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This paper provides a comprehensive analysis of the current state of intelligent ophthalmology in China, including technological advancements, academic exchange platforms, policy support, future challenges, and potential solutions. Technologically, remarkable progress have been made in various areas of intelligent ophthalmology in China, including diabetic retinopathy, fundus image analysis, and crucial aspects such as quality assessment of medical artificial intelligence products, clinical research methods, technological evaluation, and industrial standards. Researchers are constantly improving the safety and standardization of intelligent ophthalmology technology by formulating clinical application guidelines and standards. Academic exchange platforms have been established to provide extensive collaboration opportunities for professionals across diverse fields, and various academic journals serve as publication platforms for intelligent ophthalmology research. Regarding public policy, the Chinese government has not only established a supportive policy environment for the advancement of intelligent ophthalmology through various documents and regulations, but provided a legal basis and management framework. However, there are still challenges to overcome, such as technological innovation, data privacy and security, outdated regulations, and talent shortages. To tackle these issues, there is a requirement for increased technological research and development, the establishment of regulatory frameworks, talent cultivation, and greater awareness and acceptance of new technologies among patients. By comprehensively addressing these challenges, intelligent ophthalmology in China is expected to continue leading the industry's global development, bringing more innovation and convenience to the field of ophthalmic healthcare.
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Engineering efficient enzymes or microbial cell factories should help to establish green bio-manufacturing process for chemical overproduction. The rapid advances and development in synthetic biology, systems biology and enzymatic engineering accerleate the establishing feasbile bioprocess for chemical biosynthesis, including expanding the chemical kingdom and improving the productivity. To consolidate the latest advances in chemical biosynthesis and promote green bio-manufaturing, we organized a special issue on chemical bioproduction that including review or original research papers about enzymatic biosynthesis, cell factory, one-carbon based biorefinery and feasible strategies. These papers comprehensively discussed the latest advaces, the challenges as well as the possible solutions in chemical biomanufacturing.
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Synthetic Biology , Carbon , Metabolic EngineeringABSTRACT
Objective:To develop a prediction model based on imaging features by contrast-enhanced MRI radiomics combined with clinical features for early recurrence of hepatocellular carcinoma (HCC) after radical resection.Methods:A retrospective study was carried out on 109 HCC patients who underwent radical resection at the Fifth Affiliated Hospital of Wenzhou Medical University from January 2015 to December 2020. Of 109 patients enrolled in this study, there were 96 males and 13 females, aged (58.3±10.7) years. Based on whether there was recurrence within 12 months after operation, the patients were divided into the early recurrence group ( n=31) and the control group ( n=78). These 109 patients were then randomly divided into the validation set ( n=23) and the training set ( n=86) at a ratio of 1∶4. Based on preoperative multi-phase contrast-enhanced MRI scanning, the tumor lesions were delineated on the Radcloud platform, and 1 409 quantitative radiomic features were extracted. Dimension reduction and screening of these features were carried out using variance threshold, SelectKBest and LASSO. Combined with clinical features (alpha fetoprotein, tumor size), several prediction model were established through machine learning. The predictive efficiencies of these models were evaluated using the area under the receiver operating characteristic (ROC) curve, accuracy rate, recall rate and balanced F score. Results:The proportions of irregular tumor shape and unclear tumor boundary, as well as maximum tumor diameter in the early recurrence group were significantly higher than that in the control group, but the proportion of pseudocapsule was significantly lower than that in the control group (all P<0.05). A total of 465 features were screened from the 1 409 features using the variance threshold method, followed by 38 features were screened using the method of SelectKBest. Finally 7 optimal radiomic features were screened based on the LASSO method. When combined with clinical features, 5 prediction models were established through machine learning. These models were support vector machine, Gaussian naive bayes, logistic regression, Multinomial naive bayes and K-nearest neighbor (KNN), respectively. Among these 5 models, the prediction efficiency of the KNN model was relatively highest, with the area under the ROC curve, accuracy rate, recall rate and balanced F score being 0.90, 0.98, 0.74 and 0.84 in the training set, and 0.76, 0.92, 0.75 and 0.83 in the verification set, respectively. Thus, the KNN model was selected as the best prediction model in this study. Conclusion:The prediction model of KNN was developed for early recurrence of HCC after radical resection based on preoperative contrast-enhanced MRI radiomics combined with clinical features.
