Structural variants drive context-dependent oncogene activation in cancer.

Higher-order chromatin structure is important for the regulation of genes by distal regulatory sequences1,2. Structural variants (SVs) that alter three-dimensional (3D) genome organization can lead to enhancer-promoter rewiring and human disease, particularly in the context of cancer3. However, only a small minority of SVs are associated with altered gene expression4,5, and it remains unclear why certain SVs lead to changes in distal gene expression and others do not. To address these questions, we used a combination of genomic profiling and genome engineering to identify sites of recurrent changes in 3D genome structure in cancer and determine the effects of specific rearrangements on oncogene activation. By analysing Hi-C data from 92 cancer cell lines and patient samples, we identified loci affected by recurrent alterations to 3D genome structure, including oncogenes such as MYC, TERT and CCND1. By using CRISPR-Cas9 genome engineering to generate de novo SVs, we show that oncogene activity can be predicted by using 'activity-by-contact' models that consider partner region chromatin contacts and enhancer activity. However, activity-by-contact models are only predictive of specific subsets of genes in the genome, suggesting that different classes of genes engage in distinct modes of regulation by distal regulatory elements. These results indicate that SVs that alter 3D genome organization are widespread in cancer genomes and begin to illustrate predictive rules for the consequences of SVs on oncogene activation.

Dynamic regulation of histone modifications and long-range chromosomal interactions during postmitotic transcriptional reactivation.

During mitosis, transcription of genomic DNA is dramatically reduced, before it is reactivated during nuclear reformation in anaphase/telophase. Many aspects of the underlying principles that mediate transcriptional memory and reactivation in the daughter cells remain unclear. Here, we used ChIP-seq on synchronized cells at different stages after mitosis to generate genome-wide maps of histone modifications. Combined with EU-RNA-seq and Hi-C analyses, we found that during prometaphase, promoters, enhancers, and insulators retain H3K4me3 and H3K4me1, while losing H3K27ac. Enhancers globally retaining mitotic H3K4me1 or locally retaining mitotic H3K27ac are associated with cell type-specific genes and their transcription factors for rapid transcriptional activation. As cells exit mitosis, promoters regain H3K27ac, which correlates with transcriptional reactivation. Insulators also gain H3K27ac and CCCTC-binding factor (CTCF) in anaphase/telophase. This increase of H3K27ac in anaphase/telophase is required for posttranscriptional activation and may play a role in the establishment of topologically associating domains (TADs). Together, our results suggest that the genome is reorganized in a sequential order, in which histone methylations occur first in prometaphase, histone acetylation, and CTCF in anaphase/telophase, transcription in cytokinesis, and long-range chromatin interactions in early G1. We thus provide insights into the histone modification landscape that allows faithful reestablishment of the transcriptional program and TADs during cell division.

NS7a of SADS-CoV promotes viral infection via inducing apoptosis to suppress type III interferon production.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered swine coronavirus with potential cross-species transmission risk. Although SADS-CoV-induced host cell apoptosis and innate immunity antagonization has been revealed, underlying signaling pathways remain obscure. Here, we demonstrated that infection of SADS-CoV induced apoptosis in vivo and in vitro, and that viral protein NS7a is mainly responsible for SADS-CoV-induced apoptosis in host cells. Furthermore, we found that NS7a interacted with apoptosis-inducing factor mitochondria associated 1 (AIFM1) to activate caspase-3 via caspase-6 in SADS-CoV-infected cells, and enhanced SADS-CoV replication. Importantly, NS7a suppressed poly(I:C)-induced expression of type III interferon (IFN-λ) via activating caspase-3 to cleave interferon regulatory factor 3 (IRF3), and caspase-3 inhibitor protects piglets against SADS-CoV infection in vivo. These findings reveal how SADS-CoV induced apoptosis to inhibit innate immunity and provide a valuable clue to the development of effective drugs for the clinical control of SADS-CoV infection.IMPORTANCEOver the last 20 years, multiple animal-originated coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), middle east respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2, have caused millions of deaths, seriously jeopardized human health, and hindered social development, indicating that the study of animal-originated coronaviruses with potential for cross-species transmission is particularly important. Bat-originated swine acute diarrhea syndrome coronavirus (SADS-CoV), discovered in 2017, can not only cause fatal diarrhea in piglets, but also infect multiple human cells, with a potential risk of cross-species transmission, but its pathogenesis is unclear. In this study, we demonstrated that NS7a of SADS-CoV suppresses IFN-λ production via apoptosis-inducing factor mitochondria associated 1 (AIFM1)-caspase-6-caspase-3-interferon regulatory factor 3 (IRF3) pathway, and caspase-3 inhibitor (Z-DEVD-FMK) can effectively inhibit SADS-CoV replication and protect infected piglets. Our findings in this study contribute to a better understanding of SADS-CoV-host interactions as a part of the coronaviruses pathogenesis and using apoptosis-inhibitor as a drug as potential therapeutic approaches for prevention and control of SADS-CoV infection.

