Shikonin and its derivatives are important medicinal secondary metabolites accumulating in roots of Lithospermum erythrorhizon. Although some membrane proteins have been identified as transporters of ...secondary metabolites, the mechanisms underlying shikonin transport and accumulation in L. erythrorhizon cells still remain largely unknown. In this study, we isolated a cDNA encoding LeMRP, an ATP-binding cassette transporter from L. erythrorhizon, and further investigated its functions in the transport and biosynthesis of shikonin using the yeast transformation and transgenic hairy root methods, respectively. Real-time PCR was applied for expression analyses of LeMRP and shikonin biosynthetic enzyme genes. Functional analysis of LeMRP using the heterologous yeast cell expression system showed that LeMRP could be involved in shikonin transport. Transgenic hairy roots of L. erythrorhizon demonstrated that LeMRP overexpressing hairy roots produced more shikonin than the empty vector (EV) control. Real-time PCR results revealed that the enhanced shikonin biosynthesis in the overexpression lines was mainly caused by highly up-regulated expression of genes coding key enzymes (LePAL, HMGR, Le4CL and LePGT) involved in shikonin biosynthesis. Conversely, LeMRP RNAi decreased the accumulation of shikonin and effectively down-regulated expression level of the above genes. Typical inhibitors of ABC proteins, such as azide and buthionine sulphoximine, dramatically inhibited accumulation of shikonin in hairy roots. Our findings provide evidence for the important direct or indirect role of LeMRP in transmembrane transport and biosynthesis of shikonin.
This experiment was conducted to evaluate the effects of supplementary Moringa oleifera leaf (MOL) on performance, egg quality, plasma parameters and organ histopathological indices of layers. A ...total of 360 27-week-old Hy-Line Grey commercial layers were randomly allotted to four groups. Each group consisted of six replicates with 15 birds and 3 birds were placed in one cage. The control group was fed a corn-soybean meal based diet and the experimental groups were fed on control diet supplemented with 5%, 10% or 15% MOL (MOL5, MOL10 and MOL15 group). The experiment lasted for 8 weeks. No significant differences were observed in egg weight or feed intake among all groups (p > .05). The birds in MOL15 group had higher feed conversation ratio and lower egg production compared with those in control group (p < .05). Layers in MOL5 had a deeper yolk colour than those in control group (p < .05). The albumen height and Haugh unit increased with increasing level of MOL when eggs were stored at 4 °C and 28 °C for 4 weeks (p < .05). Layers in MOL15 group had higher aspartate aminotransferase activity and lower uric acid concentration than other groups (p < .05). Layers in MOL10 and MOL15 groups had higher malondialdehyde content than those in control group (p < .05). Supplementary MOL increased the activity of glutathione peroxidase (p < .05). In conclusion, dietary supplementation with 5% MOL could improve yolk colour value and protein absorption without adverse effects on laying performance and egg quality.
This study evaluated the mechanical and ultrastructural changes during eggshell formation in laying hens by using the optimal levels of organic and inorganic manganese (Mn). A total of 270 62-wk-old ...Hy-Line Brown laying hens were fed a basal diet containing 25.1 mg Mn per kg feed for 2 wks, after which they were randomly allocated into 3 groups and fed the basal diet (control) or the basal diet supplemented with 120 mg Mn per kg feed from monohydrate Mn sulfate (an inorganic source of Mn), or 80 mg Mn per kg feed from an amino acid-Mn complex (an organic source of Mn) for 12 wks. For each group, 6 replicates of 15 hens were used with one hen per cage. Dietary Mn supplementation significantly increased eggshell-breaking strength and thickness in laying hens (P < 0.05). In neither was the elasticity of their eggshell membranes, measured during the nucleation and mammillary knob formation stages, affected by dietary Mn compared with the control (P > 0.05), whereas the breaking strength of the eggshells was greater at the linear and terminate deposition stages compared with the control (P < 0.05). Dietary Mn supplementation decreased the width of the mammillary knobs and the proportion of mammillary thickness, and increased the proportion of effective thickness of the whole eggshells (P < 0.05). Ultrastructural changes during the eggshell formation indicated that dietary Mn supplementation increased the nucleation site and mammillary knob densities, decreased the mammillary thickness, and increased the proportion of effective thickness and total thickness of the eggshells compared with the control (P < 0.05). Therefore, dietary Mn supplementation can improve the breaking strength and ultrastructure of the eggshells during their formation, and the mammillary and palisade layers are both crucial structures affected by Mn.
