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BackgroundThe prognostic value and immune significance of T-cell proliferation regulators (TCRs) in hepatocellular carcinoma (HCC) have not been previously reported. This study aimed to develop a new prognostic model based on TCRs in patients with HCC.MethodThis study used The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and International Cancer Genome Consortium-Liver Cancer-Riken, Japan (ICGC-LIRI-JP) datasets along with TCRs. Differentially expressed TCRs (DE-TCRs) were identified by intersecting TCRs and differentially expressed genes between HCC and non-cancerous samples. Prognostic genes were determined using Cox regression analysis and were used to construct a risk model for HCC. Kaplan-Meier survival analysis was performed to assess the difference in survival between high-risk and low-risk groups. Receiver operating characteristic curve was used to assess the validity of risk model, as well as for testing in the ICGC-LIRI-JP dataset. Additionally, independent prognostic factors were identified using multivariate Cox regression analysis and proportional hazards assumption, and they were used to construct a nomogram model. TCGA-LIHC dataset was subjected to tumor microenvironment analysis, drug sensitivity analysis, gene set variation analysis, and immune correlation analysis. The prognostic genes were analyzed using consensus clustering analysis, mutation analysis, copy number variation analysis, gene set enrichment analysis, and molecular prediction analysis.ResultsAmong the 18 DE-TCRs, six genes (DCLRE1B, RAN, HOMER1, ADA, CDK1, and IL1RN) could predict the prognosis of HCC. A risk model that can accurately predict HCC prognosis was established based on these genes. An efficient nomogram model was also developed using clinical traits and risk scores. Immune-related analyses revealed that 39 immune checkpoints exhibited differential expression between the high-risk and low-risk groups. The rate of immunotherapy response was low in patients belonging to the high-risk group. Patients with HCC were further divided into cluster 1 and cluster 2 based on prognostic genes. Mutation analysis revealed that HOMER1 and CDK1 harbored missense mutations. DCLRE1B exhibited an increased copy number, whereas RAN exhibited a decreased copy number. The prognostic genes were significantly enriched in tryptophan metabolism pathways.ConclusionsThis bioinformatics analysis identified six TCR genes associated with HCC prognosis that can serve as diagnostic markers and therapeutic targets for HCC.

Abstract Hepatocellular carcinoma (HCC) represents a major global health threat with diverse and complex pathogenesis. Aldo–keto reductase family 1 member B10 (AKR1B10), a tumor-associated enzyme, exhibits abnormal expression in various cancers. However, a comprehensive understanding of AKR1B10's role in HCC is lacking. This study aims to explore the expression characteristics of AKR1B10 in HCC and its correlation with clinicopathological features, survival prognosis, and tumor immune microenvironment, further investigating its role and potential regulatory mechanisms in HCC. This study conducted comprehensive analyses using various bioinformatics tools and databases. Initially, differentially expressed genes related to HCC were identified from the GEO database, and the expression of AKR1B10 in HCC and other cancers was compared using TIMER and GEPIA databases, with validation of its specificity in HCC tissue samples using the HPA database. Furthermore, the relationship of AKR1B10 expression with clinicopathological features (age, gender, tumor size, staging, etc.) of HCC patients was analyzed using the TCGA database's LIHC dataset. The impact of AKR1B10 expression levels on patient prognosis was evaluated using Kaplan–Meier survival analysis and the Cox proportional hazards model. Additionally, the correlation of AKR1B10 expression with tumor biology-related signaling pathways and tumor immune microenvironment was studied using databases like GSEA, Targetscan, and others, identifying microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate AKR1B10 expression to explore potential regulatory mechanisms. Elevated AKR1B10 expression was significantly associated with gender, primary tumor size, and fibrosis stage in HCC tissues. High AKR1B10 expression indicated poor prognosis and served as an independent predictor for patient outcomes. Detailed mechanism analysis revealed a positive correlation between high AKR1B10 expression, immune cell infiltration, and pro-inflammatory cytokines, suggesting a potential DANCR-miR-216a-5p-AKR1B10 axis regulating the tumor microenvironment and impacting HCC development and prognosis. The heightened expression of AKR1B10 in HCC is not only related to significant clinical-pathological traits but may also influence HCC progression and prognosis by activating key signaling pathways and altering the tumor immune microenvironment. These findings provide new insights into the role of AKR1B10 in HCC pathogenesis and highlight its potential as a biomarker and therapeutic target.

