Search

Abstract Potato black scurf caused by Rhizoctonia solani Kühn is widespread worldwide. The exploration and analysis of the infection mechanism of Rhizoctonia solani Kühn has important scientific significance to enhance the disease resistance of potato and other horticultural crops, and then break the restriction of fungal harm to agricultural production. The physiological and biochemical indexes and the expression levels of related genes were measured at 0, 1, 4, 8 and 16 days (T0, T1, T2, T3, T4) after inoculation with pathogenic bacteria. The results showed that the contents of L-phenylalanine ammonia-lyase (PAL), peroxidase (POD), lignin, total phenols (TP), and flavonoids increased significantly in potato after infection by Rhizoctonia solani Kühn, with the contents of PAL and POD reaching a peak at 8 d and then decreasing, and the contents of lignin and total phenols changing most significantly, reaching the highest levels at day 8 (T3) and day 16 (T4), respectively. During the infestation, the content of eight phenolic compounds increased, and the genes responsible for the lignin synthesis pathway were upregulated. However, in the later stage of infestation, the expression of two genes (PAL PG0031457 and PG2021549, HCT PG0014959, and COMT PG0011266) was down-regulated. In the correlation analysis, gene expression levels of all the genes, except POD (PG0005062), CCoAOMT (PG0018688), and COMT (PG0011266), were found to be positively correlated with the contents of lignin, total phenols, flavonoids, PAL, POD, and eight phenolic substances. Therefore, based on a sound understanding of the occurrence mechanism of Potato black scurf, this experiment analyzed the effect of Rhizoctonia solani Kühn infestation on the content of relevant metabolites in the lignin synthesis pathway as well as gene expression in potatoes, which provides a scientific basis for the prevention and control management of potato black scurf. Graphical Abstract

Abstract Background Continuous monocropping obstacles are common in plants, especially medicinal plants, resulting in disease outbreaks and productivity reductions. Foliar disease, mainly caused by Fusarium oxysporum, results in a severe decrease in the yield of Pseudostellaria heterophylla annually. Determining an effective biomethod to alleviate this disease is urgently needed to improve its productivity and quality. Results This study screened thirty-two keystone bacterial genera induced by pathogens in P. heterophylla rhizosphere soil under continuous monocropping conditions. Pseudomonas, Chryseobacterium, and Flavobacterium, referred to as the beneficial microbiota, were significantly attracted by pathogen infection. The P. palleroniana strain B-BH16-1 can directly inhibit the growth and spore formation of seven primary pathogens of P. heterophylla foliar disease by disrupting fusaric acid production via the emission of volatile organic compounds (VOCs). In addition, strain B-BH16-1 enhances the disease resistance of P. heterophylla by obliterating the pathogen and assembling beneficial microbiota. Conclusion Pathogen-induced Pseudomonas reshaped phyllosphere microbial communities via direct antagonism of pathogens and indirect disruption of the pathogen virulence factor biosynthesis to enhance disease suppression and improve yields. These results show that inhibiting pathogen virulence biosynthesis to reshape the plant microbial community using disease-induing probiotics will be an innovative strategy for managing plant disease, especially under continuous monoculture conditions.

Abstract Background With the rapid development of the economy and society, soil pollution is becoming more and more serious. Heavy metal cadmium (Cd) pollution is one of the typical problems, which poses a potentially serious threat to crop production and human health. Cinnamyl alcohol dehydrogenase (CAD) is a key enzyme in lignin synthesis and plays an important role in plant resistance to external stress. In this study, combined with bioinformatics analysis and expression pattern analysis, the members of the potato CAD family were identified, and their physical and chemical properties, evolutionary characteristics and chromosome location were clarified, as well as their regulatory effects on Cd tolerance. Results A total of 50 StCAD genes belonging to 6 subfamilies were obtained, and all of them were located in the cytoplasm. Members of the same family had similar gene structures and functional domains. The promoter region of each StCAD family member contains at least 5 or more abiotic stress response elements, indicating that the family had potential functions in regulating stress. According to the expression pattern analysis, most genes in this family were upregulated after Cd stress, further enhanced CAD activity and significantly promoted lignin accumulation in potato roots. Conclusion In summary, the StCAD family plays an important role in potato response to Cd stress. This study lays a foundation for further studies on the functions of the StCAD family and provides candidate genes for Cd resistance molecular breeding in potato. Graphical Abstract

Abstract Glaucoma is a complex neurodegenerative disorder characterized by the progressive loss of retinal ganglion cells (RGC) and optic nerve axons, leading to irreversible visual impairment. Despite its clinical significance, the underlying mechanisms of glaucoma pathogenesis remain poorly understood. In this study, we aimed to unravel the multifaceted nature of glaucoma by investigating the interaction between T cells and retinas. By utilizing clinical samples, murine glaucoma models, and T cell transfer models, we made several key findings. Firstly, we observed that CD4+ T cells from glaucoma patients displayed enhanced activation and a bias towards T helper (Th) 1 responses, which correlated with visual impairment. Secondly, we identified the infiltration of Th1 cells into the retina, where they targeted RGC and integrated into the pro-inflammatory glial network, contributing to progressive RGC loss. Thirdly, we discovered that circulating Th1 cells upregulated vascular cell adhesion protein 1 (VCAM-1) on retinal microvessels, facilitating their entry into the neural retina. Lastly, we found that Th1 cells underwent functional reprogramming before reaching the retina, acquiring a phenotype associated with lymphocyte migration and neurodegenerative diseases. Our study provides novel insights into the role of peripheral CD4+ T cells in glaucoma pathogenesis, shedding light on the mechanisms underlying their infiltration into the retina and offering potential avenues for innovative therapeutic interventions in this sight-threatening disease. Graphical Abstract

This paper investigates the disturbance compensation-based optimal tracking control for nonlinear systems in the presence of uncertain dynamic drift and extraneous disturbance by using the adaptive dynamic programming (ADP). First, an extended state observer (ESO)-based disturbance rejection controller is designed to estimate the comprehensive disturbances of system. Then, a novel composite controller capable of online learning is developed based on disturbance rejection controller and optimal regulation law, where the optimal regulation law is conducted by ADP framework to stabilize the dynamics of tracking error and minimize predefined value function. Particularly, an improved critic-only weight updating algorithm is inserted in ADP for ensuring the finite time convergence of critic weight without resorting to traditional actor-critic structures enduring remarkable computational burden. Based on Lyapunov analysis, it is proved that the tracking errors and weight estimation errors of critic network are uniformly ultimately bounded and the pursued controller approximates to the optimal policy. Finally, simulation results are shown to check the superiority of involved strategy, and the value function can be decreased by 25% with consistent tracking performance.

