Subtype-Specific Association of Mitochondrial DNA Copy Number With Poststroke/TIA Outcomes in 10†241 Patients in China.

BACKGROUND: Mitochondrial DNA copy number (mtDNA-CN) is associated with the severity and mortality in patients with stroke, but the associations in different stroke subtypes remain unexplored. METHODS: We conducted an observational prospective cohort analysis on patients with ischemic stroke or transient ischemic attack enrolled in the Third China National Stroke Registry. We applied logistic models to assess the association of mtDNA-CN with functional outcome (modified Rankin Scale score, 3-6 versus 0-2) and Cox proportional hazard models to assess the association with stroke recurrence (treating mortality as a competing risk) and mortality during a 12-month follow-up, adjusting for sex, age, physical activity, National Institutes of Health Stroke Scale at admission, history of stroke and peripheral artery disease, small artery occlusion, and interleukin-6. Subgroup analyses stratified by age and stroke subtypes were conducted. RESULTS: The Third China National Stroke Registry enrolled 15 166 patients, of which 10 241 with whole-genome sequencing data were retained (mean age, 62.2 [SD, 11.2] years; 68.8% men). The associations between mtDNA-CN and poststroke/transient ischemic attack outcomes were specific to patients aged ≤65 years, with lower mtDNA-CN significantly associated with stroke recurrence in 12 months (subdistribution hazard ratio, 1.15 per SD lower mtDNA-CN [95% CI, 1.04-1.27]; P=5.2×10-3) and higher all-cause mortality in 3 months (hazard ratio, 2.19 [95% CI, 1.41-3.39]; P=5.0×10-4). Across subtypes, the associations of mtDNA-CN with stroke recurrence were specific to stroke of undetermined cause (subdistribution hazard ratio, 1.28 [95% CI, 1.11-1.48]; P=6.6×10-4). In particular, lower mtDNA-CN was associated with poorer functional outcomes in stroke of undetermined cause patients diagnosed with embolic stroke of undetermined source (odds ratio, 1.53 [95% CI, 1.20-1.94]; P=5.4×10-4), which remained significant after excluding patients with recurrent stroke (odds ratio, 1.49 [95% CI, 1.14-1.94]; P=3.0×10-3). CONCLUSIONS: Lower mtDNA-CN is associated with higher stroke recurrence rate and all-cause mortality, as well as poorer functional outcome at follow-up, among stroke of undetermined cause, embolic stroke of undetermined source, and younger patients.

Health characteristics and factors associated with transition shock in newly graduated registered nurses: a latent class analysis.

BACKGROUND: Transition shock occurs at a vulnerable time in newly graduated registered nurses' careers and has a clear impact on both newly graduated registered nurses' productivity and patient recovery outcomes. Identifying classification features of transition shock and targeting interventions to support newly graduated registered nurses is imperative. The study aimed to explore potential transition shock subgroups of newly graduated registered nurses and further explore the impact of population characteristics and two indices of health on transition shock. METHODS: A descriptive, cross-sectional design was conducted. An online questionnaire was sent via WeChat to newly graduated registered nurses who started work in 2021 at seven hospitals between August and November 2021, and 331 nurses filled out the questionnaire. Latent class analysis was used to identify the potential class of the transition shock of newly graduated registered nurses, and multinomial logistic regression analyses were used to determine the factors of potential classification. RESULTS: The study identified four classes of transition shock in newly graduated registered nurses, namely, "high transition shock", "physical fatigue-lack of knowledge", "development adaptation" and "low transition shock-worry" groups. Newly graduated registered nurses who urinated less than 4 times per day (OR = 0.051, 95% CI = 0.005-0.502) were likely to be in the "high transition shock" group. Newly graduated registered nurses who did not delay urination (OR = 4.267, 95% CI = 1.162-11.236) were more likely to belong to the "low transition shock-worry" group. Newly graduated registered nurses without sleep disturbance were more likely to be in the "physical fatigue - lack of knowledge" (OR = 3.109, 95% CI = 1.283-7.532), "development adaptation" (OR = 8.183, 95% CI = 2.447-27.066), and "low transition shock-worry" (OR = 8.749, 95% CI = 1.619-47.288) groups than in the 'high transition shock' group. CONCLUSIONS: This study highlights potential patterns of transition shock among newly graduated registered nurses. Two indices of health, namely, delayed urination and sleep disturbance, can predict the subgroups of newly graduated registered nurses with transition shock.

