Heterojunction polarization enhancement and shielding for AlGaN-based solar-blind ultraviolet avalanche detectors.

AlGaN-based solar-blind ultraviolet avalanche detectors have huge potentials in the fields of corona discharge monitoring, biological imaging, etc. Here, we study the impact of the heterojunction polarization-related effects on the AlGaN-based solar-blind ultraviolet avalanche detectors. Our work confirms that the polarization heterojunction is beneficial to reducing avalanche bias and lifting avalanche gain by improving the electric field in the depletion region, while the polarization-induced fixed charges will lead to a redistribution of the electrons, in turn shielding the charges and weakening the electric field enhancement effect. This shielding effect will need external bias to eliminate, and that is why the polarization heterojunction cannot work at relatively low bias but has an enhancement effect at high bias. Controlling the doping level between the hetero-interface can affect the shielding effect. An unintentionally doped polarization heterojunction can effectively reduce the shielding effect, thus reducing the avalanche bias. The conclusions also hold true for the negative polarization regime. We believe our findings can provide some useful insights for the design of the AlGaN-based solar-blind ultraviolet detectors.

Host protein EPCAM interacting with EtMIC8-EGF is essential for attachment and invasion of Eimeria tenella in chickens.

The five epidermal growth factor-like domains (EGF) of Eimeria tenella microneme protein 8 (EtMIC8) (EtMIC8-EGF) plays a vital role in host cell attachment and invasion. These processes require interactions between parasite proteins and receptors on the surface of host cells. In this study, five chicken membrane proteins potentially interacting with EtMIC8-EGF were identified using the GST pull-down assay and mass spectrometry analysis, and only chicken (Gallus gallus) epithelial cell adhesion molecule (EPCAM) could bind to EtMIC8-EGF. EPCAM-specific antibody and recombinant EPCAM protein (rEPCAM) inhibited the EtMIC8-EGF binding to host cells in a concentration-dependent manner. Furthermore, the rEPCAM protein showed a binding activity to sporozoites in vitro, and a significant reduction of E. tenella invasion in DF-1 cells was further observed after pre-incubation of sporozoites with rEPCAM. The specific anti-EPCAM antibody further significantly decreased weight loss, lesion score and oocyst output during E. tenella infection, displaying partial inhibition of E. tenella infection. These results indicate that chicken EPCAM is an important EtMIC8-interacting host protein involved in E. tenella-host cell adhesion and invasion. The findings will contribute to a better understanding of the role of adhesion-associated microneme proteins in E. tenella.

Classification of high-risk depressed mood groups in cancer patients based on Health Ecology Model.

BACKGROUND: Depressed mood affects a significant number of patients with cancer, and can impair their quality of life and interfere with successful treatment. Our study aims to create a predictive model for identifying high-risk groups of depressed mood in cancer patients, offering a theoretical support for preventing depressed mood in these individuals. METHODS: The China Health and Retirement Longitudinal Study (CHARLS) provided the data for this research, which used CES-D as a tool to identify individuals with depressed mood. Influencing factors of depressed mood in cancer patients was analyzed using a binary logistic regression model. Using the Harvard Cancer Index, we classified the high-risk patients for depressed mood. RESULTS: In present study, 52.96 % of cancer patients met criteria for depressed mood based on the CES-D. Significant correlations were found between depressed mood and factors such as gender, self-rated health, sleep duration, exercise, satisfaction with family, residence, education, life satisfaction, and medical insurance. Utilizing the Harvard Cancer Index, we classified patients into five risk levels for depressed mood, revealing a significant variation in the number of depressive patients across these levels (x2=99.82, P < 0.05). Notably, the incidence of depressed mood increased with the risk level among cancer patients (x2=103.40, P < 0.05). LIMITATIONS: Lack of data on tumor typing and subgroups makes it unlikely to explore the specifics of depressed mood in patients with various types of cancer. CONCLUSION: The determinants of depressed mood in cancer patients are multi-dimensional. The Harvard Cancer Index may be helpful in identifying high-risk populations.

A candidate virulence factor of Eimeria tenella (EtROP30) predicted by virulence enhancement of transgenic Toxoplasma gondii.

