gene putatively associated with malic acid. MdMYB21 was significantly associated with fruit malic acid content, accounting for ~7.48% of the observed phenotypic variation in the apple germplasm collection. Analyses of transgenic apple calli, fruits and tomatoes demonstrated that MdMYB21 negatively regulated malic acid accumulation. The apple fruit acidity-related MdMa1 and its tomato ortholog, SlALMT9, exhibited lower expression profiles in apple calli, mature fruits and tomatoes in which MdMYB21 was overexpressed, compared with their corresponding wild-type variety. MdMYB21 directly binds to the MdMa1 promoter and represses its expression. Interestingly, a 2-bp variation in the MdMYB21 promoter region altered its expression and regulation of its target gene, MdMa1, expression. Our findings not only demonstrate the efficiency of integrating QTL and association mapping in the identification of candidate genes controlling complex traits in apples, but also provide insights into the complex regulatory mechanism of fruit malic acid accumulation.

Allelic variation of BBX24 is a dominant determinant controlling red coloration and dwarfism in pear.

Variation in anthocyanin biosynthesis in pear fruit provides genetic germplasm resources for breeding, while dwarfing is an important agronomic trait, which is beneficial to reduce the management costs and allow for the implementation of high-density cultivation. Here, we combined bulked segregant analysis (BSA), quantitative trait loci (QTL), and structural variation (SV) analysis to identify a 14-bp deletion which caused a frame shift mutation and resulted in the premature translation termination of a B-box (BBX) family of zinc transcription factor, PyBBX24, and its allelic variation termed PyBBX24ΔN14. PyBBX24ΔN14 overexpression promotes anthocyanin biosynthesis in pear, strawberry, Arabidopsis, tobacco, and tomato, while that of PyBBX24 did not. PyBBX24ΔN14 directly activates the transcription of PyUFGT and PyMYB10 through interaction with PyHY5. Moreover, stable overexpression of PyBBX24ΔN14 exhibits a dwarfing phenotype in Arabidopsis, tobacco, and tomato plants. PyBBX24ΔN14 can activate the expression of PyGA2ox8 via directly binding to its promoter, thereby deactivating bioactive GAs and reducing the plant height. However, the nuclear localization signal (NLS) and Valine-Proline (VP) motifs in the C-terminus of PyBBX24 reverse these effects. Interestingly, mutations leading to premature termination of PyBBX24 were also identified in red sports of un-related European pear varieties. We conclude that mutations in PyBBX24 gene link both an increase in pigmentation and a decrease in plant height.

ForestSubtype: a cancer subtype identifying approach based on high-dimensional genomic data and a parallel random forest.

BACKGROUND: Cancer subtype classification is helpful for personalized cancer treatment. Although, some approaches have been developed to classifying caner subtype based on high dimensional gene expression data, it is difficult to obtain satisfactory classification results. Meanwhile, some cancers have been well studied and classified to some subtypes, which are adopt by most researchers. Hence, this priori knowledge is significant for further identifying new meaningful subtypes. RESULTS: In this paper, we present a combined parallel random forest and autoencoder approach for cancer subtype identification based on high dimensional gene expression data, ForestSubtype. ForestSubtype first adopts the parallel RF and the priori knowledge of cancer subtype to train a module and extract significant candidate features. Second, ForestSubtype uses a random forest as the base module and ten parallel random forests to compute each feature weight and rank them separately. Then, the intersection of the features with the larger weights output by the ten parallel random forests is taken as our subsequent candidate features. Third, ForestSubtype uses an autoencoder to condenses the selected features into a two-dimensional data. Fourth, ForestSubtype utilizes k-means++ to obtain new cancer subtype identification results. In this paper, the breast cancer gene expression data obtained from The Cancer Genome Atlas are used for training and validation, and an independent breast cancer dataset from the Molecular Taxonomy of Breast Cancer International Consortium is used for testing. Additionally, we use two other cancer datasets for validating the generalizability of ForestSubtype. ForestSubtype outperforms the other two methods in terms of the distribution of clusters, internal and external metric results. The open-source code is available at https://github.com/lffyd/ForestSubtype . CONCLUSIONS: Our work shows that the combination of high-dimensional gene expression data and parallel random forests and autoencoder, guided by a priori knowledge, can identify new subtypes more effectively than existing methods of cancer subtype classification.

