Current industry practices for large-scale mammalian cell cultures typically employ a standard platform fed-batch process with fixed volume bolus feeding. Although widely used, these processes are unable to respond to actual nutrient consumption demands from the culture, which can result in accumulation of by-products and depletion of certain nutrients. This work demonstrates the application of a fully automated cell culture control, monitoring, and data processing system to achieve significant productivity improvement via dynamic feeding and media optimization. Two distinct feeding algorithms were used to dynamically alter feed rates. The first method is based upon on-line capacitance measurements where cultures were fed based on growth and nutrient consumption rates estimated from integrated capacitance. The second method is based upon automated glucose measurements obtained from the Nova Bioprofile FLEX® autosampler where cultures were fed to maintain a target glucose level which in turn maintained other nutrients based on a stoichiometric ratio. All of the calculations were done automatically through in-house integration with a Delta V process control system. Through both media and feed strategy optimization, a titer increase from the original platform titer of 5 to 6.3 g/L was achieved for cell line A, and a substantial titer increase of 4 to over 9 g/L was achieved for cell line B with comparable product quality. Glucose was found to be the best feed indicator, but not all cell lines benefited from dynamic feeding and optimized feed media was critical to process improvement. Our work demonstrated that dynamic feeding has the ability to automatically adjust feed rates according to culture behavior, and that the advantage can be best realized during early and rapid process development stages where different cell lines or large changes in culture conditions might lead to dramatically different nutrient demands.

Technological innovation and high-quality economic development are inevitable requirements of sustainable development, and the digital economy has gradually become a new engine to enhance technological innovation and the high-quality development of China’s economy. Deeply discussing the effect of digital economy on high-quality economic development and clarifying the mechanism behind it can effectively grant the boosting power of digital economy to China’s high-quality development, which is of great practical significance to China’s sustainable economic development. In this study, the mechanism, effect, and regional heterogeneity of the impact of the digital economy on the level of high-quality economic development in 30 Chinese provinces from 2011–2019 were measured and empirically tested using a mediating effects model and a spatial Durbin model, among others. The results showed that the overall level of digital economy and high-quality development is not high, and there were both high agglomeration and low agglomeration, with obvious spatial path dependence and spatial lock-in. Digital economy could promote the high-quality development level of the economy, and the spatial spillover effect was remarkable. In addition, the function of digital economy in promoting high-quality economic development in the eastern, central, and western regions was gradually weakened. Besides, the technological innovation was an important transmission path of digital economy to high-quality economic development. Based on these findings, it is proposed that decision-makers should strengthen digitalization efforts so that the digital economy can become a powerful tool to narrow the digital divide. Further, the dynamic and differentiated digital economy development strategy should be implemented to reduce regional development imbalances in an effective manner.

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Degradation of native j-carrageenan was performed using acid hydrolysis aided with microwave heating. Combined with nonofiltration membrane (cut-off molecular weight 250 Da) separation, 1. 400 Da -50 kDa low-molecular-weight (LMW) j-carrageenans were obtained. Narrow molecular weight distribution of LMW j-carrageenans could be prepared under pH 2.18 during the microwave power range investigated. The in vivo anti-influenza virus (IV) activity of three kinds of LMW j-carrageenans (3, 5, and 10 kDa), their acetylated derivatives (acetylation degree of 1.5), as well as an acetylated and sulfated derivative of 3 kDa carrageenan (acetylation degree of 1.0 and sulfation degree of 2.4), were investigated using FM1-induced pulmonary oedema model. These LMW j-carrageenans showed significant inhibition against FM1-induced pulmonary oedema as compared with the virus control, although their activities were inferior to that of positive control, Rabivirin. Introduction of acetyl groups greatly increased their anti-IV activity. The acetylated 3-kDa j-carrageenan exhibited comparative activity with Rabivirin at both doses of 6 and 30 2. mg/kgÁd, and the acetylated and sulfated derivative of 3 kDa carrageenan displayed higher activity than Rabivirin at the dose of 30 mg/kgÁd. These results disclosed that 3 kDa j-carrageenan with proper acetylation degree and sulfation degree was a potential candidate against influenza virus.

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A highly sensitive and selective colorimetric assay based on a multifunctional molecular beacon with palindromic tail (PMB) was proposed for the detection of target p53 gene. The PMB probe can serve as recognition element, primer, and polymerization template and contains a nicking site and a C-rich region complementary to a DNAzyme. In the presence of target DNA, the hairpin of PMB is opened, and the released palindromic tails intermolecularly hybridize with each other, triggering the autonomous polymerization/nicking/displacement cycles. Although only one type of probe is involved, the system can execute triple and continuous polymerization strand displacement amplifications, generating large amounts of G-quadruplex fragments. These G-rich fragments can bind to hemin and form the DNAzymes that possess the catalytic activity similar to horseradish peroxidase, catalyzing the oxidation of ABTS by HO and producing the colorimetric signal. Utilizing the newly proposed sensing system, target DNA can be detected down to 10 pM with a linear response range from 10 pM to 200 nM, and mutant target DNAs are able to be distinguished even by the naked eye. The desirable detection sensitivity, high specificity, and operation convenience without any separation step and chemical modification demonstrate that the palindromic molecular beacon holds the potential for detecting and monitoring a variety of nucleic acid-related biomarkers.