Difficulties of in vitro culture and genetic manipulation of Eimeria tenella have hindered the screening of virulence factors in this parasite. In this study, the E. tenella rhoptry protein 30 (EtROP30) was expressed in Toxoplasma gondii (RH∆Ku80-EtROP30), and its effect on the proliferation and virulence of parasites was investigated. The results revealed that the expression of EtROP30 had no impact on the invasion and egress processes. However, the RH∆Ku80-EtROP30 strain formed larger plaques compared to the RH∆Ku80, indicating that the EtROP30 expression promotes T. gondii proliferation. Furthermore, the RH∆Ku80-EtROP30 strain exhibited greater pathogenicity, resulting in earlier mortality and shorter overall survival time compared to RH∆Ku80. These results imply that EtROP30 expression facilitates parasite intracellular proliferation and virulence in mice, suggesting that EtROP30 might be a candidate virulence factor of E. tenella.

Construction and evaluation of a novel multi-antigenic Mycobacterium tuberculosis subunit vaccine candidate BfrB-GrpE/DPC.

Tuberculosis poses a significant threat to human health due to the lack of an effective vaccine. Although promising progress has been made in the development of tuberculosis vaccines, new vaccines that broaden the antigenic repertoire need to be developed to eradicate this illness. In this study, we used Mycobacterium tuberculosis ferritin BfrB and heat-shock protein GrpE to construct a novel multi-antigenic fusion protein, BfrB-GrpE (BG). BG protein was stably overexpressed in the soluble form in Escherichia coli at a high yield and purified via sequential salt fractionation and hydrophobic chromatography. Purified BG was emulsified in an adjuvant containing N, N'-dimethyl-N, N'-dioctadecylammonium bromide, polyinosinic-polycytidylic acid, and cholesterol (DPC) to construct the BG/DPC vaccine, which stimulated strong cellular and humoral immune responses in mice. Moreover, combination of BG with our previously developed vaccine, Mtb10.4-HspX (MH), containing antigens from both the proliferating and dormant stages, significantly reduced the bacterial counts in the lungs and spleens of M. tuberculosis-infected mice. Importantly, mice that received BG + MH/DPC after M. tuberculosis H37Rv infection survived slightly better (100% survival) than those that received the BCG vaccine (80% survival), although the difference was not statistically significant. Our findings can aid in the selection of antigens and optimization of vaccination regimens to improve the efficacy of tuberculosis vaccines.

Synthesis of salicylaldehyde tailored PAMAM dendrimers/chitosan for adsorption of aqueous Hg(II): Performance and mechanism.

Water pollution caused by Hg(II) exerts hazardous effect to environmental safety and human health. Herein, a family of salicylaldehyde tailored poly(amidoamine) (PAMAM) dendrimers/chitosan composites (G0-S/CTS, G1-S/CTS, and G2-S/CTS) were prepared and used for the removal of Hg(II) from water solution. The adsorption performance of the as-prepared composites for Hg(II) was thoroughly demonstrated by determining various influencing factors. G0-S/CTS, G1-S/CTS and G2-S/CTS exhibited competitive adsorption capacity and good adsorption selective property for Hg(II). The maximum adsorption capacity of G0-S/CTS, G1-S/CTS and G2-S/CTS for Hg(II) were 1.86, 2.18 and 4.47 mmol‧g-1, respectively. The adsorption for Hg(II) could be enhanced by raising initial Hg(II) concentration and temperature. The adsorption process was dominated by film diffusion processes with monolayer adsorption behavior. The functional groups of NH2, CONH, CN, OH, CO and CN were mainly responsible for the adsorption of Hg(II). G0-S/CTS, G1-S/CTS and G2-S/CTS displayed good regeneration property and the regenerate rate maintained 95.00 % after five adsorption-desorption cycles. The as-prepared adsorbents could be potentially used for the efficient removal of Hg(II) from aqueous solution.

Corrigendum: Loss of hepatic Surf4 depletes lipid droplets in the adrenal cortex but does not impair adrenal hormone production.

[This corrects the article DOI: 10.3389/fcvm.2021.764024.].

Optimizing metal/n-AlGaN contact by recessed AlGaN heterostructure with a polarization effect.