Plasma versican and plasma exosomal versican as potential diagnostic markers for non-small cell lung cancer.

BACKGROUND AND AIMS: This study aimed to investigate the expression of plasma versican and plasma exosomal versican in non-small cell lung cancer (NSCLC) and its correlation with clinicopathological features, and to evaluate its diagnostic performance in NSCLC and its predictive function for NSCLC incidence and metastasis risk. MATERIALS AND METHODS: There were 110 instances of NSCLC, 42 cases of benign lung disease, and 55 healthy controls from September 2018 to October 2020 at Tongji Hospital Affiliated to Tongji University. Blood was collected and plasma was separated before surgery, and plasma exosomes were extracted by ExoQuick kit. Morphological and molecular phenotype identification of exosomes was performed by transmission electron microscopy, Nanosight particle tracking analysis, and western blotting. Plasma versican and plasma exosomal versican were detected in all subjects to assess their expression levels and diagnostic value in NSCLC. Clinicopathological data were collected to explore correlations between abnormal plasma versican and plasma exosomal versican expression and clinicopathological parameters. Receiver operating characteristic (ROC) curve was used to judge its diagnostic performance in NSCLC, and binary logistic regression analysis was used to predict the risk of NSCLC incidence and metastasis. RESULTS: Plasma versican and plasma exosomal versican expression in NSCLC patients was significantly upregulated and was significantly higher in T3 + T4 patients compared with T1 + T2 patients (P < 0.05); the levels of plasma versican and plasma exosomal versican were positively correlated with lymph node metastasis, distant metastases (e.g., brain, bone), and mutation(e.g., EGFR,ALK)in NSCLC patients (all P < 0.05). Furthermore, ROC curve analysis showed that plasma versican and plasma exosomal versican had higher AUC values than NSE, CYFRA21-1, and SCC, and better diagnostic performance in NSCLC patients. However, the AUC and diagnostic performances of plasma versican and plasma exosomal versican in advanced-stage NSCLC patients were not shown to be significantly better than CEA. The results of binary logistic regression analysis showed that high levels of plasma exosomal versican had higher predictive value for lung cancer incidence, while high levels of plasma versican had higher predictive value for lung cancer metastasis. CONCLUSION: Our findings showed that plasma versican and plasma exosomal versican might be potential diagnostic markers for NSCLC. High plasma exosomal versican expression can be used as a predictor of NSCLC risk and high plasma versican expression can be used as a predictor of NSCLC metastasis risk.

[Formulation of expert consensus on clinical application of external ethnic medicine: taking Baimai Ointment as an example].

The concept of ethnic medicine is divided into a broad sense and a narrow sense. The broad concept refers to the traditional medicine of the Chinese nation, and the narrow concept refers to the traditional medicine of Chinese ethnic minorities. The external medicine is one of the main forms of ethnic medicine, and it is also the important content of ethnic medicine for external use, which is widely used in clinical practice. As the theory of ethnic medicine is unique, the application methods have certain characteristics, which are the key technical parts of clinical practice. However, the existing traditional Chinese medicine consensus formulation me-thods cannot meet the needs of the consensus formulation of the external ethnic medicine. Therefore, the methods suitable for expert consensus on external ethnic medicine are required. This article took Expert opinion on clinical application of Baimai Ointment as an exa-mple, and explorde a reasonable, effective, multi-dimensional, and multi-stage method to formulate expert consensus on the external ethnic medicine. In this research, three-dimensional sources of information, including ancient classics, clinical research evidence, and expert application experiences, were systematically and scientifically collected. After organization and analysis, the information was formed into comprehensive evidence. In a formal consensus meeting, part of the recommendations reached consensus. As to the issues that did not reach agreement, in-depth interviews were used to explore the reasons for the differences and resolve the disagreements. Finally, unanimous recommendations were reached. There are common problems during the formulation process of Expert opinion on clinical application of Baimai Ointment. This study is expected to provide references for the formulation of expert consensus on other external ethnic medicine.

