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Abstract As a remarkably common clinical symptom of many diseases, dysphagia has become a major public health issue. Texture-modified foods is a widespread therapeutic strategy for dysphagia, but the design of texture-modified foods is a challenging task. Considering that the implementation of standardized terms and definitions are helpful for the texture modification of food, literature reviews has been conducted in this paper and relevant classification standards in different countries were summarized. And the techniques and means for food texture modification, such as traditional dietary softening approaches, use of biopolymers, as well as emerging structural technologies were also discussed. In addition, potential research directions have been suggested for the design of texture-modified foods.

IntroductionChaetomium subaffine LB-1 is a novel biocontrol strain that produces non-volatile metabolites that inhibit the growth of Botrytis cinerea. However, the specific metabolites and antimicrobial mechanism of the strain LB-1 remains unclear.MethodsIn this study, the antifungal substances produced by strain LB-1, as well as the underlying mechanism of its inhibitory effect against B. cinerea, were explored using metabolomic and transcriptomic analysis.ResultsThe results found that 45 metabolites might be the key antifungal substances, such as ouabain, ferulic acid, chlorogenic acid, spermidine, stachydrine, and stearic acid. The transcriptomic analysis indicated that the inhibition effect of LB-1 on B. cinerea resulted in the upregulation of genes related to adenosine triphosphate (ATP)-binding cassette (ABC) transporters, peroxisome, ER stress, and multiple metabolic pathways, and in downregulation of many genes associated with the synthesis of cell walls/membranes, carbohydrate metabolism, cell cycle, meiosis, and DNA replication.DiscussionThese results suggested that the inhibitory effect of strain LB-1 against B. cinerea might be due to the destroyed cell wall and membrane integrity exerted by antimicrobial substances, which affect cell metabolism and inhibit cell proliferation.

The impact of cyclodextrins (CDs) on wine quality and stability remains largely unknown. This study systematically assessed the protective effect of the post-fermentation addition of CDs on color stability of red wine from the viewpoints of color characteristics, copigmentation and phenolic profiles. The grey relational analysis (GRA) and principal component analysis (PCA) methods were employed to dissect the key effective determinants related to color quality. The addition of CDs induced a significant hyperchromic effect of 8.19–25.40%, a significant bathochromic effect and an enhancement of the color intensity. Furthermore, the evolution of anthocyanin forms and the content of monomeric anthocyanins revealed that β-CD is a superior favorable cofactor during wine aging, but for long-term aging, 2-HP-β-CD and 2-HP-γ-CD are more beneficial in promoting the formation of polymerized anthocyanins and color stability. This work provides an important reference for the use of CDs to enhance the color quality and stability of red wines.

Wheat sharp eyespot, a stem disease caused by the soilborne fungus Rhizoctonia cerealis van der Hoeven, has become a threat to wheat production worldwide. Exploiting resistance resources from wild relatives of wheat is a promising strategy for controlling this disease. In this study, a new wheat–Dasypyrum villosum T2DS·2V#4L translocation line in the background of Chinese Spring (CS) showed stable resistance to R. cerealis. Introgression of the T2DS·2V#4L chromosome into wheat cultivar Aikang 58 by backcrossing produced a marked increase in sharp eyespot resistance in NIL-T2DS·2V#4L in comparison with NIL-T2DS·2DL, and no detrimental effects of 2V#4L on agronomic traits were observed in the BC2F2, BC2F2:3, and BC2F2:4 generations. Flow-sorted sequencing of 2V#4L yielded 384.3 Mb of assembled sequence, and 8836 genes were predicted of which 6154 had orthologs in at least one of the 2AL, 2BL, and 2DL arms of CS, whereas 1549 genes were unique to 2V#4L. About 100,000 SNPs were detected in genes of 2V#4L and 2DL in 10 sequenced bread wheat cultivars. A Kompetitive Allele Specific Polymerase chain reaction and 30 conserved ortholog sequence markers were developed to trace the 2V#4L chromatin in wheat backgrounds. T2DS·2V#4L compensating translocation lines represent novel germplasm with sharp eyespot resistance and the markers will allow rapid detection in breeding programs.

As a new non thermal pretreatment technology, pulsed electric field (PEF) has excellent characteristics such as short time consumption, low energy consumption and green environmental protection. In this paper, the mechanism of pulsed electric field and its application as pretreatment technology in the field of fruit and vegetable drying, such as hot air drying, freeze drying, microwave drying, osmotic drying, spray drying and vacuum drying, are reviewed. Compared with untreated, PEF pretreatment can improve the dehydration rate, reduce production costs, improve the retention rate of nutrients in the sample, and make the quality of dried products better. However, PEF has some problems, such as the specificity between the parameters and the processing matrix, and the safety of the pretreated food. In the future, it is necessary to strengthen the parameter matching and safety research of PEF, so as to provide new ideas and references for the in-depth research of PEF pretreatment in the field of fruit and vegetable drying.

