Vector Group Research Articles

Selective Nrf2 Overexpression in the RVLM ameliorates Obesity-induced Sympathoexcitation

The rostral part of the ventrolateral medulla (RVLM) in the brainstem is an important region responsible for both the resting levels and the reflex control of sympathetic nerve activity (SNA). Oxidative stress-induced hyperactivation of the glutamatergic neurons in the RVLM has been associated with increases in SNA. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major transcription factor ubiquitously expressed in all cell types and regulates the expression of several antioxidant and anti-inflammatory genes. Previous studies from our lab have demonstrated that obesity-induced sympathoexcitation was associated with Nrf2 dysfunction in the RVLM. Based on this, we hypothesized that Nrf2 overexpression at the level of the RVLM would reverse obesity-induced sympathoexcitation. To address this hypothesis, we selectively overexpressed Nrf2 at the level of the RVLM using a Nrf2 lentiviral vector (HIV-CamKIIa-GFP-Nrf2). This vector drives Nrf2 gene overexpression under the control of CamKIIa promoter that specifically targets the excitatory glutamatergic neurons. A control GFP vector (CamKIIa-GFP-virus) was used in the sham surgeries. For this experiment, two-month-old C57BL/6J mice (n=34, both sexes) were fed a high-fat diet (HFD; 60kcal% fat) or a chow diet (Control; 10kcal% fat) for 4-6 months. The animals were then subdivided into four subgroups (each group included an equal number of animals of both sexes): Chow + Control GFP lentiviral vector, HFD + Control GFP lentiviral vector, Chow + Nrf2 lentiviral vector, HFD + Nrf2 lentiviral vector. After 16 weeks of dietary treatment, the animals were microinjected with either control GFP or Nrf2 lentiviral vector in the RVLM. Two weeks after the microinjection surgery, radiotelemeters were implanted in the mice, and hemodynamic parameters were measured. Hexamethonium, a ganglionic blocker was injected into the animals to measure the drop in MAP, which is an indirect measurement of the whole-body SNA. Major findings from this study include a) As expected, HFD treatment increased systolic blood pressure (SBP), and mean arterial pressure (MAP). Nrf2 overexpression in the RVLM reversed SBP but not MAP in HFD mice when compared to control GFP vector group. b) Consistent with our earlier findings, animals fed with HFD diet showed a significant drop in blood pressure after hexamethonium injection compared to the control animals indicating HFD-induced increase in SNA. Nrf2 overexpression was also able to reduce the drop in MAP in response to hexamethonium in the HFD animals compared to control GFP vector group, suggesting Nrf2 overexpression attenuated obesity-mediated sympathoexcitation. These results indicate that Nrf2 upregulation in the RVLM can be a potential therapeutic option for obesity-induced increase in blood pressure and sympathoexcitation. Supported by: National Heart, Blood and Lung Institute grant R15HL148844 and American Heart Association Institutional Research Enhancement Award - 959725 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The pluripotent factor OCT4A enhances the self-renewal of human dental pulp stem cells by targeting lncRNA FTX in an LPS-induced inflammatory microenvironment