Neddylation-mediated Nedd4-2 activation regulates ubiquitination modification of renal NBCe1.

The sodium-coupled bicarbonate cotransporter 1 (NBCe1) plays an essential role in the maintenance of acid-base homeostasis in the human body. However, little research has been done regarding the modification of NBCe1. Nedd4-2 is one of the most important ubiquitin E3 ligases in the kidney where it is responsible for mediating the ubiquitylation level of many important ion channel proteins; therefore, influencing their expression and membrane localization. In this study, we performed experiments based on a prediction from bioinformatics analysis that NBCe1 might be a Nedd4-2 target protein. The results of co-immunoprecipitation and glutathione S-transferase pull-down assays showed that Nedd4-2 interacted with NBCe1. An in vitro ubiquitination assay further demonstrated that Nedd4-2 is indeed the NBCe1 ubiquitin E3 ligase. The overexpression of Nedd4-2 decreased NBCe1 expression, while MG132 rescued the changes. Nedd4-2 overexpression also altered the subcellular distribution of NBCe1. Furthermore, the kidney specific Nedd4-2-knockout mice certified the alteration of NBCe1. In addition, we speculate that neddylation activates Nedd4-2. A co-immunoprecipitation analysis indicated that Nedd4-2 interacted with Nedd8. In vitro neddylation experiments further demonstrated that Nedd4-2 underwent neddylation modification. The overexpression of Nedd8 led to decreased NBCe1 expression, while Nedd4-2 inhibition rescued the changes. These findings demonstrate that Nedd4-2 acts as the ubiquitin E3 ligase of NBCe1, mediating the degradation and altering the subcellular distribution of NBCe1, and that the neddylation modification downregulated NBCe1 expression by upregulating Nedd4-2 activity.

[Systematic review of efficacy and safety of Ginkgo biloba extract 50 in treatment of ischemic stroke].

The present study aimed to systematically evaluate the efficacy and safety of Ginkgo biloba extract 50(GBE50) in the treatment of ischemic stroke. The databases including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library were searched for randomized controlled trial(RCT) of GBE50 for the treatment of ischemic stroke reported between database inception and May 2020. The methodological quality of the included RCTs was evaluated via the Cochrane risk of bias tool. The RevMan 5.4 was used for Meta-analysis. Sixteen RCTs were included, involving 1 615 patients with acute ischemic stroke. Most of the included RCTs reported the methods of random sequence generation, but only two performed the concealment of random sequence. All RCTs failed in blinding. Two RCTs reported the information of cases lost to follow-up and drop-outs. Since the number was small, the baselines of groups remained balanced. All RCTs reported key outcomes of ischemic stroke, which made selective reporting bias in a low risk. Meta-analysis results revealed that GBE50 combined with routine therapies could effectively lower the score of the National Institutes of Health stroke scale(NIHSS) and restore cognitive function and daily activity in ischemic stroke patients. Compared with routine therapies, the combination is advantageous in treating patients with ischemic stroke. However, high-quality multicenter RCTs with large sample sizes are still required for verification.

Comparison of multiple algorithms to reliably detect structural variants in pears.

BACKGROUND: Structural variations (SVs) have been reported to play an important role in genetic diversity and trait regulation. Many computer algorithms detecting SVs have recently been developed, but the use of multiple algorithms to detect high-confidence SVs has not been studied. The most suitable sequencing depth for detecting SVs in pear is also not known. RESULTS: In this study, a pipeline to detect SVs using next-generation and long-read sequencing data was constructed. The performances of seven types of SV detection software using next-generation sequencing (NGS) data and two types of software using long-read sequencing data (SVIM and Sniffles), which are based on different algorithms, were compared. Of the nine software packages evaluated, SVIM identified the most SVs, and Sniffles detected SVs with the highest accuracy (> 90%). When the results from multiple SV detection tools were combined, the SVs identified by both MetaSV and IMR/DENOM, which use NGS data, were more accurate than those identified by both SVIM and Sniffles, with mean accuracies of 98.7 and 96.5%, respectively. The software packages using long-read sequencing data required fewer CPU cores and less memory and ran faster than those using NGS data. In addition, according to the performances of assembly-based algorithms using NGS data, we found that a sequencing depth of 50× is appropriate for detecting SVs in the pear genome. CONCLUSION: This study provides strong evidence that more than one SV detection software package, each based on a different algorithm, should be used to detect SVs with higher confidence, and that long-read sequencing data are better than NGS data for SV detection. The SV detection pipeline that we have established will facilitate the study of diversity in other crops.

