A Data Matrix Code Recognition Method Based on L-Shaped Dashed Edge Localization Using Central Prior.

The recognition of data matrix (DM) codes plays a crucial role in industrial production. Significant progress has been made with existing methods. However, for low-quality images with protrusions and interruptions on the L-shaped solid edge (finder pattern) and the dashed edge (timing pattern) of DM codes in industrial production environments, the recognition accuracy rate of existing methods sharply declines due to a lack of consideration for these interference issues. Therefore, ensuring recognition accuracy in the presence of these interference issues is a highly challenging task. To address such interference issues, unlike most existing methods focused on locating the L-shaped solid edge for DM code recognition, we in this paper propose a novel DM code recognition method based on locating the L-shaped dashed edge by incorporating the prior information of the center of the DM code. Specifically, we first use a deep learning-based object detection method to obtain the center of the DM code. Next, to enhance the accuracy of L-shaped dashed edge localization, we design a two-level screening strategy that combines the general constraints and central constraints. The central constraints fully exploit the prior information of the center of the DM code. Finally, we employ libdmtx to decode the content from the precise position image of the DM code. The image is generated by using the L-shaped dashed edge. Experimental results on various types of DM code datasets demonstrate that the proposed method outperforms the compared methods in terms of recognition accuracy rate and time consumption, thus holding significant practical value in an industrial production environment.

Intracellular accumulation of c-di-GMP and its regulation on self-flocculation of the bacterial cells of Zymomonas mobilis.

Zymomonas mobilis is an emerging chassis for being engineered to produce bulk products due to its unique glycolysis through the Entner-Doudoroff pathway with less ATP produced for lower biomass accumulation and higher product yield. When self-flocculated, the bacterial cells are more productive, since they can self-immobilize within bioreactors for high density, and are more tolerant to stresses for higher product titers, but this morphology needs to be controlled properly to avoid internal mass transfer limitation associated with their strong self-flocculation. Herewith we explored the regulation of cyclic diguanosine monophosphate (c-di-GMP) on self-flocculation of the bacterial cells through activating cellulose biosynthesis. While ZMO1365 and ZMO0919 with GGDEF domains for diguanylate cyclase activity catalyze c-di-GMP biosynthesis, ZMO1487 with an EAL domain for phosphodiesterase activity catalyzes c-di-GMP degradation, but ZMO1055 and ZMO0401 contain the dual domains with phosphodiesterase activity predominated. Since c-di-GMP is synthesized from GTP, the intracellular accumulation of this signal molecule through deactivating phosphodiesterase activity is preferred for activating cellulose biosynthesis to flocculate the bacterial cells, because such a strategy exerts less perturbance on intracellular processes regulated by GTP. These discoveries are significant for not only engineering unicellular Z. mobilis strains with the self-flocculating morphology to boost production but also understanding mechanism underlying c-di-GMP biosynthesis and degradation in the bacterium.

D-allulose, a versatile rare sugar: recent biotechnological advances and challenges.

D-Allulose is the C-3 epimer of D-fructose, and widely regarded as a promising substitute for sucrose. It's an excellent low-calorie sweetener, with 70% sweetness of sucrose, 0.4 kcal/g dietary energy, and special physiological functions. It has been approved as GRAS by the U.S. Food and Drug Administration, and is allowed to be excluded from total and added sugar counts on the food labels. Therefore, D-allulose gradually attracts more public attention. Owing to scarcity in nature, the bioproduction of D-allulose by using ketose 3-epimerase (KEase) has become the research hotspot. Herein, we give a summary of the physicochemical properties, physiological function, applications, and the chemical and biochemical synthesis methods of D-allulose. In addition, the recent progress in the D-allulose bioproduction using KEases, and the possible solutions for existing challenges in the D-allulose industrial production are comprehensively discussed, focusing on the molecular modification, immobilization, food-grade expression, utilizing low-cost biomass as feedstock, overcoming thermodynamic limitation, as well as the downstream separation and purification. Finally, Prospects for further development are also proposed.

The History of Flow Chemistry at Eli Lilly and Company.