BackgroundRegulating the pluripotency of human dental pulp stem cells (hDPSCs) is key for the self-repair of injured dental pulp. We previously found that OCT4A promotes the proliferation and odontogenic differentiation of human dental pulp cells (hDPCs). Recent studies have shown the interaction between OCT4A and lncRNAs in pluripotency maintenance of various stem cells. The aim of this study was to explore the underlying roles and mechanisms of OCT4A and its related lncRNAs in the proliferation and multidirectional differentiation of hDPSCs in an inflammatory microenvironment.MethodsHuman lncRNA microarrays were applied to screen out the differentially expressed lncRNAs in hDPSCs between the OCT4A-overexpressing and vector groups. Lipopolysaccharide (LPS) was used to simulate the inflammatory microenvironment. The effects of OCT4A and the lncRNA FTX on the proliferation and multidifferentiation of hDPSCs were observed by the CCK-8 assay, EdU staining, real-time PCR, western blotting, and Alizarin red and oil red O staining. Bioinformatics analysis and chromatin immunoprecipitation (ChIP) assays were performed to clarify the targeted mechanism of OCT4A on FTX. The regulation by FTX of the expression of OCT4A and its downstream pluripotent transcription factors SOX2 and c-MYC was further detected by real-time PCR and western blotting.ResultsThe microarray results showed that 978 lncRNAs (250 of which were upregulated and 728 downregulated) were potentially differentially expressed genes (fold change ≥ 2, P < 0.05). LPS stimulation attenuated the self-renewal of hDPSCs. OCT4A enhanced the cell proliferation and multidifferentiation capacities of hDPSCs in an inflammatory microenvironment, while FTX exhibited the opposite effects. OCT4A negatively regulated FTX function by binding to specific regions on the FTX promoter, thereby inhibiting the transcription of FTX. Moreover, overexpression of FTX downregulated the expression of OCT4A, SOX2 and c-MYC, whereas knockdown of FTX facilitated their expression.ConclusionsOCT4A was found to be a crucial factor maintaining the self-renewal of hDPSCs by transcriptionally targeting FTX in an inflammatory microenvironment. Moreover, we proposed a novel function of FTX in negatively regulating the pluripotency and multilineage differentiation capacity of hDPSCs. The hierarchical organization between OCT4A and FTX expanded the understanding of the network between transcription factors and lncRNAs in fine-tuning the pluripotency/differentiation balance of adult stem cells, and provided prospective targets for optimizing dental-derived stem cell sources for regenerative endodontics.

Host associations of biting midges (Diptera: Ceratopogonidae: Culicoides) at deer farms in Florida, USA.

Documenting the host use of vector species is important for understanding the transmission dynamics of vector-borne pathogens. Biting midges (Diptera: Ceratopogonidae: Culicoides) are vectors of epizootic hemorrhagic disease virus (EHDV) and bluetongue virus (BTV) worldwide. However, relative to mosquitoes and many other vector groups, host associations of this group are poorly documented. In this study, we used PCR-based bloodmeal analysis to determine species-level host associations of 3,603 blood-engorged specimens belonging to 18 Culicoides species at 8 deer farms in Florida, USA. We used a binomial mixed model with a Bayesian framework to compare the effect of host composition on the feeding patterns of Culicoides spp. and employed the Morisita-Horn Index to investigate the similarity of host use between farms for Culicoides stellifer and Culicoides insignis. Results show that the estimated probability of Culicoides spp. feeding upon white-tailed deer depends on the availability of cattle or exotic game and demonstrates differences in host-feeding selection among species. Culicoides insignis had high host similarity across farms suggesting that its host-use patterns are somewhat conserved. Culicoides stellifer had lower host similarity across farms suggesting that it is a more opportunistic feeder. White-tailed deer are fed upon by many Culicoides species on deer farms in Florida, and while most Culicoides species feed on white-tailed deer, the ratio of white-tailed deer bloodmeals to other bloodmeals is likely influenced by host availability. Culicoides spp. taking a majority of their bloodmeals from farmed white-tailed deer should be assessed for their vector competence for EHDV and BTV.

Recombinant Adenovirus-Mediated HIF-lα Ameliorates Neurological Dysfunction by Improving Energy Metabolism in Ischemic Penumbra After Cerebral Ischemia-Reperfusion in Rats.