Exosomal circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-ß1 axis.

BACKGROUND: Colorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Exosome shave emerged as crucial regulators of intercellular communication and that abundant Circular RNAs (circRNAs) are enriched within exosomes. CircRNAs are novel members of noncoding RNAs regulating cancer proliferation and progression. However, the function and regulatory mechanism of cancer-derived exosomal circRNAs in CRC remains unclear. METHODS: CRC cells-derived exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blot. CCK-8, wound healing and transwell assays, and flow cytometry assays were conducted to assess whether exosomes would affect the proliferation, metastasis, and apoptosis of CRC cells, respectively. Moreover, we performed the RNA sequencing and RT-qPCR to identify circRNAs in exosome-stimulated CRC cells. Fluorescence in situ hybridization (FISH) assay was used to detect the cellular distribution of circPACRGL. Bioinformatic analyses (StarBase 2.0) were used to pool the miRNA targets of circPACRGL. Luciferase assays were performed to verify the direct interaction. Finally, flow cytometry was used to detect the differentiation of N1-N2 neutrophils. RESULTS: Our study identified a novel CRC-derived exosomal circRNA, circPACRGL. We found circPACRGL was significantly upregulated in CRC cells after tumor-derived exosomes addition. Moreover, circPACRGL serves as a sponge for miR-142-3p/miR-506-3p to facilitate the transforming growth factor-ß1 (TGF-ß1) expression. As a result, circPACRGL promoted CRC cell proliferation, migration and invasion, as well as differentiation of N1 to N2 neutrophils via miR-142-3p/miR-506-3p-TGF-ß1 axis. CONCLUSION: Our study, the first to reveal that cancer-derived exosomal circPACRGL plays an oncogenic role in CRC proliferation and metastasis, providing mechanistic insights into the roles of circRNAs in CRC progression and a valuable marker for CRC treatment.

[Variant analysis on steroid 5-reductase type 2 deficiency caused by a novel SRD5A2 mutation].

This article reported the clinical characteristics and SRD5A2 gene mutation pattern of a child with steroid 5-α reductase type 2 deficiency. The 2-month-old boy showed hypospadias and short penis shortly after birth. DNA was extracted from the peripheral blood of the child and his parents. The endocrine disease-related genes were captured and sequenced by high-throughput sequencing technology, and the family DNA samples were verified by Sanger sequencing. The results showed that c.680G>A(p.R227Q) and c.608G>A(p.G203D) compound heterozygous mutations existed in the SRD5A2 gene of the child. The c.680G>A mutation inherited from his father, which was a known pathogenic mutation. The c.608G>A mutation originated from his mother, which was a novel mutation discovered in this study. These results provide molecular evidence for the etiological diagnosis of the child and genetic counseling for the family, as well as extend the mutation spectrum of SRD5A2 gene.

Fast image enhancement method for display images in ambient light.

Display images under high illumination may appear to have lower lightness and attenuated contrast. In this paper, we review the image degradation phenomenon in ambient light through photoreceptor physiology. The influence of different environmental parameters and their effects on various gray areas in images can be evaluated by the cone response difference. Based on this, we propose a fast global tone mapping method to minimize the cone response difference at different pixel intensity levels of images displayed at different illumination levels. This method has a superior computational efficiency and higher evaluation score than existing algorithms.

Cumulative health risk assessment of halogenated and parent polycyclic aromatic hydrocarbons associated with particulate matters in urban air.