Flow chemistry was initially used for speed to early phase material delivery in the development laboratories, scaling up chemical transformations that we would not or could not scale up batch for safety reasons. Some early examples included a Newman Kwart Rearrangement, Claisen rearrangement, hydroformylation, and thermal imidazole cyclization. Next, flow chemistry was used to enable safe scale up of hazardous chemistries to manufacturing plants. Examples included high pressure hydrogenation, aerobic oxidation, and Grignard formation reactions. More recently, flow chemistry was used in Small Volume Continuous (SVC) processes, where highly potent oncolytic molecules were produced by fully continuous processes at about 10 kg/day including reaction, extraction, distillation, and crystallization, using disposable equipment contained in fume hoods.

Flagella disruption in Bacillus subtilis increases amylase production yield.

BACKGROUND: Bacillus subtilis is a Gram-positive bacterium used as a cell factory for protein production. Over the last decades, the continued optimization of production strains has increased yields of enzymes, such as amylases, and made commercial applications feasible. However, current yields are still significantly lower than the theoretically possible yield based on the available carbon sources. In its natural environment, B. subtilis can respond to unfavorable growth conditions by differentiating into motile cells that use flagella to swim towards available nutrients. RESULTS: In this study, we analyze existing transcriptome data from a B. subtilis α-amylase production strain at different time points during a 5-day fermentation. We observe that genes of the fla/che operon, essential for flagella assembly and motility, are differentially expressed over time. To investigate whether expression of the flagella operon affects yield, we performed CRISPR-dCas9 based knockdown of the fla/che operon with sgRNA target against the genes flgE, fliR, and flhG, respectively. The knockdown resulted in inhibition of mobility and a striking 2-threefold increase in α-amylase production yield. Moreover, replacing flgE (required for flagella hook assembly) with an erythromycin resistance gene followed by a transcription terminator increased α-amylase yield by about 30%. Transcript levels of the α-amylase were unaltered in the CRISPR-dCas9 knockdowns as well as the flgE deletion strain, but all manipulations disrupted the ability of cells to swim on agar. CONCLUSIONS: We demonstrate that the disruption of flagella in a B. subtilis α-amylase production strain, either by CRISPR-dCas9-based knockdown of the operon or by replacing flgE with an erythromycin resistance gene followed by a transcription terminator, increases the production of α-amylase in small-scale fermentation.

Metabolic engineering of microorganisms for L-alanine production.

L-alanine is extensively used in chemical, food, and medicine industries. Industrial production of L-alanine has been mainly based on the enzymatic process using petroleum-based L-aspartic acid as the substrate. L-alanine production from renewable biomass using microbial fermentation process is an alternative route. Many microorganisms can naturally produce L-alanine using aminotransferase or L-alanine dehydrogenase. However, production of L-alanine using the native strains has been limited due to their low yields and productivities. In this review, metabolic engineering of microorganisms for L-alanine production was summarized. Among them, the Escherichia coli strains developed by Dr. Lonnie Ingram's group which can produce L-alanine with anaerobic fermentation process had several advantages, especially having high L-alanine yield, and it was the first one that realized commercialization. L-alanine is also the first amino acid that could be industrially produced by anaerobic fermentation.

Zhang Weishen: A Pioneer in the Development and Industrial Production of Penicillin in New China.

The research and development of penicillin started with difficulty before 1949 and achieved certain results. In 1951, after the founding of the People's Republic of China, Zhang Weishen, as the only Chinese scientist who had been trained and worked in a penicillin research and development center in the United States for many years, overcame many difficulties and returned to China. In 1953, with the efforts of Zhang Weishen and his colleagues, China realized the industrialized production of penicillin, alleviating the urgent needs of the masses. Antibiotics has also become the first discipline to achieve major scientific and technological achievements after the founding of the New China. In the mid-1950s, the technical breakthrough in the localization of lactose substitutes marked the localization of the raw materials of the penicillin-producing culture medium, which paved the way for the industrialized production of penicillin with Chinese characteristics. Antibiotics have become one of the most widely used and affordable drugs for hundreds of millions of patients in China, and China has since ended the humiliating history of the "Sick Man of East Asia".