Hypoxia inducible factor-1α (HIF-1α) regulates glucose metabolism during ischemia. This study investigated the effect of recombinant adenovirus HIF-1ɑ on neurological function and energy metabolism in a rat cerebral ischemia-reperfusion model. Rats were divided into four groups: sham-operated (Sham) group, cerebral ischemia-reperfusion (CIR) group, recombinant adenovirus empty vector (Ad) group, and recombinant adenovirus-mediated HIF-1α (AdHIF-1α) group. The AdHIF-1α group and the Ad group were injected with AdHIF-1α and Ad in the lateral ventricle. The mNSS was performed at post-ischemia day 0 (P0) and P1, P14 and P28. At P14, the cerebral infarct volume was compared. At P28, HE staining, Nissl stains and TUNEL staining were performed. The expression of HIF-1α, GLUT1 and PFKFB3 were evaluated by Western Blot and immunohistochemistry. High performance liquid chromatography (HPLC) was used to determine the expression of GLUT1 and PFKFB3, and the level of energy metabolites: ATP, ADP and AMP. mNSS scores in the AdHIF-1α group were consistently lower than those in the CIR and Ad groups from P14 (P < 0.05) and Ad groups (P < 0.05). The cerebral infarct volume was reduced in the AdHIF-1α group compared with that in CIR group and Ad group (P < 0.05). At P28, HE showed better pathological changes in AdHIF-1α group. The number of Nissl bodies was increased in the AdHIF-1α group compared with the CIR and Ad groups (P < 0.05). The number of apoptotic cells in the AdHIF-1α group was fewer than that in the CIR and Ad groups (P < 0.05). The expression of HIF-1α, GLUT1 and PFKFB3 was significantly higher in the AdHIF-1α group compared with the CIR and Ad groups (P < 0.05). The ATP, ADP and AMP in the ischemic penumbra were also higher in the AdHIF-1α group (P < 0.05). HIF-lα promoted neurological function recovery and decreased cerebral infarct volume in rats after cerebral ischemia-reperfusion injury by improving energy metabolism.

Inhibitory effect of miR-138-5p on choroidal fibrosis in lens-induced myopia guinea pigs via suppressing the HIF-1α signaling pathway

Myopia is one of the most common eye diseases in children and adolescents worldwide. Currently, there is no effective treatment in clinical practice. Ocular tissue fibrosis is involved in the development of myopia and this study aimed to investigate the effect of miR-138-5p on choroidal fibrosis in myopic guinea pigs via regulating the HIF-1α signaling pathway. First, guinea pigs were randomly divided into a normal control (NC) group, a lens-induced myopia (LIM) group, a LIM + miR-138-5p-carried Lentivirus treatment (LV) group, and a LIM + miR-138-5p-Vector treatment (VECTOR) group. All animals were induced experimental myopia with a −6.0 diopter lens except those in the NC group. Meanwhile, animals in the LV group were supplemented with 5 μl of miR-138-5p-carried Lentivirus, while those in the VECTOR group were only supplemented with the same volume of miR-138-5p-Vector. After myopia induction for 2 and 4 weeks, the refractive status and other ocular parameters of the guinea pigs were measured. Further, the expression of hypoxia-inducible factor (HIF)-1α, transforming growth factor (TGF)-β, collagen I, hydroxyproline (HYP), interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and a-smooth muscle actin (α-SMA) in choroidal tissues was investigated. Results showed that the refraction and axial length of the experimental myopic guinea pigs increased, and choroid fibrosis aggravated after experimental myopic induction. miR-138-5p can efficiently decrease the refraction and ocular length, and ameliorate the choroidal fibrosis of the experimental myopic guinea pigs via downregulating the fibrosis-related TGF-β1, collagen I, HYP, IL-1β, TNF-α, and α-SMA expression through inhibiting the HIF-1α signaling pathway. Our results provide new insight into controlling myopic development using microRNAs in clinical practice.

CLASH of the Titans: How CAR-T Cells Can Triumph Over Tumors.

CLASH of the Titans: How CAR-T Cells Can Triumph Over Tumors.

A Levenberg-Marquardt Method for Tensor Approximation

This paper presents a tensor approximation algorithm, based on the Levenberg–Marquardt method for the nonlinear least square problem, to decompose large-scale tensors into the sum of the products of vector groups of a given scale, or to obtain a low-rank tensor approximation without losing too much accuracy. An Armijo-like rule of inexact line search is also introduced into this algorithm. The result of the tensor decomposition is adjustable, which implies that the decomposition can be specified according to the users’ requirements. The convergence is proved, and numerical experiments show that it has some advantages over the classical Levenberg–Marquardt method. This algorithm is applicable to both symmetric and asymmetric tensors, and it is expected to play a role in the field of large-scale data compression storage and large-scale tensor approximation operations.

