quinone oxidoreductase 1 (NQO1), an obligate two-electron reductase, plays an important role in reducing reactive quinones to less reactive and less toxic hydroquinones. Genetic variations in NQO1 gene that impede its enzyme function may be considered as putative risk factor for cancer. Numerous studies have been performed to investigate the association between NQO1 Pro187Ser polymorphism and bladder cancer risk; nevertheless, the results remain controversial.

Cucumber (Cucumis sativus L.) is threatened by substantial yield losses due to the south root-knot nematode (Meloidogyne incognita). However, understanding of the molecular mechanisms underlying the process of nematode infection is still limited. In this study, we found that M. incognita infection affected the structure of cells in cucumber roots and treatment of the cytoskeleton inhibitor (cytochalasin D) reduced root-knot nematode (RKN) parasitism. It is known that Actin-Depolymerizing Factor (ADF) affects cell structure, as well as the organization of the cytoskeleton. To address the hypothesis that nematode-induced abnormal cell structures and cytoskeletal rearrangements might be mediated by the ADF genes, we identified and characterized eight cucumber ADF (CsADF) genes. Phylogenetic analysis showed that the cucumber ADF gene family is grouped into four ancient subclasses. Expression analysis revealed that CsADF1, CsADF2-1, CsADF2-2, CsADF2-3 (Subclass I), and CsADF6 (Subclass III) have higher transcript levels than CsADF7-1, CsADF7-2 (Subclass II genes), and CsADF5 (Subclass IV) in roots. Members of subclass I genes (CsADF1, CsADF2-1, CsADF2-2, and CsADF2-3), with the exception of CsADF2-1, exhibited a induction of expression in roots 14 days after their inoculation (DAI) with nematodes. However, the expression of subclass II genes (CsADF7-1 and CsADF7-2) showed no significant change after inoculation. The transcript levels of CsADF6 (Subclass III) showed a specific induction at 21 DAI, while CsADF5 (Subclass IV) was weakly expressed in roots, but was strongly up-regulated as early as 7 DAI. In addition, treatment of roots with cytochalasin D caused an approximately 2-fold down-regulation of the CsADF genes in the treated plants. These results suggest that CsADF gene mediated actin dynamics are associated with structural changes in roots as a consequence of M. incognita infection.

Termites are considered among the most efficient bioreactors, with high capacities for lignocellulose degradation and utilization. Recently, several studies have characterized the gut microbiota of diverse termites. However, the temporal dynamics of the gut microbiota within a given termite with dietary diversity are poorly understood. Here, we employed 16S rDNA barcoded pyrosequencing analysis to investigate temporal changes in bacterial diversity and richness of the gut microbiota of wood-feeding higher termite Mironasutitermes shangchengensis under three lignocellulose content-based diets that feature wood, corn stalks, and filter paper. Compositions of the predominant termite gut residents were largely constant among the gut microbiomes under different diets, but each diet caused specific changes in the bacterial composition over time. Notably, microbial communities exhibited an unexpectedly strong resilience during continuous feeding on both corn stalks and filter paper. Members of five bacterial phyla, that is, Spirochaetes, Firmicutes, Actinobacteria, Tenericutes, and Acidobacteria, were strongly associated with the resilience. These findings provide insights into the stability of the gut microbiota in higher termites and have important implications for the future design of robust bioreactors for lignocellulose degradation and utilization.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease affecting predominantly females. To discover additional genetic risk variants for SLE on the X chromosome, we performed a follow-up study of our previously published genome-wide association study (GWAS) data set in this study.