With increasing Al mole fraction, n-contact has become an important issue limiting the development of Al-rich AlGaN-based devices. In this work, we have proposed an alternative strategy to optimize the metal/n-AlGaN contact by introducing a heterostructure with a polarization effect and by etching a recess structure through the heterostructure beneath the n-contact metal. Experimentally, we inserted an n-Al0.6Ga0.4N layer into an Al0.5Ga0.5N p-n diode on the n-Al0.5Ga0.5N layer to form a heterostructure, where a high interface electron concentration of 6 × 1018 cm-3 was achieved with the aid of a polarization effect. As a result, a quasi-vertical Al0.5Ga0.5N p-n diode with a ∼1 V reduced forward voltage was demonstrated. Numerical calculations verified that the increased electron concentration beneath the n-metal induced by the polarization effect and recess structure was the main reason for the reduced forward voltage. This strategy could simultaneously decrease the Schottky barrier height as well as provide a better carrier transport channel, enhancing both the thermionic emission and tunneling processes. This investigation provides an alternative approach to obtain a good n-contact, especially for Al-rich AlGaN-based devices, such as diodes and LEDs.

[Research progress of Wallis dynamic stabilization system for lumbar degenerative diseases].

Wallis dynamic stabilization system is a surgical approach in the non-fusion technique of lumbar spine, consisting of interspinous blockers and dacron artificial ligaments that provide stability to the spine while maintaining a degree of motion in the affected segment. Recent studies have demonstrated the significant benefits of Wallis dynamic stabilization system in treating lumbar degenerative diseases. It not only improves clinical symptoms, but also effectively delays complications such as adjacent segmental degeneration. This paper aims to review the literature related to the Wallis dynamic stabilization system and degenerative diseases of the lumbar spine to describe the long-term prognostic effect of this system in the treatment of such diseases. This review provides a theoretical basis and reference for selecting surgical methods to treat degenerative diseases of the lumbar spine.

Surf4 (Surfeit Locus Protein 4) Deficiency Reduces Intestinal Lipid Absorption and Secretion and Decreases Metabolism in Mice.

BACKGROUND: Postprandial dyslipidemia is a causative risk factor for cardiovascular disease. The majority of absorbed dietary lipids are packaged into chylomicron and then delivered to circulation. Previous studies showed that Surf4 (surfeit locus protein 4) mediates very low-density lipoprotein secretion from hepatocytes. Silencing hepatic Surf4 markedly reduces the development of atherosclerosis in different mouse models of atherosclerosis without causing hepatic steatosis. However, the role of Surf4 in chylomicron secretion is unknown. METHODS: We developed inducible intestinal-specific Surf4 knockdown mice (Surf4IKO) using Vil1Cre-ERT2 and Surf4flox mice. Metabolic cages were used to monitor mouse metabolism. Enzymatic kits were employed to measure serum and tissue lipid levels. The expression of target genes was detected by qRT-PCR and Western Blot. Transmission electron microscopy and radiolabeled oleic acid were used to assess the structure of enterocytes and intestinal lipid absorption and secretion, respectively. Proteomics was performed to determine changes in protein expression in serum and jejunum. RESULTS: Surf4IKO mice, especially male Surf4IKO mice, displayed significant body weight loss, increased mortality, and reduced metabolism. Surf4IKO mice exhibited lipid accumulation in enterocytes and impaired fat absorption and secretion. Lipid droplets and small lipid vacuoles were accumulated in the cytosol and the endoplasmic reticulum lumen of the enterocytes of Surf4IKO mice, respectively. Surf4 colocalized with apoB and co-immunoprecipitated with apoB48 in differentiated Caco-2 cells. Intestinal Surf4 deficiency also significantly reduced serum triglyceride, cholesterol, and free fatty acid levels in mice. Proteomics data revealed that diverse pathways were altered in Surf4IKO mice. In addition, Surf4IKO mice had mild liver damage, decreased liver size and weight, and reduced hepatic triglyceride levels. CONCLUSIONS: Our findings demonstrate that intestinal Surf4 plays an essential role in lipid absorption and chylomicron secretion and suggest that the therapeutic use of Surf4 inhibition requires highly cell/tissue-specific targeting.