Industrial Production of Organophosphate Flame Retardants (OPFRs): Big Knowledge Gaps Need to Be Filled?

Since the phase-out of traditional halogenated flame retardants (HFRs), interests of research are gradually being shifted to organophosphate flame retardants (OPFRs), and this can be reflected by the increasing number of publications on OPFRs year by year. Here, an extensive survey is conducted in an attempt to generate a list of OPFRs that are being produced in factories, and to investigate the annual production volume (APV). This survey suggests that at least n = 56 OPFR monomers and n = 62 OPFR mixtures are being currently produced in 367 factories around the world, and 201 out of them are in Mainland China. APV of OPFRs was estimated as 598,422 metric tons, and this number could be underestimated due to the limitation of available information. We also notice that current researches are confined to a limited number of OPFRs, especially for OP esters (OPEs), and other OPFRs with different structures from OPEs has been rarely studied. Based on all the collected datasets, we provide five recommendations for how to proceed with future research to more comprehensively understand the currently-produced OPFRs in the environment.

Socioeconomic impact due to COVID-19: An empirical assessment.

Starting from December 2019, the novel COVID-19 threatens human lives and economies across the world. It was a matter of grave concern for the governments of all the countries as the deadly virus started expanding its paws over neighboring regions of infected areas. The spread got uncontrollable, thereby leaving no choice for the nations but to impose and observe nationwide lockdown. The lockdown further sorely hit many sectors, which in turn impacted the economy. Manufacturing, agriculture, and the service sector - the three pillars of the economy - have been adversely affected giving a major slow down to the economy belonging to every nation. Several schemes and policies were introduced by different state and central governments to absorb the impact of subsequent lockdowns on individuals. In this paper, we present a then and now analysis of the economy using a socioeconomic framework focusing on factors- unemployment, industrial production, import-export trade, equity markets, currency exchange rate, and gold and silver prices. For all these, we consider India as a case study because the Indian sub-continent has a wide landscape and rich cultural heritage presenting itself as a potential hub for economic activities. A thorough assessment has been made for the period January 2020- June 2020. The assessment will be beneficial to observe the long-term impact of any infectious disease outbreak such as COVID-19 locally and globally.

Exploiting endophytic microbes as micro-factories for plant secondary metabolite production.

Plant secondary metabolites have significant potential applications in a wide range of pharmaceutical, food, and cosmetic industries by providing new chemistries and compounds. However, direct isolation of such compounds from plants has resulted in over-harvesting and loss of biodiversity, currently threatening several medicinal plant species to extinction. With the breakthrough report of taxol production by an endophytic fungus of Taxus brevifolia, a new era in natural product research was established. Since then, the ability of endophytic microbes to produce metabolites similar to those produced by their host plants has been discovered. The plant "endosphere" represents a rich and unique biological niche inhabited by organisms capable of producing a range of desired compounds. In addition, plants growing in diverse habitats and adverse environmental conditions represent a valuable reservoir for obtaining rare microbes with potential applications. Despite being an attractive and sustainable approach for obtaining economically important metabolites, the industrial exploitation of microbial endophytes for the production and isolation of plant secondary metabolites remains in its infancy. The present review provides an updated overview of the prospects, challenges, and possible solutions for using microbial endophytes as micro-factories for obtaining commercially important plant metabolites.Key points• Some "plant" metabolites are rather synthesized by the associated endophytes.• Challenges: Attenuation, silencing of BGCs, unculturability, complex cross-talk.• Solutions: Simulation of in planta habitat, advanced characterization methods.

Recent development in the production strategies of microbial carotenoids.

Carotenoids are a diverse group of lipid-soluble pigments that exhibit potent biological activities such as antioxidant, anti-inflammatory, and provitamin A activities. The potent health benefits of carotenoids result in the surge in the market demands for carotenoids, especially natural carotenoids from sustainable sources. Microbial carotenoids have attracted considerable interests for many industrial applications because of the low costs and ease of scaling-up with shorter production time. There is a growing interest in the search of new and sustainable microbial sources and cost-efficient production strategies following the high economical values and vast commercial applications of carotenoids. This article presents a review on the industrial production strategies of microbial carotenoids from microalgae, fungi, and bacteria sources. The industrial significance of the mass production of microbial carotenoids is also discussed. The structure, classification, and biosynthesis pathway of the carotenoids are also presented in this review.