Abstract Several studies have reported the effects of DJ-1 gene and miR-199a/b-3p on HCC development. However, whether miR-199a/b-3p regulates HCC progression through a novel compensatory signaling pathway involving DJ-1, Ras, and PI3K/AKT remains unknown. We used (TCGA, HPA, miRWalk and Target scan) databases, cancer and para-tissue HCC patients, dual-luciferase reporter gene analysis, proteomic imprinting, qPCR, cell proliferation, scratch, transport, and flow cytometry to detect the molecular mechanism of DJ-1 and miR-199a/b-3p co-expression in HCC cell lines. Bioinformatics analysis showed that DJ-1 was highly expressed in HCC ((P

IntroductionMonoecy is usually interpreted as an important evolutionary route of the plant sexual system from hermaphroditism to dioecy. This floral mechanism can effectively reduce self-interference during the reproductive process, and the services provided by pollinators may play an essential role in monoecious species; however, relevant research is still lacking. Thus, we aimed to determine whether monoecious plants could effectively avoid self-interference and promote the evolution of monoecy under the service of pollinators.MethodsHere, we successfully performed manipulation experiments to test self-compatibility, pollinator behavior, and self-interference between male and female functions in Akebia trifoliata, a typical monoecious species.ResultsWe demonstrated that experimental self-pollination did not yield any fruit, and supplemental pollination significantly increased fruit set and fruit weight compared to natural pollination, suggesting that this species is completely self-incompatible and experiences strong pollen limitation. Simultaneous self- and cross-pollination and self-pollination prior to cross-pollination significantly reduced reproductive fitness, but self-pollination after cross-pollination did not, indicating self-interference in this plant. Moreover, both male flower probing preference and switching modes within inflorescences by pollinators successfully reinforced self-interference and were also responsible for decreasing reproductive fitness in A. trifoliata.DiscussionIn summary, pollinator-mediated self-interference significantly reduced selfing, providing potential dynamics for the maintenance and evolution of monoecy.

In this paper, we define second-order $ \lambda $-Hadamard product of a class of meromorphic Janowski function and study the closure properties of the above product.

Abstract Background The Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and cirrhosis. Besides, some papers showed that GP73 levels are correlated with liver fibrosis. This study conducts a meta-analysis to evaluate the value of GP73 in diagnosing HCC and differential diagnosing HCC from liver cirrhosis. Methods 36 studies with a sample size of 8314 cases concerning the accuracy of GP73 in the diagnosis of HCC were selected through a systematic review. Seven of these studies included a total of 438 HCC samples and 426 cirrhosis samples and calculated the sensitivity and specificity of GP73 for differential diagnosing HCC from cirrhosis. QUADAS (quality assessment of diagnostic accuracy studies) was used to evaluate the quality of literature. Statistical analyses were performed using StataSE16 software. Results The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve were 0.79(95%CI 0.74–0.83),0.85(95%CI 0.80–0.89),5.4(95%CI 3.8–7.5), 0.25(95%CI 0.20–0.31), 22(95%CI 13–35), and 0.88 for GP73 diagnosing HCC;0.74(95%CI 0.64–0.81),0.70(95%CI 0.49–0.85),2.40(95%CI 1.3–4.7),0.38(95%CI 0.23–0.61),6(95%CI 2–19), and 0.78 for GP73 differential diagnosing HCC from liver cirrhosis. Conclusion The results suggest that GP73 has a high diagnostic value for HCC and a moderate value for differential diagnosis of HCC from liver cirrhosis.