Synthesis of functional poly(amidoamine) dendrimer decorated apple residue cellulose for efficient removal of aqueous Hg(II).

Water pollution caused by Hg(II) exerts hazardous effect to the environment and public health. The design and fabrication of eco-friendly bioadsorbents for efficient removal of Hg(II) from aqueous solution is a promising strategy. Herein, a series of bioadsorbents were synthesized by the decoration of apple residue cellulose with different generation (G) Schiff base functionalized poly(amidoamine) (PAMAM) dendrimers (SA-G0/CE, SA-G1.0/CE and SA-G2.0/CE). The structures of SA-G0/CE, SA-G1.0/CE and SA-G2.0/CE were characterized and their adsorption performances were determined comprehensively by considering various factors. The maximum adsorption capacity of SA-G0/CE, SA-G1.0/CE and SA-G2.0/CE for Hg(II) are 1.18, 1.73 and 1.88 mmol·g-1, respectively. The as-prepared bioadsorbents exhibit competitive adsorption capacity as compared with other reported adsorbents. Moreover, they exhibit remarkable adsorption selectivity toward Hg(II) with the coexistence of Ni(II), Cd(II), Mn(II), or Pb(II). The bioadsorbents display satisfactory adsorption performance in real water sample and can be reused with good regeneration property. Adsorption mechanism reveals that the functional groups of OH, -CONH-, CN and NC take part in the adsorption for Hg(II). The work not only opens a pathway to realize the reuse of apple residue, but also provides a promising strategy to construct efficient bioadsorbents for the decontamination of Hg(II) from aqueous solution.

Synthesis of hyperbranched polyamine dendrimer/chitosan/silica composite for efficient adsorption of Hg(II).

The pollution of water system with Hg(II) exerts hazardous effect to ecosystem and public health. Adsorption is considered to be a promising strategy to remove Hg(II) from aqueous solution. Herein, hyperbranched polyamine dendrimer/chitosan/silica composite (SiO2-FP) was synthesized for the adsorption of aqueous Hg(II). The adsorption performance of SiO2-FP was comprehensively determined by considering various influencing factors. SiO2-FP displays good adsorption performance for Hg(II) with the adsorption capacity of 0.79 mmol·g-1, which is higher than the corresponding chitosan functionalized silica (SiO2-CTS) by 46.30 %. The optimal solution pH for the adsorption of Hg(II) is 6. Adsorption kinetic indicates the adsorption for Hg(II) can reach equilibrium at 250 min. Adsorption kinetic process can be well fitted by pseudo-second-order (PSO). Adsorption isotherm reveals the adsorption for Hg(II) can be promoted by increasing initial Hg(II) concentration and adsorption temperature. The adsorption isotherm indicates the adsorption process can be described by Langmuir model and the adsorption is a spontaneous, endothermic and entropy-increased process. SiO2-FP displays excellent adsorption selectivity and can 100 % adsorb Hg(II) with the coexisting of Ni(II), Zn(II), Pb(II), Mn(II), and Co(II). Adsorption mechanism demonstrates -NH-, -NH2, CN, CONH, -OH, and CO participated in the adsorption. SiO2-FP exhibits good regeneration property and the regeneration rate can maintain approximately 90 % after five adsorption-desorption cycles.

Construction of a Lactobacillus plantarum-based claudin-3 targeting delivery system for the development of vaccines against Eimeria tenella.