Acinetobacter schindleri is an endophyte of Pseudostellaria heterophylla, a traditional Chinese herbal plant. It has high degradation activity to toxins produced by fungal pathogen Fusarium graminearum. Here, we deployed PacBio single-molecule real-time long-read sequencing technology to generate a complete genome assembly for the Acinetobacter schindleri H4-3-C1 strain and obtained 1.59 Gb of clean reads. These reads were assembled to a single circular DNA chromosome with a length of 3,265,024 bp, and no plasmid was found in the genome. Totals of 3,193 coding sequences, 91 transfer RNA, 21 ribosomal RNA, and 75 small RNAs were identified in the genome. This high-quality genome assembly and gene annotation resource will facilitate the excavation of the zearalenone degradation gene and provide valuable resources for preventing and controlling toxigenic fungal diseases of P. heterophylla. [Graphic: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Zearalenone (ZEN) is a mycotoxin produced by Fusarium spp., which commonly and severely contaminate food/feed. ZEN severely affects food/feed safety and reduces economic losses owing to its carcinogenicity, genotoxicity, reproductive toxicity, endocrine effects, and immunotoxicity. To explore efficient methods to detoxify ZEN, we identified and characterized an efficient ZEN-detoxifying microbiota from the culturable microbiome of Pseudostellaria heterophylla rhizosphere soil, designated Bacillus amyloliquefaciens D-1. Its highest ZEN degradation rate reached 96.13% under the optimal condition. And, D-1 can almost completely remove ZEN (90 μg·g−1) from coix semen in 24 h. Then, the D-1 strain can detoxify ZEN to ZEM, which is a new structural metabolite, through hydrolyzation and decarboxylation at the ester group in the lactone ring and amino acid esterification at C2 and C4 hydroxy. Notably, ZEM has reduced the impact on viability, and the damage of cell membrane and nucleus DNA and can significantly decrease the cell apoptosis in the HepG2 cell and TM4 cell. In addition, it was found that the D-1 strain has no adverse effect on the HepG2 and TM4 cells. Our findings can provide an efficient microbial resource and a reliable reference strategy for the biological detoxification of ZEN.

Background: Cox proportional hazard regression (CPH) model relies on the proportional hazard (PH) assumption: the hazard of variables is independent of time. CPH has been widely used to identify prognostic markers of the transcriptome. However, the comprehensive investigation on PH assumption in transcriptomic data has lacked. Results: The whole transcriptomic data of the 9,056 patients from 32 cohorts of The Cancer Genome Atlas and the 3 lung cancer cohorts from Gene Expression Omnibus were collected to construct CPH model for each gene separately for fitting the overall survival. An average of 8.5% gene CPH models violated the PH assumption in TCGA pan-cancer cohorts. In the gene interaction networks, both hub and non-hub genes in CPH models were likely to have non-proportional hazards. Violations of PH assumption for the same gene models were not consistent in 5 non-small cell lung cancer datasets (all kappa coefficients

Background: The role of alcohol in carcinogenesis has received increasing attention in recent years. Evidence shows its impacts on various aspects, including epigenetics alteration. The DNA methylation patterns underlying alcohol-associated cancers are not fully understood.Methods: We investigated the aberrant DNA methylation patterns in four alcohol-associated cancers based on the Illumina HumanMethylation450 BeadChip. Pearson coefficient correlations were identified between differential methylated CpG probes and annotated genes. Transcriptional factor motifs were enriched and clustered using MEME Suite, and a regulatory network was constructed.Results: In each cancer, differential methylated probes (DMPs) were identified, and 172 hypermethylated and 21 hypomethylated pan-cancer DMPs (PDMPs) were examined further. Annotated genes significantly regulated by PDMPs were investigated and enriched in transcriptional misregulation in cancers. The CpG island chr19:58220189–58220517 was hypermethylated in all four cancers and silenced in the transcription factor ZNF154. Various biological effects were exerted by 33 hypermethylated and seven hypomethylated transcriptional factor motifs grouped into five clusters. Eleven pan-cancer DMPs were identified to be associated with clinical outcomes in the four alcohol-associated cancers, which might provide a potential point of view for clinical outcome prediction.Conclusion: This study provides an integrated insight into DNA methylation patterns in alcohol-associated cancers and reveals the corresponding features, influences, and potential mechanisms.

BackgroundThe WD40-encoding RNA antisense to p53 (WRAP53) is an antisense gene of TP53 with three transcriptional start sites producing three transcript variants involved in the progression of non-small cell lung cancer. However, the mechanism by which these different transcript variants regulate non-small cell lung cancer cell behaviors is to be elucidated.MethodsTwo non-small cell lung cancer cell lines, A549 cells with wild-type p53 and H1975 with mutated p53, were transfected with WRAP53-1α and WRAP53-1β siRNA. The biological effects were assessed via colony formation, cell viability, apoptosis, cell cycle, wound healing and cell invasion assays, as well as immunoblotting.ResultsKnockdown of WRAP53-1α increased the mRNA and protein levels of p53; suppressed colony formation and proliferation of A549 cells but promoted them in H1975 cells; increased the proportion of cells in the G0/G1 phase in A549 cells but decreased that in H1975 cells; and suppressed migration and invasion in A549 cells but not in H1975 cells. Conversely, knockdown of WRAP53-1β had no effect on p53 expression; promoted the growth of A549 cells but not of H1975 cells; decreased the proportion of cells in the G0/G1 phase in A549 cells but not in H1975 cells; and promoted migration and invasion in A549 cells but not in H1975 cells. Knockdown of both WRAP53-1α and WRAP53-1β promoted apoptosis in A549 cells but not in H1975 cells.ConclusionsWRAP53 transcript variants exerted different functions in non-small cell lung cancer cells and regulated non-small cell lung cancer cell behaviors depending on the p53 expression.