The A disintegrin and metalloproteinase 9 (ADAM9) protein has been suggested to promote carcinoma invasion and appears to be overexpressed in various human cancers. However, its role has rarely been investigated in gliomas and, thus, in the current study we have evaluated ADAM9 expression in gliomas and examined the relevance of its expression in the prognosis of glioma patients. Clinical characteristics, RNA sequence data, and the case follow-ups were reviewed for 303 patients who had histological, confirmed gliomas. The ADAM9 expression between lower-grade glioma (LGG) and glioblastoma (GBM) patients was compared and its association with progression-free survival (PFS) and overall survival (OS) was assessed to evaluate its prognostic value. Our data suggested that GBM patients had significantly higher expression of ADAM9 in comparison to LGG patients (p < 0.001, t-test). In addition, among the LGG patients, aggressive astrocytic tumors displayed significantly higher ADAM9 expression than oligodendroglial tumors (p < 0.001, t-test). Moreover, high ADAM9 expression also correlated with poor clinical outcome (p < 0.001 and p < 0.001, log-rank test, for PFS and OS, respectively) in LGG patients. Further, multivariate analysis suggested ADAM9 expression to be an independent marker of poor survival (p = 0.002 and p = 0.003, for PFS and OS, respectively). These results suggest that ADAM9 mRNA expression is associated with tumor grade and histological type in gliomas and can serve as an independent prognostic factor, specifically in LGG patients.

The cell cortex is a layer of cytoskeletal networks underneath the plasma membrane, formed by filamentous actin (F-actin) and cortex proteins including spectrin, adducin, and myosin. It provides cells with proper stiffness, elasticity, and surface tension to allow morphogenesis, division, and migration. Although its architecture and formation have been widely studied in red blood cells, they are poorly understood in non-erythrocytes due to structural complexity and versatile functions. In this study, we identify the actin-binding protein abLIM1 as a novel non-erythroid cell-specific cortex organizer. Endogenous abLIM1 colocalized with cortical βII spectrin but upon overexpression redistributed to thick cortical actin bundles. abLIM1 associated with major cortex proteins such as spectrins and adducin in vivo. Depletion of abLIM1 by RNAi induced prominent blebbing during membrane protrusions of spreading or migrating RPE1 cells and impaired migration efficiency. Reducing cortical tensions by culturing the cells to confluency or inhibiting myosin activity repressed the blebbing phenotype. abLIM1-depleted RPE1 or U2OS cells lacked the dense interwoven cortical actin meshwork observed in control cells but were abundant in long cortical actin bundles along the long axis of the cells. In-vitro assays indicated that abLIM1 was able to crosslink and bundle F-actin to induce dense F-actin network formation. Therefore, abLIM1 governs the formation of dense interconnected cortical actin meshwork in non-erythroid cells to prevent mechanical tension-induced blebbing during cellular activities such as spreading and migration.

Hematopoietic progenitor kinase 1 (HPK1) belongs to the mitogen activated protein kinase kinase kinase kinase (MAP4K) family of serine/threonine kinases, which have been associated with the incidence and progression of a variety of gastrointestinal malignant tumors in humans. However, the potential association between HPK1 expression and breast cancer, particularly invasive ductal carcinoma‑not otherwise specified (IDC‑NOS) development, has not yet been examined. To address this gap, the present study aimed to evaluate HPK1 expression in IDC‑NOS samples and to determine a relationship with clinical prognostic indicators, such as the expression levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as overall survival of the patients with IDC‑NOS. HPK1 mRNA and protein expression in samples from 148 patients with IDC‑NOS were detected using immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction. A total of 54 out of 148 (36.5%) samples were HPK1‑positive, and 100 out of 148 (67.6%) were ER‑positive. Of the latter, 28% (28/100) were HPK1‑positive, and a significant negative association of HPK1 expression with ER positivity was observed (P=0.002; r=‑0.254). In addition, 43.2% (64/148) and 32.4% (48/100) of IDC‑NOS tissues were PR‑ or HER2‑positive, respectively; however, neither indicator correlated with HPK1 (P=0.109 and P=0.558, respectively). HPK1 expression, axillary lymph node metastasis and tumor‑node‑metastasis (TNM) stage were identified as independent factors of overall survival (OS) in the ER‑positive group (P<0.05), and HPK1 positivity was associated with increased OS (P=0.048). HPK1 mRNA levels did not differ between IDC‑NOS and normal adjacent breast tissues, whereas HPK1 protein levels were lower in IDC‑NOS (P<0.05). These results suggested that HPK1 protein may be a potentially effective IDC-NOS therapeutic target.