Identification of a Prunus MAX1 homolog as a unique strigol synthase.

Strigol is the first identified and one of the most important strigolactones (SLs), but the biosynthetic pathway remains elusive. We functionally identified a strigol synthase (cytochrome P450 711A enzyme) in the Prunus genus through rapid gene screening in a set of SL-producing microbial consortia, and confirmed its unique catalytic activity (catalyzing multistep oxidation) through substrate feeding experiments and mutant analysis. We also reconstructed the biosynthetic pathway of strigol in Nicotiana benthamiana and reported the total biosynthesis of strigol in the Escherichia coli-yeast consortium, from the simple sugar xylose, which paves the way for large-scale production of strigol. As proof of concept, strigol and orobanchol were detected in Prunus persica root extrudes. This demonstrated a successful prediction of metabolites produced in plants through gene function identification, highlighting the importance of deciphering the sequence-function correlation of plant biosynthetic enzymes to more accurately predicate plant metabolites without metabolic analysis. This finding revealed the evolutionary and functional diversity of CYP711A (MAX1) in SL biosynthesis, which can synthesize different stereo-configurations of SLs (strigol- or orobanchol-type). This work again emphasizes the importance of microbial bioproduction platform as an efficient and handy tool to functionally identify plant metabolism.

A transferrable and integrative type I-F Cascade for heterologous genome editing and transcription modulation.

The Class 1 type I CRISPR-Cas systems represent the most abundant and diverse CRISPR systems in nature. However, their applications for generic genome editing have been hindered due to difficulties of introducing the class-specific, multi-component effectors (Cascade) in heterologous hosts for functioning. Here we established a transferrable Cascade system that enables stable integration and expression of a highly active type I-F Cascade in heterologous bacterial hosts for various genetic exploitations. Using the genetically recalcitrant Pseudomonas species as a paradigm, we show that the transferred Cascade displayed substantially higher DNA interference activity and greater editing capacity than both the integrative and plasmid-borne Cas9 systems, and enabled deletion of large fragments such as the 21-kb integrated cassette with efficiency and simplicity. An advanced I-F-λred system was further developed to enable editing in genotypes with poor homologous recombination capacity, clinical isolates lacking sequence information, and cells containing anti-CRISPR elements Acrs. Lastly, an 'all-in-one' I-F Cascade-mediated CRISPRi platform was developed for transcription modulation by simultaneous introduction of the Cascade and the programmed mini-CRISPR array in one-step. This study provides a framework for expanding the diverse type I Cascades for widespread, heterologous genome editing and establishment of editing techniques in 'non-model' bacterial species.

Metal-Oxide Heterojunction: From Material Process to Neuromorphic Applications.

As technologies like the Internet, artificial intelligence, and big data evolve at a rapid pace, computer architecture is transitioning from compute-intensive to memory-intensive. However, traditional von Neumann architectures encounter bottlenecks in addressing modern computational challenges. The emulation of the behaviors of a synapse at the device level by ionic/electronic devices has shown promising potential in future neural-inspired and compact artificial intelligence systems. To address these issues, this review thoroughly investigates the recent progress in metal-oxide heterostructures for neuromorphic applications. These heterostructures not only offer low power consumption and high stability but also possess optimized electrical characteristics via interface engineering. The paper first outlines various synthesis methods for metal oxides and then summarizes the neuromorphic devices using these materials and their heterostructures. More importantly, we review the emerging multifunctional applications, including neuromorphic vision, touch, and pain systems. Finally, we summarize the future prospects of neuromorphic devices with metal-oxide heterostructures and list the current challenges while offering potential solutions. This review provides insights into the design and construction of metal-oxide devices and their applications for neuromorphic systems.

RAGE-TLR4 Crosstalk Is the Key Mechanism by Which High Glucose Enhances the Lipopolysaccharide-Induced Inflammatory Response in Primary Bovine Alveolar Macrophages.