The skeletal anterior crossbite is a common malocclusion in clinic. However, there have been no reports on the maxillary sagittal expansion to correct the premaxillary hypoplasia, which greatly influences the facial morphology and masticatory function, using finite element analysis. In the present study, a three-dimensional finite element model of craniomaxillofacial complex with maxillary sagittal hypoplasia is constructed and the treatment for premaxillary hypoplasia by the sagittal screw expander appliance is simulated. The hypoplasia of the left premaxilla is more serious than that of the right and thus the size of the left part of premaxillary expander baseplate is designed to be larger than that of the right part and the loading is applied at 10° leftward to the sagittal plane and 30° forward and downward to the maxillary occlusal plane. The displacements or equivalent stress distributions of the maxilla, teeth and their periodontal ligaments, are analyzed under the loads of 5.0 N, 10.0 N, 15.0 N, and 20.0 N. Consequently, as the load increases, the displacements or equivalent stresses of the maxilla, teeth and their periodontal ligaments all increase. Almost the whole premaxilla markedly move forward, downward, and leftward while other areas in the craniomaxillofacial complex remain almost static or have little displacement. The equivalent stress concentration zone of the maxilla mainly occurs around and in front of the incisive foramina. The displacements of left premaxilla are generally greater than those of the right under the loading forces. The maximum equivalent stress on the teeth and their periodontal ligaments are 2.34E-02 MPa and 2.98E-03 MPa, respectively. Taken together, the sagittal screw expander appliance can effectively open the premaxillary suture to promote the growth of the premaxilla. An asymmetrical design of sagittal screw expander appliance achieves the asymmetric expansion of the premaxilla to correct the uneven hypoplasia and obtains the more symmetrical aesthetic presentation. This study might provide a solid basis and theoretical guidance for the clinical application of sagittal screw expander appliance in the efficient, accurate, and personalized treatment of premaxillary hypoplasia.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by inflammation, demyelination, and neurodegeneration. It mainly affects young adults, imposing a heavy burden on families and society. The epidemiology, clinical features, and management of MS are distinct among different countries. Although MS is a rare disease in China, there are 1.4 billion people in China, so the total number of MS patients is not small. Because of the lack of specific diagnostic biomarkers for MS, there is a high misdiagnosis rate in China, as in other regions. Due to different genetic backgrounds, the clinical manifestations of MS in Chinese are different from those in the West. Herein, this review aims to summarize the disease comprehensively, including clinical profile and the status of disease-modifying therapies in China based on published population-based observation and cohort studies, and also to compare with data from other countries and regions, thus providing help to develop diagnostic guideline and the novel therapeutic drugs. Meanwhile, we also discuss the problems and challenges we face, specifically for the diagnosis and treatment of MS in the middle- and low-income countries.

Abstract Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs), which play a pivotal role in inducing either inflammatory or tolerogenic response based on their subtypes and environmental signals. Emerging evidence indicates that DCs are critical for initiation and progression of autoimmune diseases, including multiple sclerosis (MS). Current disease-modifying therapies (DMT) for MS can significantly affect DCs’ functions. However, the study on the impact of DMT on DCs is rare, unlike T and B lymphocytes that are the most commonly discussed targets of these therapies. Induction of tolerogenic DCs (tolDCs) with powerful therapeutic potential has been well-established to combat autoimmune responses in laboratory models and early clinical trials. In contrast to in vitro tolDC induction, in vivo elicitation by specifically targeting multiple cell-surface receptors has shown greater promise with more advantages. Here, we summarize the role of DCs in governing immune tolerance and in the process of initiating and perpetuating MS as well as the effects of current DMT drugs on DCs. We then highlight the most promising cell-surface receptors expressed on DCs currently being explored as the viable pharmacological targets through antigen delivery to generate tolDCs in vivo.

Itaconate has been identified as an immunomodulatory metabolite produced by activated macrophages, but methods for detecting itaconate in live cells are lacking. Here, the authors develop a fluorescent biosensor named BioITA for detecting itaconate in subcellular compartments of living macrophages.

Excessive consumption of fructose contributes to cancer development, but the underlying mechanisms are poorly understood. Here, the authors show that glucose deprivation induces fructolysis through selective activation of ATF4 translation, thereby supporting malignant progression of human glioblastoma.

Prohibitins recruit ChATG24 into the mitochondria to modulate mitophagy, thereby affecting the virulence of Colletotrichum higginsianum.

Covered stent graft implantation is currently the most commonly used modality for the management of adult aortic coarctation. Although the risk of descending thoracic aortic dissection after covered stent graft implantation is low, sometimes it may cause serious medical consequences or even death. We report one adult aortic coarctation patient with early postoperative descending thoracic aortic dissection after covered stent graft implantation. The patient underwent second operation of thoracic endovascular aortic reconstruction and was discharged 6 days after the operation. This case is not rare, but we hope that the complete diagnosis and treatment process of this case and discussion pertaining to surgical treatment method and its complications could serve as a reference for clinicians in dealing with such situations.