Halogenated polycyclic aromatic hydrocarbons (HPAHs) have been reported to occur widely in urban air. Nevertheless, knowledge about the human health risk associated with inhalation exposure to HPAHs is scarce so far. In the present study, nine HPAHs and 16 PAHs were determined in atmospheric particulate matter (PM) collected from Shenzhen, China to address this issue. Concentrations of Σ9HPAHs varied from 0.1 to 1.5 ng/m(3) and from 0.09 to 0.4 ng/m(3) in PM10 and PM2.5 samples, respectively. As for individuals, 9-bromoanthracene, 7-bromobenz(a)anthracene, and 9,10-dibromoanthracene were the dominant congeners. Levels of Σ16PAHs in PM10 and PM2.5 samples ranged from 3.2 to 81 ng/m(3) and from 2.8 to 85 ng/m(3), respectively. Among individual PAHs, chrysene, benzo[b]fluoranthene, and indeno[1,2,3-c,d]pyrene were the main congeners. According to the season, concentrations of HPAHs and PAHs in atmospheric PM10/PM2.5 samples show a similar decreasing trend with an order: winter>autumn>spring>summer. The daily intake (DI) of PM10/PM2.5-bound HPAHs and PAHs were estimated. Our results indicated that children have the highest DI levels via inhalation exposure. The incremental lifetime cancer risk (ILCR) induced by PM10/PM2.5-bound HPAHs and PAHs were calculated. The ILCR values showed a similar decreasing trend with an order: adults>children>seniors>adolescent. Overall, the ILCR values induced by HPAHs and PAHs were far below the priority risk level (10(-4)), indicating no obvious cancer risk. To our knowledge, this is the first study to investigate the human health risk associated with inhalation exposure to PM10/PM2.5-bound HPAHs.

The detection efficacy of noninvasive prenatal genetic testing (NIPT) for sex chromosome abnormalities and copy number variation and its differentiation in pregnant women of different ages.

Objective: To analyze the efficacy of noninvasive prenatal genetic testing (NIPT) in detecting fetal sex chromosome abnormalities and copy number variation (CNV), compare the efficacy between NIPT and serological screening alone, and further analyze the fetal sex chromosome abnormalities and CNV differentiation in pregnant women of different ages, so as to provide a reference for the prevention and control of fetal birth defects. Methods: Clinical data from 22,692 pregnant women admitted to our hospital from January 2013 to December 2022 were retrospectively analyzed. All participants underwent serological screening and NIPT screening to compare fetal chromosomal abnormalities between the two screening modalities. 145 women whose fetus were diagnosed as sex chromosome abnormalities and 36 women whose fetus were diagnosed as CNV abnormalities based on NIPT screening were selected for prenatal diagnosis by amniocentesis or karyotyping. Taking prenatal diagnosis as the standard, the four-grid table method was used to detect the positive predictive value of NIPT screening for fetal sex chromosomal abnormalities and CNV. According to the age, pregnant women were divided into 18-30 years old (n = 9844), 31-35 years old (n = 7612), >35 years old (n = 5236), and then the detection rates of sexual fetal chromosomal abnormalities, CNV and total chromosomal abnormalities were compared in pregnant women. Results: Among the 22,692 pregnant women in this study, the high-risk proportion of serologic screening with 4.38% was higher than that of NIPT screening with 1.93% (P < 0.05). Among the 145 women with fetal sex chromosome abnormalities screened by NIPT, 122 cases of fetal sex chromosome abnormalities were diagnosed prenatally, including 45, X/47, XXX/47, XYY/47, XXY. The positive predictive values of NIPT screening were 25.00%, 58.82%, 85.71%, and 85.71%, respectively, with an overall predictive value of 44.26%. The positive predictive value of fetal sex chromosome abnormalities in NIPT screening was higher than that of serological screening (P < 0.05). Among the 36 pregnant women with fetal CNV, NIPT screening showed that CNVs≤10 Mb and CNVs>10 Mb were 33.33% and 66.67%, respectively. There were 12 cases of prenatal diagnosis of fetal CNV, among which the NIPT-screened positive predictive values of fetal copy number deletion, duplicate, deletion and duplicate were 50.00%, 57.14% and 100.00%, respectively, with an overall predictive value of 58.33%. The positive predictive value of CNV in NIPT screening was higher than that of serological screening without statistically significant difference (P > 0.05). The results of NIPT screening showed that the detection rate of fetal sex chromosome abnormalities and total abnormalities of pregnant women over 35 years of age was significantly higher than that of pregnant women aged 18-30 and 31-35 years (P < 0.05). Conclusion: NIPT screening could greatly improve the detection efficacy of fetal sex chromosome abnormalities, CNV and other chromosome abnormalities, and decline the false positive rate. However, the positive predictive value of NIPT screening was relatively low, and further prenatal testing and genetic counseling are still required. In addition, NIPT screening for fetal sex chromosome abnormalities, and the detection rate of total abnormalities in pregnant women older than 35 years old were increased significantly, and pregnancy at an advanced age may be one of the risk factors for fetal chromosomal abnormalities.