The receptor of advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4) are important receptors for inflammatory responses induced by high glucose (HG) and lipopolysaccharide (LPS) and show crosstalk phenomena in inflammatory responses. However, it is unknown whether RAGE and TLR4 can influence each other's expression through a crosstalk mechanism and whether the RAGE-TLR4 crosstalk related to the molecular mechanism of HG enhances the LPS-induced inflammatory response. In this study, the implications of LPS with multiple concentrations (0, 1, 5, and 10 µg/mL) at various treatment times (0, 3, 6, 12, and 24 h) in primary bovine alveolar macrophages (BAMs) were explored. The results showed that a 5 µg/mL LPS treatment at 12 h had the most significant increment on the pro-inflammatory cytokine interleukin 1ß (IL-1ß), IL-6, and tumor necrosis factor (TNF)-α levels in BAMs (p < 0.05) and that the levels of TLR4, RAGE, MyD88, and NF-κB p65 mRNA and protein expression were upregulated (p < 0.05). Then, the effect of LPS (5 µg/mL) and HG (25.5 mM) co-treatment in BAMs was explored. The results further showed that HG significantly enhanced the release of IL-1ß, IL-6, and TNF-α caused by LPS in the supernatant (p < 0.01) and significantly increased the levels of RAGE, TLR4, MyD88, and NF-κB p65 mRNA and protein expression (p < 0.01). Pretreatment with FPS-ZM1 and TAK-242, the inhibitors of RAGE and TLR4, significantly alleviated the HG + LPS-induced increment of RAGE, TLR4, MyD88, and NF-κB p65 mRNA and protein expression in the presence of HG and LPS (p < 0.01). This study showed that RAGE and TLR4 affect each other's expression through crosstalk during the combined usage of HG and LPS and synergistically activate the MyD88/NF-κB signaling pathway to promote the release of pro-inflammatory cytokines in BAMs.

The mediating role of cognitive emotion regulation in the relationship between self-concealment and quality of life among breast cancer chemotherapy patients.

PURPOSE: This study aimed to explore whether self-concealment (SC) affects the quality of life (QOL), and whether cognitive emotion regulation (CER) mediates the relationship between SC and QOL among breast cancer chemotherapy patients. METHODS: This cross-sectional study was conducted among 228 breast cancer chemotherapy patients from November 2021 to March 2022 in Anhui Province, China. Data were collected using the Self-Concealment Scale, Cognitive Emotion Regulation Questionnaire, and Short Form 36 Questionnaire. Descriptive statistics, independent-sample t test, one-way analysis of variance, and structural equation modeling were used to explore associations among SC, CER, and QOL. RESULTS: QOL levels differed significantly by participant age, monthly per capita household income and home location. SC was negatively correlated with QOL. SSC was negatively correlated with adaptive-CER strategies and positively correlated with maladaptive-CER strategies. Adaptive-CER strategies were positively correlated with QOL. Maladaptive-CER strategies were negatively correlated with QOL. CER fully mediated the association between SC and QOL in breast cancer chemotherapy patients. CONCLUSION: Nursing staff should help breast cancer chemotherapy patients reduce the use of maladaptive-CER strategies in the care of patients in the future. Helping patients reduce SC is more conductive to improving the QOL of breast cancer chemotherapy patients.

Research progress on the correlation between transforming growth factor-ß level and symptoms of depression. / è½¬åŒ–ç”Ÿé•¿å› å­-ßæ°´å¹³ä¸ŽæŠ‘éƒç—‡ç–—æ•ˆç›¸å ³.

Transforming growth factor (TGF)-ß is a group of cytokines with anti-inflammatory effects in the TGF family, which participates in the development of stress and depression-related mechanisms, and plays roles in the regulation of inflammatory response in depression and the recovery of various cytokine imbalances. The core symptoms of depression is associated with TGF-ß level, and the psychological symptoms of depression are related to TGF-ß gene polymorphism. Various antidepressants may up-regulate TGF-ß level through the complex interaction between neurotransmitters and inflammatory factors, inhibiting inflammatory response and regulating cytokine imbalance to improve depressive symptoms. Studies have shown that recombinant TGF-ß1 protein has beneficial effects in mouse depression models, indicating TGF-ß1 might be a potential therapeutic target for depression and nasal sprays having the advantage of being fast acting delivery method. This article reviews the research progress on dynamic changes of TGF-ß level before and after depression treatment and the application of TGF-ß level as an indicator for the improvement of depressive symptoms. We provide ideas for the development of new antidepressants and for the evaluation of the treatment efficacy in depression.