Global Dynamics of Porcine Enteric Coronavirus PEDV Epidemiology, Evolution, and Transmission.

With a possible origin from bats, the alphacoronavirus Porcine epidemic diarrhea virus (PEDV) causes significant hazards and widespread epidemics in the swine population. However, the ecology, evolution, and spread of PEDV are still unclear. Here, from 149,869 fecal and intestinal tissue samples of pigs collected in an 11-year survey, we identified PEDV as the most dominant virus in diarrheal animals. Global whole genomic and evolutionary analyses of 672 PEDV strains revealed the fast-evolving PEDV genotype 2 (G2) strains as the main epidemic viruses worldwide, which seems to correlate with the use of G2-targeting vaccines. The evolving pattern of the G2 viruses presents geographic bias as they evolve tachytely in South Korea but undergo the highest recombination in China. Therefore, we clustered six PEDV haplotypes in China, whereas South Korea held five haplotypes, including a unique haplotype G. In addition, an assessment of the spatiotemporal spread route of PEDV indicates Germany and Japan as the primary hubs for PEDV dissemination in Europe and Asia, respectively. Overall, our findings provide novel insights into the epidemiology, evolution, and transmission of PEDV, and thus may lay a foundation for the prevention and control of PEDV and other coronaviruses.

SE-FSCNet: full-scale connection network for single-shot phase demodulation.

The accuracy of phase demodulation has significant impact on the accuracy of fringe projection 3D measurement. Currently, researches based on deep learning methods for extracting wrapped phase mostly use U-Net as the subject of network. The connection method between its hierarchies has certain shortcomings in global information transmission, which hinders the improvement of wrapped phase prediction accuracy. We propose a single-shot phase demodulation method for fringe projection based on a novel full-scale connection network SE-FSCNet. The encoder and decoder of the SE-FSCNet have the same number of hierarchies but are not completely symmetrical. At the decoder a full-scale connection method and feature fusion module are designed so that SE-FSCNet has better abilities of feature transmission and utilization compared with U-Net. A channel attention module based on squeeze and excitation is also introduced to assign appropriate weights to features with different scales, which has been proved by the ablation study. The experiments conducted on the test set have demonstrated that the SE-FSCNet can achieve higher precision than the traditional Fourier transform method and the U-Net in phase demodulation.

Variance-components tests for genetic association with multiple interval-censored outcomes.

Massive genetic compendiums such as the UK Biobank have become an invaluable resource for identifying genetic variants that are associated with complex diseases. Due to the difficulties of massive data collection, a common practice of these compendiums is to collect interval-censored data. One challenge in analyzing such data is the lack of methodology available for genetic association studies with interval-censored data. Genetic effects are difficult to detect because of their rare and weak nature, and often the time-to-event outcomes are transformed to binary phenotypes for access to more powerful signal detection approaches. However transforming the data to binary outcomes can result in loss of valuable information. To alleviate such challenges, this work develops methodology to associate genetic variant sets with multiple interval-censored outcomes. Testing sets of variants such as genes or pathways is a common approach in genetic association settings to lower the multiple testing burden, aggregate small effects, and improve interpretations of results. Instead of performing inference with only a single outcome, utilizing multiple outcomes can increase statistical power by aggregating information across multiple correlated phenotypes. Simulations show that the proposed strategy can offer significant power gains over a single outcome approach. We apply the proposed test to the investigation that motivated this study, a search for the genes that perturb risks of bone fractures and falls in the UK Biobank.