BackgroundThe incidence, clinicopathologic characteristics, treatment patterns, and survival of early-onset pancreatic neuroendocrine neoplasms (EOPanNENs) have not been well explored.MethodsPatients diagnosed with PanNENs were identified from the SEER database between 2000 and 2018. EOPanNENs were defined as diagnosis in patients aged less than 50 years, while the remaining were defined as later-onset pancreatic neuroendocrine neoplasms (LOPanNENs). Incidence, clinical features, management, and prognosis were analyzed in our study. Multivariable analyses were performed to identify factors associated with overall survival (OS) in EOPanNENs and LOPanNENs, respectively.ResultsA total of 5172 patients with PanNENs were included: 1267 (24.5%) in the EOPanNENs cohort and 3905 (75.5%) in the LOPanNENs cohort. The age-adjusted incidence rate significantly increased among later-onset cases, while it remained relatively stable in early-onset cases. EOPanNENs were more frequently to be female, unmarried, and with better tumor differentiation compared with LOPanNENs. Of note, early-onset patients presented with a higher rate of lymph node involvement, and they were more likely to receive surgical treatment. For local-regional disease at presentation, surgery alone was the most frequently used regimen over the last two decades. With regard to distant stage, a combination of surgery and chemotherapy was more often utilized. Risk factors for PanNENs survival were more correlated with LOPanNENs compared with EOPanNENs. The OS and cancer-specific survival (CSS) were significantly better in the EOPanNENs group. Further analyses showed that EOPanNENs ≤ 2cm were associated with more favorable survival outcomes than EOPanNENs>2cm.ConclusionEOPanNENs are a clinically rare and distinct entity from LOPanNENs. The advantages in survival for the EOPanNENs cohort over time were largely driven by the indolent clinical courses including better tumor differentiation and intensified surgical treatment. Further investigations are warranted to better understand the characteristics of this disease subgroup.

Abstract Background Oral squamous cell carcinoma (OSCC) is one of the common cancers worldwide. The lack of specific biomarkers and therapeutic targets leads to delayed diagnosis and hence the poor prognosis of OSCC patients. Thus, it is urgent to identify effective biomarkers and therapeutic targets for OSCC. Methods We established the golden hamster carcinogenic model of OSCC induced by 7,12-dimethylbenz(a) anthrancene (DMBA) and used mRNA microarrays to detect the differentially expressed genes (DEGs). DEGs were validated in OSCC clinical tissue microarrays using immunohistochemistry method. Whole transcriptome sequencing was performed to obtain an overview of biological functions of Lsm12. PCR assay and sequencing were employed to investigate the alternative splicing of genes regulated by Lsm12. Cell proliferation, colony formation, Transwell migration and invasion assay and in vivo tumor formation assay were performed to investigate the roles of Lsm12 and two transcript variants of USO1 in OSCC cells. Results Lsm12 was identified to be significantly up-regulated in the animal model of OSCC tumorigenesis, which was validated in the clinical OSCC samples. In the paired normal tissues, Lsm12 staining was negative (91%, 92/101) or weak, while in OSCC tissues, positive rate is 100% and strong staining spread over the whole tissues in 93 (93/101, 92%) cases. Lsm12 overexpression significantly promoted OSCC cell growth, colony formation, migration and invasion abilities, while Lsm12 knockdown showed the opposite trends on these phenotypes and obviously inhibited the tumor formation in vivo. Furthermore, Lsm12 overexpression caused the inclusion of USO1 exon 15 and Lsm12 knockdown induced exon 15 skipping. Exon 15-retained USO1 significantly promoted the malignant phenotypes of OSCC cells when compared with the exon 15-deleted USO1. Conclusions We identified Lsm12, a novel tumorigenesis-related gene, as an important regulator involved in OSCC tumorigenesis. Lsm12 is a novel RNA-splicing related gene and can regulate the alternative splicing of USO1 exon 15 which was associated closely with OSCC carcinogenesis. Our findings thus provide that Lsm12 might be a potent biomarker and potential therapeutic target for OSCC.

The antifungal effect and mucolytic activity of a newly screened biocontrol strain Chaetomium subaffine LB-1 were researched in this study. The results found that LB-1 has good antifungal effects on the test plant pathogenic fungi Botrytis cinerea Pers. ex Fr., Fusarium oxysporum f. sp. cucumerinum Owen and Alternaria solani (Ellis & Martin) Sorauer in dual culture assay, with the inhibition rates of 61.39, 50.34 and 51.22%, respectively. Flocculated and dissolved hyphae of the phytopathogenic fungi were observed at the interaction zone on a dual-cultured PDA plate, but the hyphae of LB-1 were normal. The LB-1 cell-free filtrate has significant inhibitory effects on the three tested fungi in the poison plate assay; dissolved colonies, vesiculated and flocculated hyphae of the test pathogenic fungi were also found on the PDA plates supplemented with the LB-1 cell-free filtrate. Clear halo zones around the LB-1 colonies were found on the protease test plate, pectinase test plate and cellulose test plate, indicating that LB-1 could produce mucolytic enzymes of protease, pectinase and cellulase. However, the activities of chitinase and β-l,3-glucase were not detected on their test plates from LB-1. An obvious oil-displaced circle was formed in the oil spreading test, indicating that a surface-active substance might be contained in the LB-1 cell-free filtrate. These results proved that the biocontrol agent of C. subaffine LB-1 could exert its antifungal effects via living competition and mycolysis, and the latter may be obtained by production of mycolytic enzymes and surface-active substances. .