Abstract Background and objective Sympathetic activity plays an important role in the proliferation and differentiation of stem cells, and it changes over time, thereby exerting differential effects on various stem cell types. Aging causes sympathetic hyperactivity in aged tissues and blunts sympathetic nerves regulation, and sympathetic abnormalities play a role in aging-related diseases. Currently, the effect of sympathetic activity on skeletal muscle stem cells, namely satellite cells (SCs), is unclear. This study aimed to investigate the effects of skeletal muscle sympathetic activity on SC aging and skeletal muscle repair. Materials and methods To evaluate skeletal muscle and fibrotic areas, numbers of SCs and myonuclei per muscle fiber, β2-adrenoceptor (β2-ADR) expression, muscle repair, and sympathetic innervation in skeletal muscle, aged mice, young mice that underwent chemical sympathectomy (CS) were utilized. Mice with a tibialis anterior muscle injury were treated by barium chloride (BaCl2) and clenbuterol (CLB) in vivo. SCs or C2C12 cells were differentiated into myotubes and treated with or without CLB. Immunofluorescence, western blot, sirius red, and hematoxylin–eosin were used to evaluate SCs, myogenic repair and differentiation. Results The number of SCs, sympathetic activity, and reparability of muscle injury in aged mice were significantly decreased, compared with those in young mice. The above characteristics of young mice that underwent CS were similar to those of aged mice. While CLB promoted the repair of muscle injury in aged and CS mice and ameliorated the reduction in the SC number and sympathetic activity, the effects of CLB on the SCs and sympathetic nerves in young mice were not significant. CLB inhibited the myogenic differentiation of C2C12 cells in vitro. We further found that NF-κB and ERK1/2 signaling pathways were activated during myogenic differentiation, and this process could be inhibited by CLB. Conclusion Normal sympathetic activity promoted the stemness of SCs to thereby maintain a steady state. It also could maintain total and self-renewing number of SCs and maintain a quiescent state, which was correlated with skeletal SCs via β2-ADR. Normal sympathetic activity was also beneficial for the myogenic repair of injured skeletal muscle.

Abstract Background Human endogenous retrovirus‐H long terminal repeat‐associating protein 2 (HHLA2) is a member of B7 family, which is upregulated in multiple tumors. However, its exact functions in non‐small cell lung cancer (NSCLC) have not been fully understood. This study aimed to investigate the biological roles of HHLA2 in human NSCLC and the relevant mechanisms. In addition, the effects of tumor cell‐derived HHLA2 on tumor‐associated macrophage (TAM) polarization were explored. Methods NSCLC cell growth, migration, and invasion were assessed by colony formation and modified Boyden chamber assays. Cell cycle and the CD163+ TAMs were examined by flow cytometry. A co‐culture model of THP‐1 macrophages and NSCLC cells was conducted to investigate the impacts of tumor cell‐derived HHLA2 on THP‐1 macrophage polarization. Moreover, a xenograft nude mouse model was established to explore the effects of HHLA2 on tumorigenesis in vivo. Results HHLA2 was upregulated in A549 and H1299 cells compared with the normal lung epithelial BEAS‐2B cells. HHLA2 deficiency inhibited NSCLC cell proliferation, migration, invasion, and induced G0/G1 phase arrest partially via inhibiting EGFR/MAPK/ERK signaling pathway. Furthermore, HHLA2 knockdown inhibited M2 polarization of TAMs via downregulating IL‐10. In addition, knockdown of HHLA2 inhibited tumor growth in vivo. Conclusion HHLA2 downregulation inhibited NSCLC growth and TAM M2 polarization. HHLA2 may serve as a therapeutic target and promising prognostic biomarker in NSCLC.

Abstract Background As one of the most common malignancy, lung adenocarcinoma (LUAD) is characterized by low 5-year survival rate. This research aimed to investigate the effects of ribonucleotide reductase regulatory subunit M2 (RRM2) on malignant biological behaviors and activation of cGAS/STING pathway. We also explored the synergistic sensitization mechanisms of RRM2 and radiotherapy. Methods Bioinformatic tools were used to evaluate the clinical significance of RRM2 in LUAD patients. The roles of RRM2 in malignant phenotype and DNA damage in LUAD cells were investigated with cell proliferation, colony formation, immunofluorescence, modified Boyden chamber and comet assays. The mouse models were used to evaluate the biological significance of RRM2 in vivo. Cytotoxic T cell infiltration was evaluated via flow cytometric analysis and immunohistochemistry staining in C57BL/6 mice. We also explored the synergistic effects of RRM2 silencing and radiation on LUAD cells with apoptosis assay and immunoblotting in vitro. Results Bioinformatic analysis revealed that RRM2 had diagnostic values for LUAD patients. Higher levels of RRM2 predicted worse prognosis. RRM2 silencing inhibited LUAD cell proliferation, invasion and migration. RRM2 knockdown induced S phase arrest and DNA damage. RRM2 silencing induced cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway, and the downstream targets were regulated in a STING-dependent manner. Knockdown of RRM2 suppressed tumor growth in the xenograft tumor models. RRM2 deficiency increased CD8 + T cells in the tumor tissues and spleens. Furthermore, RRM2 silencing had synergistic effects with radiation on inhibiting cell proliferation and promoting apoptosis. Meanwhile, this combination promoted the activation of cGAS/STING signaling pathway synergistically, and simultaneously increased expression of IFNβ, CCL5 and CXCL10. Conclusion Our results demonstrated that RRM2 silencing had anti-tumor values and activated the cGAS/STING signaling pathway. RRM2 silencing increased CD8 + T cells infiltration. RRM2 silencing cooperated with radiation to inhibit LUAD cell proliferation, promote apoptosis and enhance the activation of cGAS/STING signaling pathway. RRM2 could be a promising target for tumor regression through cancer immunotherapy in LUAD.

This paper investigates a novel adaptive fixed-time disturbance observer (AFXDO)-based approximate optimal tracking control architecture for nonlinear systems with partially unknown dynamic drift and perturbation under an adaptive dynamic programming (ADP) scheme. To attenuate the impact of disturbance, a novel AFXDO was designed based on the principle of a fixed-time stable system without prior information of disturbance, making disturbance observer errors converge to zero in a fixed time independent of initial estimation error. Additionally, approximate optimal control is conducted by incorporating the real-time estimation of AFXDO into a critic-only ADP framework to stabilize the dynamics of tracking errors and strike a balance between consumption and performance. In particular, to address the heavy calculation burden and oscillation phenomenon in the traditional actor–critic structure, an improved adaptive update law with a variable learning rate was developed to update the weight for adjusting the optimal cost function and optimal control policy simultaneously, avoiding the initial chattering phenomenon and achieving a prescribed convergence without resorting to dual networks. With the efforts of AFXDO and a weight law with a variable learning rate, the track errors were achieved with fast transient performance and low control consumptions in a fixed time. By revisiting Lyapunov stability, the tracking error and weight estimation error were proven to be uniformly ultimately bounded, and the designed control tended to optimal control. The simulations were carried out on quadrotor tracking to demonstrate the effectiveness of the developed control scheme, which achieves rapid convergence by lower control consumption in 4 s, where the cost function is reduced by 19.13%.

