The mrp gene of SS2 human strain Habb was truncated and cloned into a prokaryotic expression vector pGEX4T-2,and a fusion-expressed protein MRP-GST of 61 000 was obtained in E.coli.The GST was cut from MRP-GST with thrombin protease to gain the purified MRP of 35 000 which showed a strong reaction to the SS2 positive sera in Western blotting.BALB/c mice were immunitied intraperitoneally with purified MRP protein.Murine myeloma cells were fused with the splenocytes of the immunized mice after the third immunization.An indirect ELISA coated with purified MRP was used to screen hybridomas for production of specific antibody.The six McAb recognized MRP specially.According to the results of 71 standard strains (48 SS and 34 SS2)by Sandwich ELISA,the coincidence rate was 97.2%,but for 34 SS standard serotype was 100 %.The ELISA method has a potential value for clinical and epidemiological applicationgs.

Objective To analyze the serum levels of medium-and long-chain free fatty acids (FFAs)in patients with hyperlipidemic non-alcoholic fatty liver disease (NAFLD) in order to shed some light on prevention and treatment of NAFLD.Methods The clinical data of 125 patients with high triglyceride (TG)levels who were treated in Hebei General Hospital from January 2011 to May 2011 were analyzed in this study.They were further divided into HF group (n =64) and H group (n =61) based on the presence of NAFLD or not.In addition,63 healthy individuals were recruited from the Central Hospital of Handan during the same period as the control group (N group).Serum medium-and long-chain FFAs were detected by gas chromatography.The body mass index (BMI),abdominal circumference,blood pressure,fasting blood glucose (FBG),and serum lipids including TG,total cholesterol (TC),high-density lipoprotein cholesterol (HDL-C),and low-density lipoprotein cholesterol (LDL-C) were measured.Results Compared with the N group,the H group had significantly higher BMI [(25.24 ± 1.41) kg/m2 vs.(24.32 ± 1.12) kg/m2,P =0.004],abdominal circumference [(84.72 ± 1.34) cm vs.(77.33 ±0.89) cm,P =0.010],and diastolic blood pressure [(77.35±1.21) mmHgvs.(75.21 ±1.61) mmHg,P=0.014]; also,the serum TG [(2.86±0.55) mmol/Lvs.(0.93±0.27) mmol/L,P=0.000] andTC levels [(4.56±0.66) mmol/Lvs.(4.36±0.47) mmol/L,P=0.000],serum myristic acid (C14∶0) [(0.49±0.04)％ vs.(0.36±0.01)％,P=0.011],palmitic acid (C16 ∶ 0) [(18.36 ± 0.47) ％ vs.(15.97 ± 0.30) ％,P =0.000],palmitoleic acid (C16∶ 1) [(1.00±0.12)％ vs.(0.58±0.02)％,P=0.001],and oleic acid (C18 ∶ 1) [(18.20±0.70) ％ vs.(12.23 ± 0.37) ％,P =0.000] all significantly increased,while stearic acid (C18 ∶ 0) [(7.52 ±0.22)％ vs.(8.15 ±0.28)％,P=0.012],eicosadienoic acid (C20 ∶ 2) [(0.61 ±0.07)％ vs.(1.03 ±0.17) ％,P =0.000],eicosatrienoic acid (C20 ∶ 3) [(1.77 ± 0.15) ％ vs.(2.49 ± 0.18) ％,P =0.002],and docosahexenoic acid (C22 ∶ 6) [(1.44 ± 0.08) ％ vs.(1.67 ± 0.09) ％,P =0.014] significantly decreased.Compared with the H group,the HF group had significantly higher weight [(85.76 ± 3.10) kg vs.(71.45 ±2.88) kg,P =0.003],abdominal circumference [(96.30 ±2.05) cm vs.(84.72 ± 1.34) cm,P=0.000],systolic blood pressure [(117.12 ±1.15) mmHg vs.(113.23 ±1.25) mmHg,P=0.009],and diastolic blood pressure [(79.54 ± 1.42) mmHg vs.(77.35 ± 1.21) mmHg,P =0.016],whereas the sreum FGB,TG,TC,HDL-C,and LDL-C showed no significant differentces; serum palmitic acid (C16 ∶ 0)[(19.54 ± 0.30) ％ vs.(18.36 ± 0.47) ％,P =0.000] also significantly increased.The serum level of eicosadienoic acid (C20 ∶ 2) in HF group was between that in N group and H group [(0.78 ± 0.09) ％ vs.(1.03 ±0.17)％,(0.78±0.09)％ vs.(0.61 ±0.07)％,both P=0.000].Conclusions The increased serum level of palmitic acid may be a risk factor for NAFLD.Reducing saturated fatty acids and increasing unsaturated acids in diets may be helpful for preventing NAFLD.