Swine acute diarrhea syndrome coronavirus Nsp1 suppresses IFN-λ1 production by degrading IRF1 via ubiquitin-proteasome pathway.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine enteric coronavirus that causes acute watery diarrhea, vomiting, and dehydration in newborn piglets. The type III interferon (IFN-λ) response serves as the primary defense against viruses that replicate in intestinal epithelial cells. However, there is currently no information available on how SADS-CoV modulates the production of IFN-λ. In this study, we utilized IPI-FX cells (a cell line of porcine ileum epithelium) as an in vitro model to investigate the potential immune evasion strategies employed by SADS-CoV against the IFN-λ response. Our results showed that SADS-CoV infection suppressed the production of IFN-λ1 induced by poly(I:C). Through screening SADS-CoV-encoded proteins, nsp1, nsp5, nsp10, nsp12, nsp16, E, S1, and S2 were identified as antagonists of IFN-λ1 production. Specifically, SADS-CoV nsp1 impeded the activation of the IFN-λ1 promoter mediated by MAVS, TBK1, IKKε, and IRF1. Both SADS-CoV and nsp1 obstructed poly(I:C)-induced nuclear translocation of IRF1. Moreover, SADS-CoV nsp1 degraded IRF1 via the ubiquitin-mediated proteasome pathway without interacting with it. Overall, our study provides the first evidence that SADS-CoV inhibits the type III IFN response, shedding light on the molecular mechanisms employed by SADS-CoV to evade the host immune response.

A Coupled Calibration Method for Dual Cameras-Projector System with Sub-Pixel Accuracy Feature Extraction.

Binocular structured light systems are widely used in 3D measurements. In the condition of complex and local highly reflective scenes, to obtain more 3D information, binocular systems are usually divided into two pairs of devices, each having a Single Camera and a Projector (SCP). In this case, the binocular system can be seen as Dual Cameras-Projector (DCP) system. In the DCP calibration, the Left-SCP and Right-SCP need to be calibrated separately, which leads to inconsistent parameters for the same projector, thus reducing the measurement accuracy. To solve this problem and improve manoeuvrability, a coupled calibration method using an orthogonal phase target is proposed. The 3D coordinates on a phase target are uniquely determined by the binocular camera in DCP, rather than being calculated separately in each SCP. This ensures the consistency of the projector parameters. The coordinates of the projector image plane are calculated through the unwrapped phase, while the parameters are calibrated by the plane calibration method. In order to extract sub-pixel accuracy feature points, a method based on polynomial fitting using an orthogonal phase target is exploited. The experimental results show that the reprojection error of our method is less than 0.033 pixels, which improves the calibration accuracy.

Comparative genomics reveal the convergent evolution of CYP82D and CYP706X members related to flavone biosynthesis in Lamiaceae and Asteraceae.

Distant species producing the same secondary metabolites is an interesting and common phenomenon in nature. A classic example of this is scutellarein whose derivatives have been used clinically for more than 30 years. Scutellarein occurs in significant amounts in species of two different orders, Scutellaria baicalensis and Erigeron breviscapus, which diverged more than 100 million years ago. Here, according to the genome-wide selection and functional identification of 39 CYP450 genes from various angiosperms, we confirmed that only seven Scutellaria-specific CYP82D genes and one Erigeron CYP706X gene could perform the catalytic activity of flavone 6-hydroxylase (F6H), suggesting that the convergent evolution of scutellarein production in these two distant species was caused by two independently evolved CYP450 families. We also identified seven Scutellaria-specific CYP82D genes encoding flavone 8-hydroxylase (F8H). The evolutionary patterns of CYP82 and CYP706 families via kingdom-wide comparative genomics highlighted the evolutionary diversity of CYP82D and the specificity of CYP706X in angiosperms. Multi-collinearity and phylogenetic analysis of CYP82D in Scutellaria confirmed that the function of F6H evolved from F8H. Furthermore, the SbaiCYP82D1A319D , EbreCYP706XR130A , EbreCYP706XF312D and EbreCYP706XA318D mutants can significantly decrease the catalytic activity of F6H, revealing the contribution of crucial F6H amino acids to the scutellarein biosynthesis of distant species. This study provides important insights into the multi-origin evolution of the same secondary metabolite biosynthesis in the plant kingdom.