Discovery of triterpenoids as potent dual inhibitors of pancreatic lipase and human carboxylesterase 1.

Pancreatic lipase (PL) is a well-known key target for the prevention and treatment of obesity. Human carboxylesterase 1A (hCES1A) has become an important target for the treatment of hyperlipidaemia. Thus, the discovery of potent dual-target inhibitors based on PL and hCES1A hold great potential for the development of remedies for treating related metabolic diseases. In this study, a series of natural triterpenoids were collected and the inhibitory effects of these triterpenoids on PL and hCES1A were determined using fluorescence-based biochemical assays. It was found that oleanolic acid (OA) and ursolic acid (UA) have the excellent inhibitory effects against PL and hCES1A, and highly selectivity over hCES2A. Subsequently, a number of compounds based on the OA and UA skeletons were synthesised and evaluated. Structure-activity relationship (SAR) analysis of these compounds revealed that the acetyl group at the C-3 site of UA (compound 41) was very essential for both PL and hCES1A inhibition, with IC50 of 0.75 µM and 0.014 µM, respectively. In addition, compound 39 with 2-enol and 3-ketal moiety of OA also has strong inhibitory effects against both PL and hCES1A, with IC50 of 2.13 µM and 0.055 µM, respectively. Furthermore, compound 39 and 41 exhibited good selectivity over other human serine hydrolases including hCES2A, butyrylcholinesterase (BChE) and dipeptidyl peptidase IV (DPP-IV). Inhibitory kinetics and molecular docking studies demonstrated that both compounds 39 and 41 were effective mixed inhibitors of PL, while competitive inhibitors of hCES1A. Further investigations demonstrated that both compounds 39 and 41 could inhibit adipocyte adipogenesis induced by mouse preadipocytes. Collectively, we found two triterpenoid derivatives with strong inhibitory ability on both PL and hCES1A, which can be served as promising lead compounds for the development of more potent dual-target inhibitors targeting on PL and hCES1A.

Harnessing the type I CRISPR-Cas systems for genome editing in prokaryotes.

Genetic analysis is crucial to the understanding, exploitation, and control of microorganisms. The advent of CRISPR-Cas-based genome-editing techniques, particularly those mediated by the single-effector (Cas9 and Cas12a) class 2 CRISPR-Cas systems, has revolutionized the genetics in model eukaryotic organisms. However, their applications in prokaryotes are rather limited, largely owing to the exceptional diversity of DNA homeostasis in microorganisms and severe cytotoxicity of overexpressing these nuclease proteins in certain genotypes. Remarkably, CRISPR-Cas systems belonging to different classes and types are continuously identified in prokaryotic genomes and serve as a deep reservoir for expansion of the CRISPR-based genetic toolkits. ~90% of the CRISPR-Cas systems identified so far belong to the class 1 system which hinges on multi-protein effector complexes for DNA interference. Harnessing these widespread native CRISPR-Cas systems for 'built-in' genome editing represents an emerging and powerful genetic tool in prokaryotes, especially in the genetically recalcitrant non-model species and strains. In this progress review, we introduce the general workflow of this emerging editing platform and summarize its establishment in a growing number of prokaryotes by harnessing the most widespread, diverse type I CRISPR-Cas systems present in their genomes. We also discuss the various factors affecting the success and efficiency of this editing platform and the corresponding solutions.

Characterizing the hyper- and hypometabolism in temporal lobe epilepsy using multivariate machine learning.

Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy, presenting both structural and metabolic abnormalities in the ipsilateral mesial temporal lobe. While it has been demonstrated that the metabolic abnormalities in MTLE actually extend beyond the epileptogenic zone, how such multidimensional information is associated with the diagnosis of MTLE remains to be tested. Here, we explore the whole-brain metabolic patterns in 23 patients with MTLE and 24 healthy controls using [18 F]fluorodeoxyglucose PET imaging. Based on a multivariate machine learning approach, we demonstrate that the brain metabolic patterns can discriminate patients with MTLE from controls with a superior accuracy (>95%). Importantly, voxels showing the most extreme contributing weights to the classification (i.e., the most important regional predictors) distribute across both hemispheres, involving both ipsilateral negative weights over the anterior part of lateral and medial temporal lobe, posterior insula, and lateral orbital frontal gyrus, and contralateral positive weights over the anterior frontal lobe, temporal lobe, and lingual gyrus. Through region-of-interest analyses, we verify that in patients with MTLE, the negatively weighted regions are hypometabolic, and the positively weighted regions are hypermetabolic, compared to controls. Interestingly, despite that both hypo- and hypermetabolism have mutually contributed to our model, they may reflect different pathological and/or compensative responses. For instance, patients with earlier age at epilepsy onset present greater hypometabolism in the ipsilateral inferior temporal gyrus, while we find no evidence of such association with hypermetabolism. In summary, quantitative models utilizing multidimensional brain metabolic information may provide additional assistance to presurgical workups in TLE.

Exploring the potential of engineering polygalacturonase-inhibiting protein as an ecological, friendly, and nontoxic pest control agent.

In plants, polygalacturonase-inhibiting proteins (PGIPs) play critical roles for resistance to fungal disease by inhibiting the pectin-depolymerizing activity of endopolygalacturonases (PGs), one type of enzyme secreted by pathogens that compromises plant cell walls and leaves the plant susceptible to disease. Here, the interactions between PGIPs from Phaseolus vulgaris (PvPGIP1 and PvPGIP2) and PGs from Aspergillus niger (AnPG2), Botrytis cinerea (BcPG1 and BcPG2), and Fusarium moniliforme (FmPG3) were reconstituted through a yeast two hybrid (Y2H) system to investigate the inhibition efficiency of various PvPGIP1 and 2 truncations and mutants. We found that tPvPGIP2_5-8, which contains LRR5 to LRR8 and is only one-third the size of the full length peptide, exhibits the same level of interactions with AnPG and BcPGs as the full length PvPGIP2 via Y2H. The inhibitory activities of tPvPGIP2_5-8 on the growth of A. niger and B. cinerea were then examined and confirmed on pectin agar. On pectin assays, application of both full length PvPGIP2 and tPvPGIP2_5-8 clearly slows down the growth of A. niger and B. cinerea. Investigation on the sequence-function relationships of PGIP utilizing a combination of site directed mutagenesis and a variety of peptide truncations suggests that LRR5 could have the most essential structural feature for the inhibitory activities, and may be a possible target for the future engineering of PGIP with enhanced activity. This study highlights the potential of plant-derived PGIPs as a candidate for future in planta evaluation as a pest control agent.

Fabrication of the Polymersomes with Unique and Even Nonequilibrium Morphologies.

Herein, efficient fabrication of polymersomes that have unique and nonequilibrium morphologies is reported. Starting from preparing big polymeric vesicles sized around 2 µm with a flexible but crosslinkable structure, a controllable morphological transformation process from the vesicles via prolate vesicles and the pearl-chain-like structure, which are the two intermediate structures, to vesicle-end-capped tubes is conducted. Significantly, each of the intermediates is a regular polymersome and occupies a distinct phase space in the transformation process and thus can be separately processed and prepared. By crosslinking the structures, respectively, regular polymersomes with unique but stable morphologies are fabricated. Furthermore, the 1D polymersomes contain narrow necks. These narrow necks are sensitive to ultrasound vibration and broken by gentle ultrasound treatment to form regular open-ended tubes and open-ended vesicles, which are nonequilibrium but stable morphologies and difficult to prepare by existing methods.

Complete biosynthesis of noscapine and halogenated alkaloids in yeast.