ObjectiveBipolar disorder (BD) and major depressive disorder (MDD) are two common psychiatric disorders. Due to the overlapping clinical symptoms and the lack of objective diagnostic biomarkers, bipolar disorder (BD) is easily misdiagnosed as major depressive disorder (MDD), which in turn affects treatment decisions and prognosis. This study aimed to investigate biomarkers that could be used to differentiate BD from MDD.MethodsNuclear magnetic resonance (NMR) spectroscopy was performed to assess serum metabolic profiles in depressed patients with BD (n = 59), patients with MDD (n = 14), and healthy controls (n = 10). Data was analyzed using partial least squares discriminant analysis, orthogonal partial least squares discriminant analysis and t-tests. Different metabolites (VIP > 1 and p < 0.05) were identified and further analyzed using Metabo Analyst 5.0 to identify relevant metabolic pathways.ResultsThe metabolic phenotypes of the BD and MDD groups were significantly different from those of the healthy controls, and there were different metabolite differences between them. In the BD group, the levels of 3-hydroxybutyric acid, n-acetyl glycoprotein, β-glucose, pantothenic acid, mannose, glycerol, and lipids were significantly higher than those in the healthy control group, and the levels of lactate and acetoacetate were significantly lower than those in the healthy control group. In the MDD group, the levels of 3-hydroxybutyric acid, n-acetyl glycoprotein, pyruvate, choline, acetoacetic acid, and lipids were significantly higher than those of healthy controls, and the levels of acetic acid and glycerol were significantly lower than those of healthy controls.ConclusionGlycerolipid metabolism is significantly involved in BD and MDD. Pyruvate metabolism is significantly involved in MDD. Pyruvate, choline, and acetate may be potential biomarkers for MDD to distinguish from BD, and pantothenic acid may be a potential biomarker for BD to distinguish from MDD.

In this present investigation, the authors obtain Fekete-Szegö inequality for certain normalized analytic function $ f(\zeta) $ defined on the open unit disk for which $ (f'(\zeta)^{\vartheta}\left( \frac{\zeta f'(\zeta )}{f(\zeta )}\right)^{1-\vartheta} \prec 1+\sin \zeta ; \qquad (0\leq \vartheta \leq 1) $ lies in a region starlike with respect to $ 1 $ and symmetric with respect to the real axis. As a special case of this result, the Fekete-Szegö inequality for a class of functions defined through Poisson distribution series is obtained. Further, we discuss the second Hankel inequality for functions in this new class.

ObjectivesThis study compared different extraction methods of Yizhiqingxin formula (YQF) and its neuroprotective effects based on pharmacodynamic indices such as learning and memory ability, brain tissue histopathology and morphology, and inflammatory factor expression in a mouse model of Alzheimer’s disease (AD).MethodsThe pharmaceutical components of YQF were extracted using three extraction processes, and the components were analyzed by high performance liquid chromatography. Donepezil hydrochloride was used as a positive control drug. Fifty 7–8-month-old 3 × Tg AD mice were randomly divided into three YQF groups (YQF-1, YQF-2, and YQF-3), a donepezil group, and a model group. Ten age-matched C57/BL6 mice were used as normal controls. YQF and Donepezil were administered by gavage at a clinically equivalent dose of 2.6 and 1.3 mg⋅kg–1⋅d–1, respectively, with a gavage volume of 0.1 ml/10 g. Control and model groups received equal volumes of distilled water by gavage. After 2 months, the efficacy was evaluated using behavioral experiments, histopathology, immunohistochemistry, and serum assays.ResultsThe main components in YQF are ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, epiberberine, coptisine chloride, palmatine, berberine, and ferulic acid. YQF-3 (alcohol extraction) has the highest content of active compounds, followed by YQF-2 (water extraction and alcohol precipitation method). Compared to the model group, the three YQF groups showed alleviated histopathological changes and improved spatial learning and memory, with the effect in YQF-2 being the most significant. YQF showed protection of hippocampal neurons, most significantly in the YQF-1 group. YQF significantly reduced Aβ pathology and tau hyperphosphorylation, decreased expressions of serum pro-inflammatory factors interleukin-2 and interleukin-6 as well as serum chemokines MCP-1 and MIG.ConclusionYQF prepared by three different processes showed differences in pharmacodynamics in an AD mouse model. YQF-2 was significantly better than the other extraction processes in improving memory.

In this paper, we introduce a class of meromorphic starlike function by subordination relationship and generalized λ-Hadamard product. We obtain the necessary and sufficient conditions and closure properties of the class. In addition, some new results of the class are given.