Nature, a rich source of bioactive natural products, serves as a massive pool of drug candidates for the pharmaceutical industry. However, the supply of these structurally complex chemicals is costly as most of the natural products are scarce in nature, thus requiring de novo synthesis. The supply chain issue hinders the development of novel therapeutic agents from natural products. Microbial synthesis, based on the expression of biosynthetic genes in a suitable microbial host to produce certain chemicals, is a sustainable strategy to produce complex natural products. However, this strategy requires gaining insights into the biosynthesis of target molecules. Most natural products are biosynthetically unknown or not fully elucidated; thus, the sole application of microbial synthesis strategy to produce a given molecule is challenging. In this review, we highlight a strategy that combines microbial and chemical syntheses to tackle the supply chain issue in developing drugs from natural products. We believe this strategy can revive the drug development pipeline for natural products.
Biological Products/chemistry* ; Aminoglycosides

Objective To evaluate the efficiency and safety of genipin collagen crosslinking (G-CXL) on rabbit corneas in vivo.Methods Forty healthy New Zealand white rabbits were randomly divided into 0.20％ G-CXL,0.25％ G-CXL,standard UVA-CXL and normal control group.And the right eyes were treated in different grouping.No procedures were performed in the normal control group.The corneal curvature (Km) and central corneal thickness (CCT) of right eyes were evaluated before,7 days and 14 days after crosslinking treatment.Cornea strips were harvested from the right eyes and tensile strain measurements were performed 7 days and 14 days after crosslinking treatment.The structure of corneal stroma was observed under light microscope (LM) and transmission electron microscope (TEM).Results No statistically significant differences in Km were observed among different groups or different timepoints (Fgroup =0.301,P=0.825;Ftime =1.287,P=0.284).Significant difference in CCTs was noticed among different time pionts (Ftime =3.786,P =0.029).Compared with preoperative,the CCTs of all the groups were significantly increased 7 days after crosslinking (all at P＜0.05).No significant difference in CCT was found among the groups (Fgroup =0.557,P=0.646).Seven days after crosslinking treatment,the Young's modulus at 10％ strain was (1 1.96±5.74),(21.24±6.77),(18.76±3.34) and (11.56±4.37) MPa in 0.20％ G-CXL group,0.25％ G-CXL group,UVA-CXL group and normal control group,respectively;the stress at 10％ strain was (0.68 ±0.24),(1.20 ± 0.25),(1.0l ± 0.30) and (0.69 ± 0.26) MPa,respectively;the Young's modulus and stress in 0.25％ G-CXL group was significantly increased when compared with those in 0.20％ G-CXL and normal control group (both at P＜0.05).No significant difference in Young's modulus and stress was observed between 0.25％ G-CXL group and UVA-CXL group (all at P＞0.05).Forteen days after crosslinking treatment,Young's modulus at 10％strain was (16.65±3.19),(19.12±2.39),(22.83 ±4.38) and (12.70±2.72)MPa in 0.20％ G-CXL group,0.25％ G-CXL group,UVA-CXL group and normal control group,respectively;stress at 10％ strain was (0.83 ±0.12),(0.97±0.04),(1.23±0.30) and (0.65±0.20) MPa,respectively;the Young's modulus and stress in UVA-CXL group was significantly increased,when compared with 0.20％ G-CXL group and normal control group (all at P＜0.05).Statistical significance of stress was observed between 0.25％ G-CXL group and UVA-CXL group (P =0.046).There is no significant difference in Young's modulus between 0.25％ G-CXL and UVA-CXL group (P =0.090).LM showed the reduction of keratocytes existed in superficial stroma of 0.20％ and 0.25 ％ G-CXL groups,while the reduction of keratocyte was found in anterior and intermediate stroma of UVA-CXL group.In 0.20％ and 0.25％ G-CXL groups,the ultrastructure of keratocytes was normal except vacuole in some keratocytes.Keratocytes apoptosis was noticed in UVA-CXL group and keratocytes was normal in deep stroma under TEM.Conclusions 0.25％ has a similar biomechanics effect when compared to UVA-CXL.Moreover,histological observation proves a better safety of G-CXL in comparison of UVA-CXL.

