Genome sequencing and comparative genomics reveal insights into pathogenicity and evolution of Fusarium zanthoxyli, the causal agent of stem canker in prickly ash.

BACKGROUND: Fusarium zanthoxyli is a destructive pathogen causing stem canker in prickly ash, an ecologically and economically important forest tree. However, the genome lack of F. zanthoxyli has hindered research on its interaction with prickly ash and the development of precise control strategies for stem canker. RESULTS: In this study, we sequenced and annotated a relatively high-quality genome of F. zanthoxyli with a size of 43.39 Mb, encoding 11,316 putative genes. Pathogenicity-related factors are predicted, comprising 495 CAZymes, 217 effectors, 156 CYP450s, and 202 enzymes associated with secondary metabolism. Besides, a comparative genomics analysis revealed Fusarium and Colletotrichum diverged from a shared ancestor approximately 141.1 ~ 88.4 million years ago (MYA). Additionally, a phylogenomic investigation of 12 different phytopathogens within Fusarium indicated that F. zanthoxyli originated approximately 34.6 ~ 26.9 MYA, and events of gene expansion and contraction within them were also unveiled. Finally, utilizing conserved domain prediction, the results revealed that among the 59 unique genes, the most enriched domains were PnbA and ULP1. Among the 783 expanded genes, the most enriched domains were PKc_like kinases and those belonging to the APH_ChoK_Like family. CONCLUSION: This study sheds light on the genetic basis of F. zanthoxyli's pathogenicity and evolution which provides valuable information for future research on its molecular interactions with prickly ash and the development of effective strategies to combat stem canker.

Reactive oxygen species-responsive polymer drug delivery systems.

Applying reactive polymer materials sensitive to biological stimuli has recently attracted extensive research interest. The special physiological effects of reactive oxygen species (ROS) on tumors or inflammation and the application of ROS-responsive polymers as drug-delivery systems in organisms have attracted much attention. ROS is a vital disease signal molecule, and the unique accumulation of ROS-responsive polymers in pathological sites may enable ROS-responsive polymers to deliver payload (such as drugs, ROS-responsive prodrugs, and gene therapy fragments) in a targeted fashion. In this paper, the research progress of ROS-responsive polymers and their application in recent years were summarized and analyzed. The research progress of ROS-responsive polymers was reviewed from the perspective of nanoparticle drug delivery systems, multi-responsive delivery systems, and ROS-responsive hydrogels. It is expected that our work will help understand the future development trends in this field.

Functional Macromolecular Adhesives for Bone Fracture Healing.

Compared with traditional internal fixation devices, bone adhesives are expected to exhibit remarkable advantages, such as improved fixation of comminuted fractures and maintained spatial location of fractured scattered bone pieces in treating bone injuries. In this review, different bone adhesives are summarized from the aspects of bone tissue engineering, and the applications of bone adhesives are emphasized. The concepts of "liquid scaffold" and "liquid plate" are proposed to summarize two different research directions of bone adhesives. Furthermore, significant advances of bone adhesives in recent years in mechanical strength, osseointegration, osteoconductivity, and osteoinductivity are discussed. We conclude this topic by providing perspectives on the state-of-the-art research progress and future development trends of bone adhesives. We hope this review will provide a comprehensive summary of bone adhesives and inspire more extensive and in-depth research on this subject.

Parasite-Derived Excretory-Secretory Products Alleviate Gut Microbiota Dysbiosis and Improve Cognitive Impairment Induced by a High-Fat Diet.

High-fat (HF) diet-induced neuroinflammation and cognitive decline in humans and animals have been associated with microbiota dysbiosis via the gut-brain axis. Our previous studies revealed that excretory-secretory products (ESPs) derived from the larval Echinococcus granulosus (E. granulosus) function as immunomodulators to reduce the inflammatory response, while the parasitic infection alleviates metabolic disorders in the host. However, whether ESPs can improve cognitive impairment under obese conditions remain unknown. This study aimed to investigate the effects of E. granulosus-derived ESPs on cognitive function and the microbiota-gut-brain axis in obese mice. We demonstrated that ESPs supplementation prevented HF diet-induced cognitive impairment, which was assessed behaviorally by nest building, object location, novel object recognition, temporal order memory, and Y-maze memory tests. In the hippocampus (HIP) and prefrontal cortex (PFC), ESPs suppressed neuroinflammation and HF diet-induced activation of the microglia and astrocytes. Moreover, ESPs supplementation improved the synaptic ultrastructural impairments and increased both pre- and postsynaptic protein levels in the HIP and PFC compared to the HF diet-treated group. In the colon, ESPs reversed the HF diet-induced gut barrier dysfunction, increased the thickness of colonic mucus, upregulated the expression of zonula occludens-1 (ZO-1), attenuated the translocation of bacterial endotoxins, and decreased the colon inflammation. Notably, ESPs supplementation alleviated the HF diet-induced microbiota dysbiosis. After clarifying the role of antibiotics in obese mice, we found that broad-spectrum antibiotic intervention abrogated the effects of ESPs on improving the gut microbiota dysbiosis and cognitive decline. Overall, the present study revealed for the first time that the parasite-derived ESPs alleviate gut microbiota dysbiosis and improve cognitive impairment induced by a high-fat diet. This finding suggests that parasite-derived molecules may be used to explore novel drug candidates against obesity-associated neurodegenerative diseases.