The genome of Corydalis reveals the evolution of benzylisoquinoline alkaloid biosynthesis in Ranunculales.

Species belonging to the order Ranunculales have attracted much attention because of their phylogenetic position as a sister group to all other eudicot lineages and their ability to produce unique yet diverse benzylisoquinoline alkaloids (BIAs). The Papaveraceae family in Ranunculales is often used as a model system for studying BIA biosynthesis. Here, we report the chromosome-level genome assembly of Corydalis tomentella, a species of Fumarioideae, one of the two subfamilies of Papaveraceae. Based on comparisons of sequenced Ranunculalean species, we present clear evidence of a shared whole-genome duplication (WGD) event that has occurred before the divergence of Ranunculales but after its divergence from other eudicot lineages. The C. tomentella genome enabled us to integrate isotopic labeling and comparative genomics to reconstruct the BIA biosynthetic pathway for both sanguinarine biosynthesis shared by papaveraceous species and the cavidine biosynthesis that is specific to Corydalis. Also, our comparative analysis revealed that gene duplications, especially tandem gene duplications, underlie the diversification of BIA biosynthetic pathways in Ranunculales. In particular, tandemly duplicated berberine bridge enzyme-like genes appear to be involved in cavidine biosynthesis. In conclusion, our study of the C. tomentella genome provides important insights into the occurrence of WGDs during the early evolution of eudicots, as well as into the evolution of BIA biosynthesis in Ranunculales.

Pyridinic Nitrogen Modification for Selective Acetylenic Homocoupling on Au(111).

On-surface acetylenic homocoupling has been proposed to construct carbon nanostructures featuring sp hybridization. However, the efficiency of linear acetylenic coupling is far from satisfactory, often resulting in undesired enyne products or cyclotrimerization products due to the lack of strategies to enhance chemical selectivity. Herein, we inspect the acetylenic homocoupling reaction of polarized terminal alkynes (TAs) on Au(111) with bond-resolved scanning probe microscopy. The replacement of benzene with pyridine moieties significantly prohibits the cyclotrimerization pathway and facilitates the linear coupling to produce well-aligned N-doped graphdiyne nanowires. Combined with density functional theory calculations, we reveal that the pyridinic nitrogen modification substantially differentiates the coupling motifs at the initial C-C coupling stage (head-to-head vs head-to-tail), which is decisive for the preference of linear coupling over cyclotrimerization.

Elevated LILRB1 expression predicts poor prognosis and is associated with tumor immune infiltration in patients with glioma.

BACKGROUND: Leukocyte immunoglobulin-like receptor subfamily B1 (LILRB1) is regarded as an inhibitory molecule. However, the importance of LILRB1 expression in glioma has not yet been determined. This investigation examined the immunological signature, clinicopathological importance and prognostic value of LILRB1 expression in glioma. METHODS: We used data from the UCSC XENA database, the Cancer Genome Atlas (TCGA) database, the Chinese Glioma Genome Atlas (CGGA) database, the STRING database, the MEXPRESS database and our clinical glioma samples to perform bioinformatic analysis and used vitro experiments to examine the predictive value and potential biological roles of LILRB1 in glioma. RESULTS: Higher LILRB1 expression was considerably present in the higher WHO grade glioma group and was linked to a poorer prognosis in patients with glioma. Gene set enrichment analysis (GSEA) revealed that LILRB1 was positively correlated with the JAK/STAT signaling pathway. LILRB1 combined with tumor mutational burden (TMB) and microsatellite instability (MSI) may be a promising indicator for the effectiveness of immunotherapy in patients with glioma. Increased LILRB1 expression was positively linked with the hypomethylation, M2 macrophage infiltration, immune checkpoints (ICPs) and M2 macrophage makers. Univariate and multivariate Cox regression analyses determined that increased LILRB1 expression was a standalone causal factor for glioma. Vitro experiments determined that LILRB1 positively enhanced the proliferation, migration and invasion in glioma cells. MRI images demonstrated that higher LILRB1 expression was related with larger tumor volume in patients with glioma. CONCLUSION: Dysregulation of LILRB1 in glioma is correlated with immune infiltration and is a standalone causal factor for glioma.