Fruit epidermal features such as the number and size of trichomes or spines are important fruit quality traits in cucumber production. Little is known about the molecular mechanisms underlying fruit spine formation in cucumber. Here, we report functional characterization of the cucumber CsMYB6 gene, which encodes a MIXTA-like MYB transcription factor that plays an important role in regulating fruit trichome development. Spatial-temporal expression analyses revealed high-level expression of CsMYB6 in the epidermis of cucumber ovaries during fruit spine initiation, which was similar to the expression of CsTRY, a homolog of the Arabidopsis TRY gene that also plays a key role in trichome development. Overexpression of CsMYB6 and CsTRY in cucumber and Arabidopsis revealed that CsMYB6 and CsTRY act as negative regulators of trichome initiation in both species, and that CsMYB6 acted upstream of CsTRY in this process. CsMYB6 was found to bind to the three MYB binding sites inside the promoter region of CsTRY, and protein-protein interaction assays suggested that CsTRY also directly interacted with CsMYB6 protein. The results also revealed conserved and divergent roles of CsMYB6 and its Arabidopsis homolog AtMYB106 in trichome development. Collectively, our results reveal a novel mechanism in which the CsMYB6-CsTRY complex negatively regulates fruit trichome formation in cucumber.

Tylorrhynchus heterochaetus is a widespread benthic polychaete worm found in coastal brackish waters of the west Pacific. It has high ecological and economic value as a biomarker of water quality and as a high-quality feed in aquaculture and fisheries and is considered a delicacy in some areas of Asia. However, it has experienced a marked reduction in recent years due to overexploitation as well as changes in the environment and climate. Here, to comprehensively understand its genetic background and thus provide insights for better conservation and utilization of this species, we assessed the genetic variability and demographic history of T. heterochaetus individuals sampled from eight locations along the coasts of southeast China and north Vietnam based on mitochondrial cytochrome c oxidase I ( COI) sequences. We observed high haplotype diversity ( Hd), with an average of 0.926, but relatively low nucleotide diversity ( π), with a mean of 0.032 across all samples. A total of 94 polymorphic sites and 85 haplotypes were identified among 320 individuals. The pairwise genetic distances among haplotypes ranged from 0.001 to 0.067, with the high intraspecific divergence possibly reflecting geographic isolation and gene pool fragmentation. Significant genetic structures were revealed among the studied locations; specifically, the eight locations could be treated as six genetically different populations based on pairwise Φ ST results (0.026-0.951, P<0.01). A significant pattern of isolation-by-distance was detected between the genetic and geographic distances ( r=0.873, P=0.001). Three geographic lineages were defined based on phylogenetic tree and network analyses of COI haplotypes. AMOVA results indicated that genetic variations mainly occurred among the three lineages (89.96%). Tests of neutrality and mismatch distribution suggested that T. heterochaetus underwent recent population expansion. These results provide the first report on the genetic status of T. heterochaetus and will be valuable for the management of genetic resources and better understanding of the ecology and evolution in this species.

Current techniques of patterned material deposition require separate steps for patterning and material deposition. The complexity and harsh working conditions post serious limitations for fabrication. Here, we introduce a single-step and easy-to-adapt method that can deposit materials in-situ. Its methodology is based on the semiconductor nanoparticle assisted photon-induced chemical reduction and optical trapping. This universal mechanism can be used for depositing a large selection of materials including metals, insulators and magnets, with quality on par with current technologies. Patterning with several materials together with optical-diffraction-limited resolution and accuracy can be achieved from macroscopic to microscopic scale. Furthermore, the setup is naturally compatible with optical microscopy based measurements, thus sample characterisation and material deposition can be realised in-situ. Various devices fabricated with this method in 2D or 3D show it is ready for deployment in practical applications. This method will provide a distinct tool in material technology.