Associations of Serum Cytokine Levels and Interleukin-6-572C/G Polymorphism with Myelin Damage in Chinese Children with Autism Spectrum Disorder.

Increasing evidence suggests that immunological disturbances and abnormalities in axonal myelination are involved in the pathophysiology of autism spectrum disorder (ASD). The present study aimed to determine the role of cytokines in myelin damage in Chinese children with ASD and the role of cytokine dysregulation, myelin damage, and cytokine polymorphisms in ASD in Chinese children. The present case-control study included 98 ASD subjects and 252 typically developing (TD) controls; the levels of serum cytokines and myelin basic protein (MBP) were determined using enzyme-linked immunosorbent assay. Cytokine polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Autistic clinical manifestations were assessed by the Childhood Autism Rating Scale (CARS). The results showed that serum levels of interleukin (IL)-1ß, IL-2R, IL-6, IL-8, and MBP were higher in children with ASD compared with those in TD children. In individuals with ASD, serum MBP level was significantly positively associated with the CARS total score, and serum levels of IL-1ß, IL-2R, IL-6, and MBP demonstrated positive correlations. The data identified IL-6*MBP as a factor that influenced the risk of ASD, and IL-2R*MBP was identified as a factor that influenced symptom severity, which influenced auxiliary diagnosis of ASD. The presence of the interleukin-6-572CC genotype was associated with significantly higher serum levels of IL-6 and MBP but did not influence the risk and symptom severity of ASD. Therefore, the results suggested inflammatory responses and myelin damage in Chinese children with ASD. Cytokine dysregulation influenced myelin damage in ASD; moreover, the interactions of the cytokines and myelin damage influenced the risk and symptom severity of ASD. The IL-6-572C/G genotypes may be associated with myelin damage in ASD by influencing the circulating level of IL-6.

Comprehensive evaluation of candidate reference genes for quantitative real-time PCR-based analysis in Caucasian clover.

The forage species Caucasian clover (Trifolium ambiguum M. Bieb.), a groundcover plant, is resistant to both cold and drought. However, reference genes for qRT-PCR-based analysis of Caucasian clover are lacking. In this study, 12 reference genes were selected on the basis of transcriptomic data. These genes were used to determine the most stably expressed genes in various organs of Caucasian clover under cold, salt and drought stress for qRT-PCR-based analysis. Reference gene stability was analyzed by geNorm, NormFinder, BestKeeper, the ∆Ct method and RefFinder. Under salt stress, RCD1 and PPIL3 were the most stable reference genes in the leaves, and NLI1 and RCD1 were the most stable references genes in the roots. Under low-temperature stress, APA and EFTu-GTP were the most stable reference genes in the leaves, and the RCD1 and NLI2 genes were highly stable in the roots. Under 10% PEG-6000 stress, NLI1 and NLI2 were highly stable in the leaves, and RCD1 and PPIL3 were the most stable in the roots. Overall, RCD1 and NLI2 were the most stable reference genes in organs under normal conditions and across all samples. The most and least stable reference genes were validated by assessing their appropriateness for normalization via WRKY genes.

Synthesis of spirocyclic Δ4-isoxazolines via [3 + 2] cycloaddition of indanone-derived ketonitrones with alkynes.

A [3 + 2] cycloaddition of indanone-derived nitrones and alkynes under mild conditions is developed, allowing facile synthesis of spirocyclicindenyl isoxazolines with structural diversity. The sequential protocol of generated in situ ketonitrone from unsaturated ketones and N-alkylhydroxylamines is also achieved successfully, affording the desired products in considerable yield with moderate to good diastereoselectivity. Moreover, the spirocyclic product can be conveniently transformed into indenyl-based allylic alcohol and enamide.

Microarray Analysis of lncRNA and mRNA Reveals Enhanced Lipolysis Along With Metabolic Remodeling in Mice Infected With Larval Echinococcus granulosus.