Ulcerative colitis (UC) is a chronic inflammatory disease, characterized by recurrent flares of mucosal inflammation, which is limited in the colon and rectum. Compromised epithelial barrier functions have been indicated in the initiation of UC. Carnosol (CA), a natural active ortho-diphenol diterpene compound, is one of the active ingredients in plants such as rosemary and sage. The anti-inflammatory and anti-oxidative effects of CA have been reported in several animal models, but its effect on mucosal inflammation remains elusive. We established a mouse experimental colitis model characterized by epithelial barrier destruction using dextran sulfate sodium (DSS). CA was intraperitoneally administrated. Flow cytometry was performed to determine phenotypes of intraepithelial lymphocytes and lamina propria cells. qRT-PCR was used for gene expression. ER stress in the colon was determined by immunofluorescence staining and qRT-PCR. Thapsigargin was used to induce ER stress in HCT-116 cells in vitro. We found CA significantly alleviated DSS-induced colitis in mice marked by relieved clinical symptoms and colonic pathological damage. Inflammatory cell infiltration and cytokine expression in the colon were suppressed by CA during colitis. Furthermore, CA restored epithelial barrier functions and intestinal intraepithelial lymphocyte (IEL) homeostasis in mice with DSS insults. Mechanistically, we induced endoplasmic reticulum (ER) stress in HCT-116 cells (an intestinal epithelial cell line) with thapsigargin, and CA reversed this effect. In addition, we collected inflamed mucosal biopsies from 23 patients with UC, and cultured overnight with or without CA, showing CA significantly reduced expression of ER stress signaling molecule and pro-inflammatory agents. Our data demonstrate that CA acts as an effective drug for experimental colitis and maintains proper epithelial barrier functions via suppressing epithelial ER stress, providing new evidence that CA might be a promising therapeutic candidate for UC.

Abstract Background The expression of long non‐coding RNA (lncRNA) prostate cancer‐associated ncRNA transcripts 1 (PCAT1) is increased in non‐small cell lung cancer (NSCLC). It stimulates tumour growth and metastasis, but its role in the radioimmune responses remain unknown. We aimed to explore the impacts of PCAT1 on tumorigenesis and radioimmune responses and the underlying molecular mechanisms in NSCLC. Methods Comprehensive bioinformatics analysis was performed to identify immunosuppressive lncRNAs involved with tumour invasion in NSCLC. The expression levels of PCAT1 were analysed by in situ hybridisation in 55 paired NSCLC tissues and adjacent normal tissues. Both loss‐ and gain‐of‐function assays were performed to examine the effects of PCAT1 and SOX2 on NSCLC cell behaviours in vivo and in vitro. Bioinformatic analyses, chromatin isolation by RNA purification (ChIRP) and dual‐luciferase reporter assays were applied to validate the regulatory effects of PCAT1 on SOX2 expression. Chromatin immunoprecipitation, luciferase and rescue assays were utilised to identify the relationship between SOX2 and the cGAS/stimulator of interferon genes (STING) signalling. Results PCAT1 was immunosuppressive and related with NSCLC invasion. Increased PCAT1 was negatively correlated with immune cell infiltration in NSCLC. PCAT1 knockdown restrained proliferation, increased apoptosis, and repressed cell metastasis in vivo and in vitro. PCAT1 activated SOX2 that accelerated tumorigenesis and immunosuppression. SOX2 promoted tumour growth through inhibiting cytotoxic T‐cell immunity. Moreover, SOX2 restrained cGAS transcription and hampered downstream type I interferon (IFN)‐induced immune responses. Inhibition of PCAT1/SOX2 in collaboration with radiation further inhibited tumour growth, and initiated the cGAS/STING signalling pathway, which enhanced the immune responses of radiotherapy in NSCLC. Conclusions PCAT1/SOX2 axis promoted tumorigenesis and immunosuppression through inhibition of cGAS/STING signalling‐mediated T‐cell activation. Inhibition of PCAT1 and SOX2 synergised with radiotherapy to activate the immune response and could serve as potential therapeutic targets.

Fusarium wilt (FW) is a primary replant disease that affects Pseudostellaria heterophylla (Taizishen) and is caused by Fusarium oxysporum, which occurs widely in China under the continuous monocropping regime. However, the ternary interactions among the soil microbiota, P. heterophylla, and F. oxysporum remain unknown. We investigated the potential interaction relationship by which the pathogen-mediated P. heterophylla regulates the soil and the tuberous root microbiota via high-throughput sequencing. Plant–pathogen interaction assays were conducted to measure the arrival of F. oxysporum and Pseudomonas poae at the tuberous root via qPCR and subsequent seedling disease incidence. A growth assay was used to determine the effect of the tuberous root crude exudate inoculated with the pathogen on P. poae. We observed that pathogen-mediated P. heterophylla altered the diversity and the composition of the microbial communities in its rhizosphere soil and tuberous root. Beneficial microbe P. poae and pathogen F. oxysporum were significantly enriched in rhizosphere soil and within the tuberous root in the FW group with high severity. Correlation analysis showed that, accompanied with FW incidence, P. poae co-occurred with F. oxysporum. The aqueous extract of P. heterophylla tuberous root infected by F. oxysporum substantially promoted the growth of P. poae isolates (H1-3-A7, H2-3-B7, H4-3-C1, and N3-3-C4). These results indicated that the extracts from the tuberous root of P. heterophylla inoculated with F. oxysporum might attract P. poae and promote its growth. Furthermore, the colonization assay found that the gene copies of sucD in the P. poae and F. oxysporum treatment (up to 6.57 × 1010) group was significantly higher than those in the P. poae treatment group (3.29 × 1010), and a pathogen-induced attraction assay found that the relative copies of sucD of P. poae in the F. oxysporum treatment were significantly higher than in the H2O treatment. These results showed that F. oxysporum promoted the colonization of P. poae on the tuberous root via F. oxysporum mediation. In addition, the colonization assay found that the disease severity index in the P. poae and F. oxysporum treatment group was significantly lower than that in the F. oxysporum treatment group, and a pathogen-induced attraction assay found that the disease severity index in the F. oxysporum treatment group was significantly higher than that in the H2O treatment group. Together, these results suggest that pathogen-mediated P. heterophylla promoted and assembled plant-beneficial microbes against plant disease. Therefore, deciphering the beneficial associations between pathogen-mediated P. heterophylla and microbes can provide novel insights into the implementation and design of disease management strategies.