Avian coccidiosis causes huge economic losses to the poultry industry worldwide and currently lacks effective live vector vaccines. Achieving efficient antigen delivery to mucosa-associated lymphoid tissue (MALT) is critical for improving the effectiveness of vaccines. Here, chicken claudin-3 (CLDN3), a tight junction protein expressed in MALT, was identified as a target, and the C-terminal region of Clostridium perfringens enterotoxin (C-CPE) was proven to bind to chicken CLDN3. Then, a CLDN3-targeting Lactobacillus plantarum NC8-expressing C-CPE surface display system (NC8/GFP-C-CPE) was constructed to successfully express the heterologous protein on the surface of L. plantarum. The colonization level of NC8/GFP-C-CPE was significantly increased compared to the non-targeting strain and could persist in the intestine for at least 72 h. An oral vaccine strain expressing five EGF domains of Eimeria tenella microneme protein 8 (EtMIC8-EGF) (NC8/EtMIC8-EGF-C-CPE) was constructed to evaluate the protective efficacy against E. tenella infection. The results revealed that CLDN3-targeting L. plantarum induced stronger mucosal immunity in gut-associated lymphoid tissues (GALT) as well as humoral responses and conferred better protection in terms of parasite replication and pathology than the non-targeting strain. Overall, we successfully constructed a CLDN3-targeting L. plantarum NC8 surface display system characterized by MALT-targeting, which is an efficient antigen delivery system to confer enhanced protective efficacy in chickens against E. tenella infection.

Feasible synthesis of bifunctional polysilsesquioxane microspheres for robust adsorption of Hg(II) and Ag(I): Behavior and mechanism.

The pollution of Hg(II) and Ag(I) to water system exerts hazardous effect to aquatic ecosystem and public security. Simple strategy for constructing adsorbents to efficient remove them is greatly desired. Thus, a series of thiol and amino groups containing bifunctional polysilsesquioxanes (ASPSS) microspheres with adjustable porous structure and functional group content were synthesized by one-step feasible sol-gel process. The adsorption behavior and mechanism of ASPSS microspheres toward Hg(II) and Ag(I) was thoroughly determined. The maximum adsorption capacity of ASPSS for Hg(II) and Ag(I) are 4.32 and 3.86 mmol·g-1 under 25 â„ƒ. The as-prepared ASPSS microspheres can 100% selectively capture Hg(II) with the coexisting of Mn(II), Co(II), Pb(II), Cd(II), Cu(II), Fe(III). And they can 100% adsorb Ag(I) with the presence of Cd(II), Pb(II), Co(II), Ni(II), and Zn(II). Moreover, the ASPSS microspheres exhibit good removal efficiency for Hg(II) and Ag(I) from simulated industrial wastewater with the coexistence of multiple pollutants. Adsorption mechanism suggests the adsorption for Hg(II) and Ag(I) is the synergistic coordination effect of amino and thiol groups. The excellent adsorption selectivity for Hg(II) and Ag(I) is attributed to the super binding ability of these functional group. ASPSS microspheres also exhibit good regeneration ability and could be reused for removing Hg (II) and Ag(I) from aqueous solution with practical value.

Construction of constitutive expression of Eimeria tenella eukaryotic initiation factor U6L5H2 on the surface of Lactobacillus plantarum and evaluation of its immunoprotective efficiency against chicken coccidiosis.

Lactobacillus strains exhibit preferable properties that make them attractive candidates for vaccine delivery systems because of their ability to regulate intestinal mucosal immunity in the body. To date, live Lactobacillus delivery vaccines reported for the defense against Eimeria tenella have been inducer-dependent systems whose applications are significantly limited due to their unattainable induction conditions in vivo. Here, a constitutive expression of Lactobacillus plantarum NC8 surface display system was constructed. Then, this system was used to prepare a live oral vaccine to constitutively express the E. tenella U6L5H2 (EtU6) protein on the NC8 surface and to evaluate its protective efficacy against E. tenella challenge in chickens. The results showed that the heterologous protein (EGFP or EtU6) was successfully expressed on the surface of L. plantarum NC8 without any inducer. The immunoprotection of EtU6 with constitutive expression in L. plantarum NC8 system (NC8/Pc-EtU6) was significantly stronger than that of EtU6 with induced expression of L. plantarum NC8 system (NC8/Pi-EtU6) (ACI: 168.28 vs. 152.74) as evidenced by increased body weight, decreased oocyst output and lesion scores. Furthermore, the constitutive system NC8/Pc-EtU6 produced higher levels of specific cecal SIgA, serum IgG, transcription of cytokines IFN-γ and IL-2, and lymphocyte proliferation than the induced system NC8/Pi-EtU6. These results indicate that, compared to the inducible system, the constitutive surface display system of L. plantarum has the advantages of continuously expressing antigens in vivo and stimulating the host immune system. It could be an ideal platform for vaccine expression. The live vector vaccine for coccidiosis constructed by this constitutive system greatly improves the application potential in chicken production and provides a novel platform for the prevention of coccidiosis in chickens.

