Development of automated metabolite control using mid-infrared probe for bioprocesses and vaccine manufacturing.

Automation of metabolite control in fermenters is fundamental to develop vaccine manufacturing processes more quickly and robustly. We created an end-to-end process analytical technology (PAT) and quality by design (QbD) focused process by replacing manual control of metabolites during the development of fed-batch bioprocesses with a system that is highly adaptable, and automation enabled. Mid-infrared (MIR) spectroscopy with an attenuated total reflectance probe in-line, and simple linear regression using the Beer-Lambert Law, were developed to quantitate key metabolites (glucose and glutamate) from spectral data that measured complex media during fermentation. This data was digitally connected to a process information management system (PIMS), to enable continuous control of feed pumps with proportional-integral-derivative (PID) controllers, that maintained nutrient levels throughout fed-batch stirred-tank fermenter processes. Continuous metabolite data from mid-infrared spectra of cultures in stirred-tank reactors enabled feedback loops and control of the feed pumps in pharmaceutical development laboratories. This improved process control of nutrient levels by 20-fold and the drug substance yield by an order of magnitude. Furthermore, the method is adaptable to other systems and enables soft sensing, such as consumption rate of metabolites. The ability to develop quantitative metabolite templates quickly and simply for changing bioprocesses was instrumental for project acceleration and heightened process control and automation.

Comparative study on fatigue evaluation of suspenders by introducing actual vehicle trajectory data.

Suspenders play a crucial role in transmitting loads from the bridge deck to the main cable in a suspension bridge. They are susceptible to fatigue due to repeated dynamic loads, particularly traffic loads. Traffic Load Models (TLMs), typically created using Monte-Carlo simulation and Weigh-In-Motion (WIM) data, are employed to evaluate this fatigue. However, these models often overlook practical vehicle trajectories and spatio-temporal distribution, which compromises the precision of fatigue assessments. In this study, we introduce a novel 2D Intelligent Driver Model (2D-IDM) that incorporates actual vehicle trajectories, with a particular focus on transverse vehicle movement. This enhancement aims to improve the fidelity of existing TLMs. To provide a clear, qualitative, and quantitative understanding of the effects of fatigue evaluation with or without actual trajectory characteristics, we have structured this paper as a comparative study. We compare our proposed model, denoted as TLM S-3, with two observation-based models (O-1 and O-2) and two simulation-based models (S-1 and S-2). We conducted an experimental case study on a long-span suspension bridge, where the actual traffic load trajectory was obtained using a WIM-Vision integrated system. To calculate fatigue damage considering both longitudinal and transverse directions, we established a multi-scale Finite Element Model (FEM) using solid element types to simulate the bridge girder. This model can generate the stress influence surface of the bridge and has been verified in both static and dynamic aspects. Our detailed comparative analysis demonstrates the consistency of the proposed 2D-IDM with the actual measured traffic load trajectories. This indicates that our approach can enhance the fidelity and precision of fatigue evaluations for bridge suspenders.

Value of the triglyceride-glucose index and non-traditional blood lipid parameters in predicting metabolic syndrome in women with polycystic ovary syndrome.

PURPOSE: Insulin resistance (IR) is common in patients with polycystic ovary syndrome (PCOS). Metabolic syndrome (MS) includes, inter alia, IR, hypertension, dyslipidemia, and disturbances in glucose metabolism. The triglyceride-glucose (TyG) index and non-traditional lipid parameters are strong predictors of IR and cardiovascular disease and can be considered as screening indicators for MS. This study aimed to evaluate the predictive potential of non-traditional lipid parameters and the TyG index to identify MS in PCOS. METHODS: This cross-sectional study included 134 women diagnosed with PCOS (50 patients with comorbid MS and 84 patients without MS). Biochemical indices were collected, and triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC)/HDL-C, low-density lipoprotein cholesterol (LDL-C)/HDL-C, non-HDL-C, TyG, and TyG-BMI indices were calculated. Logistic regression analysis was used to compare and determine the association of the six parameters with MS, and the receiver operating characteristic (ROC) curve was used to evaluate the performance of each parameter in identifying MS in the PCOS population. RESULTS: After adjusting for age and body mass index (BMI), TG/HDL-C, TC/HDL-C, LDL-C/HDL-C, non-HDL-C, TyG, and TyG-BMI were associated with MS (all P<0.05). The odds ratios were 4.075 (0.891, 1.107), 3.121 (1.844, 5.282), 3.106 (1.734, 5.561), 2.238 (1.302, 3.848), 13.422 (4.364, 41.282), and 1.102 (1.056, 1.150), respectively. TG/HDL-C, TC/HDL-C, LDL-C/HDL-C, non-HDL-C, TyG, and TyG-BMI are effective predictors of MS in PCOS, and their cut-off values can be used for the early detection of MS. TyG-BMI had the strongest performance in predicting MS (area under the curve 0.905, 95% CI 0.855-0.956), and its optimal critical value for predicting MS was 202.542. CONCLUSIONS: TG/HDL-C, TC/HDL-C, LDL-C/HDL-C, non-HDL-C, TyG, and TyG-BMI are novel, clinically convenient and practical markers for the early identification of MS risk in PCOS patients.