This article develops a novel unknown system dynamic estimator-based funnel control scheme for nonlinear quadrotor attitude regulation with preassigned convergence subject to parametric uncertainties and external perturbations. An invariant manifold equipped with first-order filtering is established. To online identify the lump disturbances, an unknown system dynamic estimator is employed with a simple formula, which need a lower computation burden. Based on aforementioned estimator, a novel funnel control via utilizing funnel variable is investigated, where an exponentially decaying funnel function is preset with a prior preassigned convergence for regulation angle error. The angle tracking errors are proved to be ultimately uniformly bounded, and angle regulation error can evolve within the preset funnel boundary. Simulation results demonstrate the effectiveness of the developed control scheme.

Non-small cell lung cancer (NSCLC) has high mortality rates worldwide. Agrin contributes to immune synapse information and is involved in tumor metastasis. However, its roles in NSCLC and tumor immune microenvironment remain unclear. This study examined the effects and the underlying mechanisms of Agrin in NSCLC and tumor-infiltrated immune cells. Clinical tissue samples were used to confirm the bioinformatic predictions. NSCLC cells were used to investigate the effects of Agrin on cell cycle and proliferation, as well as invasion and migration. Tumor xenograft mouse model was used to confirm the effects of Agrin on NSCLC growth and tumor-infiltrated regulatory T cells (Tregs) in vivo. Agrin levels in NSCLC cells were closely related to tumor progression and metastasis, and its function was enriched in the PI3K/AKT pathway. In vitro assays demonstrated that Agrin knockdown suppressed NSCLC cell proliferation and metastasis, while PI3K/AKT activators reversed the inhibitory effects of Agrin deficiency on NSCLC cell behaviors. Agrin expression was negatively associated with immunotherapy responses in NSCLC patients. Agrin knockdown suppressed Tregs, as well as interleukin (IL)-6 expression and secretion, while PI3K/AKT activators and exogenous IL-6 rescued the inhibitory effects. In the mouse model, Agrin downregulation alleviated NSCLC cell growth and Treg infiltration in vivo. Our results indicated that Agrin promotes tumor cell growth and Treg infiltration via increasing IL-6 expression and secretion through PI3K/AKT pathway in NSCLC. Our studies suggested Agrin as a therapeutically potential target to increase the efficacy of immunotherapy in NSCLC patients.

Flower color not only determines the quality and commercial value of ornamental plants, but it also plays a vital role in ecological processes such as pollinator attraction. This study aimed to investigate the relationship between flower color and the cellular physicochemical factors of Bletilla striata. The color space values of 21 samples were initially determined, followed by a selection of five samples with significant color differences for testing cell shape, total flavonoid content (ranging from 1.86 to 5.42 mg/g), total anthocyanin content (ranging from 0.52 to 292.62 (A530 − 0.25 ∗ A657)/g), cell pH (varying between 5.03 and 5.74), and metal ion content (including Al3+, Ca2+, Fe3+, K+, Mg2+, Na+, P5+, Zn2+, Mo6+, Cu2+, and Mn2+). The flowers of Bletilla were predominantly purple, pink, and yellow; and distributed in quadrants I, II, and IV on the a* and b* rectangular coordinate. The a* value was identified as the primary color indicator for this species. Total anthocyanin content and Zn2+ showed a significant positive correlation with a*, while Al3+, Ca2+, Fe3+, Mg2+, Na+, and Mn2+ demonstrated negative correlations. Cell shape, flavonoid content, and pH had nonsignificant correlations with a*. In conclusion, the total anthocyanin content and metal ions play crucial roles in determining the flower color of B. striata, which can have implications for pollinator attraction. Future research should focus on understanding the complex interactions between these factors to develop novel ornamental plant varieties with desirable flower colors and enhanced ecological functions.

This paper studies the consensus of first-order discrete-time multi-agent systems with fixed and switching topology, and there exists cooperative and antagonistic interactions among agents. A signed graph is used to model the interactions among agents, and some sufficient conditions for consensus are obtained by analyzing the eigenvalues of a Laplacian matrix in the case of fixed topology. The results indicate that having a spanning tree is only a necessary condition for the consensus of multi-agent systems with signed graphs, which is also affected by edge weights. Consensus is further discussed in the case of switching topology, and the results reveal that consensus can be reached if the controller gain and the union graphs among some consecutive time intervals satisfy some conditions. Finally, several simulation examples further confirm the theoretical results.

Semen coicis is not only a traditional Chinese medicine (TCM), but also a typical food in China, with significant medical and healthcare value. Because semen coicis is rich in starch and oil, it can be easily contaminated with Aspergillus flavus and its aflatoxins (AFs). Preventing and controlling the contamination of semen coicis with Aspergillus flavus and its aflatoxins is vital to ensuring its safety as a drug and as a food. In this study, the endosphere bacteria Pseudomonas palleroniana strain B-BH16-1 produced volatiles that strongly inhibited the mycelial growth and spore formation activity of A. flavus. Gas chromatography–mass spectrometry profiling revealed three volatiles emitted from B-BH16-1, of which 1-undecene was the most abundant. We obtained authentic reference standards for these three volatiles; these significantly reduced mycelial growth and sporulation in Aspergillus, with dimethyl disulfide showing the most robust inhibitory activity. Strain B-BH16-1 was able to completely inhibit the biosynthesis of aflatoxins in semen coicis samples during storage by emitting volatile bioactive components. The microscope revealed severely damaged mycelia and a complete lack of sporulation. This newly identified plant endophyte bacterium was able to strongly inhibit the sporulation and growth of Aspergillus and the synthesis of associated mycotoxins, thus not only providing valuable information regarding an efficient potential strategy for the prevention of A. flavus contamination in TCM and food, but potentially also serving as a reference in the control of toxic fungi.

Ulcerative colitis (UC) is considered an immune disease, which is related to the dysbiosis of intestinal microbiota and disorders of the host immune system and metabolism. Sophora flavescens Aiton has been used for the clinical treatment of UC in China and East Asia for thousands of years. It has many traditional prescriptions and modern preparations, and its curative effects are definite. We are the first to report that the flavonoids in Sophora flavescens (S. flavescens) Aiton EtOAc extract (SFE) could potentially attenuate the dextran sodium sulfate–induced UC in mice, which changed the current understanding of considering alkaloids as the only anti-UC pharmacological substances of S. flavescens Aiton. Based on the 16S rRNA gene sequencing and metabolomic analysis, it was found that the anti-UC effects of SFE were due to the regulation of gut microbiota, reversing the abnormal metabolisms, and regulation of the short-chain fatty acids synthesis. Notably, according to the interaction networks of specific bacteria and “bacteria and metabolites” co-expression network, the SFE could enrich the abundance of the commensal bacterium Lactobacillus, Roseburia, norank_f__Muribaculaceae, Anaerotruncus, Candidatus_Saccharimona, and Parasutterella, which are proposed as potentially beneficial bacteria, thereby playing vital roles in the treatment of UC.