Noncoding RNA (ncRNA) is a kind of RNA that plays an important role in many biological processes, diseases, and cancers, while cannot translate into proteins. With the development of next-generation sequence technology, thousands of novel RNAs with long open reading frames (ORFs, longest ORF length > 303 nt) and short ORFs (longest ORF length ≤ 303 nt) have been discovered in a short time. How to identify ncRNAs more precisely from novel unannotated RNAs is an important step for RNA functional analysis, RNA regulation, etc. However, most previous methods only utilize the information of sequence features. Meanwhile, most of them have focused on long-ORF RNA sequences, but not adapted to short-ORF RNA sequences. In this paper, we propose a new reliable method called NCResNet. NCResNet employs 57 hybrid features of four categories as inputs, including sequence, protein, RNA structure, and RNA physicochemical properties, and introduces feature enhancement and deep feature learning policies in a neural net model to adapt to this problem. The experiments on benchmark datasets of 8 species shows NCResNet has higher accuracy and higher Matthews correlation coefficient (MCC) compared with other state-of-the-art methods. Particularly, on four short-ORF RNA sequence datasets, specifically mouse, Saccharomyces cerevisiae, zebrafish, and cow, NCResNet achieves greater than 10 and 15% improvements over other state-of-the-art methods in terms of accuracy and MCC. Meanwhile, for long-ORF RNA sequence datasets, NCResNet also has better accuracy and MCC than other state-of-the-art methods on most test datasets. Codes and data are available at https://github.com/abcair/NCResNet.

Cutaneous malignant melanoma (CMM) is one of the most dangerous types of skin cancer. The prognosis of CMM patients with ulcers, regional lymph node metastasis or organ metastasis is poor. In this process, resistance to anoikis is a critical step in tumor cell metastasis. Tumor cells survive in the vascular and lymphatic system through the escape of anoikis to finally form clones in the distal tissue. The present study revealed that muscle intestine and stomach expression 1 (MIST1), a secreting cell-restricted transcription factor, was overexpressed in melanoma cells. At the same time, the expression of SNAI1 was also high. High expression of MIST1 and SNAI1 all contributed to melanoma cells bypassing anoikis. By changing the expression of MIST1, SNAI1 was indicated to be a downstream gene of MIST1. Chromatin immunoprecipitation and luciferase reporter gene technology revealed that MIST1 promoted the expression of SNAI1 by directly binding to its promoter region. Furthermore, inhibition of the phosphorylation/activity of Akt by LY294002 and knockdown of phosphatase and tensin homologue (PTEN) with simultaneous upregulation or knockdown of MIST1 revealed that SNAI1 improved the phosphorylation of Akt by inhibiting the expression of PTEN. These results suggested that MIST1 hijacked the PTEN/AKT signaling pathway through directly regulating SNAI1 and affected the anoikis resistance capacity of melanoma cells.

This study, for the first time in fish, compared the transcriptome of fresh and frozen-thawed sperm, and would help to better understand the effect of cryopreservation on fish sperm and then better preserve the aquatic germplasm resources. Here, we employed high-throughput sequencing technology to obtain the transcriptome of yellow catfish from fresh sperm, cryopreserved sperm with and without cryoprotectant. When cryoprotectant (Me2SO) was excluded, down-regulated genes were significantly enriched into calcium ion binding, cytoskeletal protein binding, microfilament motor activity, calmodulin binding and carnitine O-acyltransferase activity, which affected Ca2+ regulation, cellular morphology, motility and metabolism. Moreover, heat shock proteins and genes associated with regulation of cholesterol, HCO3- and protein tyrosine phosphorylation (PTP) were down-regulated, and thus would impair ability against stress, membrane rigidity, pH regulation and signal transduction of cryopreserved sperm. After Me2SO was added, the amounts of DEGs decreased significantly and down-regulation of genes were found mainly in cytoskeleton and heat shock proteins, thereby suggesting that Me2SO effectively reduced the impact caused by low temperature on gene expression. Whether adding Me2SO or not, the up-regulated genes were mainly found in ribosomal proteins genes. However, when Me2SO was added, over-expression of some genes might contribute to maintain normal function of cryopreserved sperm.