ObjectiveTo evaluate the efficacy and safety of acupuncture in treating symptoms for Cancer-related Insomnia(CRI) patients.MethodsSeven databases were searched from the time of database establishment to 31 March 2022. Randomized Controlled Trials (RCTs) on acupuncture intervention for CRI were collected. Literature screening and data extraction were performed independently by two researchers. Meta-analysis was performed using RevMan 5.4 software.ResultsA total of 13 articles with 1,109 participants were included. Five hundred and seventeen in the treatment group and 592 in the control group. Ten of the RCTs used the PSQI rating scale and four randomized controlled trials used the ISI rating scale, and the PSQI and ISI were analyzed together as continuous data. The results of the meta-analysis were: MD = −1.83, 95%CI = [−2.71, −0.94], P < 0.0001, indicating a significant improvement in PSQI scores in patients with CRI by acupuncture intervention; MD = 0.79, 95%CI = [−0.46, 2.03], P = 0.22. Acupuncture was not statistically significant on ISI scores for patients with CRI compared to controls, which does not yet indicate that acupuncture is effective for symptoms in patients with CRI. The results of the meta-analysis of the other 4 items using sleep disorder logs as efficacy analysis data were as follow, relative risk RR = 0.47, 95%CI = [0.33, 0.66], P < 0.0001. The difference was statistically significant, indicating that acupuncture can improve the symptoms of CRI patients compared to control group.ConclusionAcupuncture can improve the symptoms of patients with CRI to some extent, but due to the relatively small number and low quality of the included literature in this study, more high-quality clinical trials are needed as supplement the evidences in future.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/.

Abstract In the present study, we aimed to find the target of Tanshinone IIA (Tan-IIA) in Cholangiocarcinoma by network pharmacology-based prediction and investigate the possible mechanism through experimental verification. In this study, we combined Tan-IIA-specific and Cholangiocarcinoma-specific targets with protein–protein interactions (PPI) to construct a Tan-IIA targets-Cholangiocarcinoma network, and network pharmacology approach was applied to identify potential targets and mechanisms of Tan-IIA in the treatment of Cholangiocarcinoma. The anti-cancer effects of Tan-IIA were investigated by using subcutaneous tumorigenic model in nude mice and in the human Cholangiocarcinoma cell lines in vitro. Our results showed that Tan-IIA treatment considerably suppressed the proliferation and migration of Cholangiocarcinoma cells while inducing apoptosis of Cholangiocarcinoma cells. Western blot results demonstrated that the expression of PI3K, p-Akt, p-mTOR, and mTOR were inhibited by Tan-IIA. Meanwhile, After treatment with Tan-IIA, the level of Bcl2 was downregulated and cleaved caspase-3 expression increased. Further studies revealed that the anticancer effects of Tan-IIA were severely mitigated by pretreatment with a PI3K agonist. Our research provides a new anticancer strategy and strengthens support for the use of Tan-IIA as an anticancer drug for the treatment of CCA.

The object of this work was to study the effects of preliminary vacuum drying (VD), pulsed electric field (PEF) treatment, frying temperature on color, oil uptake, and acrylamide (AA) content in fried potato chips. The results of this study indicated that an increase of frying temperature from 120 to 180°C led to a decrease of frying time of around 70% for untreated and PEF pre-treated samples. The color value of L* and a* decreased with the increase of frying temperature, and those values of the sample pre-treated by PEF were significantly higher compared to those obtained from untreated samples. The PEF pre-treatment promoted the reduction of oil content of fried samples by up to 17.6, 14.2, and 16% compared with untreated samples at the frying temperatures of 120, 150, and 180°C, respectively. Higher efficiency was observed by applying the preliminary VD in the case of the frying temperature of 150°C. Furthermore, it was revealed that PEF pre-treatment and preliminary VD application lead to a synergetic effect on the reduction of AA content in potato chips. For example, with the initial moisture ratio of 0.5, pre-dried by VD and pre-treated by PEF, the AA content was noticeably decreased from 2,220 to 311 μg/kg compared to untreated and undehydrated samples at the frying temperature of 150°C. Our findings provide reference for a new pre-treatment to mitigate AA formation and to improve the quality of potato chips.

The effects of pulsed electric fields (PEF) and blanching pretreatments on frying kinetics, oil content, color, texture, acrylamide (AA) content, and microstructure have been investigated in this paper. The total PEF pretreatment duration was tPEF = 0.2 s with an intensity of E = 1 kV/cm; blanching was studied at 85 °C for 5 min. The results demonstrated that pretreatment significantly reduced the moisture ratio and oil content by 25% and 40.33%, respectively. The total color change ΔE value of the pretreated samples was lower than that of the untreated samples. In addition, pretreatment increased the hardness of the sample after frying, and the AA content in the fried samples pretreated with PEF + blanching was reduced by approximately 46.10% (638 μg/kg). Finally, fried sweet potato chips obtained by the combined pretreatment exhibited a smoother and flatter cross-sectional microstructure.

The calcium/calcineurin signaling pathway plays a key role in the development and virulence of plant pathogenic fungi, but the regulation of this signaling pathway is still not clear. In this study, we identified a calcineurin regulator MoRCN1 in the plant pathogenic fungus Magnaporthe oryzae and found it is important for virulence by regulating the calcineurin pathway. MoRCN1 deletion mutants were severely decreased in colony growth and conidia formation. More importantly, the deletion of MoRCN1 led to a significant reduction in virulence due to defects in appressorium formation and invasive growth. The ΔMorcn1 mutants were more sensitive to different stresses and induced host ROS accumulation, suggesting a role of MoRCN1 in stress adaptation. We found that MoRCN1 directly interacted with the calcineurin catalytic subunit MoCNA and affected its protein stability, which was therefore important for regulating the calcineurin pathway. Transcriptome analysis showed that MoRCN1 significantly activated 491 genes and suppressed 337 genes in response to calcium ion, partially overlapped with the MoCRZ1-bound genes. Gene Ontology and KEGG pathway analyses indicated that MoRCN1-regulated genes were enriched in stress adaptation, lipid metabolism, and secondary metabolite biosynthesis, reflecting a function of MoRCN1 in host cell adaptation. Altogether, these results suggest MoRCN1 functions as a regulator of the calcium/calcineurin signaling pathway for fungal development and infection of host cells.