Chemokines exhibited complicated functions in antitumor immunity, with their expression profile and clinical importance of lung adenocarcinoma (LUAD) patients remaining largely undetermined. This study aimed to explore the expression patterns of chemokine family in LUAD and construct a predictive chemokine family-based signature. A total of 497 samples were downloaded from the Cancer Genome Atlas (TCGA) data portal as the training set, and the combination of 4 representative Gene Expression Omnibus (GEO) datasets, including GSE30219, GSE50081, GSE37745, and GSE31210, were utilized as the validation set. A three gene-based signature was constructed using univariate and stepwise multivariate Cox regression analysis, classifying patients into high and low risk groups according to the overall survival. The independent GEO datasets were utilized to validate this signature. Another multivariate analysis revealed that this signature remained an independent prognostic factor in LUAD patients. Furthermore, patients in the low risk group featured immunoactive tumor microenvironment (TME), higher IPS scores and lower TIDE scores, and was regarded as the potential beneficiaries of immunotherapy. Finally, the role of risky CCL20 was validated by immunohistochemistry (IHC), and patients possessed higher CCL20 expression presented shorter overall survival ( P = 0.011).

Abstract P450 119 peroxygenase was found to catalyze the sulfoxidation of thioanisole and the sulfonation of sulfoxide in the presence of tert‐butyl hydroperoxide (TBHP) for the first time with turnover rates of 1549 min−1 and 196 min−1 respectively. Several mutants were designed to improve the peroxygenation activity and thioanisole specificity by site‐directed mutagenesis. The F153G/T213G mutant gave an increase of sulfoxide yield and a decrease of sulfone yield. Moreover the S148P/I161T/K199E/T214V mutant and the K199E mutant with acidic Glu residue contributed to improving the product ratio of sulfoxide to sulfone. Addition of short‐alkyl‐chain organic acids to the P450 119 peroxygenase‐catalyzed sulfur oxidation of thioanisole was investigated. Octanoic acid was found to induce a preferred sulfoxidation of thioanisole catalyzed by the F153G/T213G mutant to give approximately 2.4‐fold increase in turnover rate with a kcat value of 3687 min−1 relative to that of the wild‐type, and by the F153G mutant to give the R‐sulfoxide up to 30 % ee. The experimental control and the proposed mechanism for the P450 119 peroxygenase‐catalyzed sulfoxidation of thioanisole in the presence of octanoic acid suggested that octanoic acid could partially occupy the substrate pocket; meanwhile the F153G mutation could enhance the substrate specificity, which could lead to efficiently regulate the spatial orientation of thioanisole and facilitate the formation of Compound I. This is the most effective catalytic system for the P450 119 peroxygenase‐catalyzed sulfoxidation of thioanisole.

Tumor microenvironment (TME) has critical impacts on the pathogenesis of lung adenocarcinoma (LUAD). However, the molecular mechanism of TME effects on the prognosis of LUAD patients remains unclear. Our study aimed to establish an immune-related gene pair (IRGP) model for prognosis prediction and internal mechanism investigation. Based on 702 TME-related differentially expressed genes (DEGs) extracted from The Cancer Genome Atlas (TCGA) training cohort using the ESTIMATE algorithm, a 10-IRGP signature was established to predict LUAD patient prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that DEGs were significantly associated with tumor immune response. In both TCGA training and Gene Expression Omnibus validation datasets, the risk score was an independent prognostic factor for LUAD patients using Lasso-Cox analysis, and patients in the high-risk group had poorer prognosis than those in the low-risk one. In the high-risk group, M2 macrophage and neutrophil infiltrations were higher, while the levels of T cell follicular helpers were significantly lower. The gene set enrichment analysis results showed that DNA repair signaling pathways were involved. In summary, we established an IRGP signature as a potential biomarker to predict the prognosis of LUAD patients.

Background and PurposeHead and neck squamous carcinoma (HNSCC), characterized by immunosuppression, is a group of highly heterogeneous cancers. Although immunotherapy exerts a promising influence on HNSCC, the response rate remains low and varies in assorted primary sites. Immunological mechanisms underlying HNSCC pathogenesis and treatment response are not fully understood. This study aimed to develop a differentially expressed genes (DEGs)–based risk model to predict immunotherapy efficacy and stratify prognosis of HNSCC patients.Materials and MethodsThe expression profiles of HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The tumor microenvironment and immune response were estimated by cell type identification via estimating relative subset of known RNA transcripts (CIBERSORT) and immunophenoscore (IPS). The differential expression pattern based on human papillomavirus status was identified. A DEGs-based prognostic risk model was developed and validated. All statistical analyses were performed with R software (version 3.6.3).ResultsBy using the TCGA database, we identified DKK1, HBEGF, RNASE7, TNFRSF12A, INHBA, and IPIK3R3 as DEGs that were associated with patients’ overall survival (OS). Patients were stratified into the high- and low-risk subgroups according to a DEGs-based prognostic risk model. Significant difference in OS was found between the high- and low-risk patients (1.64 vs. 2.18 years, P = 0.0017). In multivariate Cox analysis, the risk model was an independent prognostic factor for OS (hazard radio = 1.06, 95% confidence interval [1.02–1.10], P = 0.004). More CD8+ T cells and regulatory T cells were observed in the low-risk group and associated with a favorable prognosis. The IPS analysis suggested that the low-risk patients possessed a higher IPS score and a higher immunoreactivity phenotype, which were correlated with better immunotherapy response.ConclusionCollectively, we established a reliable DEGs-based risk model with potential prognostic value and capacity to predict the immunophenotype of HNSCC patients.

Impedimetric aptasensors without signal amplification exhibit poor sensitivity for the detection of small molecule contaminants. In this work, biotinylated nanoparticles of biotin-FNPs were readily prepared by the self-assembly of biotin-phenylalanine (biotin-Phe) monomers. The biotin-FNPs were then used for the development of competitive impedimetric aptasensors by streptavidin–biotin (SA–biotin) coupling chemistry. Specifically, capture of biotinylated DNA (biotin-DNA) by the aptamer-modified electrode allowed for the in situ formation of SA–biotin-FNPs networks on the electrode surface, hampering the electron transfer by creating an insulating layer. The target–aptamer interaction prevented the capture of biotin-DNA, thus inhibiting the formation of SA–biotin-FNPs networks on the electrode surface and allowing for the electron transfer. To demonstrate the analytical performances of the strategy, aflatoxin B1 (AFB1) was determined as the model analyte. The aptasensor exhibited a linear range of 0.05–3 pg/mL. The detectable concentration is much lower than that achieved by other impedimetric aptasensors. The strategy may provide a general way for the design of biosensors to determine various small molecules by matching sequence-specific aptamers.