Effects of brain-derived neurotrophic factor and adeno-associated viral vector on morphine-induced condition through target concentration changes in the ventral tegmental area and nucleus accumbens

Morphine remains the standard analgesic for severe pain. However, the clinical use of morphine is limited by the innate tendency of opiates to become addictive. Brain-derived neurotrophic factor (BDNF) is a growth factor that is protective against many mental disorders. This study aimed to evaluate the protective function of BDNF on morphine addiction based on the behavioural sensitisation (BS) model and assess potential changes in downstream molecular tropomyosin-related kinase receptor B (TrkB) and cyclic adenosine monophosphate response element binding protein (CREB) expression caused by overexpression of BDNF. We divided 64 male C57BL/6 J mice into saline, morphine, morphine plus adeno-associated viral vector (AAV), and morphine plus BDNF groups. After administering the treatments, behavioural tests were conducted during the development and expression phases of BS, followed by a western blot analysis. All data were analysed by one- or two-way analysis of variance. The overexpression of BDNF in the ventral tegmental area (VTA) caused by BDNF-AAV injection decreased the total distance of locomotion in mice who underwent morphine-induced BS and increased the concentrations of BDNF, TrkB, and CREB in the VTA and nucleus accumbens (NAc). BDNF exerts protective effects against morphine-induced BS by altering target gene expression in the VTA and NAc.

Reported COVID-19 vaccines side effects among Algerian athletes: a comparison between inactivated virus, adenoviral vector, and mRNA COVID-19 vaccines

ABSTRACT Objectives Many types of COVID19 vaccines are administered globally, yet there is not much evidence regarding their side effects among athletes. This study evaluated the selfreported postvaccination side effects of inactivated virus, adenoviral vector, and mRNA COVID19 vaccines among Algerian athletes. Methods A cross-sectional survey-based study was carried out in Algeria between March 01 and 4 April 2022. The study used a validated questionnaire with twenty-five multiple-choice items covering the participants’ anamnestic characteristics, post-vaccination side effects (their onset and duration), post-vaccination medical care, and risk factors. Results A total of 273 athletes completed the survey. Overall, (54.6%) of the athletes reported at least one local side effect, while (46.9%) reported at least one systemic side effect. These side effects were more prevalent among the adenoviral vector group compared to the inactivated virus and mRNA groups. The most common local side effect was injection site pain (29.9%), while Fever (30.8%) was the most prevalent systemic side effect. The age group of 31–40 years, allergy, previous infection with COVID-19, and the first dose of vaccines were associated with an increased risk of side effects for all groups of COVID-19 vaccines. Logistic regression analysis further revealed that compared to males, the incidence of reported side effects was significantly higher in females (odd ratio (OR) = 1.16; P = 0.015*) only for the adenoviral vector vaccine group. In addition, a significantly higher percentage of athletes group of high dynamic/moderate static or high dynamic /high static components suffered from post-vaccination side effects compared to the group of athletes with high dynamic/low static components (OR = 14.68 and 14.71; P < 0.001, respectively). Conclusions The adenoviral vector vaccines have the highest rate of side effects, followed by the inactivated virus and mRNA COVID-19 vaccines. COVID‑19 vaccines were well-tolerated among Algerian athletes and there were no reports of serious side effects. Nevertheless, further long-term follow-up study with a larger sample size of athletes (from different types and sports categories) is warranted to establish the long-term safety of the COVID-19 vaccine.

Analysis of checkpoint effect with fork head associated-and ring finger fusion enhanced green fluorescent protein on nasopharyngeal carcinoma 5–8F cells

As an oncogene related to mitosis cycle, checkpoint with fork head associated-(FHA) and ring finger (CHFR) participates in cell cycle and nasopharyngeal carcinoma (NPC). Enhanced Green fluorescent protein (EGFP) is a new type of fluorescent probe. In this study, the effect of CHFR fusion enhanced green fluorescent protein (EGFP) on nasopharyngeal carcinoma cells was analyzed. 5–8F human NPC cells were divided into control group, empty vector group (NC) and CHFR group (transfected with CHFR-pEGFP-N1-5–8F cell line). 12 BALB/c-nu mice were divided into control group, empty vector group and CHFR group. The following processes were assessed: cell proliferation, mitosis cycle, expression of CHFR, Aurora A, Cyclin-dependent kinase 2 (CDC2) and Cyclin B1, and tumor volume. Cell proliferation in the CHFR group was significantly lower at 24, 48 and 72 h. The NC and CHFR groups had increased cells in the G0/G1 phase and reduced cells in the S phase 24 h after subculture, without difference between the NC and CHFR groups. The CHFR group had decreased levels of Aurora A, CDC2 and CyclinB1, while tumor volume in 3 groups increased with increased time, and decreased at each time point for the CHFR group compared with other groups (p &lt; 0.05). CHFR was highly expressed in the CHFR tumor group, which was significantly higher than other groups. The CHFR fusion EGFP protein can significantly inhibit Aurora A activity and expression of Aurora A, CDC2 and CyclinB1 by up-regulating the CHFR. The NPC cells were retained in the G0/G1 phase, blocking progression of cell mitosis, and further inhibiting cell proliferation while reducing tumor volume, and inhibiting the tumorigenic ability of NPC cells.