Hepatocellular carcinoma is one of the most malignant tumors, and the therapeutic effects of traditional treatments are poor. It is urgent to explore and identify new biomarkers and therapeutic targets to develop novel treatments which are individualized and effective. Three hallmarks, including E2F targets, G2M checkpoint and DNA repair, were collected by GSEA analysis. The panel of E2F-related gene signature consisted of five genes: HN1, KIF4A, CDCA3, CDCA8 and SSRP1. They had various mutation rates ranging from 0.8 to 5% in hepatocellular carcinoma, and patients with gene mutation had poorer prognosis. Among these genes, HN1 has the greatest mutation rate, and SSRP1 has the greatest impact on the model with a B (COX) value of 0.8842. Patients with higher expression of these genes had poorer prognosis. Kaplan-Meier curves in stratified survival analysis confirmed that patients with high risk scores had poor prognosis (p < 0.05). The results of univariate and multivariate COX survival analysis showed that risk score was closely related to the overall survival of patients with hepatocellular carcinoma. For clinical validation, we found that all the genes in the model were upregulated in hepatocellular carcinoma tissues compared to normal liver tissues, which was consistent with the previous results we obtained. Our study demonstrated that a panel of E2F target genes signature including five genes could predict the prognosis of hepatocellular carcinoma. This panel gene signature can facilitate the development of individualized and effective treatment for hepatocellular carcinoma.

Abstract Background The mortality rate of hepatocellular carcinoma (HCC) remains high worldwide despite surgery and chemotherapy. Immunotherapy is a promising treatment for the rapidly expanding HCC spectrum. Therefore, it is necessary to further explore the immune-related characteristics of the tumour microenvironment (TME), which plays a vital role in tumour initiation and progression. Methods In this research, 866 immune-related differentially expressed genes (DEGs) were identified by integrating the DEGs of samples from The Cancer Genome Atlas (TCGA)-HCC dataset and the immune-related genes from databases (InnateDB; ImmPort). Afterwards, 144 candidate prognostic genes were defined through weighted gene co-expression network analysis (WGCNA). Results Seven immune-related prognostic DEGs were identified using the L1-penalized least absolute shrinkage and selection operator (LASSO) Cox proportional hazards (PH) model, and the ImmuneRiskScore model was constructed on this basis. The prognostic index of the ImmuneRiskScore model was then validated in the relevant dataset. Patients were divided into high- and low-risk groups according to the ImmuneRiskScore. Differences in the immune cell infiltration of patients with different ImmuneRiskScore values were clarified, and the correlation of immune cell infiltration with immunotherapy biomarkers was further explored. Conclusion The ImmuneRiskScore of HCC could be a prognostic marker and can reflect the immune characteristics of the TME. Furthermore, it provides a potential biomarker for predicting the response to immunotherapy in HCC patients.

A visual and easy-to-implement representation approach of red wine color is proposed in this work. The wine color under standard conditions, called feature color, was reproduced in the form of a circular spot. The feature color was further decomposed into two orthogonal aspects, the chromatic and light–dark components, characterized in the form of chromaticity distribution plane and lightness distribution plane, respectively. The color characterization of wine samples showed that this method well represented the color characteristics and can provide intuitive visual perception of wine color, in a way that is more reliable and convenient than the photographic method. The applications for monitoring the color evolution during winery and laboratory fermentation and the age discrimination of 175 commercial red wines suggest that this visual method is effective for color management and control of wine during fermentation and aging. The proposed method is a convenient way to present, store, convey, understand, analyze and compare the color information of wines.

In order to study the decision-making behavior of the participating groups in shared manufacturing, this paper constructs a tripartite evolutionary game model of shared manufacturing by manufacturing companies under government regulation mechanism. Using evolutionary game theory, it is to analyze the evolutionary stable strategy (ESS) of the model. The utilization efficiency of government regulatory input and the influence of government nonregulation in the proportion of regulatory income are discussed. MATLAB numerical simulation is used to analyze the influence of different parameter changes on the evolution result. It is concluded that the initial sharing probability of manufacturing companies, the level of trust in the company, the government’s penalties for nonsharing parties, the utilization efficiency of government inputs and the rewards given to the government by the state all play a positive role in promoting shared manufacturing and government regulation of manufacturing companies. The lower the ratio of government nonregulation to the income of regulation is, the more active government regulation is. In addition, the shared income should be distributed reasonably. Therefore, in the shared manufacturing process, all the above factors should be considered.