Effects of Sitagliptin on Metabolic Indices and Hormone Levels in Polycystic Ovary Syndrome: a Meta-analysis of Randomized Controlled Trials.

To evaluate the effects of sitagliptin on the metabolic indices and hormone levels in patients with polycystic ovary syndrome (PCOS). PubMed, EMBASE, Web of Science, Cochrane Library, WanFang Data, and China National Knowledge Infrastructure (CNKI) were searched for randomized controlled trials (RCTs) published up to March 2022. Eligible studies were identified based on the inclusion criteria. The primary outcomes included the homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), and total testosterone level (TT). Other outcomes included levels of sex hormones, glucose, and lipid metabolism. Forty-five studies were initially identified, and 6 RCTs with 394 patients were finally included in this study. The meta-analysis results suggest that sitagliptin improved HOMA-IR (WMD = - 0.35; 95% CI (- 0.62, - 0.08); P = 0.01), BMI (WMD = - 1.27; 95% CI (- 1.76, - 0.77); P < 0.00001), TT (SMD = - 0.66; 95% CI (- 1.25, - 0.07); P = 0.03), and HDL-C (SMD = 0.11; 95% CI (0.03, 0.18); P = 0.005). No significant differences were observed between the sitagliptin and control groups in other outcomes and in terms of adverse events. Evidence from meta-analyses suggests that sitagliptin was superior in improving insulin sensitivity, total serum testosterone, high-density lipoprotein, and body mass index. However, due to the limitations of published studies, it is difficult to draw a definite conclusion. Larger, higher-quality studies are needed to evaluate the efficacy of sitagliptin in women with PCOS.

Fatigue Tests and Analysis on Welded Joints of Weathering Steel.

To investigate the fatigue performance of vertical web stiffener to deck plate welded joints in weathering steel box girders, six specimens of the weathering steel (WS) Q345qNH, four specimens of WS Q420qNH, and four specimens of the plain carbon steel (CS) Q345q for comparison were tested by a vibratory fatigue testing machine, considering different steel grades, yield strengths, stiffener plate thicknesses, and weld types. The fatigue strength was evaluated based on S-N curves and the crack propagation was analyzed by linear elastic fracture mechanics (LEFM). The results show that the fatigue crack of the welded joints was initiated from the end weld toe of the deck plate and subsequently propagated both along the thickness of the deck plate and in the direction perpendicular to the stiffener plate. The fatigue crack initiation and propagation life of WS Q345qNH specimens were longer than those of CS Q345q specimens. The fatigue crack propagation life of WS Q345qNH specimens was longer than that of WS Q420qNH specimens, while the initiation life bore little relationship to the yield strength. Increasing the stiffener plate thickness effectively delayed crack initiation and slowed down its propagation. Compared with fillet welds, full penetration welds extended the fatigue crack propagation life, while no significant improvement was implied for the initiation life. The WS and CS specimens could be classified as having the same fatigue strengths by nominal stress, hot spot stress, and effective notch stress approaches, which were FAT 50, FAT 100, and FAT 225, respectively. Meanwhile, their material constants for LEFM were relatively close to each other.

Effect of tomato consumption on fasting blood glucose and lipid profiles: A systematic review and meta-analysis of randomized controlled trials.