AIM:To observe the effect of different time of wearing overnight orthokeratology lens(OOK lens)on the meibomian gland and detection rate of demodex.METHODS:Case-control study. Totally 47(91 eyes)patients who wearing keratoscopy were enrolled from June 2019 to December 2019 in Hanyang Aier Eye Hospital. According to the wearing time, they were divided into short-term group(wearing time RESULTS: The three groups of NI-BUT were 12.68±4.59s, 12.37±4.97s, 10.45±6.04s,(P>0.05). BRS respectively were 0.99±0.41, 0.90±0.37, 0.84±0.35,(P>0.05). Meibomian gland score for all three groups: 1(0, 1)(P>0.05). In the three groups, the detection rate and quantity of demodex were 42%, 1(1, 2); 39%, 2(1, 2); 33%, 1(1, 2),(P>0.05). Among the patients with corneal staining, 5 were mite positive and 11 were mite negative(P>0.05). Meibomian gland score: 4 eyes were 0 grade, 12 eyes were 1 grade above(P>0.05). Short-term group 6 eyes, long-term group 10 eyes(P>0.05). CONCLUSION:There was no significant effect on meibomian gland, the detection rate and quantity of demodex in patients wearing OOK lens. Whereas no significant relationship between meibomian gland score/ demodex detection rate and corneal staining.

Background: Bipolar disorder (BD) is a serious mental disease with complex clinical manifestations and high recurrence rate. The purpose of this study was to detect metabolites related to the diagnosis and efficacy evaluation of bipolar depression in plasma samples by metabolomics.Methods: Thirty-one bipolar depression patients were recruited and completed 8 weeks medication and a matched group of 47 healthy controls (HCs) was recruited. Nuclear magnetic resonance spectroscopy was used to profile plasma samples of bipolar depression patients at baseline and after 8 weeks medication, and HCs. Then Multivariate statistical analysis was performed to analyze differences of plasma metabolites among the three groups.Results: We detected seven specific differential metabolites in bipolar depression. Six of the metabolites were returned to the normal levels in different degrees after 8 weeks medication, only Glycine continuously decreased in the acute and significant improvement stages of bipolar depression (VIP > 1 and p < 0.05). These differential metabolites involved several metabolic pathways.Limitations: The small sample size was one of the most prominent limitations. Each BD patient was given an individualized medication regimen according to the clinical guidelines.Conclusion: There were metabolites changes before and after 8 weeks medication. Glycine may be a characteristic marker of bipolar depression and does not change with the improvement of bipolar depression, while other 6 differential metabolites may be biomarkers associated with the pathological development or the improvement of bipolar depression. And, these differential metabolites mainly related to energy metabolism, amino acid metabolism and gut microbiota metabolism.

Alzheimer’s disease (AD) is the most common form of dementia. Although the incidence of AD is high, the rates of diagnosis and treatment are relatively low. Moreover, effective means for the diagnosis and treatment of AD are still lacking. MicroRNAs (miRNAs, miRs) are non-coding RNAs that play regulatory roles by targeting mRNAs. The expression of miRNAs is conserved, temporal, and tissue-specific. Impairment of microRNA function is closely related to AD pathogenesis, including the beta-amyloid and tau hallmarks of AD, and there is evidence that the expression of some microRNAs differs significantly between healthy people and AD patients. These properties of miRNAs endow them with potential diagnostic and therapeutic value in the treatment of this debilitating disease. This review provides comprehensive information about the regulatory function of miRNAs in AD, as well as potential applications as diagnostic biomarkers.

Aerobic glycolysis is a recognized feature shared by tumors, leading to the accumulation of lactic acid in their local microenvironments. Like the tumors, the blastocysts, placenta, trophoblasts and decidual immune cells can also produce a large amount of lactic acid through aerobic glycolysis during the early pregnancy. Moreover, the placenta expresses the transporters of the lactic acid. While several studies have described the role of lactic acid in the tumor microenvironment, especially lactic acid's modulation of immune cells, the role of lactic acid produced during pregnancy is still unclear. In this paper, we reviewed the scientific evidence detailing the effects of lactic acid in the tumor microenvironment. Based on the influence of the lactic acid on immune cells and tumors, we proposed that lactic acid released in the unique uterine environment could have similar effects on the trophoblast cells and immune cells during the early pregnancy.