Abstract Ubiquitin-specific protease (UBP) family is the largest group of deubiquitinases, which plays important roles in eukaryotic organisms. Comprehensive analysis of UBP genes has not been conducted in the plant pathogenic fungi. In this study, 11 putative UBP genes were identified and characterized in the rice blast fungus Magnaporthe oryzae. Expression profile analysis showed that UBP3, UBP6, UBP12 and UBP14 were highly expressed in different tissues of M. oryzae. In all ubp mutants, especially Δubp3, Δubp12 and previously reported Δubp14, the ubiquitination levels were evidently elevated, which is consistent with their molecular roles in de-ubiquitination. The Δubp1, Δubp3, Δubp4, Δubp8 and Δubp14 mutants were reduced in colony growth. Most of the ubp mutants were severely reduced in conidia production capacity, indicating important roles of the UBPs in conidia formation. Except for Δubp2 and Δubp16, all of the other mutants were decreased in virulence to host plants and defective in invasive growth. These ubp mutants also induced massive ROS accumulation in host cells. We also found that the UBPs may function as both positive and negative regulators in stress response and nutrient utilization of M. oryzae. Collectively, UBPs are important for development, stress response, nutrient utilization and infection of M. oryzae.

How cancer cells absorb enough glucose to support their rapid growth is poorly understood. We have recently demonstrated that palmitoyl transferase DHHC9 palmitoylates glucose transporter GLUT1 at Cys207 to maintain GLUT1 plasma membrane localization. DHHC9-mediated GLUT1 palmitoylation supports glycolysis, proliferation, colony formation, and tumorigenicity of glioblastoma cells.

The application of spectral reflectance indices (SRIs) as proxies to screen for yield potential (YP) and heat stress (HS) is emerging in crop breeding programs. Thus, a comparison of SRIs and their associations with grain yield (GY) under YP and HS conditions is important. In this study, we assessed the usefulness of 27 SRIs for indirect selection for agronomic traits by evaluating an elite spring wheat association mapping initiative (WAMI) population comprising 287 elite lines under YP and HS conditions. Genetic and phenotypic analysis identified 11 and 9 SRIs in different developmental stages as efficient indirect selection indices for yield in YP and HS conditions, respectively. We identified enhanced vegetation index (EVI) as the common SRI associated with GY under YP at booting, heading and late heading stages, whereas photochemical reflectance index (PRI) and normalized difference vegetation index (NDVI) were the common SRIs under booting and heading stages in HS. Genome-wide association study (GWAS) using 18704 single nucleotide polymorphisms (SNPs) from Illumina iSelect 90K identified 280 and 43 marker-trait associations for efficient SRIs at different developmental stages under YP and HS, respectively. Common genomic regions for multiple SRIs were identified in 14 regions in 9 chromosomes: 1B (60–62 cM), 3A (15, 85–90, 101– 105 cM), 3B (132–134 cM), 4A (47–51 cM), 4B (71– 75 cM), 5A (43–49, 56–60, 89–93 cM), 5B (124–125 cM), 6A (80–85 cM), and 6B (57–59, 71 cM). Among them, SNPs in chromosome 5A (89–93 cM) and 6A (80–85 cM) were co-located for yield and yield related traits. Overall, this study highlights the utility of SRIs as proxies for GY under YP and HS. High heritability estimates and identification of marker-trait associations indicate that SRIs are useful tools for understanding the genetic basis of agronomic and physiological traits.

In the shared manufacturing environment, on the basis of in-depth analysis of the shared manufacturing process and the allocation process of manufacturing resources, a bilevel programming model for the optimal allocation of manufacturing resources considering the benefits of the shared manufacturing platform and the rights of consumers is established. In the bilevel programming model, the flexible indicators representing the interests of the platform are the upper-level optimization target of the model and the Quality of Service (QoS) indicators representing the interests of consumers are the lower-level optimization goal. The weights of the upper indicators are determined by Analytic Hierarchy Process (AHP) and Improved Order Relation Analysis (Improved G1) combination weighting method and the bilevel programming model is solved by the Improved Fast Elitist Non-Dominated Sorting Genetic Algorithm (Improved NSGA-II). Finally, the effectiveness of the model is validated by a numerical example.

Genetic studies have shown essential functions of N-glycosylation during infection of the plant pathogenic fungi, however, systematic roles of N-glycosylation in fungi is still largely unknown. Biological analysis demonstrated N-glycosylated proteins were widely present at different development stages of Magnaporthe oryzae and especially increased in the appressorium and invasive hyphae. A large-scale quantitative proteomics analysis was then performed to explore the roles of N-glycosylation in M. oryzae. A total of 559 N-glycosites from 355 proteins were identified and quantified at different developmental stages. Functional classification to the N-glycosylated proteins revealed N-glycosylation can coordinate different cellular processes for mycelial growth, conidium formation, and appressorium formation. N-glycosylation can also modify key components in N-glycosylation, O-glycosylation and GPI anchor pathways, indicating intimate crosstalk between these pathways. Interestingly, we found nearly all key components of the endoplasmic reticulum quality control (ERQC) system were highly N-glycosylated in conidium and appressorium. Phenotypic analyses to the gene deletion mutants revealed four ERQC components, Gls1, Gls2, GTB1 and Cnx1, are important for mycelial growth, conidiation, and invasive hyphal growth in host cells. Subsequently, we identified the Gls1 N-glycosite N497 was important for invasive hyphal growth and partially required for conidiation, but didn't affect colony growth. Mutation of N497 resulted in reduction of Gls1 in protein level, and localization from ER into the vacuole, suggesting N497 is important for protein stability of Gls1. Our study showed a snapshot of the N-glycosylation landscape in plant pathogenic fungi, indicating functions of this modification in cellular processes, developments and pathogenesis.

