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 However, there are still challenges to overcome, such as technological innovation, data privacy and security, outdated regulations, and talent shortages.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.

Objective:To evaluate the value of 18F-FDG PET/CT for preoperative localization of epileptogenic foci in refractory epilepsy patients with negative MRI. Methods:Clinical data (550 lobes) of 55 epilepsy patients (38 males, 17 females, age (20.0±8.1) years) with negative MRI who underwent preoperative 18F-FDG PET/CT-MRI between January 2014 and June 2020 at the First Affiliated Hospital of Jinan University were retrospectively analyzed. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG PET/CT, video electroencephalogram (VEEG), PET/CT+ VEEG and PET/CT-VEEG for localizing epileptogenic foci were calculated using stereoelectroencephalography (SEEG) and the outcomes of at least 1 year of postoperative follow-up as reference standards. χ2 test was used to compare the efficiencies of different examination modalities for unilobar, multilobar and all patients. Results:The correct lateralization rate of epileptogenic foci was 92.6%(25/27) using PET/CT. The sensitivity, specificity, accuracy, PPV and NPV of PET/CT for localization of epileptogenic foci were 65.1%(54/83), 77.9%(364/467), 76.0%(418/550), 34.4%(54/157) and 92.6%(364/393), respectively. The sensitivities of PET/CT-VEEG for localization of epileptogenic foci in all patients and patients with multilobar epilepsy were higher than those of VEEG alone (75.9%(63/83) vs 45.8%(38/83), 68.6%(35/51) vs 31.4%(16/51); χ2 values: 15.80, 14.16, both P<0.001). The specificities of PET/CT+ VEEG for localization of epileptogenic foci in all patients and patients with unilobar epilepsy were higher than those of VEEG alone (97.6%(456/467) vs 94.6%(442/467), 97.9%(282/288) vs 94.1%(271/288); χ2 values: 5.66, 5.48; P values: 0.017, 0.019). The sensitivity of PET/CT-VEEG (PET/CT and VEEG concordance) for localization of epileptogenic foci was higher than that of PET/CT+ VEEG (PET/CT and VEEG discordance) (8/9 vs 28.4%(21/74); χ2=10.40, P=0.001), and its specificity and accuracy were higher than those of PET/CT-VEEG (PET/CT and VEEG discordance) (93.4%(57/61) vs 71.7%(291/406), 92.9%(65/70) vs 72.1%(346/480); χ2 values: 13.23, 13.96; both P<0.001). Conclusions:18F-FDG PET/CT can localize and lateralize epileptogenic foci in patients with negative MRI. The combination of 18F-FDG PET/CT and VEEG improves the sensitivity, specificity, and accuracy for epileptogenic foci detection. 18F-FDG PET/CT is more accurate in detecting epileptogenic foci when it is concordant with VEEG.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

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.
Synthetic Biology ; Carbon ; Metabolic Engineering

Fatty acids (FA) are widely used as feed stocks for the production of cosmetics, personal hygiene products, lubricants and biofuels. Ogataea polymorpha is considered as an ideal chassis for bio-manufacturing, due to its outstanding characteristics such as methylotroph, thermal-tolerance and wide substrate spectrum. In this study, we harnessed O. polymorpha for overproduction of fatty acids by engineering its fatty acid metabolism and optimizing the fermentation process. The engineered strain produced 1.86 g/L FAs under the optimized shake-flask conditions (37℃, pH 6.4, a C/N ratio of 120 and an OD₆₀₀ of seed culture of 6-8). The fed-batch fermentation process was further optimized by using a dissolved oxygen (DO) control strategy. The C/N ratio of initial medium was 17.5, and the glucose medium with a C/N ratio of 120 was fed when the DO was higher than 30%. This operation resulted in a titer of 18.0 g/L FA, indicating the potential of using O. polymorpha as an efficient cell factory for the production of FA.
Culture Media ; Fatty Acids ; Fermentation ; Metabolic Engineering ; Saccharomycetales/metabolism*

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.

Methylotrophic yeasts are considered as promising cell factories for bio-manufacturing due to their several advantages such as tolerance to low pH and high temperature. In particular, their methanol utilization ability may help to establish a methanol biotransformation process, which will expand the substrate resource for bio-refinery and the product portfolio from methanol. This review summarize current progress on engineering methylotrophic yeasts for production of proteins and chemicals, and compare the strengths and weaknesses with the model yeast Saccharomyces cerevisiae. The challenges and possible solutions in metabolic engineering of methylotrophic yeasts are also discussed. With the developing efficient genetic tools and systems biology, the methylotrophic yeasts should play more important roles in future green bio-manufacturing.
Metabolic Engineering ; Methanol ; Saccharomyces cerevisiae/genetics* ; Yeasts

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.

Objective To analyze pharmacologic action features of single Chinese herbal medicine for the treatment of fatty liver based on literature; To provide references for clinical treatment of fatty liver.Methods Animal research literature about single Chinese herbal medicine for the treatment of fatty liver in CNKI, Wanfang database, and VIP from January 2003 to December 2014 was retrieved by computers. The number of single Chinese herbal medicine and the pharmacologic action features of active ingredients (or extracts) were statistically concluded. Results A total of 279 articles were retrieved, including 67 kinds of single Chinese herbal medicine, among which 8 were used to treat AFLD, 45 were used to treat NAFLD, and 14 were used to treat AFLD and NAFLD simultaneously. Pharmacologic action features of the medicine for AFLD mainly included reducing lipid, protecting liver, antioxidation, and anti-inflammation. Pharmacologic action features of the medicine for NAFLD had the effects of improving insulin resistance additionally.Conclusion Chinese herbal medicine for the treatment of AFLD and NAFLD shows significant efficacy, having the features of multiple pathways and liver damage resistance, which provide references for clinical treatment of fatty liver.