Effect of long non-coding RNA 114227 on gastric cancer cell proliferation and migration.

Gastric cancer is a common cancer of the digestive system. Long non-coding RNA (lncRNA) plays an important role in the formation and development of gastric cancer. This study aims to investigate the effect of long non-coding lncRNA 114227 on biologic behaviors in gastric cancer cells. The experiment was divided into 4 groups: a negative control (NC) group, a lncRNA 114227 small interference (si-lncRNA 114227) group, an empty vector (Vector) group, and an overexpression vector (OE-lncRNA 114227) group. The expressions of lncRNA 114227 in gastric mucosa and gastric cancer tissues, gastric mucosal epithelial cells and different gastric cancer strains were determined by real-time reverse transcription PCR (real-time RT-PCR).The proliferation were detected by CCK-8 assay in gastric cancer cells. The epithelial-mesenchymal transformation (EMT) was utilized by Transwell assay, scratch healing assay, and Western blotting in gastric cancer cells. The effect of lncRNA 114227 on proliferation of gastric cancer cells was detected by tumor bearing experiment in nude mice in vivo. The expression level of lncRNA 114227 in the gastric cancer tissues was significantly lower than that in the gastric mucosa tissues, and in 4 kinds of gastric cancer strains was all significantly lower than that in gastric mucosal epithelial cells (all P<0.01). In vitro, the proliferation and migration abilities of gastric cells were significantly reduced after overexpressing lncRNA 114227, and cell proliferation and migration were enhanced after silencing lncRNA 114227 (all P<0.05). The results of in vivo subcutaneous tumorigenesis in nude mice showed that the tumorigenic volume of the tumor-bearing mice in the OE-lncRNA 114227 group was significantly smaller than that of the Vector group, and the tumorigenic quality was lower than that of the Vector group (P<0.05), indicating that lncRNA 114227 inhibited tumorigenesis. The expression of lncRNA 114227 is downregulated in gastric cancer gastric cancer tissues and cell lines. LncRNA 114227 may inhibit the proliferation and migration of gastric cancer cells through EMT process.

Efficient and Privacy-Preserving Search Over Edge–Cloud Collaborative Entity in IoT

Limited by the storage and computing capacity of Internet of Things (IoT) devices, outsourcing encrypted entity data has become a prevalent trend. The existing IoT entity search methods lack the integration and utilization of both edge and cloud resources and the protection of user privacy. Besides, the traditional searchable encryption mode is inapplicable to state-time-varying entities in IoT. Therefore, in this article, an edge–cloud collaborative entity search method with privacy protection in IoT is proposed, fusing the advantages of edge and cloud resources to fulfill users’ needs for real-time search and privacy protection. Specifically, a secure search architecture and search method for edge–cloud collaboration is designed to support various needs of users, such as real-time search and global search. Then, an adaptive discrimination method for similar interested entities through attribute analysis and feature extraction is proposed to construct attribute-distinguished encrypted index and query vector groups, enabling efficient entity search meanwhile ensuring fast index update. Simulation results demonstrate that the proposed method with privacy protection can effectively improve the efficiency of entity search in IoT while safeguarding user privacy.

Preventive effects of Mycobacterium tuberculosis DNA vaccines on the mouse model with latent tuberculosis infection.