Circ_0018909 knockdown inhibits the development of pancreatic cancer via the miR-545-3p/FASN axis and reduces macrophage polarization to M2.

Multiple circular RNAs (circRNAs) were proven to regulate the development of pancreatic cancer. However, the action of circ_0018909 in pancreatic cancer was still unclear. The expression of circ_0018909, microRNA-545-3p (miR-545-3p), and fatty acid synthase (FASN) was measured using quantitative reverse-transcriptase PCR (qRT-PCR). Cell growth, cell cycle arrest, apoptotic cells, metastasis, and epithelial to mesenchymal transition (EMT) were determined using EdU assay, flow cytometry, wound-healing assay, transwell invasion, and western blotting, respectively. The expression of the macrophage markers, including CD80, MCP-1, iNOS, and IL-6 (M1 markers), as well as CD206 and CD163 (M2 markers), was analyzed using qRT-PCR. Circ_0018909 knockdown dramatically depressed cell growth, migration, invasion, EMT, and elevated the number of apoptotic cells in pancreatic cancer cells, and repressed tumor growth in mice. Moreover, we proved that the absence of miR-545-3p rescued the action of circ_0018909 downregulation on cell growth, metastasis, apoptosis, and EMT in pancreatic cancer cells. MiR-545-3p bound to FASN and FASN overexpression hindered the impacts of miR-545-3p on the progression of pancreatic cancer. Besides this, our data demonstrated that circ_0018909 induced polarization from M0 macrophages to M2 macrophages. Circ_0018909 knockdown retarded the development of pancreatic cancer by modulating miR-545-3p to regulate FASN expression.

Simultaneous removal of phosphate and tetracycline using LaFeO3 functionalised magnetic biochar by obtained ultrasound-assisted sol-gel pyrolysis: Mechanisms and characterisation.

Excessive phosphate and tetracycline (TC) contaminants pose a serious risk to human health and the ecological environment. As such exploring the simultaneous adsorption of phosphate and TC is garnering increasing attention. In this study, an efficient lanthanum ferrate magnetic biochar (FLBC) was synthesised from crab shells using an ultrasound-assisted sol-gel method to study its performance and mechanisms for phosphate and TC adsorption in aqueous solutions in mono/bis systems. According to the Langmuir model, the developed exhibited a maximum adsorption capacity of 65.62 mg/g for phosphate and 234.1 mg/g for TC (pH:7.0 ± 0.1, and 25 °C). Further, it exhibited high resistance to interference and pH suitability. In practical swine wastewater applications, whereby the concentrations of phosphate and TC are 37 and 19.97 mg/L, respectively, the proposed material demonstrated excellent performance. In addition, electrostatic adsorption, chemical precipitation and ligand exchange were noted to be the main mechanisms for phosphate adsorption by FLBC, whereas hydrogen bonding and π-π interaction were the main adsorption mechanisms for TC adsorption. Therefore, this study successfully prepared a novel and efficient adsorbent for phosphate and TC.

Nicotine, alcohol, and caffeine use among individuals with untreated obstructive sleep apnea.