Objective:To investigate the changes in total radioactivity in patient body with differentiated thyroid carcinoma (DTC) after 131I treatment and the factors influencing its metabolism. Methods:The clinical data from 218 patients after DTC treatment in the Department of Nuclear Medicine, the Second Affiliated Hospital of Air Force Medical University from September 2021 to April 2022 were retrospectively analyzed. Based on administrated 131I dose, 171 patients were divided into low-dose group (≤ 3.7 GBq) and 47 into high-dose group (>3.7 GBq) . A whole body dynamic radiation monitoring system was used to measure the in vivo residual activity of 131I 24, 48 and 72 h after 131I administration and to explore their influencing factors. Results:24, 48 and 72 h after adimination of 131I, the residual activity of 131I in the low-dose group patients was significantly lower than in the high-dose group patients ( t= -7.46, -3.31, -2.01, P<0.05) . The discharge compliance rate at 24 and 48 h in the low-dose group was significantly higher than that in the high-dose group (21.0% vs. 4.3%, 98.2% vs. 89.4%, χ2 = 7.23, 5.91, P<0.05) , and all patients could meet the discharge criteria at 72 h. Univariate analysis showed that the residual 131I activity at 24 and 48 h was dependent on age, body mass index (BMI) , basal metabolism rate (BMR) and thyroid stimulating hormone (TSH) . As have been shown by multiple linear regression analysis, in the low-dose group, the older age, the higher BMR and the higher TSH level at 24 h tended to the higher 131I residual activity in the body. At 48 h, the higher BMI and the higher TSH level lead to the higher 131I residual activity in patient body. Meanwhile, in the high-dose group, the higher age and BMR at 24 h, tended to the higher in vivo131I residual activity. The influencing factors were analyzed in terms that 131I residual activity reaching 400 MBq in patient body at 24 and 36 h. The result showed that at 24 h the lower TSH level leaded to the lower 131I residual activity in patient body. At 36 h, the younger age, the lower TSH level, and the smaller 131I treatment dose tended to the lower in vivo131I residual activity. Conclusions:Age, BMI, BMR and TSH levels are the influencing factors for the change in total activity in patient body after 131I treatment of DTC. Radiation dose assessment based on the above indicators can provide a reference for adjusting the length of hospitalization time.

Background Keratoconus is a chronic and progressive non-inflammatory ectatic disorder characterized by corneal thinning and irregular corneal topography,and its pathgenesis is a hot topic.A suitable animal model of keratoconus is still lacking,which limits the progress of relevant research.Corneal ectasia is a main anatomical basis of keratoconus,so we assume that keratoconus model could be constructed by simulating corneal ectasia.Objective This study was to investigate the influence of collagenase type Ⅱ on biomechanical responses detected by corneal visualization Scheimpflug technology (Corvis ST) and the feasibility of construction of rabbit model of corneal ectasia using coliagenase type Ⅱ.Methods This study protocol was approved by Ethic Committee of Peking University First Hospital and followed the Statement about experimental animal use and care from Association for Research in Vision and Ophthalmology (ARVO).Keratectasia models were established in 10 right eyes of 10 New Zealand white rabbits by soaking 8 mm-diameter central cornea using collagenase type Ⅱ solution prepared by PBS solution containing 15％ dextran (200 μl of 5 mg/ml) for 30 minutes after epithelial debridement,and only 200 μl PBS solution containing 15％ dextran was used in the same way in the left eyes as controls.The average corneal curvature (Km) and central corneal thickness (CCT) were measured with hand-held electronic corneal curvature meter and corneal ultra-sonic pachymetry respectively before modeling and 14 days after modeling.Corneal biomechanical parameters and intraocular pressure were measured in vivo by using Corvis ST at day 14 after modeling.The rabbits were sacrificed at day 14 after modeling,and corneal sections were prepared for hematoxylineosin staining and transmission electron microscopic examination.Results There were no significant differences in Km and C CT between model group and control group before modeling (Km:[48.28±2.29] D vs.[48.82± 1.63] D;CCT:[356.50± 19.13] μm vs.[356.20±21.66] μm;both at P＞0.05).The Km increased to (48.87±2.27) D and CCT decreased to (340.40±19.84)μm at day 14 after modeling,which were significantly different from (46.86±1.47) D and (367.80±23.38)μm (both at P＜0.01).The maximal deformation amplitude of model group and control group was (1.25±0.07) mm and (1.15 ±0.13) mm,respectively,showing a considerable difference between them (t=2.65,P＜0.05).No significant differences were found in applanation 1/2 time,applanation 1/2 length,applanation velocity,radius of curvature and peak distance between the two groups (all at P＞0.05).The morphology and ultrastructure examinations revealed that the arrangement of collagen fibers was loose and disorder and the interfiber space was enlarged in comparison with control group.Conclusions Collagenase type Ⅱ can lower corneal biomechanical properties.Soaking of cornea with collagenase type Ⅱ may be a potential way to establish a keratectasia animal model.