[The health issues in self-appraisal of workers of industrial production and social sector].

The article considers issues of health, safety and well-being of working citizens in such sectors of economy having great importance for every state such as production and social sphere. The problem of health preservation and working place safety is actual for working population all around the world, going beyond interests of individual citizens and their families and playing primary role in issues of labor safety and productivity, competitiveness and development of enterprises, stability of national economy sectors. The actuality of the study is conditioned by the fact that human resources and labor market are key institutional factors impacting the level of state socioeconomic development and determining health status of working citizens. In Russia, the issues of support by employers safe working conditions in various spheres of national economy to contribute to preservation of their employees health, to occupational diseases prevention ultimately determine both labor productivity at particular enterprise and development and stability of national economy as a whole. The study of self-assessment of health status of workers in industrial production and social sphere was carried out on the basis of results of survey implemented in September 2020 among medical personnel of the Municipal Hospital No. 11 of the city of Ryazan and employees of the oil refining plant - JSC Ryazan Oil Refinery. The analysis of the study results permitted to conclude that, in answering question about health status assessment, workers of social sphere consider themselves to be healthier than workers in industrial production.

Growth years and post-harvest processing methods have critical roles on the contents of medicinal active ingredients of Scutellaria baicalensis.

Optimizing the processing technology is an effective way to improve the yield of active ingredients for the industrial production of medicinal crops. Baikal Skullcap (Scutellaria baicalensis Georgi) is a perennial herb in the Lamiaceae family and its dried root is used as a famous traditional Chinese medicine (TCM). Modern pharmacological studies have shown that the active ingredients of S. baicalensis have important pharmacological effects including anti-oxidation, anti-bacterial, anti-viral, anti-tumor, and anti-inflammation. Specifically, it is recently found that S. baicalensis has significant curative effects on the treatment of corona virus disease 2019 (COVID-19). In recent years, the market demand for the medicinal products of S. baicalensis is increasing because of its great medicinal values. However, the annual yield of active ingredients originated from the root of S. baicalensis is limited due to that little progress has been made on the traditional processing technology used in the extraction process. A pressing issue faced by both herbalists and scientists is how to improve the processing efficiency, thereby obtaining the maximum yield of products for S. baicalensis. In this study, a systematic analysis on the effects of growth years and post-harvest processing on the contents of medicinal active ingredients of S. baicalensis was conducted. The contents of eight active ingredients (baicalin, wogonoside, baicalein, wogonin, scutellarin, scutellarein, apigenin, and chrysin) in roots of S. baicalensis of different growth years (ranging from 1 year to 15 years) were estimated using high performance liquid chromatography (HPLC) and further analyzed to determine the optimal harvest period. In particular, the contents of six active ingredients in different parts (cortex and stele) of the root of S. baicalensis were estimated and compared. Meanwhile, the dynamic changes of the contents of active ingredients in fresh-crush and fresh-cut roots of S. baicalensis at room temperature were compared and analyzed to reveal the influence of post-harvest treatment on the contents of active ingredients. In addition, the effects of six different post-harvest treatments on the contents of active ingredients were systematically designed and compared to determine the best primary processing technology. The results showed that the best harvesting period for S. baicalensis should be determined as 2-3 years based on comprehensive evaluation of active ingredient content, annual yield increment, and land use efficiency. The contents of active ingredients including baicalin, wogonoside, baicalein, and wogonin in cortex were significantly higher than those in stele (P ≤  0.05). The contents of baicalin, wogonoside, and scutellarin in fresh roots of S. baicalensis significantly reduced as the storage time increased, but the reduction of fresh-cutting was significantly lower than that of fresh-crushing. For the effects of different processing treatments, the contents of four main active ingredients (baicalin, wogonoside, baicalein, and wogonin) under drying (D) and cutting-drying (C-D) treatments were significantly higher than those of the other four treatments (P ≤  0.05). Collectively, the above results will not only provide novel processing methods that will improve the yield of active ingredients for S. baicalensis, but also shed light on the optimization of processing technology for the industrial production of medicinal crops.