Identification and Characterization of Eimeria tenella Rhoptry Protein 35 (EtROP35).

Rhoptry proteins (ROPs) of Apicomplexa are crucial secreted virulence factors and sources of vaccine candidates. To date, Eimeria tenella ROPs are not well studied. This study identified and characterized a novel E. tenella ROP (EtROP35), which showed the highest levels among 28 putative ROPs in previous sporozoite and merozoite transcriptomes. Sequence analysis showed that EtROP35 contains an N-terminal secretory signal and a protein kinase domain including eight conserved ROP35-subfamily motifs. Subsequent experiments confirmed that it is a secretory protein. Subcellular localization revealed it localized at the apical end of the sporozoites and merozoites, which was consistent with the ROPs of other Apicomplexan parasites. To further understand the biological meaning of EtROP35, expression levels in different developmental stages and sporozoite invasion-blocking assay were investigated. EtROP35 showed significantly higher levels in sporozoites (6.23-fold) and merozoites (7.00-fold) than sporulated oocysts. Sporozoite invasion-blocking assay revealed that anti-EtROP35 polyclonal antibody significantly reduced the sporozoite invasion rate, suggesting it might participate in host cell invasion and be a viable choice as a vaccine candidate. The immunological protective assays showed that EtROP35 could induce a high level of serum IgY and higher mean body weight gain, and lower cecum lesion score and oocysts excretion than the challenged control group. These data indicated that EtROP35 had good immunogenicity and may be a promising vaccine candidate against E. tenella.

Identification and characterization of Eimeria tenella EtTrx1 protein.

Thioredoxin (Trx) is a widespread protein regulator of redox reactions in all organisms. It operates together with NADPH and thioredoxin reductase as a general protein disulfide catalytic system. Recently, Trx has been found to be related to the process by which apicomplexan protozoa invade host cells. In this study, Eimeria tenella thioredoxin (EtTrx1) was identified and its gene structural features, expression levels at different developmental stages, localization in sporozoites, roles in adhesion and invasion, and immunogenicity were investigated. Sequence analysis indicated that EtTrx1 contains a Trx domain with a WCGPC motif in 29-33 aa and a typical Trx fold, and belongs to thioredoxin family. EtTrx1 was detected on the surface of sporozoites using anti-EtTrx1 polyclonal antibodies under non-permeabilized conditions by indirect immunofluorescence assay (IFA) and also in a secretion form. EtTrx1 protein was highly transcribed and expressed in merozoites and sporozoites by quantitative PCR and western blot. The attachment assay showed that the adherence rates of yeast cells expressing EtTrx1 on the surface to host cells were 3.1-fold higher than those of the blank control. Specific anti-EtTrx1 antibodies inhibited the invasion of sporozoites into DF-1 cells. The highest inhibition rate was up to 36.75% compared to the control group. Immunization with recombinant EtTrx1 peptides also showed significant protection against lethal infections in chickens. It could offer moderate protective efficacy (Anticoccidial Index [ACI]: 163.70), induce humoral responses, and be an effective candidate for the development of new vaccines.

Spatial-temporal variations and pollution risks of mercury in water and sediments of urban lakes in Guangzhou City, South China.

This study aims to investigate the spatial and temporal characteristics, pollution degrees, and potential ecological risks of mercury (Hg) in urban lake waters and sediments in Guangzhou, where is a typical area of Hg emission and population-economic-industrial concentration in South China. In different districts of this city, the water from 15 lakes were collected continuously from June 2020 to May 2021, and the sediments from 9 lakes were collected in 2015 and 2021. The seasonal changes of Hg concentration (Hg-C) in the water were found to be high in winter and low in summer. The spatial distribution of Hg-C in sediments showed that it was high in urban central areas and low in suburbs. The Nemero index and geological accumulation index showed that there were uncontaminated of Hg in the collected lake water, and above moderately contaminated in the lake sediments in urban center, respectively. The Hg pollution potential ecological risk index showed that there was low risk in the collected water, high and extremely high risk in the lake sediments in urban center, respectively. The principal component analysis (PCA) and correlation analysis (CA) of Hg and meteorological factors showed that precipitation, temperature, and vapor pressure had negative effects on the seasonal changes of Hg-C in water, and air pressure and wind direction had positive effects. The PCA and CA of Hg and other geochemical elements showed that anthropogenic emissions may be the main sources of Hg in sediments, which was also supported by the data of population density, road density, and motor vehicles per 1000 people. This study provided a reference for urban lake pollution treatment, resident health, and ecological environment protection.