Microbial biosynthesis of plant natural products from simple building blocks is a promising approach toward scalable production and modification of high-value compounds. The pathway for biosynthesis of noscapine, a potential anticancer compound, from canadine was recently elucidated as a 10-gene cluster from opium poppy. Here we demonstrate the de novo production of noscapine in Saccharomyces cerevisiae, through the reconstruction of a biosynthetic pathway comprising over 30 enzymes from plants, bacteria, mammals, and yeast itself, including 7 plant endoplasmic reticulum (ER)-localized enzymes. Optimization directed to tuning expression of pathway enzymes, host endogenous metabolic pathways, and fermentation conditions led to an over 18,000-fold improvement from initial noscapine titers to ∼2.2 mg/L. By feeding modified tyrosine derivatives to the optimized noscapine-producing strain we further demonstrated microbial production of halogenated benzylisoquinoline alkaloids. This work highlights the potential for microbial biosynthetic platforms to support the synthesis of valuable and novel alkaloid compounds, which can advance alkaloid-based drug discovery and development.

From Molecular Reconstruction of Mesoscopic Functional Conductive Silk Fibrous Materials to Remote Respiration Monitoring.

Turning insulating silk fibroin materials into conductive ones turns out to be the essential step toward achieving active silk flexible electronics. This work aims to acquire electrically conductive biocompatible fibers of regenerated Bombyx mori silk fibroin (SF) materials based on carbon nanotubes (CNTs) templated nucleation reconstruction of silk fibroin networks. The electronical conductivity of the reconstructed mesoscopic functional fibers can be tuned by the density of the incorporated CNTs. It follows that the hybrid fibers experience an abrupt increase in conductivity when exceeding the percolation threshold of CNTs >35 wt%, which leads to the highest conductivity of 638.9 S m-1 among organic-carbon-based hybrid fibers, and 8 times higher than the best available materials of the similar types. In addition, the silk-CNT mesoscopic hybrid materials achieve some new functionalities, i.e., humidity-responsive conductivity, which is attributed to the coupling of the humidity inducing cyclic contraction of SFs and the conductivity of CNTs. The silk-CNT materials, as a type of biocompatible electronic functional fibrous material for pressure and electric response humidity sensing, are further fabricated into a smart facial mask to implement respiration condition monitoring for remote diagnosis and medication.

Yeast as a promising heterologous host for steroid bioproduction.

With the rapid development of synthetic biology and metabolic engineering technologies, yeast has been generally considered as promising hosts for the bioproduction of secondary metabolites. Sterols are essential components of cell membrane, and are the precursors for the biosynthesis of steroid hormones, signaling molecules, and defense molecules in the higher eukaryotes, which are of pharmaceutical and agricultural significance. In this mini-review, we summarize the recent engineering efforts of using yeast to synthesize various steroids, and discuss the structural diversity that the current steroid-producing yeast can achieve, the challenge and the potential of using yeast as the bioproduction platform of various steroids from higher eukaryotes.

Uncoupled Quorum Sensing Modulates the Interplay of Virulence and Resistance in a Multidrug-Resistant Clinical Pseudomonas aeruginosa Isolate Belonging to the MLST550 Clonal Complex.

Pseudomonas aeruginosa is a prevalent and pernicious pathogen equipped with extraordinary capabilities both to infect the host and to develop antimicrobial resistance (AMR). Monitoring the emergence of AMR high-risk clones and understanding the interplay of their pathogenicity and antibiotic resistance is of paramount importance to avoid resistance dissemination and to control P. aeruginosa infections. In this study, we report the identification of a multidrug-resistant (MDR) P. aeruginosa strain PA154197 isolated from a blood stream infection in Hong Kong. PA154197 belongs to a distinctive MLST550 clonal complex shared by two other international P. aeruginosa isolates VW0289 and AUS544. Comparative genome and transcriptome analysis of PA154197 with the reference strain PAO1 led to the identification of a variety of genetic variations in antibiotic resistance genes and the hyperexpression of three multidrug efflux pumps MexAB-OprM, MexEF-OprN, and MexGHI-OpmD in PA154197. Unexpectedly, the strain does not display a metabolic cost and a compromised virulence compared to PAO1. Characterizing its various physiological and virulence traits demonstrated that PA154197 produces a substantially higher level of the P. aeruginosa major virulence factor pyocyanin (PYO) than PAO1, but it produces a decreased level of pyoverdine and displays decreased biofilm formation compared with PAO1. Further analysis revealed that the secondary quorum-sensing (QS) system Pqs that primarily controls the PYO production is hyperactive in PA154197 independent of the master QS systems Las and Rhl. Together, these investigations disclose a unique, uncoupled QS mediated pathoadaptation mechanism in clinical P. aeruginosa which may account for the high pathogenic potentials and antibiotic resistance in the MDR isolate PA154197.