AIM: To observe the effect of orthokeratology on the positive relative accommodation of juvenile with myopia. METHODS: Retrospective analysis of cases. All 122 cases(244 eyes)of juvenile with myopic from September 2016 to December 2017 in our hospital were analyzed. 63 cases were corrected by orthokeratology lens and 59 cases were corrected by glasses. data of the binocular positive relative accommodation before treatment and 6mo after treatment were compared between the two groups. RESULTS:Before treatment, the average PRA value of the orthokeratology group(-0.83±0.23)D and the average PRA value of the glasses group(-0.77±0.24)D were no significant difference(t= -1.457, P>0.05). There was no significant difference between the two groups before treatment in eye axis(orthokeratology group 24.84±0.90mm, glasses group 24.78±0.86mm, t=0.550, P>0.05). PRA in the orthokeratology group -2.27±0.37D was significantly higher than that in the pre-treatment group -0.83±0.23D(t=37.070, Pt=1.565, P>0.05). After treatment, the PRA of orthokeratology group was better than that of glasses group, and the difference was statistically significant(t=-25.271, Pt=-2.453, Pt=39.135, Pt=-0.932,P>0.05). CONCLUSION: The corrected visual acuity of juvenile myopia by orthokeratology was significantly higher than that by using glasses 6mo after treatment, but there was no significant difference between the two groups in eye axis during 6mo.

Viral infections trigger the innate immune system, serving as the first line of defense, and are characterized by the production of type I interferon (IFN). Type I IFN is expressed in a broad spectrum of cells and tissues in the host and includes various subtypes (IFN-α, IFN-β, IFN-δ, IFN-ε, IFN-κ, IFN-τ, IFN-ω, IFN-ν, and IFN-ζ). Since the discovery of type I IFN, our knowledge of the biology of type I IFN has accumulated immensely, and we now have a substantial amount of information on the molecular mechanisms of the response and induction of type I IFN, as well as the strategies utilized by viruses to evade the type I IFN response. Foot-and-mouth disease virus (FMDV) can selectively alter cellular pathways to promote viral replication and evade antiviral immune activation of type I IFN. RNA molecules generated by FMDV are sensed by the cellular receptor for pathogen-associated molecular patterns (PAMPs). FMDV preferentially activates different sensor molecules and various signal transduction pathways. Based on knowledge of the virus or RNA pathogen specificity as well as the function-structure relationship of RNA sensing, it is necessary to summarize numerous signaling adaptors that are reported to participate in the regulation of IFN gene activation.

Objective(s): Both caloric restriction (CR) and resveratrol (RSV) have been shown to improve learning and memory, but their potential effects in juvenile animals were unknown. Here, we evaluated the effects of RSV and CR on learning and memory function in juvenile mice and investigated potential molecular mechanisms. Methods: Six-week-old C57BL/6J mice were assigned to one of three different dietary groups: normal control (stock diet) (n=12), CR diet (30% caloric reduction diet) (n=12), and RSV diet (stock diet supplemented with 18.6 mg/kg RSV) (n=12), for 6 months. Body weight and blood glucose were measured every 4 weeks. Serum cholesterol and serum triglyceride levels were examined using biochemical methods. Serum insulin and insulin-like growth factor 1 (IGF-1) levels were evaluated using enzyme linked immunosorbant assay (ELISA), and protein expression of silent mating type information regulation 2 homology 1 (SIRT1), p53, p16, peroxisome proliferator-activated receptor γ (PPARγ), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), phosphorylated-cAMP response element-binding protein (p-CREB), and IGF-1 were examined with immunohistochemistry. Results:Although long-term CR diet did not alter physiological conditions in juvenile mice relative to control, RSV supplementation slightly elevated blood glucose, serum triglyceride, and serum insulin levels. Both CR and RSV improved learning and memory function, although the effect of CR was significantly greater. Both CR and RSV downregulated p53 and upregulated IGF-1 in hippocampal CA1 region of mice. Conclusion:We demonstrate that CR and RSV may improve learning and memory by downregulating p53 and upregulating IGF-1 in hippocampal CA1 region of juvenile mice.