Loss of Hepatic Surf4 Depletes Lipid Droplets in the Adrenal Cortex but Does Not Impair Adrenal Hormone Production.

The adrenal gland produces steroid hormones to play essential roles in regulating various physiological processes. Our previous studies showed that knockout of hepatic Surf4 (Surf4LKO) markedly reduced fasting plasma total cholesterol levels in adult mice, including low-density lipoprotein and high-density lipoprotein cholesterol. Here, we found that plasma cholesterol levels were also dramatically reduced in 4-week-old young mice and non-fasted adult mice. Circulating lipoprotein cholesterol is an important source of the substrate for the production of adrenal steroid hormones. Therefore, we investigated whether adrenal steroid hormone production was affected in Surf4LKO mice. We observed that lacking hepatic Surf4 essentially eliminated lipid droplets and significantly reduced cholesterol levels in the adrenal gland; however, plasma levels of aldosterone and corticosterone were comparable in Surf4LKO and the control mice under basal and stress conditions. Further analysis revealed that mRNA levels of genes encoding enzymes important for hormone synthesis were not altered, whereas the expression of scavenger receptor class B type I (SR-BI), low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methyl-glutaryl-CoA reductase was significantly increased in the adrenal gland of Surf4LKO mice, indicating increased de novo cholesterol biosynthesis and enhanced LDLR and SR-BI-mediated lipoprotein cholesterol uptake. We also observed that the nuclear form of SREBP2 was increased in the adrenal gland of Surf4 LKO mice. Taken together, these findings indicate that the very low levels of circulating lipoprotein cholesterol in Surf4LKO mice cause a significant reduction in adrenal cholesterol levels but do not significantly affect adrenal steroid hormone production. Reduced adrenal cholesterol levels activate SREBP2 and thus increase the expression of genes involved in cholesterol biosynthesis, which increases de novo cholesterol synthesis to compensate for the loss of circulating lipoprotein-derived cholesterol in the adrenal gland of Surf4LKO mice.

Identification and Characterization of Eimeria tenella Microneme Protein (EtMIC8).

Microneme proteins (MICs) of Eimeria tenella play key roles in motility, migration, attachment, and invasion processes. More than 20 apicomplexan parasite's MICs have been identified, with nine Eimeria MICs being reported. In this study, a novel E. tenella MIC was identified, and its gene structural features, developmental expression levels, localization, role in adhesion and invasion, and immunogenicity were studied. The results showed that the open reading frame was 1,650 bp, encoding 550 amino acids. It contains a signal sequence, a transmembrane region, four low-complexity boxes, and five epidermal growth factor-like domains (EGF). Subcellular localization revealed its distribution on the membrane surface of the parasite. These characteristics are consistent with the common features of MICs and are named EtMIC8. Anti-EtMIC8 antibodies recognized a specific binding of about 100 kDa in E. tenella, which was twice as large as the prokaryotic expression (about 50 kDa), suggesting that MIC8 may exist naturally as a dimer. EtMIC8 was expressed at higher levels in sporozoites (3.08-fold) and merozoites (2.1-fold) than in sporulated oocysts. The attachment assays using a yeast surface display of MIC8 and its different domains showed that the adherence rates of EtMIC8 to host cells were significantly higher than those of the control (3.17-fold), which was the full contribution of EGF, but neither was alone. Anti-EtMIC8 antibodies significantly reduced the invasion rate of sporozoites into host cells compared to those of the control (P < 0.01). Recombinant EtMIC8-EGF peptides could provide moderate protective efficacy (anticoccidial index [ACI]: 169.7), induce humoral responses, and upregulate CD3+CD8+ lymphocyte cells.