Construction of artificial cell factory to produce specific compounds of interest needs wild strain to be genetically engineered. In recent years, with the reconstruction of many genome-scale metabolic networks, a number of methods have been proposed based on metabolic network analysis for predicting genetic modification targets that lead to overproduction of compounds of interest. These approaches use constraints of stoichiometry and reaction reversibility in genome-scale models of metabolism and adopt different mathematical algorithms to predict modification targets, and thus can discover new targets that are difficult to find through traditional intuitive methods. In this review, we introduce the principle, merit, demerit and application of various strain optimization methods in detail. The main problems in existing methods and perspectives on this emerging research field are also discussed, aiming to provide guidance to choose the appropriate methods according to different types of products and the reliability of the predicted results.
Algorithms ; Biotechnology ; methods ; Computer Simulation ; Genome ; Industrial Microbiology ; Metabolic Engineering ; methods ; Metabolic Networks and Pathways ; Models, Theoretical ; Reproducibility of Results

Objective To investigate the efficacy of progressive resistance exercise for improving the lower limb motor function of hemiplegic stroke patients. Methods Eighty-nine hemiplegic patients were randomly divided into a treatment group (n =46) and a control group ( n = 43 ) . Both groups received routine rehabilitation training, while the treatment group also undertook progressive resistance training. The control group received extra quadriceps femoris training. Before and after the treatment, motor function was evaluated with the Fugl-Meyer lower limb assessment, functional ambulation category (FAC) classification and the modified Barthel index (MBI). Results Before intervention, there were no significant differences between the two groups in any of the assessments. Four weeks later, all the assessment scores obtained with the Fugl-Meyer lower limb assessment, FCA classification and MBI in the treatment group were significantly better than those in the control group. Conclusion Progressive resistance training combined with routine rehabilitation treatment can improve motor function in the lower limbs, ambulation and ability in the activities of daily living of hemiplegic patients after stroke.

Objective To observe the effects of systems of progressive resistance exercise on lower limb extensors （quadriceps femoris） of stroke patients. Methods 89 stroke patients with weak lower limbs were randomly divided into progressive resistance exercise group (n=46) and control group (n=43), both receiving corresponding treatment for 4 weeks. They were assessed with Manual Muscle Test (MMT), integrated electromyogram (iEMG) and root mean square (RMS) of surface electromyography on quadriceps femoris before and after the treatment. Results The incidence of improvement with MMT was 94.3% in progressive resistance exercise group, and 63.8% in control group （P<0.01）. The iEMG and RMS of the exercise group was significantly higher than that of the control （P<0.01）. Conclusion The systems of progressive resistance exercise could improve the muscle strength of lower limbs extensors of stroke patients more effectively.

Objective:To analyze the protective effect of weight-loss based exercises on the knee joints of patients with simple obesity.Methods:This study was a randomized controlled trial, 60 patients with simple obesity who met the inclusion and exclusion criteria and treated at the Affiliated Panyu Central Hospital of Guangzhou Medical University from April 2021 to April 2022 were selected as subjects. The patients were randomly divided into a power bicycle group (weight-loss, 30 cases) and a moving treadmill training group (non-weight-loss, 30 cases) using the random envelope method. High intensity interval exercise training was conducted in the hospital: slow warm-up for 1 minute, followed by rapid exercise for 3 minutes, and then rest for 1 minute. Repeated this cycle twice to form one set, and to perform 3 sets per session, 5 times per week, for a continuous training of 12 weeks. In addition, patients were not allowed to participate in other sports activities, and they should maintain their original dietary habits and patterns unchanged. Body mass index and body fat percentage were measured before and after treatment, and the cases with knee pain were recorded. The volume of knee cartilage was measured using magnetic resonance imaging. The local skin temperature of the knee was measured using an electronic thermometer before and after each training session. The t-tests, Pearson-tests and Mann-Whitney U tests were used to compare the differences in the above indicators between two groups before and after intervention to analyze the protective effect of weight-loss based exercise on the knee joints of patients with simple obesity. Results:There was no statistically significant difference in baseline data such as gender, age, height, and weight between the two groups before the intervention (all P>0.05). After the intervention, the body mass index, percentage of body fat, and knee cartilage volume of both groups were significantly lower than before the intervention, and the incidence of knee pain and local skin temperature of knee were significantly higher than before the intervention (all P<0.001). The incidence of the knee pain, reduction in knee cartilage volume, and elevation in local skin temperature in the power cycling group were all significantly lower than those in the moving treadmill training group [16.67% vs 100%, 0.12 (0.05, 0.27) vs 1.68 (1.15, 2.21) cm 3, (0.17±0.09) vs (0.64±0.15)℃, respectively] (all P<0.001). And there was no statistically significant difference in body mass index and body fat percentage between the two groups (both P>0.05). Conclusion:The weight-loss based exercise has a protective effect on the knee joint of patients with simple obesity, which can avoid a reduction in volume of knee cartilage and elevation in local skin temperature, and reduce the occurrence of pain.