The oral microbiome has major impacts on oral health and disease. Antimicrobial peptides (AMPs), such as nisin and cecropin, have been widely used as food preservatives or feed additives, and are thus inevitably ingested by consumers through their oral cavity. However, as broad-spectrum antimicrobial reagents, the effect of AMPs on the oral microbiome of consumer’s remains poorly characterized. In this study, we performed 16S rDNA high-throughput sequencing to investigate the effect of nisin and cecropin on the oral microbiomes of rats. Our results suggest that although nisin and cecropin have different effects on the oral microbiome of rats, both AMPs impact the composition of oral microbial communities at the phylum and genus levels. Cecropin significantly reduced the diversity and richness of rat oral microbial communities. Notably, the relative abundance of the pathogen Acinetobacter baumannii increased in the oral microbial community of rats fed cecropin-containing feed. In addition, nisin significantly reduced the amount of secretory immunoglobulin A in the saliva of rats.

Abstract Background Dysregulation of miRNAs is associated with cancer development by coordinately suppressing abundant target genes. Emerging evidence indicates that miR-31 plays a dual role in tumorigenicity. However, whether miR-31 plays as an oncogene in esophageal squamous cell carcinoma (ESCC) and the potential target molecules are still unclear. MiR-31 role in ESCC was investigated and an association of the target molecules with EMT was identified in the progression of ESCC. Methods Western blot assays and qRT-PCR was performed to detect the protein and mRNA levels. We investigated the role of miR-31 in the regulation of LATS2 expression in ESCC cell lines via functional assays both in vivo and in vitro. The luciferase reporter assays was conducted to confirm LATS2 is a potential target of miR-31. Immunohistochemistry was used to measure LATS2 and TAZ expression in normal and ESCC tissue. Results LATS2 is a component of the Hippo tumor-suppressive signaling pathway. Frequent loss of heterozygosity of LATS2 has been reported in esophageal cancer. We analyzed the reciprocal expression regulation of miR-31 and LATS2 and demonstrated that LATS2 expression was elevated by down-regulation of miR-31 at the post-transcriptional level in ESCC. Moreover, miR-31 significantly suppressed the luciferase activity of mRNA combined with the LATS2 3′-UTR, a key molecule in the Hippo pathway. Then, LATS2 consequently promoted the translocation of TAZ, which was examined using immunohistochemistry. Silencing of miR-31 significantly inhibited the cell proliferation, induced apoptosis and decreased the ability of migration/invasion in vitro. LATS2 impedes ESCC cell proliferation and invasion by suppressing miR-31, as well as mice xenograft model in vivo. Meanwhile, the nuclear localization of LATS2 constrained the phosphorylation of TAZ. Then, the expression level of TAZ was notably heightened with a high risk of recurrence compared to that observed in the low-risk patients, as well as, the higher expression associated with a poor survival. Conclusions Our study demonstrated that overexpression of miR-31 undertook an oncogenic role in ESCC by repressing expression of LATS2 via the Hippo Pathway and activating epithelial-mesenchymal transition. LATS2 and TAZ could be potential novel molecular markers for predicting the risk of recurrence and prognosis of ESCC.

NIX/BNIP3L is known as a proapoptotic protein that is also related to mitophagy. Previous reports have shown that NIX could be involved in neuronal apoptosis after intracerebral hemorrhage, but it also plays a protective role in mitophagy in ischemic brain injury. How NIX works in traumatic brain injury (TBI) is unclear. Thus, this study was designed to observe the expression of NIX and perform a preliminary exploration of the possible effects of NIX in a rat TBI model. The results showed that NIX expression decreased after damage, and colocalized with neuronal cells in cortical areas. Moreover, when we induced upregulation of NIX, autophagy was increased, while neuronal apoptosis and brain water content decreased along with neurological deficits. These findings remind us that NIX probably plays a neuroprotective role in TBI through autophagy and apoptosis pathways.

Emerging evidence has shown that microRNAs (miRNAs) play essential roles in regulating human cancers development and progression. However, the underlying mechanisms remain to be further explored. MiRNAs are a class of endogenous, non-coding, 18-24 nucleotide length single-strand RNAs that moderate gene expression primarily at post-transcriptional level. There is a growing body of literature that recognizes the importance of microRNA (miR)-129 during the development of cancers. Aberrant expression of miR-129 has been detected in various types of human cancers and the validated target genes are involved in cancer-related biological processes such as DNA methylation, cell proliferation, apoptosis, cell cycle, and metastasis. In this review, we summarized the roles of miR-129 family members and their target genes in tumorigenesis and clinical treatment of human cancers, highlighting the potential roles of miR-129 as biomarkers for cancer diagnosis and prognosis, and promising tools for cancer treatment.

Lung cancer is the leading cause of cancer death around the world. The advanced discovery of numerous long noncoding RNAs (lncRNAs) has dramatically changed the understanding of biology of human cancers, including lung cancer. LncRNAs are a group of noncoding RNAs (ncRNAs) with a length greater than 200 nucleotides with limited or no protein-coding capacity. Increasing evidence has shown that specific lncRNAs may be implicated in the process of tumorigenesis. Because of their roles in the regulation of multiple molecular pathways associated with changes in gene expression, lncRNAs can serve as potential diagnostic biomarkers or therapeutic targets in lung cancer. Importantly, dysregulated lncRNAs is reported to be correlated with the sensitivity of lung cancer cells to anticancer therapies, including chemotherapy, molecular-targeted therapy, etc. Herein, we review the recent progress of lncRNAs in lung cancer, with a particular focus on the multiple molecular roles of regulatory lncRNAs on the molecular signaling pathways involved in tumorigenesis and the resistance to such therapies.

Cancer remains one of the most threatening causes of human health impairment, and the mechanisms underlying tumorigenesis have not been completely characterized. MicroRNAs (miRNAs) are a group of endogenous, small (18∼25 nucleotides) non-coding RNAs which negatively regulate gene expressions by directly binding to the 3'-untranslated regions (3'-UTRs) of the target messenger RNAs (mRNAs). Increasing evidence has demonstrated abnormal miRNA profiles and confirmed their involvement in tumor initiation and progression. As one important member of the miR-200 family, microRNA (miR)-141 is aberrantly expressed in many human malignant tumors, participating in various cellular processes including epithelial-mesenchymal transition (EMT), proliferation, migration, invasion, and drug resistance. In the present review, we briefly describe the mechanisms underlying miR-141-mediated tumorigenesis and the possible future of miR-141 as a potential diagnostic and prognostic parameter as well as therapeutic target in clinical applications.