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Objectives To investigate the occipital cortex metabolite alterations in repetitive and severe neonatal hypoglycemia rats treated with sodium pyruvate and to reveal the protective role of sodium pyruvate using high resolution 1H nuclear magnetic resonance spectroscopy.Methods Thirty-six 2-dayold Sprague-Dawley rats were randomly divided into hypoglycemia group and pyruvate group with 18 rats in each group.Rats in both groups received intraperitoneal injections of insulin (40 U/kg body weight) at 2,4 and 6 days of age to induce severe hypoglycemia (blood glucose value ≤ 1.4 mmol/L).In the hypoglycemia group,2.5 hours after insulin injection,intraperitoneal injection of 50％ glucose (2 ml/kg) was administered to terminate hypoglycemia,while in the pyruvate group,50％ glucose (2 ml/kg) and sodium pyruvate solution 2.5 ml/kg (500 mg/kg) were injected.Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay was used to observe the status of injured neurons in six neonatal rats,and metabolite changes in occipital cortex of the other 12 rats were detected by 1H nuclear magnetic resonance spectroscopy.The difference between the two groups was compared by independent-samples t test.Results Neonatal rats of both groups reached severe hypoglycemia level 2.5 hours after insulin injection.Compared with hypoglycemia group,pyruvate group had fewer injured neurons (45±5 vs 113 ± 12,t=0.782,P=0.013) and lower injured index in the occipital cortex (0.15 ± 0.03 vs 0.36 ± 0.06,t=l.143,P=0.020).Pyruvate group showed significant decreases in the concentration of taurine [(13.31 ± 2.06) vs (18.44 ± 3.86) mol/kg,t=8.231],glutamine[(1.50 ± 0.24) vs (2.02 ± 0.40) mol/kg,t=3.137],glutamate[(7.04 ± 0.95) vs (9.40 ± 1.73) mol/kg,t=6.449],aspartate[(1.51 ± 0.28) vs (2.15 ± 0.58) mol/kg,t=2.561] and creatine [(6.37±0.99) vs (8.46± 1.77) mol/kg,t =4.226] in the occipital cortex (all P'＜0.017).Conclusions Simultaneous use of glucose and sodium pyruvate to terminate hypoglycemia in repetitive and severe neonatal hypoglycemia rats can effectively alleviate severe hypoglycemia-induced occipital lobe damage via regulating excitatory amino acid neurotransmitters,energy metabolism and other metabolic pathways.
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Bioactive natural products are the material bases of Chinese materia medica resources. With successful applications of synthetic biology strategies to the researches and productions of taxol, artemisinin and tanshinone, etc, the potential ability of synthetic biology in the sustainable utilization of Chinese materia medica resources has been attracted by many researchers. This paper reviews the development of synthetic biology, the opportunities of sustainable utilization of Chinese materia medica resources, and the progress of synthetic biology applied to the researches of bioactive natural products. Furthermore, this paper also analyzes how to apply synthetic biology to sustainable utilization of Chinese materia medica resources and what the crucial factors are. Production of bioactive natural products with synthetic biology strategies will become a significant approach for the sustainable utilization of Chinese materia medica resources.
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Sclareol is a member of labdane type diterpenes mostly used as fragrance ingredient. To enable microbial production of sclareol, synthetic pathways were constructed by incorporating labdenediol diphosphate synthase (LPPS) and terpene synthase (TPS) of the plant Salvia sclarea into Saccharomyces cerevisiae. It was found that sclareol production could be benefited by overexpression of key enzyme for precursor biosynthesis, construction of fusion protein for substrate channeling, and removal of signal peptides from LPPS and TPS. Under optimal shake flask culture conditions, strain S6 produced 8.96 mg/L sclareol. These results provided useful information for development of heterologous hosts for production of terpenoids.
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Alkyl and Aryl Transferases , Genetics , Diterpenes , Metabolism , Metabolic Engineering , Methods , Metabolic Networks and Pathways , Genetics , Recombinant Fusion Proteins , Genetics , Saccharomyces cerevisiae , Genetics , Metabolism , Salvia , Chemistry , GeneticsABSTRACT
Tanshinones are the bioactive components of the Chinese medicinal herb Salvia miltiorrhiza, while its biosynthetic pathway remains to be characterized. Rapid identification and characterization of the genes correlated to tanshinones biosynthesis is very important. As one of the intermediates of tanshinones biosynthesis, the ferruginol content is relative low in both root and engineered bacteria. It is urgent to construct an efficient system for conversion of miltiradiene to ferruginol to obtain large amount of ferruginol as the substrates for further identifying other downstream genes involved in tanshinones biosynthesis. In this study, we constructed the whole-cell yeast biocatalysts co-expressing miltiradiene oxidase CYP76AH1 and cytochrome P450 reductases (SmCPR1) from Salvia miltiorrhiza, and then characterized it with RT-PCR. After permeabilization, the yeast whole-cell could catalyze turnover of miltiradiene to ferruginol efficiently through single-step biotransformation with a conversion efficiency up to 69.9%. The yeast whole-cell biocatalyst described here not only provide an efficient platform for producing ferruginol in recombinant yeast but also an alternative strategy for identifying other CYP genes involved in tanshinones biosynthesis.