About a quarter of the world's population with latent tuberculosis infection (LTBI) are the main source of active tuberculosis. Bacillus Calmette Guerin (BCG) cannot effectively control LTBI individuals from developing diseases. Latency-related antigens can induce T lymphocytes of LTBI individuals to produce higher IFN-γ levels than tuberculosis patients and normal subjects. Herein, we firstly compared the effects of M. tuberculosis (MTB) ag85ab and 7 latent DNA vaccines on clearing latent MTB and preventing its activation in the mouse LTBI model. A mouse LTBI model was established, and then immunized respectively with PBS, pVAX1 vector, Vaccae vaccine, ag85ab DNA and 7 kinds of latent DNAs (including rv1733c, rv2660c, rv1813c, rv2029c, rv2628, rv2659c and rv3407) for three times. The mice with LTBI were injected with hydroprednisone to activate the latent MTB. Then, the mice were sacrificed for the bacterial count, histopathological examination, and immunological evaluation. Using chemotherapy made the MTB latent in the infected mice, and then using hormone treatment reactivated the latent MTB, indicating that the mouse LTBI model was successfully established. After the mouse LTBI model was immunized with the vaccines, the lung colony-forming units (CFUs) and lesion degree of mice in all vaccines group were significantly decreased than those in the PBS group and vector group (P<0.0001, P<0.05). These vaccines could induce antigen-specific cellular immune responses. The number of IFN-γ effector T cells spots secreted by spleen lymphocytes in the ag85ab DNA group was significantly increased than those in the control groups (P<0.05). In the splenocyte culture supernatant, IFN-γ and IL-2 levels in the ag85ab, rv2029c, and rv2659c DNA groups significantly increased (P<0.05), and IL-17A levels in ag85ab and rv2659c DNA groups also significantly increased (P<0.05). Compared with the PBS and vector groups, the proportion of CD4+CD25+FOXP3+ regulatory T cells in spleen lymphocytes of ag85ab, rv2660c, rv2029c, and rv3407 DNA groups were significantly reduced (P<0.05). MTB ag85ab and 7 kinds of latent DNA vaccines showed immune preventive efficacies on a mouse model of LTBI, especially the rv2659c, and rv1733c DNA. Our findings will provide candidates for the development of new multi-stage vaccines against TB.

Motivic Euler Products and Motivic Height Zeta Functions

A motivic height zeta function associated to a family of varieties parametrised by a curve is the generating series of the classes, in the Grothendieck ring of varieties, of moduli spaces of sections of this family with varying degrees. This text is devoted to the study of the motivic height zeta function associated to a family of varieties with generic fiber having the structure of an equivariant compactification of a vector group. Our main theorem describes the convergence of this motivic height zeta function with respect to a topology on the Grothendieck ring of varieties coming from the theory of weights in cohomology. We deduce from it the asymptotic behaviour, as the degree goes to infinity, of a positive proportion of the coefficients of the Hodge-Deligne polynomial of the above moduli spaces: in particular, we get an estimate for their dimension and the number of components of maximal dimension. The main tools for this are a notion of motivic Euler product for series with coefficients in the Grothendieck ring of varieties, an extension of Hrushovski and Kazhdan’s motivic Poisson summation formula, and a motivic measure on the Grothendieck ring of varieties with exponentials constructed using Denef and Loeser’s motivic vanishing cycles.

Nanomicellar TGX221 Inhibits N-Myc to Suppress Malignant Biological Behavior of Prostate Cancer Cells by Regulating MYC/Myc-Associated Factor X (MAX)

Considering free amino N-terminal-myelocytomatosis viral oncogene homolog (N-Myc) as an important gene in prostate cancer (PC), we herein detected the impact of TGX-221 nanomicelles on N-Myc expression in PC cells. PC cells (LNCaP) were divided into blank group, empty vector group, N-Myc group and vector+N-Myc group, followed by analysis of myelocytomatosis viral oncogene homolog (MYC) and myc-associated factor (XMAX) expressions, cell proliferation, apoptosis and migration by CCK-8 method, flow cytometry and transwell experiment. Compared with blank group (4.95±0.67), N-Myc expression in the N-Myc group increased (6.25±0.78) but expressions in the empty vector (1.03±0.23) and vector+N-Myc groups (3.46±0.37) decreased significantly (P &lt;0.05), with lowest expression in the empty vector group (P &lt;0.05). Cell proliferation and migration in the N-Myc group increased within 96 h of transfection, but decreased in the empty vector and vector+N-Myc groups (P &lt;0.05), and TGX-221-loaded N-Myc obtained the lowest proliferation and migration (P &lt;0.05). N-Myc transfection decreased apoptosis, and nanomicellar TGX221 or N-Myc-loaded vector resulted in increased apoptotic cells (P &lt; 0.05), with highest apoptosis in the vector+N-Myc group. Moreover, the presence of nanomicellar TGX221 reversed their expression with lowest expression in the vector+N-Myc group, as transfection with N-Myc increased MYC/MAX mRNA expression. TGX-221 nanomicelles inhibited N-Myc and MYC/MAX expression, thereby suppressing proliferation and migration of PC cells, and inducing cell apoptosis.