Denosumab was shown to be superior to zoledronic acid in preventing skeletal related events (SRE) in patients with breast cancer and bone metastases in a randomized, double-blind phase III study. We ...evaluated further results from this study related to skeletal complications and health-related quality of life (HRQoL).
Patients were randomized 1:1 to receive subcutaneous denosumab 120 mg (n = 1,026) and intravenous placebo, or intravenous zoledronic acid 4 mg (n = 1,020) and subcutaneous placebo every 4 weeks. Analyses reported here include the proportion of patients with one or multiple on-study SREs, time to first radiation to bone, time to first SRE or hypercalcemia of malignancy, and change in HRQoL (functional assessment of cancer therapy-general).
Fewer patients receiving denosumab than zoledronic acid had an on-study SRE (31% vs. 36%, P = 0.006). The incidence of first radiation to bone was 12% (n = 123) with denosumab versus 16% (n = 162) with zoledronic acid. Denosumab prolonged the time to first radiation to bone by 26% versus zoledronic acid (HR, 0.74; 95% confidence interval CI, 0.59-0.94, P = 0.012) and prolonged the time to first SRE or hypercalcemia of malignancy by 18% (HR, 0.82; 95% CI, 0.70-0.95; P = 0.007). Ten percent more patients had a clinically meaningful improvement in HRQoL with denosumab relative to zoledronic acid, regardless of baseline pain levels.
Denosumab was superior to zoledronic acid in reducing bone-related complications of metastatic breast cancer and maintained HRQoL, providing an efficacious, well-tolerated treatment option for patients with bone metastases from breast cancer.
To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage.
...Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate.
32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34 ~ 21.15) μmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31 ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) μmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) μmol/L, respectively.
The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.
We studied the effects of dietary oxidized oils on serum lipid metabolic indices, estradiol level, and the gene expression of apolipoprotein B-100 and apolipoprotein VLDL-II in laying hens. Hy-Line ...Grey hens (280 ± 10 d old; average egg production, 90.0 ± 2.5%) were allotted to 1 of 4 dietary treatments, which were supplemented with 0 (control group), 1% (low oxidized group), 2% (moderately oxidized group), or 4% (highly oxidized group) thermally oxidized soybean oil. Each treatment contained 6 replicates, with 12 birds each. The feeding trial lasted for 30 d. Laying performance data were recorded weekly. Other indices were measured on d 0, 2, 6, 14, and 30 of the feeding trial. Hens in the moderately and highly oxidized groups had significantly lowered feed conversion ratios (P < 0.05). Those in the highly oxidized group also had decreased concentrations of serum very low density lipoprotein cholesterol on d 30 (P < 0.05) compared with the very low density lipoprotein cholesterol of hens in the moderately oxidized group. Hens in the moderately oxidized group had significantly increased expression of apolipoprotein B-100 (P < 0.05) from d 6 to 30. Consequently, hepatic triglyceride increased in this group on d 30 (P < 0.05). Serum triglyceride decreased in the moderately oxidized group on d 30 (P < 0.05), which may have been caused by the activation of peroxisome proliferator-activating receptor α. Serum estradiol levels were not significantly affected by oxidized oils at any time of measurement, but were significantly different between d 0 and 30 within the moderately oxidized group. This fact indicated that the effect of oxidized oils on apolipoprotein B-100 might partially be a cumulative result of the increasing secretion of estradiol. The results suggested that oxidized oil may affect the performance of laying hens through the regulation of apolipoproteins and estradiol.