Discovery of Unique Bis-Substituted Aromatic Amide Derivatives as Novel Highly Potent Antibiotics for Combating Methicillin-Resistant Staphylococcus aureus (MRSA).

Due to the increasing antibiotic resistance, developing novel antimicrobials to fight infections caused by resistant bacteria is imperative. Herein, a series of novel bis-substituted aromatic amides were designed and synthesized through modifying the hit compound 1, and their antimicrobial activities were evaluated. Among them, compound 4t, as the most potent lead, exhibited excellent antimicrobial activities against Gram-positive bacteria, including clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, while keeping weak hemolytic and mammalian cytotoxic activities. Furthermore, compound 4t displayed rapid bactericidal capabilities, low tendency to produce resistance, and favorable capacities to destroy bacterial biofilms. Further explorations indicated that compound 4t induces bacterial death by binding to cardiolipin (CL) on the bacterial membrane, disrupting the cell membrane, and facilitating the accumulation of reactive oxygen species (ROS). Additionally, compound 4t showed remarkable anti-MRSA activity in vivo, demonstrating compound 4t could be developed as a potential candidate to combat MRSA infections.

Kuntai capsule for the treatment of diminished ovarian reserve: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Diminished ovarian reserve (DOR) results in reduced fertility. Kuntai capsule, a Chinese patent medicine, which can nourish the heart and kidneys, has shown promising efficacy in its treatment. However, there is no enough clinical evidence to confirm the efficacy and safety of Kuntai capsule. AIM OF THE STUDY: This review aims to evaluate Kuntai capsule's potential benefits and detriments for diminished ovarian reserve. MATERIALS AND METHODS: Databases namely China National Knowledge Infrastructure, WANFANG Database, Chinese Science and Technology Journal Database, Chinese Biomedical Literature Database, PubMed, Cochrane Library, and Embase were searched from their inception to July 2023. We included randomized controlled trials (RCTs) comparing Kuntai capsule to hormone therapy (HT) and Kuntai capsule in combination with HT to HT alone for DOR treatment. The risk of bias was evaluated using RoB 1.0. A Meta-analysis was performed using RevMan 5.4 software. The primary outcomes were antral follicle count (AFC) and serum anti-Müllerian hormone (AMH), secondary outcomes were follicle-stimulating hormone (FSH) and adverse reactions. RESULTS: A Meta-analysis of 12 randomized controlled trials (RCTs), encompassing a total of 905 DOR patients was conducted. The results indicated that the combination of Kuntai capsule with HT exhibited superior efficacy in enhancing AFC (MD = 1.34, 95% CI [0.96,1.72]) and AMH levels (MD = 1.09 (ng/mL) 95% CI[0.80,1.38]), Kuntai capsule demonstrated improvements in AFC (MD = 0.65, 95% CI [0.48,0.83]) in DOR patients compared to HT alone. CONCLUSIONS: Based on the available results, the combination of Kuntai capsule with HT appears to improve the AFC, AMH and FSH levels of DOR patients. Kuntai capsule alone appears to improve the AFC and FSH levels of DOR patients. However, included trials had methodological quality issues, further standardized research is required.

A laboratory study of the increasing competitiveness of Karenia mikimotoi under rising CO2 scenario.