Follicular helper T cells (TFH cells), known as the primary "helpers" of the germinal center (GC) reaction, promote the humoral immune response to defend against various pathogens. Under conditions of infection by different types of pathogens, many shared transcription factors (TFs), such as Bcl-6, TCF-1, and Maf, are selectively enriched in pathogen-specific TFH cells, orchestrating TFH cell differentiation and function. In addition, TFH cells also coexpress environmentally associated TFs as their conventional T cell counterparts (such as T-bet, GATA-3, or ROR-γt, which are expressed in Th1, Th2, or Th17 cells, respectively). These features likely indicate both the lineage-specificity and environmental adaption of the TFH cell responses. However, the extent to which the TFH cell response relies on these environmentally specific TFs is not completely understood. Here, we found that T-bet was specifically expressed in Type I TFH cells but not Type II TFH cells. While dispensable for the early fate commitment of TFH cells, T-bet was essential for the maintenance of differentiated TFH cells, promoting their proliferation, and inhibiting their apoptosis during acute viral infection. Microarray analysis showed both similarities and differences in transcriptome dependency on T-bet in TFH and TH1 cells, suggesting the distinctive role of T-bet in TFH cells. Collectively, our findings reveal an important and specific supporting role for T-bet in type I TFH cell response, which can help us gain a deeper understanding of TFH cell subsets.

Measuring conditional relatedness between a pair of genes is a fundamental technique and still a significant challenge in computational biology. Such relatedness can be assessed by gene expression similarities while suffering high false discovery rates. Meanwhile, other types of features, e.g., prior-knowledge based similarities, is only viable for measuring global relatedness. In this paper, we propose a novel machine learning model, named Multi-Features Relatedness (MFR), for accurately measuring conditional relatedness between a pair of genes by incorporating expression similarities with prior-knowledge based similarities in an assessment criterion. MFR is used to predict gene-gene interactions extracted from the COXPRESdb, KEGG, HPRD, and TRRUST databases by the 10-fold cross validation and test verification, and to identify gene-gene interactions collected from the GeneFriends and DIP databases for further verification. The results show that MFR achieves the highest area under curve (AUC) values for identifying gene-gene interactions in the development, test, and DIP datasets. Specifically, it obtains an improvement of 1.1% on average of precision for detecting gene pairs with both high expression similarities and high prior-knowledge based similarities in all datasets, comparing to other linear models and coexpression analysis methods. Regarding cancer gene networks construction and gene function prediction, MFR also obtains the results with more biological significances and higher average prediction accuracy, than other compared models and methods. A website of the MFR model and relevant datasets can be accessed from http://bmbl.sdstate.edu/MFR .

Skin aging is a specific manifestation of the physiological aging process that occurs in virtually all organisms. In this study, we used data independent acquisition mass spectrometry to perform a comparative analysis of protein expression in volar forearm skin samples from of 20 healthy young and elderly Chinese individuals. Our quantitative proteomic analysis identified a total of 95 differentially expressed proteins (DEPs) in aged skin compared to young skin. Enrichment analyses of these DEPs (57 upregulated and 38 downregulated proteins) based on the GO, KEGG, and KOG databases revealed functional clusters associated with immunity and inflammation, oxidative stress, biosynthesis and metabolism, proteases, cell proliferation, cell differentiation, and apoptosis. We also found that GAPDH, which was downregulated in aged skin samples, was the top hub gene in a protein-protein interaction network analysis. Some of the DEPs identified herein had been previously correlated with aging of the skin and other organs, while others may represent novel age-related entities. Our non-invasive proteomics analysis of human epidermal proteins may guide future research on skin aging to help develop treatments for age-related skin conditions and rejuvenation.