RepLong: de novo repeat identification using long read sequencing data.

Motivation: The identification of repetitive elements is important in genome assembly and phylogenetic analyses. The existing de novo repeat identification methods exploiting the use of short reads are impotent in identifying long repeats. Since long reads are more likely to cover repeat regions completely, using long reads is more favorable for recognizing long repeats. Results: In this study, we propose a novel de novo repeat elements identification method namely RepLong based on PacBio long reads. Given that the reads mapped to the repeat regions are highly overlapped with each other, the identification of repeat elements is equivalent to the discovery of consensus overlaps between reads, which can be further cast into a community detection problem in the network of read overlaps. In RepLong, we first construct a network of read overlaps based on pair-wise alignment of the reads, where each vertex indicates a read and an edge indicates a substantial overlap between the corresponding two reads. Secondly, the communities whose intra connectivity is greater than the inter connectivity are extracted based on network modularity optimization. Finally, representative reads in each community are extracted to form the repeat library. Comparison studies on Drosophila melanogaster and human long read sequencing data with genome-based and short-read-based methods demonstrate the efficiency of RepLong in identifying long repeats. RepLong can handle lower coverage data and serve as a complementary solution to the existing methods to promote the repeat identification performance on long-read sequencing data. Availability and implementation: The software of RepLong is freely available at https://github.com/ruiguo-bio/replong. Contact: ywsun@szu.edu.cn or zhuzx@szu.edu.cn. Supplementary information: Supplementary data are available at Bioinformatics online.

Synthetic biology strategies toward heterologous phytochemical production.

Covering: 2006 to 2018 Phytochemicals are important sources for the discovery and development of agricultural and pharmaceutical compounds, such as pesticides and medicines. However, these compounds are typically present in low abundance in nature, and the biosynthetic pathways for most phytochemicals are not fully elucidated. Heterologous production of phytochemicals in plant, bacterial, and yeast hosts has been pursued as a potential approach to address sourcing issues associated with many valuable phytochemicals, and more recently has been utilized as a tool to aid in the elucidation of plant biosynthetic pathways. Due to the structural complexity of certain phytochemicals and the associated biosynthetic pathways, reconstitution of plant pathways in heterologous hosts can encounter numerous challenges. Synthetic biology approaches have been developed to address these challenges in areas such as precise control over heterologous gene expression, improving functional expression of heterologous enzymes, and modifying central metabolism to increase the supply of precursor compounds into the pathway. These strategies have been applied to advance plant pathway reconstitution and phytochemical production in a wide variety of heterologous hosts. Here, we review synthetic biology strategies that have been recently applied to advance complex phytochemical production in heterologous hosts.

Triple Noncovalent-Interaction-Containing Supramolecular Polymer Vesicle Chemosensors with Dynamically Tunable Detection Ranges.

Chemosensors (CSs) with dynamically tunable detection ranges have important significance for their expansion in practical applications; however, most CSs possess an unchangeable detection limit. In this work, we report the first example of a supramolecular polymer vesicle (SPV) chemosensor with a dynamically tunable detection range. SPVs containing porphyrin (PP) moieties and ß-cyclodextrin (ß-CD)/azobenzene (Azo) host-guest interactions were first constructed. The obtained SPVs were used to detect Zn2+ with a high selectivity and sensitivity over a wide detection limit range of 8.67×10-9 to 1.99×10-11 under UV light irradiation. The corresponding sensing mechanism was attributed to the synergistic effects of the triple noncovalent interactions, including the metal-ligand coordination of PP/Zn2+ and the double host-guest interactions of ß-CD/Azo and ß-CD/PP.