AIM:To measure fundamental secretion of tears in young and middle-aged people with Han nationality in Xi'an, and the fundamental secretion of tears in the same samples after they inhabited in 4 300 meter region for 1mo, in order to provide the foundation for further research on prevention and interventions of dry eye in crowd from plain to high altitude region.METHODS:The 43 normal volunteers with 86 eyes were conducted with the Schirmer test to hang the test paper at 1/3 eyelid margin. The length of stained test paper was measured after 5min. After 1mo the volunteers lived in high altitude region, the same test was conducted binocularly. RESULTS:The length of stained test paper in young and middle-aged people with Han nationality was 14.21±3.32mm in Xi'an. And then significantly increased to 20.10±6.62mm after 1mo they lived in high altitudes region.CONCLUSION:There is significant difference of fundamental secretion of tears between the people in Xi'an and those in other areas. Also there is significant difference of fundamental secretion of tears in people before and after living in Plateau.

AIM: To observe theclinical effect of acute infectious endophthalmitis by vitrectomy surgery with silicon oil tamponade.METHODS:The clinical data of 23 patients(23 eyes)diagnosed with acute endophthalmitis in our hospital from January, 2008 to February, 2013 were retrospectively analyzed, excluding the patients with intraocular foreign body. All the patients were undergone routine closed three-channel vitrectomy with silicon oil, including 6 eyes(complicated with traumatic cataract)with Ⅰ lensectomy and Ⅰ intraocular lens(IOL)implantation, 3 eyes(complicated with traumatic cataract)with Ⅰ lensectomy and Ⅱ IOL implantation, 4 eyes(complicated with cataract during silicon oil tamponade)with Ⅱ lensectomy and Ⅱ IOL implantation, 5 eyes(4 eyes with traumatic endophthalmitis and 1 eye with entophthalmia caused by glaucoma filtering bleb leaking)reserved lens, 1 eye(post-cataract surgery entophthalmia)with Ⅰ IOL explantation and Ⅱ IOL implantation, and 4 eyes(post-cataract surgery entophthalmia)reserved lens. RESULTS:Within follow-up 6～24mo, inflammation after vitrectomy surgery with silicon oil tamponade was controlled in all the 23 patients(23 eyes). Final visual acuity was improved in 21 eyes(91%). The intraocular pressure(IOP)of 2 eyes were over 30mmHg. IOP of 1 eye was controlled after silicon oil removed, and IOP of the other eye after silcon oil extraction was still high and needed to be controlled by IOP lowering drugs. CONCLUSION: The patients of acuteinfectious endophthalmitis should undergo vitrectomy with silicon oil tamponade as early as possible, which can effectively controli endophthalmitis and improve visual acuity.

There are many articles in the literature dealing with the first-order and the second-order differential subordination and superordination problems for analytic functions in the unit disk, but only a few articles are dealing with the above problems in the third-order case (see, e.g., Antonino and Miller (2011) and Ponnusamy et al. (1992)). The concept of the third-order differential subordination in the unit disk was introduced by Antonino and Miller in (2011). Let Ω be a set in the complex plane C. Also let p be analytic in the unit disk U=z:z∈C and z

Dengue is the most common arthropod-borne viral (Arboviral) illness in humans. The genetic features concerning the codon usage of dengue virus (DENV) were analyzed by the relative synonymous codon usage, the effective number of codons and the codon adaptation index. The evolutionary distance between DENV and the natural hosts (Homo sapiens, Pan troglodytes, Aedes albopictus and Aedes aegypti) was estimated by a novel formula. Finally, the synonymous codon usage preference for the translation initiation region of this virus was also analyzed. The result indicates that the general trend of the 59 synonymous codon usage of the four genotypes of DENV are similar to each other, and this pattern has no link with the geographic distribution of the virus. The effect of codon usage pattern of Aedes albopictus and Aedes aegypti on the formation of codon usage of DENV is stronger than that of the two primates. Turning to the codon usage preference of the translation initiation region of this virus, some codons pairing to low tRNA copy numbers in the two primates have a stronger tendency to exist in the translation initiation region than those in the open reading frame of DENV. Although DENV, like other RNA viruses, has a high mutation to adapt its hosts, the regulatory features about the synonymous codon usage have been 'branded' on the translation initiation region of this virus in order to hijack the translational mechanisms of the hosts.