The global effects of Covid-19-induced uncertainty.

We estimate a VAR with world-level variables to simulate the effects of the Covid-19 outbreak-related uncertainty shock. We find a peak (cumulative over one year) negative response of world output of 1.6% (14%).

Recent advances in biological production of erythritol.

Erythritol is a natural sweetener commonly used in the food and pharmaceutical industries. Produced by microorganisms as an osmoprotectant, it is an ideal sucrose substitute for diabetics or overweight persons due to its almost zero calorie content. Currently, erythritol is produced on an industrial scale through the fermentation of sugars by some yeasts, such as Moniliella sp. However, the popularity of erythritol as a sweetener is still small because of its high retail price. This creates an opportunity for further process improvement. Recent years have brought the rapid development of erythritol biosynthesis methods from the low-cost substrates, and a better understanding of the metabolic pathways leading to erythritol synthesis. The yeast Yarrowia lipolytica emerges as an organism effectively producing erythritol from pure or crude glycerol. Moreover, novel erythritol producing organisms and substrates may be taken into considerations due to metabolic engineering. This review focuses on the modification of erythritol production to use low-cost substrates and metabolic engineering of the microorganisms in order to improve yield and productivity.

An Optimized and Feasible Preparation Technique for the Industrial Production of Hydrogel Patches.

For hydrogel patches, the laboratory tests could not fully reveal the existing problems of full scale of industrial production, and there are few studies about the preparation technique for the industrial manufacturing process of hydrogel patches. So, the purpose of this work was to elucidate the effects of mainly technological operation and its parameters on the performance of hydrogel patches at the industrial-scale production. The results revealed the following: (1) the aqueous phase was obtained by polyvinylpyrrolidone (PVP) along with tartaric acid dissolved in purified water, then feeding this into a vacuum mixer as a whole in one batch, thus extended the crosslinking reaction time of hydrogel paste (matrix) and allowed the operation of coating/cutting-off to be carried out easily, and there was no permeation of backing layer; (2) the gel strength of the hydrogel patches increased with the increase of working temperature, however, once the temperature exceeded 35 ± 2 °C, the hydrogel paste would lose water severely and the resultant physical crosslinking structure which has lower gel/cohesive strength would easily bring gelatinization/residues during application; (3) the relative humidity (RH) of the standing-workshop was dynamically controlled (namely at 35 ± 2 °C, keeping the RH at 55 ± 5% for 4 days, then 65 ± 5% for 2 days), which would make patches with satisfactory characteristics such as better flexibility, higher adhesive force, smooth flat matrix surface, and without gelatinization/residues and warped edge during the using process; (4) the aging of the packaged hydrogel patches was very sensitive to storage temperature, higher temperature, higher gel strength and lower adhesiveness. The storage temperature of 10 ± 2 °C could effectively prevent matrix aging and adhesion losing, which would also facilitate the expiration date of patches extended obviously. In conclusion, this work provides an optimized and feasible preparation technique for the industrial production of the hydrogel patches and establishes the hydrogel patches as a novel carrier for transdermal drug delivery.

Engineering microbial cell factories for the production of plant natural products: from design principles to industrial-scale production.

Plant natural products (PNPs) are widely used as pharmaceuticals, nutraceuticals, seasonings, pigments, etc., with a huge commercial value on the global market. However, most of these PNPs are still being extracted from plants. A resource-conserving and environment-friendly synthesis route for PNPs that utilizes microbial cell factories has attracted increasing attention since the 1940s. However, at the present only a handful of PNPs are being produced by microbial cell factories at an industrial scale, and there are still many challenges in their large-scale application. One of the challenges is that most biosynthetic pathways of PNPs are still unknown, which largely limits the number of candidate PNPs for heterologous microbial production. Another challenge is that the metabolic fluxes toward the target products in microbial hosts are often hindered by poor precursor supply, low catalytic activity of enzymes and obstructed product transport. Consequently, despite intensive studies on the metabolic engineering of microbial hosts, the fermentation costs of most heterologously produced PNPs are still too high for industrial-scale production. In this paper, we review several aspects of PNP production in microbial cell factories, including important design principles and recent progress in pathway mining and metabolic engineering. In addition, implemented cases of industrial-scale production of PNPs in microbial cell factories are also highlighted.