BACKGROUND: Psychoactive substance use (i.e., nicotine, alcohol, and caffeine) has substantial effects on sleep architecture in healthy individuals, but their effects in those with obstructive sleep apnea (OSA) have not been well described. We aimed to describe the association between psychoactive substance use and sleep characteristics and daytime symptoms in individuals with untreated OSA. METHODS: We performed a secondary, cross-sectional analysis of The Apnea Positive Pressure Long-term Efficacy Study (APPLES). Exposures included current smoking, alcohol and caffeine use in individuals with untreated OSA. Outcome domains included subjective and objective sleep characteristics, daytime symptoms, and comorbid conditions. Linear or logistic regression assessed the association between substance use and each domain (e.g., self-reported sleep duration, total polysomnographic sleep time, sleepiness, and anxiety). RESULTS: Of the 919 individuals with untreated OSA, 116 (12.6%) were current cigarette smokers, 585 (63.7%) were moderate or heavy alcohol users, and 769 (83.7%) were moderate or heavy caffeine users. Participants were on average 52.2±11.9 years old, 65.2% were male with a median BMI of 30.6 (IQR: 27.2, 35.9, kg/m2). Current smokers exhibited lower sleep duration (0.3 h), longer sleep latency (5 min) compared with non-smokers (all p-values < 0.05). People with heavy or moderate alcohol use exhibited more REM sleep (2.5 and 5% of total sleep time respectively), as did those with moderate caffeine use (2%, p-values < 0.05). The combined smoker plus caffeine group exhibited shorter sleep duration (0.4 h, p-value < 0.05) and higher risk for chronic pain [Odds Ratio (95%CI) = 4.83 (1.57, 14.9) compared with non-users. CONCLUSIONS: Psychoactive substance use is associated with sleep characteristics and clinically relevant correlates in people with untreated OSA. Further investigation into the effects that various substances have on this population may present opportunities to understand disease mechanisms more fully and increase the effectiveness of treatment in OSA.

Recent Advances in Manganese-Based Materials for Electrolytic Water Splitting.

Developing earth-abundant and highly effective electrocatalysts for electrocatalytic water splitting is a prerequisite for the upcoming hydrogen energy society. Recently, manganese-based materials have been one of the most promising candidates to replace noble metal catalysts due to their natural abundance, low cost, adjustable electronic properties, and excellent chemical stability. Although some achievements have been made in the past decades, their performance is still far lower than that of Pt. Therefore, further research is needed to improve the performance of manganese-based catalytic materials. In this review, we summarize the research progress on the application of manganese-based materials as catalysts for electrolytic water splitting. We first introduce the mechanism of electrocatalytic water decomposition using a manganese-based electrocatalyst. We then thoroughly discuss the optimization strategy used to enhance the catalytic activity of manganese-based electrocatalysts, including doping and defect engineering, interface engineering, and phase engineering. Finally, we present several future design opportunities for highly efficient manganese-based electrocatalysts.

Genome sequencing of Inonotus obliquus reveals insights into candidate genes involved in secondary metabolite biosynthesis.

BACKGROUND: Inonotus obliquus is an important edible and medicinal mushroom that was shown to have many pharmacological activities in preclinical trials, including anti-inflammatory, antitumor, immunomodulatory, and antioxidant effects. However, the biosynthesis of these pharmacological components has rarely been reported. The lack of genomic information has hindered further molecular characterization of this mushroom. RESULTS: In this study, we report the genome of I. obliquus using a combined high-throughput Illumina NovaSeq with Oxford Nanopore PromethION sequencing platform. The de novo assembled 38.18 Mb I. obliquus genome was determined to harbor 12,525 predicted protein-coding genes, with 81.83% of them having detectable sequence similarities to others available in public databases. Phylogenetic analysis revealed the close evolutionary relationship of I. obliquus with Fomitiporia mediterranea and Sanghuangporus baumii in the Hymenochaetales clade. According to the distribution of reproduction-related genes, we predict that this mushroom possesses a tetrapolar heterothallic reproductive system. The I. obliquus genome was found to encode a repertoire of enzymes involved in carbohydrate metabolism, along with 135 cytochrome P450 proteins. The genome annotation revealed genes encoding key enzymes responsible for secondary metabolite biosynthesis, such as polysaccharides, polyketides, and terpenoids. Among them, we found four polyketide synthases and 20 sesquiterpenoid synthases belonging to four more types of cyclization mechanism, as well as 13 putative biosynthesis gene clusters involved in terpenoid synthesis in I. obliquus. CONCLUSIONS: To the best of our knowledge, this is the first reported genome of I. obliquus; we discussed its genome characteristics and functional annotations in detail and predicted secondary metabolic biosynthesis-related genes, which provides genomic information for future studies on its associated molecular mechanism.