The interval concept lattice theory, a new method of mining objects based on interval parameters, can more accurately deal with uncertain information than the classical concept lattice theory. The optimization of interval parameters has been a problem that is not well solved. From the perspective of three-way decision space, we first combine the theories of interval concept lattice and three-way decision and then put forward interval three-way decision space theory; second, in the interval three-way decision space, the positive region, negative region, and boundary region are divided by extension of interval three-way decision concept; further, the decision loss function and three-way decision rules are extracted. Through adjusting interval parameters of the lattice structure, we could find that when parameter α is roughly 0.6, more credible decision rules will be mined and decision-making becomes more clear than that under the condition α is less than 0.6; finally, we verify the model by a “Green Products Recommendation” example.

Abstract Background Increasing evidence reveals a significant correlation between gamma-synuclein (SNCG) level and tumor invasion and metastasis in various human cancers. Our previous investigation showed that SNCG could secrete into extracellular environment and promoted tumor cell motility, but the mechanism is unknown. Methods The membrane binding ability of SNCG was characterized by immunohistochemical staining, immunofluorescence staining and fractionation of colorectal cancer (CRC) cell membrane. Association between SNCG and β1 integrin was validated by coimmunoprecipitation and far Western blot. After inhibition of β1 integrin and focal adhesion kinase (FAK), effect of SNCG on cell motility was measured by transwell chamber assays and changes of protein levels were detected by Western blot. Association between SNCG and activated β1 integrin levels in human CRC tissues was determined by Spearman’s rank correlation analysis. Secreted proteins in conditioned medium (CM) were screened by antibody array. Results Extracellular SNCG bound β1 integrin on CRC cell membrane and increased levels of activated β1 integrin and FAK. Correspondingly, SNCG-enhanced cell motility was counteracted by knockdown or inhibition of β1 integrin or FAK. Further study revealed that high SNCG level indicated poor outcome and SNCG levels positively correlated with those of activated β1 integrin and phospho-FAK (Tyr397) in human CRC tissues. Additionally, extracellular SNCG promoted secretion of fibronectin (FN), vitronectin (VN), matrix metalloproteinase (MMP)-2, and MMP-24 from HCT116 cells. Protease activity of MMP-2 in the CM of HCT116 cells was increased by treatment with SNCG, which was abolished by inhibiting β1 integrin. Conclusion Our results highlight the potential role of SNCG in remodeling extracellular microenvironment and inducing β1 integrin-FAK signal pathway of CRC cells.

Ubiquitin is a small modifier protein which is usually conjugated to substrate proteins for degradation. In recent years, a number of ubiquitin-like proteins have been identified; however, their roles in eukaryotes are largely unknown. Here, we describe a ubiquitin-like protein URM1, and found it plays important roles in the development and infection process of the rice blast fungus, Magnaporthe oryzae. Targeted deletion of URM1 in M. oryzae resulted in slight reduction in vegetative growth and significant decrease in conidiation. More importantly, the Δurm1 mutant also showed evident reduction in virulence to host plants. Infection process observation demonstrated that the mutant was arrested in invasive growth and resulted in accumulation of massive host reactive oxygen species (ROS). Further, we found the Δurm1 mutant was sensitive to the cell wall disturbing reagents, thiol oxidizing agent diamide and rapamycin. We also showed that URM1-mediated modification was responsive to oxidative stresses, and the thioredoxin peroxidase Ahp1 was one of the important urmylation targets. These results suggested that URM1-mediated urmylation plays important roles in detoxification of host oxidative stress to facilitate invasive growth in M. oryzae.

Background: Blood-brain barrier (BBB) pathology exists in neuromyelitis optica spectrum disorders (NMOSD). However, the clinical use of BBB permeability, such as predicting disease severity of NMOSD, has rarely been studied in a large cohort of patients.Objectives: The current study explored the association between BBB permeability and clinical parameters in order to assess if BBB permeability could be a biomarker to predict disease severity and clinical characteristics of NMOSD.Methods: Among 69 enrolled NMOSD patients, 47 with albumin index over 5 × 10−3 were assigned to the increased BBB permeability group, and the remaining 22 were to the normal BBB permeability group. Disease severity was assessed using the Expanded Disability Status Scale (EDSS).Results: Patients in the increased BBB permeability group had significantly higher EDSS scores, anti-aquporin-4 immunoglobulin G titers, more dense cerebrospinal fluid protein concentrations, white blood cell counts, myelin basic protein levels and more dense complement 3 concentrations than found in the comparative normal BBB permeability group. The albumin index was positively correlated to the length of lesions in spinal cord.Conclusions: BBB permeability was associated with clinical features, laboratory results and radiological data of NMOSD patients, and may be a potential biomarker to predict disease severity and clinical characteristics of NMOSD.