Immune escape of bovine parvovirus by VP1 inhibiting IFN-β production through the RIG-I-like receptor pathway.

The present study aimed to explore if bovine parvovirus (BPV) impacts beta interferon (IFN-β) production and to reveal further molecular mechanism of BPV immune escape. The pCMV-Myc-BPV-VP1 recombinant plasmid was verified with both double-enzyme digestion and sequence. HEK 293T cells were transfected with this recombinant protein and then infected with the vesicular stomatitis virus (VSV). Expression levels of IFN-β mRNA were detected using qPCR. The expression level of BPV VP1 mRNA in the pCMV-Myc-BPV-VP1 group was significantly higher than those of the untreated group (UT) and pCMV-Myc vector group. BPV virus copies in bovine turbinate (BT) cells of the BPV-VP1 group were raised (P < 0.05) with an increment of 5.8 × 104. Expression levels of IFN-β mRNA of the BPV VP1 group in HEK 293T cells were decreased (P < 0.01). Following treatment of TBK1 and IRF3(5D), IFN-β expression levels in HEK 293T cells were depressed. Additionally, expression levels of TBK1, IRF3(5D), MDA5, and MAVS were less than those of the flag empty vector, respectively. pCMV-Myc-BPV-VP1 could heighten transcription levels of VP1 protein in BT cells, promote BPV proliferation, and ascend the production of IFN-β. Overexpression of pCMV-Myc-BPV-VP decreased IFN-β mRNA expression in HEK 293T cells and inhibited IFN-β production induced by TBK1 and IRF3(5D). Furthermore, BPV VP1 obviously declined expression levels of TBK1, IRF3(5D), MDA5, and MAVS in the RIG-I-like receptor (RLR) pathway. Our findings revealed a novel mechanism evolved by BPV VP1 to inhibit type I IFN production and provided a solid scientific basis into the immunosuppression of BPV.

An improved seven-phase SVPWM modulation strategy based on virtual voltage vectors

Seven-phase motors are usually powered by seven-phase voltage source inverter. The traditional seven-phase SVPWM algorithm produces a large common-mode voltage (CMV), while harmonic currents in the harmonic subspace can also produce large harmonic losses in motor. The CMV is usually reduced by deprecating the zero-vector method, but the complexity of the computation is complicated by increasing the number of phases. In order to reduce the amount of computation while reducing the harmonic currents and weakening CMV, an improved seven-phase SVPWM algorithm based on virtual voltage vector method to weaken CMV was proposed. First, the time of action of each vector was calculated by adding one constraints. Then, the virtual voltage vectors were constructed by the outermost vectors in the fundamental subspace by comparing the advantages and disadvantages of each voltage vector group. Finally, the reference voltage vectors were constructed by the virtual voltage vectors. Simulation models were built to compare and verify accuracy of proposed SVPWM algorithm.

Molecular Characterization, Expression, and Regulatory Signal Pathway Analysis of Inflammasome Component Apoptosis-Associated Speck-like Protein Containing a CARD Domain (ASC) in Large Yellow Croaker (Larimichthys crocea).

ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD)) is the only adaptor involved in the formation of multiple types of inflammasomes. Accumulating evidence demonstrates that ASC plays a critical role in the protection of the host against pathogen infection. In this study, we identified an ASC gene in the large yellow croaker (Larimichthys crocea), namely LcASC, and then investigated the expression characteristics and related signal pathways. On one hand, LcASC has several conserved protein modules, i.e., an N-terminal PYD region, a C-terminal CARD region, and twelve α-helix structures. On the other hand, it has a high variable linker between PYD and CARD domains. Moreover, LcASC has varying degrees of expression in different tissues, among which the highest expression is observed in the spleen followed by the gills and skin. It also shows induced expressions in the head kidney, liver, and spleen following immune stimulation, especially Vibrio Parahaemolyticus infection. Further subcellular localization analysis showed that LcASC formed a clear aggregated speck in the cytoplasm close to the nucleus. In addition, we found 46 DEGs in a comparative transcriptome analysis between the LcASC overexpression group and the control vector group. Notedly, the up-regulated gene Fos and down-regulated gene DOK3 in LcASC overexpressed cells play important roles in the immune system. How ASC contacts these two genes needs to be clarified in upcoming studies. These findings collectively provide new insights into finfish ASC and its potential regulatory signaling pathway as well.

The Biological and Ecological Features of Northbound Migratory Birds, Ticks, and Tick-Borne Microorganisms in the African-Western Palearctic.

Identifying the species that act as hosts, vectors, and vehicles of vector-borne pathogens is vital for revealing the transmission cycles, dispersal mechanisms, and establishment of vector-borne pathogens in nature. Ticks are common vectors for pathogens causing human and animal diseases, and they transmit a greater variety of pathogenic agents than any other arthropod vector group. Ticks depend on the movements by their vertebrate hosts for their dispersal, and tick species with long feeding periods are more likely to be transported over long distances. Wild birds are commonly parasitized by ticks, and their migration patterns enable the long-distance range expansion of ticks. The African-Palearctic migration system is one of the world's largest migrations systems. African-Western Palearctic birds create natural links between the African, European, and Asian continents when they migrate biannually between breeding grounds in the Palearctic and wintering grounds in Africa and thereby connect different biomes. Climate is an important geographical determinant of ticks, and with global warming, the distribution range and abundance of ticks in the Western Palearctic may increase. The introduction of exotic ticks and their microorganisms into the Western Palearctic via avian vehicles might therefore pose a greater risk for the public and animal health in the future.

CCT2 Gene Expression in Hepatocellular Carcinoma and its Effect on the Biological Function of Hepatocellular Carcinoma Cells

The main objective of the study is to investigate the expression level of chaperonin containing t-complex polypeptide 1 subunit 2 in hepatocellular carcinoma tissues and cell lines, and its effect on the proliferation, invasion and migration of hepatocellular carcinoma cells. Immunohistochemistry was used to detect the protein expression levels of chaperonin containing t-complex polypeptide 1 subunit 2 in 89 hepatocellular carcinoma tissues and tumor-adjacent tissues. Cell migration and invasion were detected by transwell assay. A subcutaneous xenograft model was constructed in nude mice to investigate the effect of chaperonin containing t-complex polypeptide 1 subunit 2 gene knockdown on tumor growth. Immunohistochemistry results indicated that 79.78 % of hepatocellular carcinoma patients had highly expressed chaperonin containing t-complex polypeptide 1 subunit 2 proteins and the expression in hepatocellular carcinoma tissues was significantly higher than that in tumor-adjacent tissues. The proliferation, invasion and migration of hepatoblastoma cell line HepG2 cells with chaperonin containing t-complex polypeptide 1 subunit 2 gene knockdown were inhibited, while those of human hepatoma-derived Huh-7 cells with chaperonin containing t-complex polypeptide 1 subunit 2 gene overexpression were enhanced. In vivo experiments also confirmed that the tumor growth rate in the chaperonin containing t-complex polypeptide 1 subunit 2 knockdown group was significantly slower than that in the vector group. Chaperonin containing t-complex polypeptide 1 subunit 2 is an independent poor prognostic factor of hepatocellular carcinoma and its expression is significantly upregulated in hepatocellular carcinoma tissues and cell lines. Chaperonin containing t-complex polypeptide 1 subunit 2 can significantly promote the proliferation, invasion and migration of hepatocellular carcinoma cells, suggesting that it can be an important therapeutic target for hepatocellular carcinoma.