Ocean acidification (OA) driven by elevated carbon dioxide (CO2) levels is expected to disturb marine ecological processes, including the formation and control of harmful algal blooms (HABs). In this study, the effects of rising CO2 on the allelopathic effects of macroalgae Ulva pertusa to a toxic dinoflagellate Karenia mikimotoi were investigated. It was found that high level of CO2 (1000 ppmv) promoted the competitive growth of K. mikimotoi compared to the group of present ambient CO2 level (420ppmv), with the number of algal cell increased from 32.2 × 104 cells/mL to 36.75 × 104 cells/mL after 96 h mono-culture. Additionally, rising CO2 level weakened allelopathic effects of U. pertusa on K. mikimotoi, as demonstrated by the decreased inhibition rate (50.6 % under the original condition VS 34.3 % under the acidified condition after 96 h co-culture) and the decreased reactive oxygen species (ROS) level, malondialdehyde (MDA) content, antioxidant enzymes activity (superoxide dismutase (SOD), peroxidase (POD), glutathione peroxidase (GPX), glutathione reductase (GR) and catalase (CAT) and non-enzymatic antioxidants (glutathione (GSH) and ascorbic acid (ascorbate, vitamin C). Indicators for cell apoptosis of K. mikimotoi including decreased caspase-3 and -9 protease activity were observed when the co-cultured systems were under rising CO2 exposure. Furthermore, high CO2 level disturbed fatty acid synthesis in U. pertusa and significantly decreased the contents of fatty acids with allelopathy, resulting in the allelopathy weakening of U. pertusa. Collectively, rising CO2 level promoted the growth of K. mikimotoi and weakened allelopathic effects of U. pertusa on K. mikimotoi, indicating the increased difficulties in controlling K. mikimotoi using macroalgae in the future.

LSnet: detecting and genotyping deletions using deep learning network.

The role and biological impact of structural variation (SV) are increasingly evident. Deletion accounts for 40% of SV and is an important type of SV. Therefore, it is of great significance to detect and genotype deletions. At present, high accurate long reads can be obtained as HiFi reads. And, through a combination of error-prone long reads and high accurate short reads, we can also get accurate long reads. These accurate long reads are helpful for detecting and genotyping SVs. However, due to the complexity of genome and alignment information, detecting and genotyping SVs remain a challenging task. Here, we propose LSnet, an approach for detecting and genotyping deletions with a deep learning network. Because of the ability of deep learning to learn complex features in labeled datasets, it is beneficial for detecting SV. First, LSnet divides the reference genome into continuous sub-regions. Based on the alignment between the sequencing data (the combination of error-prone long reads and short reads or HiFi reads) and the reference genome, LSnet extracts nine features for each sub-region, and these features are considered as signal of deletion. Second, LSnet uses a convolutional neural network and an attention mechanism to learn critical features in every sub-region. Next, in accordance with the relationship among the continuous sub-regions, LSnet uses a gated recurrent units (GRU) network to further extract more important deletion signatures. And a heuristic algorithm is present to determine the location and length of deletions. Experimental results show that LSnet outperforms other methods in terms of the F1 score. The source code is available from GitHub at https://github.com/eioyuou/LSnet.

NCOA4: An Immunomodulation-Related Prognostic Biomarker in Colon Adenocarcinoma and Pan-Cancer.

Treatment of cancer in humans requires a thorough understanding of the multiple pathways by which it develops. Recent studies suggest that nuclear receptor coactivator 4 (NCOA4) may be a predictive biomarker for renal cancer. In the present work, TCGA, GEPIA, and several bioinformatics approaches were used to analyze the NCOA4 expression patterns, prognostic relevance, and association between NCOA4 and clinicopathological features and immune cell infiltration. We investigated NCOA4 expression in malignancies. Low NCOA4 expression was associated with poor overall survival in individuals with malignancies such as cholangiocarcinoma, colon adenocarcinoma, and clear cell renal carcinoma. We also analyzed NCOA4 DNA methylation in normal and primary tumor tissues and investigated possible functional pathways underlying NCOA4-mediated oncogenesis. In conclusion, downregulation of NCOA4 is associated with poor prognosis, and NCOA4 may be a predictive biomarker for COAD.