Advances in pharmacology, biosynthesis, and metabolic engineering of Scutellaria-specialized metabolites.

Scutellaria Linn., which belongs to the family Lamiaceae, is a commonly used medicinal plant for heat clearing and detoxification. In particular, the roots of S. baicalensis and the entire herb of S. barbata have been widely used in traditional medicine for thousands of years. The main active components of Scutellaria, including: baicalein, wogonin, norwogonin, scutellarein, and their glycosides have potential or existing drug usage. However, the wild resources of Scutellaria plants have been overexploited, and degenerated germplasm resources cannot fulfill the requirements of chemical extraction and clinical usage. Metabolic engineering and green production via microorganisms provide alternative strategies for greater efficiency in the production of natural products. Here, we review the progress of: pharmacological investigations, multi-omics, biosynthetic pathways, and metabolic engineering of various Scutellaria species and their active compounds. In addition, based on multi-omics data, we systematically analyze the phylogenetic relationships of Scutellaria and predict candidate transcription factors related to the regulation of active flavonoids. Finally, we propose the prospects of directed evolution of core enzymes and genome-assisted breeding to alleviate the shortage of plant resources of Scutellaria. This review provides important insights into the sustainable utilization and development of Scutellaria resources.

Novel processing strategies to enhance the bioaccessibility and bioavailability of functional components in wheat bran.

Dietary fiber, polysaccharides and phenols are the representative functional components in wheat bran, which have important nutritional properties and pharmacological effects. However, the most functional components in wheat bran exist in bound form with low bioaccessibility. This paper reviews these functional components, analyzes modification methods, and focuses on novel solid-state fermentation (SSF) strategies in the release of functional components. Mining efficient microbial resources from traditional fermented foods, exploring the law of material exchange between cell populations, and building a stable self-regulation co-culture system are expected to strengthen the SSF process. In addition, emerging biotechnology such as synthetic biology and genome editing are used to transform the mixed fermentation system. Furthermore, combined with the emerging physical-field pretreatment coupled with SSF strategies applied to the modification of wheat bran, which provides a theoretical basis for the high-value utilization of wheat bran and the development of related functional foods and drugs.

Genome-wide identification of key enzyme-encoding genes and the catalytic roles of two 2-oxoglutarate-dependent dioxygenase involved in flavonoid biosynthesis in Cannabis sativa L.

BACKGROUND: Flavonoids are necessary for plant growth and resistance to adversity and stress. They are also an essential nutrient for human diet and health. Among the metabolites produced in Cannabis sativa (C. sativa), phytocannabinoids have undergone extensive research on their structures, biosynthesis, and biological activities. Besides the phytocannabinoids, C. sativa is also rich in terpenes, alkaloids, and flavonoids, although little research has been conducted in this area. RESULTS: In this study, we identified 11 classes of key enzyme-encoding genes, including 56 members involved in the flavonoid biosynthesis in C. sativa, from their physical characteristics to their expression patterns. We screened the potentially step-by-step enzymes catalyzing the precursor phenylalanine to the end flavonoids using a conjoin analysis of gene expression with metabolomics from different tissues and chemovars. Flavonol synthase (FLS), belonging to the 2-oxoglutarate-dependent dioxygenase (2-ODD) superfamily, catalyzes the dihydroflavonols to flavonols. In vitro recombinant protein activity analysis revealed that CsFLS2 and CsFLS3 had a dual function in converting naringenin (Nar) to dihydrokaempferol (DHK), as well as dihydroflavonols to flavonols with different substrate preferences. Meanwhile, we found that CsFLS2 produced apigenin (Api) in addition to DHK and kaempferol when Nar was used as the substrate, indicating that CsFLS2 has an evolutionary relationship with Cannabis flavone synthase I. CONCLUSIONS: Our study identified key enzyme-encoding genes involved in the biosynthesis of flavonoids in C. sativa and highlighted the key CsFLS genes that generate flavonols and their diversified functions in C. sativa flavonoid production. This study paves the way for reconstructing the entire pathway for C. sativa's flavonols and cannflavins production in heterologous systems or plant culture, and provides a theoretical foundation for discovering new cannabis-specific flavonoids.