Acute Intracranial hemorrhage (ICH) is a life-threatening disease that requires emergency medical attention, which is routinely diagnosed using non-contrast head CT imaging. The diagnostic accuracy of acute ICH on CT varies greatly among radiologists due to the difficulty of interpreting subtle findings and the time pressure associated with the ever-increasing workload. The use of artificial intelligence technology may help automate the process and assist radiologists for more prompt and better decision-making. In this work, we design a deep learning approach that mimics the interpretation process of radiologists, and combines a 2D CNN model and two sequence models to achieve accurate acute ICH detection and subtype classification. Being developed using the extensive 2019-RSNA Brain CT Hemorrhage Challenge dataset with over 25000 CT scans, our deep learning algorithm can accurately classify the acute ICH and its five subtypes with AUCs of 0.988 (ICH), 0.984 (EDH), 0.992 (IPH), 0.996 (IVH), 0.985 (SAH), and 0.983 (SDH), respectively, reaching the accuracy level of expert radiologists. Our method won 1st place among 1345 teams from 75 countries in the RSNA challenge. We have further evaluated our algorithm on two independent external validation datasets with 75 and 491 CT scans, respectively, and our method maintained high AUCs of 0.964 and 0.949 for acute ICH detection. These results have demonstrated the high performance and robust generalization ability of our proposed method, which makes it a useful second-read or triage tool that can facilitate routine clinical applications.

Successful gene therapy for brain tumors are often limited by two important factors, the existence of blood brain barrier (BBB) and inefficient transfection of brain tumor cells. In this study, we designed a series of peptide-based gene delivery vectors decorated with T7 segment for binding the transferrin (Tf) receptors which were highly expressed on brain tumor cells, and evaluated their ability of gene delivery. The physicochemical properties of peptide vectors or peptide/DNA complexes were studied as well. The in vitro transfection efficiency was investigated in normal and glioma cell lines. Among these complexes, PT-02/DNA complexes showed the highest transfection efficiency in glioma cells and low cytotoxicity in normal cell lines, and it could transport DNA across the BBB model in vitro. Furthermore, PT-02/DNA could deliver pIRES2-EGFP into the brain site of zebrafish in vivo. The designed peptide vectors offered a promising way for glioma gene therapy.

Glutamate dehydrogenase (Gdh), catalyzing the reversible conversion between 2-oxoglutarate and glutamate, plays an important role in the connection of nitrogen and carbon metabolism. Yet little is known about these enzymes in the amino acid-manufacturing Corynebacterium glutamicum. In the present study, we firstly identified the enzymatic characteristics of two Gdhs (GdhA and GdhB). The results showed that both GdhA and GdhB prefers NADPH as a coenzyme and have higher affinity for 2-OG than glutamate. The growth characteristics of gdhAΔ mutant and gdhBΔ mutant, gdhABΔ mutant showed GdhA serves as the main conduit for ammonium assimilation, and GdhB is the main glutamate- metabolizing enzyme in C. glutamicum. The full-genome transcriptomic analysis was used to investigate physiological response of C. glutamicum to the glutamate as nitrogen source, and gdh deletion. The results showed that the nitrogen starvation response was elicited when glutamine served as the sole nitrogen source. gdhAΔBΔ double deletion trigger a partially deregulated nitrogen starvation response, in which genes involved in nitrogen assimilation showed obviously upregulated in a certain extent. On the other hand, the genes of phosphotransferase system (PTS) and glycolysis pathway, most genes in pentose phosphate pathway were significantly upregulated, indicating that gdh deficiency initiated the enhancement of the absorption and metabolism of carbon sources. We believed that our results in this study will give new insights on the molecular mechanism of Gdh activity cross-talks with carbon and nitrogen metabolism, also setting a new background for further flux redistribution applied research of biotechnological interest.

Assessing the correlation between gut microbiota (GM) and bone homeostasis has increasingly attracted research interest. Meanwhile, GM dysbiosis has been found to be associated with abnormal bone metabolism. However, the function of GM in disuse-induced osteoporosis (DIO) remains poorly understood. In our research, we evaluated the characteristics of GM and fecal metabolomics to explore their potential correlations with DIO pathogenesis.