Prolactin (PRL) has been considered a key regulator of ion uptake in zebrafish. The genes slc12a10.2 and slc12a3, which are Na+ and chloride Cl− co-transporters, have been reported to be regulated by PRL in freshwater fish. The integrative network of PRL signaling dissected from the knockout of tissue-specific downstream PRL ion transporters remains poor. In the present study, zebrafish models with increased endogenous levels of PRL were generated through the knockout of slc12a10.2 or slc12a3, and the developmental consequences were analyzed. The increased levels of pituitary PRL were observed in both slc12a10.2- and slc12a3-deficient fish. Unlike the slc12a3-deficient fish, which could survive to adulthood, the slc12a10.2-deficient fish began to die at 9 days post-fertilization (dpf) and did not survive beyond 17 dpf. This survival defect is a result of defective Cl− uptake in this mutant, indicating that Slc12a10.2 plays an essential role in Cl− uptake. Intriguingly, compared to the levels in control fish, no significant differences in the levels of Na+ in the body were observed in slc12a10.2- or slc12a3-deficient zebrafish. The upregulations of the PRL downstream transporters, slc9a3.2, slc12a10.2, and atp1a1a.5 were observed in slc12a3-deficient fish in both the gills/skin and the pronephric duct. However, this type of response was not observed in the pronephric duct of slc12a10.2-deficient fish, except under Na+-deprived conditions. Our results show that PRL is susceptible to deficiencies in downstream ion transporters. Moreover, both the gills/skin and pronephric duct show differential expression of downstream PRL targets in response to increased levels of pituitary PRL caused by the depletion of tissue-specific ion transporters.

Cisplatin (CDDP) is one of the most effective broad-spectrum anticancer drugs, which has been employed for the treatment of lung cancer. The development of CDDP resistance is a major problem of tumor chemotherapy. MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs, involved in the initiation and progression of human cancer. Increasing evidence has shown that dysregulation of miRNAs is involved in chemo resistance of tumor cells to anti-cancer drugs, including CDDP. This article summarizes current research involving miRNAs as regulators of key target genes for CDDP resistance in lung cancer. Potential use of targeting miRNAs can lead to miRNA-based therapies, which will be helpful for overcoming drug resistance and developing more effective personalized anti-cancer treatment strategies in human lung cancers.

MicroRNAs (miRNAs) are a recently discovered class of endogenous, small (about 22 nucleotides) non-coding RNAs, which play important roles in cancer development and progression. Emerging evidence shows that microRNAs exert their regulatory effects by directly binding to the 3'- untranslated regions (UTRs) of their target genes. MicroRNA-100 (miR-100) is aberrantly expressed and functions in many human cancers by regulating multiple cell processes, such as cell cycle, proliferation, differentiation, migration, invasion and apoptosis, via post-transcriptionally regulating various target genes. A better understanding of the molecular mechanisms involved in miR-100-mediated tumor progression will provide an opportunity for exploring novel miR-100-based targeted therapies for human cancers. This review aims to summarize the recently published literature on the roles of miR-100 in regulating tumorigenesis, and explore its potential clinical applications for cancer diagnosis, prognosis and clinical treatment.

Inhibitor of growth 4 (ING4), a member of the conserved ING family, has been identified as an important tumor suppressor since it plays a critical role in the regulation of chromatin modification, cell proliferation, angiogenesis and cell migration. Some observations suggest that ING4 acts as a key regulator of tumorigenesis through modifying gene transcription in part by regulating the transcription factors p53 and NF-kappaB (NF-κB). However, these models have yet to be substantiated by further investigations. Numerous reports describe the reduced expression of ING4 in cancers, and the responsible mechanisms are involved in gene deletion, mutation, transcriptional and post-transcriptional dysregulation. This review aims to summarize the recent published literature that investigates the role of ING4 in regulating tumorigenesis and progression, and explore its potential for cancer treatment.

Myostatin (MSTN) is a negative regulator of myogenesis in vertebrates. Depletion of mstn resulted in elevated muscle growth in several animal species. However, the report on the complete ablation of mstn in teleost fish has not yet become available. In this study, two independent mstnb-deficient mutant lines in zebrafish were generated with the TALENs technique. In the mstnb-deficient zebrafish, enhanced muscle growth with muscle fiber hyperplasia was achieved. Beginning at the adult stage (80 days postfertilization), the mstnb-deficient zebrafish exhibited increased circumferences and body weights compared with the wild-type sibling control fish. Although the overall total lipid/body weight ratios remained similar between the mstnb-deficient zebrafish and the control fish, the distribution of lipids was altered. The size of the visceral adipose tissues became smaller while more lipids accumulated in skeletal muscle in the mstnb-deficient zebrafish than in the wild-type control fish. Based on the transcriptional expression profiles, our results revealed that lipid metabolism, including lipolysis and lipogenesis processes, was highly activated in the mstnb-deficient zebrafish, which indicated the transition of energy metabolism from protein-dependent to lipid-dependent in mstnb-deficient zebrafish. Our mstnb-deficient model could be valuable in understanding not only the growth trait regulation in teleosts but also the mechanisms of teleost energy metabolism.

This paper addresses the consensus of second-order multiagent systems with general topology and time delay based on the nearest neighbor rule. By using the Laplace transform technique, it is proved that the second-order multi-agent system in the presence of time-delay can reach consensus if the network topology contains a globally reachable node and time delay is bounded. The bound of time-delay only depends on eigenvalues of the Laplacian matrix of the system. The main contribution of this paper is that the accurate state of the consensus center and the upper bound of the communication delay to make the agents reach consensus are given. Some numerical simulations are given to illustrate the theoretical results.

This paper investigates the adaptive synchronization of complex dynamical networks satisfying the local Lipschitz condition with switching topology. Based on differential inclusion and nonsmooth analysis, it is proved that all nodes can converge to the synchronous state, even though only one node is informed by the synchronous state via introducing decentralized adaptive strategies to the coupling strengths and feedback gains. Finally, some numerical simulations are worked out to illustrate the analytical results.

The article examines the formation of Republican-era Chinese writers particularly Lu Xun's and Lao She's rhetorical preference of referring to Chinese people as dogs in their literary works and its potential impact on nationalistic sentiments of Chinese during that era and since. Topics include the author's use of literature such as short stories, novel and essays in studying the expression "Chinese people are dogs" and external factors that stimulated China's establishment as a modern state.