Urinary Exosomal Long Noncoding RNA TERC as a Noninvasive Diagnostic and Prognostic Biomarker for Bladder Urothelial Carcinoma.

PURPOSE: Bladder cancer is one of the most common urological malignancies worldwide, and approximately 90% of bladder cancer cases are histologically typed as bladder urothelial carcinoma (BLCA). Exosomes are 30 to 200 nm extracellular vesicles that transport microRNAs, long noncoding RNAs (lncRNAs), mRNAs, circular RNAs, and proteins across tissues and through circulation. Urinary exosomes may contain genetic information from tumor cells. Herein, we explored the clinical significance of urinary exosomal lncRNA telomerase RNA component (TERC) levels to provide an urgently needed diagnostic and prognostic biomarker for BLCA. MATERIALS AND METHODS: In this study, we used RNA-sequencing of samples from four BLCA patients and three healthy controls to identify that TERC was differentially expressed in urinary exosomes. We then used quantitative PCR in different types of clinical samples to validate the biomarker and analyzed results using receiver operating characteristic curves. RESULTS: We found that TERC was significantly upregulated in urinary exosomes from BLCA patients compared with those from healthy controls (P < 0.0001). Urinary exosomal TERC showed higher sensitivity (78.65%) and accuracy (77.78%) than existing indicators including nuclear matrix protein-22 and urine cytometry. Using the cut-off value 4.302, the area under the curve for urinary exosomal TERC was 0.836 (95% confidence interval: 0.768-0.891, P < 0.0001). Furthermore, this noninvasive assay could distinguish low-grade and high-grade tumors (P = 0.0153). CONCLUSIONS: TERC is enriched in urinary exosomes from BLCA patients. Urinary exosomal TERC could become a diagnostic and prognostic biomarker for BLCA that allows clinicians to realize noninvasive detection of BLCA.

Reynoutria japonica Houtt for Acute Respiratory Tract Infections in Adults and Children: A Systematic Review.

Introduction: Respiratory tract infections (RTIs) are a major cause of morbidity and mortality in some high-risk groups including children and older adults. There is evidence that Chinese herbal medicine has an effect on RTIs. Reynoutria japonica Houtt (better known under its synonym Fallopia japonica (Houtt.) Ronse Decr.) (F. japonica), a commonly used Chinese herbal medicine, has a high content of resveratrol and glycosides. In traditional Chinese medicine theory, F. japonica has the effect of clearing heat in the body, improving blood and qi circulation, eliminating phlegm, and relieving cough, so it may have an effect on RTIs. Methods: This systematic review was registered under PROSPERO CRD42020188604. Databases were searched for randomized controlled trials of F. japonica as a single herb, or as a component of a complex herbal formula for RTIs. Quality of methodology was assessed by two reviewers independently using the Cochrane Risk of Bias Tool. The primary outcome was symptom improvement rate. The secondary outcome measures were fever clearance time, Murray lung injury score and incidence of adverse effects. The extracted data were pooled and meta-analysed by RevMan 5.3 software. Results: Eight RCTs with 1,123 participants with acute RTIs were included in this systematic review, and all the RCTs used F. japonica as part of a herbal mixture. Only one included trial used F. japonica in a herbal mixture without antibiotics in the treatment group. The findings showed that herbal remedies that included F. japonica could increase the symptom improvement rate (risk ratio 1.14, 95% confidence intervals [1.09, 1.20], I2 = 0%, p < 0.00001, n = 7 trials, 1,013 participants), shorten fever duration, reduce Murray lung injury score and did not increase adverse events (RR 0.33, 95% CI [0.11, 1.00], I2 = 0%, p = 0.05, n = 5 trials, 676 participants). Conclusion: There is limited but some evidence that F. japonica as part of a herbal mixture may be an effective and safe intervention for acute RTIs in clinical practice. In future studies it would be preferable to evaluate the effectiveness and safety of using F. japonica without antibiotics for acute RTIs.