Tomato (Solanum lycopersicum) phytochemicals, which include phytoene, phytofluene, beta-carotene, flavonoids, lycopene, and polyphenols, have been shown to improve the effects of fasting on plasma triglyceride (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), total cholesterol (TC), and fasting blood sugar (FBS). The aim of this study was to systematically evaluate the effects of Tomato TC, TG, HDL, LDL, and FBS in humans. A systematic literature search was conducted in PubMed/MEDLINE, Web of sciences, and SCOPUS databases by two researchers for studies published until August of 2019 without language and time limitations. Results were combined with random effect models. Six studies were included in this meta-analysis. Combined results reveal a significant reduction in cholesterol (weighted mean difference [WMD]: -4.39 mg/dl, 95% CI: -7.09, -1.68, I2 = % 48, p heterogeneity: .05), TG (WMD: -3.94 mg/dl, 95% CI: -7.67, -0.21, I2 = % 90, p heterogeneity: .001), LDL levels (WMD: -2.09 mg/dl, 95% CI: -3.73, -0.81, I2 = % 78, p heterogeneity: .001), and increasing in HDL levels (WMD: 2.25 mg/dl, 95% CI: 0.41, 4.10, I2 = % 97, p heterogeneity: .001). Tomato was found to have a higher reduction effect on TG and LDL in younger participants. While pooled results indicate no significant effect on FBS levels (WMD: 0.59 mg/dl, 95% CI: -0.28, 1.46, I2 = % 95, p heterogeneity: .001). In conclusion, the results indicate a significant reduction in total cholesterol, TG, and LDL and increase in HDL levels that is caused by tomato consumption.

Fatigue Life Estimation for Suspenders of a Three-Pylon Suspension Bridge Based on Vehicle-Bridge-Interaction Analysis.

Fatigue damage of suspenders is a main concern during the life-cycle maintenance of arch bridges and suspension bridges. This paper presents a practical framework for estimating the fatigue life of suspenders under repeated traffic loads by taking a three-pylon suspension bridge as an example. First, the basic theory of vehicle-bridge interaction (VBI) is introduced and a finite element model of the bridge structure is established. Second, the fatigue load spectrum is defined in detail based on the analysis of WIM (weigh-in-motion) data. And then, parametric analysis is carried out to clarify the influence of road roughness, vehicle speed, and driving lanes. Among which, the time-dependent stress laws are simulated according to the defined fatigue load spectrum and the stress range is counted through the Rain flow counting method. At last, the fatigue life of uncorroded suspenders and naturally corroded suspenders is estimated by an S-N curve and Miner cumulative damage criterion. Results reveal that the fatigue life of suspenders is more than 100 years if no corrosion happens, while less than 20 years for short suspenders considering the influence of natural corrosion.

C-reactive protein, vitamin B12 and C677T polymorphism of N-5,10-methylenetetrahydrofolate reductase gene are related to insulin resistance and risk factors for metabolic syndrome in Chinese population.

PURPOSE: Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) are complex diseases affected by both dietary intake and genetic background. Whether N-5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, high-sensitivity C-reactive protein (hs-CRP) and dietary components folate and vitamin B12 are associated with MS in Asian has not been determined. METHODS: We hypothesized that MTHFR gene C677T, folate, vitamin B12 and hs-CRP are associated with MS and factors related to MS in northern Han Chinese. To test this hypothesis, MTHFR C677T gene polymorphism was determined by PCR-RFLP, serum insulin, folate and vitamin B12 levels by radioimmunoassay, and hs-CRP by immunoturbidimetry in newly diagnosed T2DM patients with MS (118) and without MS (40), and in 55 healthy subjects. RESULTS: Results indicated that MS-associated T2DM accounts for 75% of newly diagnosed T2DM in Han Chinese. Serum hs-CRP was higher and serum vitamin B12 was lower in subjects with TT genotype in comparison with those with CC or CT genotypes. Total T frequency was significantly higher in MS-associated T2DM patients (45.3%) compared to 26.3% in non-MS-associated T2DM patients. MTHFR C677T gene polymorphism and vitamin B12 levels were associated with MS-associated T2DM. CONCLUSION: MTHFR C677T gene polymorphism may contribute to insulin resistance in Han Chinese with MS by increasing hs-CRP and decreasing vitamin B12, and consequently play an important role in development of MS-associated T2DM.