Background Radiofrequency ablation (RFA) is safe and effective for eradicating neoplasia in Barrett's esophagus. Objective To evaluate RFA for eradicating early esophageal squamous cell neoplasia ...(ESCN) defined as moderate-grade squamous intraepithelial neoplasia (MGIN) and high-grade squamous intraepithelial neoplasia (HGIN) and early flat-type esophageal squamous cell carcinoma (ESCC). Design Prospective cohort study. Setting Tertiary referral center. Patients Esophageal unstained lesions (USLs) were identified using Lugol's chromoendoscopy. Inclusion criteria were at least 1 flat (type 0-IIb) USL 3 cm or larger, USL-bearing esophagus 12 cm or less, and a consensus diagnosis of MGIN, HGIN, or ESCC by 2 expert GI pathologists. Exclusion criteria were previous endoscopic resection or ablation, stricture, or any nonflat mucosa. Interventions Circumferential RFA creating a continuous treatment area (TA) including all USLs. At 3-month intervals thereafter, chromoendoscopy with biopsies followed by focal RFA of USLs, if present. Main Outcome Measurements Complete response (CR) at 12 months defined as absence of MGIN, HGIN, or ESCC in the TA, CR after 1 RFA session, neoplastic progression from baseline, and adverse events. Results Twenty-nine patients (14 male, mean age 60.3 years) with MGIN (n = 18), HGIN (n = 10), or ESCC (n = 1) participated. Mean USL length was 6.2 cm (TA 8.2 cm). At 3 months after 1 RFA session, 86% of patients (25/29) had a CR. At 12 months, 97% of patients (28/29) had a CR. There was no neoplastic progression. There were 4 strictures, all dilated to resolution. Limitations Single-center study with limited number of patients. Conclusions In patients with early ESCN (MGIN, HGIN, flat-type ESCC), RFA was associated with a high rate of histological complete response (97% of patients), no neoplastic progression, and an acceptable adverse event profile.
Abstract
This study evaluated the mechanism by which dietary manganese (Mn) supplementation-in either an organic or inorganic form-affects mammillary knobs of the eggshell ultrastructure in laying ...hens. A total of 225 54-week-old Hy-Line Brown laying hens were fed a basal diet containing 27.5 mg Mn/kg feed for 2 wk, after which they were randomly allocated into 3 groups and fed a basal diet (control) or a basal diet supplemented with 120 mg Mn/kg feed from monohydrate Mn sulfate (an inorganic source of Mn) or with 80 mg Mn/kg feed from an amino acid-Mn complex (an organic source of Mn) for 10 wk. For each group, 5 replicates of 15 hens each were used with 1 hen per cage. Compared with the control, dietary Mn supplementation increased the mammillary-knob density of eggs at 9.5 h post-oviposition (P < 0.05). The Mn content in both blood and eggshell gland was increased with the supplementation of Mn in inorganic and organic forms (P < 0.05), but the blood Mn content was higher after inorganic-Mn supplementation as compared with organic-Mn supplementation (P < 0.05). RNA sequencing and quantitative real-time PCR analysis of the eggshell gland showed that dietary Mn supplementation increased the expression of genes encoding some proteoglycans, glycoproteins, and calcium-binding proteins in the eggshell gland (P < 0.05), and involved in the process of the protein glycosylation and glycan metabolism in the eggshell gland (P < 0.05). Overall, dietary Mn supplementation can involve in the process of protein glycosylation and glycan metabolism and improve the expression of genes encoding proteoglycans and glycoproteins in the eggshell gland, thus increasing the mammillary-knob density during the initial deposition stage of shell formation.
Several papers reported the experimental phenomena of single crystal orthoferrite DyFeO3 samples: the sample magnetization increases with increasing temperature, under a constant low magnetic field ...along the easy magnetizing direction of the samples, and then reaches a maximum value. These phenomena are better explained using magnetic domain wall pinning at low temperatures and depinning at high temperatures, which were neglected in previous papers. In this article, we argue that the magnetic domain wall motion must be taken into consideration in order to explain these experimental phenomena. Based on an O 2p itinerant electron model, we discussed the role of the magnetic domain and the characteristics of cation magnetic moments in relevant single crystal materials.
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