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This experimental study sought to determine the repeatability of a Video Keratography System specially designed for animals with small eyes. From day 5, ten newly hatched White Leghorn chicks were reared with monocular hyperopic defocus using -5.0D (n = 3), -10.0D (n = 3), -15.0D(n = 4) spherical PMMA lenses on their right eyes; the left eyes served as controls. Two sets of corneal topographical measurements, each set separated by about 5 minutes apart, were collected from both eyes of each animal at the end of 2-wk treatment period (i. e., 19 days of age). Each set of measurements consisted of five consecutive readings of corneal astigmatism. Bland-Altman plots were used to evaluate the repeatability of 3, 4 or all 5 readings from each set of data. When all 5 consecutive readings were used, the mean difference (95% limits of agreement) for the right treated and left untreated eyes were, respectively, -0.09D (-0.81, 0.64) and -0.02D (-0.86, 0.82). There was a tendency that lesser readings from each set of data produced greater difference between the two sets of measurements, although the differences (-0.19D) were not clinically significant. The Video Keratography System specially designed for animals with small eyes produced repeatable measurements for both treated and untreated eyes in chickens. Further studies are needed to validate other biometric features associated with corneal changes during normal and abnormal eye growth.
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Animals , Astigmatism , Diagnosis , Chickens , Cornea , Corneal Topography , Equipment DesignABSTRACT
The relationship between circadian rhythm and tolerance to acute hypoxia at a Simula ted altitude of 10000m was studied in 110 micc.Bolh number of survival and surviving time were increased from 3: 00 and reached the hightidc at 5:00.From then the number of survival remained at the same level,the surviving time declined gradually.Both the number of survival and surviving time attained the lowest value at 14: 56 to 0:30.The results suggest: 1.there is a close relationship b etween circadian rhythm and tolerance to acutehypoxia; 2.when rodents arc used for this kind of study,the affect of circadian rhythm should be considered.
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Eleven male rabbits were divided into 2 groups. Normal saline(NS) group consisted of 5 animals and was treated with 0.9% NaCl solution, and hyperosmotic saline (HS) group consisted of 6 rabbits and was treated with 7.5% NaCl. The animals were exposed to hypobaric hypoxia at a simulated altitude of 4000 m and hemorrhagic shock was inflicted to them through femoral artery bleeding. The mean arterial pressure (MAP) was brought to 6.0 kPa over 10 minutes and kept at that level for 70 minutes. A certain amount of 0.9% NaCl (300 mmol/L) or 7.5% NaCl (2400 mmol/L) was intravenously infused over a 10-minute interval. The volume infused was equivalent to 10% of the total blood shed. It was found that MAP, left ventricular systolic pressure, and LV dp/dt were significantly higher in HS group than in NS group (from 3rd to 20th minute after infusion). Sodium ion concentration was significantly higher in HS (145.8?3.16 mmol/L) than in NS (135.6?2.87 mmol/L) (P
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The effects of physical activity on cardiopulmonary hemodynamics under acute hypoxia at a simulated altitude of 4000 meters were studied in 8 conscious goats. It is known that acute hypoxia alone can result in an elevation of pulmonary arterial pressure and acceleration of heart rate, but no obvious effects on cardiac output and systemic arterial pressure, and physical activity can increase the pulmonary arterial pressure, cardiac output and heart rate at sea level. It was found that a combination of physical activity and a simulated altitude of 4000m could bring about a more marked increase of cardiac output and heart rate but no further increase of pulmonary arterial pressure. The latter phenomenon might be due to increased alkalinity of the arterial blood underhypoxic condition.
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The effects of the alterations of high altitude(at 4 000m for 48h and then at 5 000m for 24h)on the pulmonary rheography were investigated in 13 healthy male volunteers.It was found that the tonic interval index(Q-aI)was gradually prolonged jthe amplitude,the mean rate of filling and the maximal ascending rate of the systolic wave were gradually decreased.When the volunteers were exposed to 5 000m,the Q-aI/RVET was increased from the sea-level value to 0.319?.010 to 0.400?.016(P