Parasitic infection improves metabolic homeostasis in "western diet"-induced obesity through the regulation of adipogenesis. However, the underlying mechanism is not yet fully understood. Using microarray analysis, this study investigated the long non-coding RNA (lncRNA) and messenger RNA (mRNA) profiles of subcutaneous adipose tissues from mice infected with Echinococcus granulosus protoscoleces. A total of 1052 mRNA (541 upregulated, 511 downregulated) and 220 lncRNA (126 upregulated, 94 downregulated) transcripts were differentially expressed (fold change ≥2, P < 0.05) in the infected subcutaneous adipose tissues. When compared with the control group, the infected mice showed a decrease in adipose tissue mass and a reduction in adipocyte size. Indirect calorimetry revealed the change in the energy metabolism after infection, characterized by a lower CO2 production and O2 consumption, a sharp decline in carbohydrate oxidation, and a slight increase in fat oxidation. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that the parasitic infection reprogrammed a complex metabolic network. Notably, "lipoxygenase" and "arginine and proline metabolism" pathways were significantly upregulated while "glycolysis," "tricarboxylic acid cycle," "de novo lipogenesis," and "lipid droplet" pathways were dramatically downregulated. In addition, several key lncRNAs were associated with insulin resistance and adipocyte differentiation. Overall, the present study suggested that E. granulosus infection could enhance lipolysis. Thus, our findings provide novel insights into parasite-mediated metabolic homeostasis, and into the mechanism of hypertrophic adipocytes in obesity.

Revealing the full-length transcriptome of caucasian clover rhizome development.

BACKGROUND: Caucasian clover (Trifolium ambiguum M. Bieb.) is a strongly rhizomatous, low-crowned perennial leguminous and ground-covering grass. The species may be used as an ornamental plant and is resistant to cold, arid temperatures and grazing due to a well-developed underground rhizome system and a strong clonal reproduction capacity. However, the posttranscriptional mechanism of the development of the rhizome system in caucasian clover has not been comprehensively studied. Additionally, a reference genome for this species has not yet been published, which limits further exploration of many important biological processes in this plant. RESULT: We adopted PacBio sequencing and Illumina sequencing to identify differentially expressed genes (DEGs) in five tissues, including taproot (T1), horizontal rhizome (T2), swelling of taproot (T3), rhizome bud (T4) and rhizome bud tip (T5) tissues, in the caucasian clover rhizome. In total, we obtained 19.82 GB clean data and 80,654 nonredundant transcripts were analysed. Additionally, we identified 78,209 open reading frames (ORFs), 65,227 coding sequences (CDSs), 58,276 simple sequence repeats (SSRs), 6821 alternative splicing (AS) events, 2429 long noncoding RNAs (lncRNAs) and 4501 putative transcription factors (TFs) from 64 different families. Compared with other tissues, T5 exhibited more DEGs, and co-upregulated genes in T5 are mainly annotated as involved in phenylpropanoid biosynthesis. We also identified betaine aldehyde dehydrogenase (BADH) as a highly expressed gene-specific to T5. A weighted gene co-expression network analysis (WGCNA) of transcription factors and physiological indicators were combined to reveal 11 hub genes (MEgreen-GA3), three of which belong to the HB-KNOX family, that are up-regulated in T3. We analysed 276 DEGs involved in hormone signalling and transduction, and the largest number of genes are associated with the auxin (IAA) signalling pathway, with significant up-regulation in T2 and T5. CONCLUSIONS: This study contributes to our understanding of gene expression across five different tissues and provides preliminary insight into rhizome growth and development in caucasian clover.

Tackling autoimmunity with nanomedicines.

Tolerogenic immunotherapy aims to blunt pathogenic inflammation without affecting systemic immunity. However, the anti-inflammatory drugs and immunosuppressive biologics that are used in the clinic usually result in nonspecific immune cell suppression and off-target toxicity. For this reason, strategies have been developed to induce antigen-specific immune tolerance through the delivery of disease-relevant antigens by nanocarriers as a benefit of their preferential internalization by antigen-presenting cells. Herein, we discuss the recent advances in the nanotechnology-based antigen-specific tolerance approaches. Some of these designs are based on nanoparticles delivering antigens and immunoregulatory agents to modulate antigen-presenting pathways, while others directly target T cells via nanoparticle-based artificial antigen-presenting cells. These antigen-specific therapies are hoped to replace systemic immune suppression and provide long-term disease remission.

Temperature-dependent gelation process in colloidal dispersions by diffusing wave spectroscopy.

Temperature-dependent microrheology of a concentrated charge-stabilized poly(methyl methacrylate) colloidal dispersion with different salt concentrations was investigated by diffusing wave spectroscopy in backscattering mode. The critical temperature where the system undergoes aggregation and gelation depends upon the particle volume fraction or salt concentration. The viscoelastic properties of the systems have been discussed using Maxwell and Kelvin-Voigt models. Temperature-dependent crossover (G' = G″) frequency has been used to calculate activation energies representing a critical energy of interaction of gel formation.