Reversible protein ubiquitination plays essential roles in regulating cellular processes. Although many reports have described the functions of ubiquitination in plant defense responses, few have focused on global changes in the ubiquitome. To better understand the regulatory roles of ubiquitination in rice pattern-triggered immunity (PTI), we investigated the ubiquitome of rice seedlings after treatment with two pathogen-associated molecular patterns, the fungal-derived chitin or the bacterial-derived flg22, using label-free quantitative proteomics. In chitin-treated samples, 144 and 167 lysine-ubiquitination sites in 121 and 162 proteins showed increased and decreased ubiquitination, respectively. In flg22-treated samples, 151 and 179 lysine-ubiquitination sites in 118 and 166 proteins showed increased and decreased ubiquitination, respectively. Bioinformatic analyses indicated diverse regulatory roles of these proteins. The ubiquitination levels of many proteins involved in the ubiquitination system, protein transportation, ligand recognition, membrane trafficking, and redox reactions were significantly changed in response to the elicitor treatments. Notably, the ubiquitination levels of many enzymes in the phenylpropanoid metabolic pathway were up-regulated, indicating that this pathway is tightly regulated by ubiquitination during rice PTI. Additionally, the ubiquitination levels of some key components in plant hormone signaling pathways were up- or down-regulated, suggesting that ubiquitination may fine-tune hormone pathways for defense responses. Our results demonstrated that ubiquitination, by targeting a wide range of proteins for degradation or stabilization, has a widespread role in modulating PTI in rice. The large pool of ubiquitination targets will serve as a valuable resource for understanding how the ubiquitination system regulates defense responses to pathogen attack.

Ubiquitination is an essential protein modification in eukaryotic cells, which is reversible. Deubiquitinating enzymes (DUBs) catalyze deubiquitination process to reverse ubiquitination, maintain ubiquitin homeostasis or promote protein degradation by recycling ubiquitins. In order to investigate effects of deubiquitination process in plant pathogenic fungus Magnaporthe oryzae, we generated deletion mutants of MoUBP14. Ortholog of MoUbp14 was reported to play general roles in ubiquitin-mediated protein degradation in Saccharomyces cerevisiae. The ΔMoubp14 mutant lost its pathogenicity and was severely reduced in mycelial growth, sporulation, carbon source utilization, and increased in sensitivity to distinct stresses. The mutant was blocked in penetration, which could due to defect in turgor generation. It is also blocked in invasive growth, which could due to reduction in stress tolerance and nutrient utilization. Deletion of UBP14 also led to accumulation of free polyubiquitin chains. Pulldown assay identified some proteins related to carbohydrate metabolism and stress response may putatively interact with MoUbp14, including two key rate-limiting enzymes of gluconeogenesis, MoFbp1 and MoPck1. These two proteins were degraded when the glucose was supplied to M. oryzae grown in low glucose media for a short period of time (∼12 h), and this process required MoUbp14. In summary, pleiotropic phenotypes of the deletion mutants indicated that MoUbp14 is required for different developments and pathogenicity of M. oryzae.

Honey maturity is an important factor in evaluating the quality of honey. We established a method for the identification of natural mature acacia honey with eighteen physicochemical parameters combined with chemometric analysis. The analysis of variance showed significant differences between mature and immature acacia honey in physicochemical parameters. The principal component analysis explained 82.64% of the variance among samples, and indicated that total phenolic content, total protein content, and total sugar (glucose, fructose, sucrose) were the major variables. The cluster analysis and orthogonal partial least squares-discriminant analysis demonstrated that samples were grouped in relation to the maturity coinciding with the results of the principal component analysis. Meanwhile, the 35 test samples were classified with 100% accuracy with the method of multi-physicochemical parameters combined with chemometric analysis. All the results presented above proved the possibility of identifying mature acacia honey and immature acacia honey according to the chemometric analysis based on the multi-physicochemical parameters.

In ship motion control process, it is difficult to design ship controller due to the effects of environmental disturbances such as wind, waves, current, and unmodelled dynamics. In order to solve these problems, a nonlinear robust controller based on L2-gain disturbance rejection is proposed in this paper. To steer ships to the desired position, an error feedback control law on account of Lyapunov functions is designed. Then, to satisfy the L2-gain disturbance rejection, proper parameters are chosen based on the system dissipative property. In order to verify the performance of the proposed controller, the MATLAB simulation results in two situations which are without and with the effects of environmental disturbances are demonstrated.

This study is aimed at examining the potential roles of circulating memory T follicular helper (Tfh) cells in patients with multiple sclerosis (MS).The numbers of different subsets of circulating memory Tfh cells in 25 patients with relapsed MS before and after treatment as well as 14 healthy controls (HC) were examined by flow cytometry. The levels of plasma IL-21 in all patients and cerebrospinal fluid (CSF) IL-21 in some MS patients and controls with non-inflammatory neuronal diseases (NND) were measured by ELISA.In comparison with that in the HC, the numbers of circulating CD3+CD4+CXCR5+CD45RA-, ICOS+, CCR7+ and CCR7+ICOS+ memory Tfh cells and the levels of plasma IL-21 significantly increased in MS patients, but significantly decreased in the patients with complete remission (CR). The levels of CSF IL-21 were significantly higher in the MS patients than that in the NND patients. The numbers of CCR7+ICOS+ memory Tfh cells were positively correlated with the EDSS scores, the levels of plasma and CSF IL-21, IgG, MBP-Ab or MOG-Ab.Our findings indicated that circulating memory Tfh cells, especially CCR7+ICOS+ memory Tfh cells, may be associated with the relapse of MS and may serve as a new therapeutic target.