Design-build-test of recombinant Bacillus subtilis chassis cell by lifespan engineering for robust bioprocesses.

Microbial cell factories utilize renewable raw materials for industrial chemical production, providing a promising path for sustainable development. Bacillus subtilis is widely used in industry for its food safety properties, but challenges remain in the limitations of microbial fermentation. This study proposes a novel strategy based on lifespan engineering to design robust B. subtilis chassis cells to supplement traditional metabolic modification strategies that can alleviate cell autolysis, tolerate toxic substrates, and get a higher mass transfer efficiency. The modified chassis cells could produce high levels of l-glutaminase, and tolerate hydroquinone to produce α-arbutin efficiently. In a 5 L bioreactor, the l-glutaminase enzyme activity of the final strain CRE15TG was increased to 2817.4 ± 21.7 U mL-1, about 1.98-fold compared with that of the wild type. The α-arbutin yield of strain CRE15A was increased to 134.7 g L-1, about 1.34-fold compared with that of the WT. To our knowledge, both of the products in this study performed the highest yields reported so far. The chassis modification strategy described in this study can Improve the utilization efficiency of chassis cells, mitigate the possible adverse effects caused by excessive metabolic modification of engineered strains, and provide a new idea for the future design of microbial cell factories.

Advancements in liposomal formulations: A comprehensive exploration of industrial production techniques.

Liposomes are nanosized, spherical vesicles consisting of an aqueous core encircled by one or more phospholipid bilayer shells. Liposomes have found extensive use in numerous biomedicine and nanomedicine applications due to their excellent biocompatibility, adaptable chemical composition, ease of preparation, and diverse structural characteristics. These applications include nanocarriers for drug delivery, immunoassays, nutraceuticals, tissue engineering, clinical diagnostics, and theranostics formulations. These applications stimulated significant efforts toward scaling up formation processes in anticipation of appropriate industrial advancement. Despite the advancements in conventional methods and the emergence of new approaches for liposome production, their inherent susceptibility to chemical and mechanical influences contributes to critical challenges, including limited colloidal stability and decreased efficiency in encapsulating cargo molecules. With this context, the current review provides brief insights into liposomes conventional and novel industrial production techniques. With a special focus on the structural parameters, and pivotal elements influencing the synthesis of an appropriate and stable formulation, followed by the various regulatory aspects of industrial production.

Application and research progress of ARTP mutagenesis in actinomycetes breeding.

Atmospheric and room temperature plasma (ARTP) is an emerging artificial mutagenesis breeding technology. In comparison to traditional physical and chemical methods, ARTP technology can induce DNA damage more effectively and obtain mutation strains with stable heredity more easily after screening. It possesses advantages such as simplicity, safety, non-toxicity, and cost-effectiveness, showing high application value in microbial breeding. This article focuses on ARTP mutagenesis breeding of actinomycetes, specifically highlighting the application of ARTP mutagenesis technology in improving the performance of strains and enhancing the biosynthetic capabilities of actinomycetes. We analyzed the advantages and challenges of ARTP technology in actinomycetes breeding and summarized the common features, specific mutation sites and metabolic pathways of ARTP mutagenic strains, which could give guidance for genetic modification. It suggested that the future research work should focus on the establishment of high throughput rapid screening methods and integrate transcriptomics, proteomics, metabonomics and other omics to delve into the genetic regulations and synthetic mechanisms of the bioactive substances in ARTP mutated actinomycetes. This article aims to provide new perspectives for actinomycetes breeding through the establishment and application of ARTP mutagenesis technology, thereby promoting source innovation and the sustainable industrial development of actinomycetes.