Despite the health benefits associated with the ingestion of the bioactive compounds in cocoa, the high concentrations of polyphenols and methylxanthines in the raw cocoa beans negatively influence the taste, confer the astringency and bitterness, and affect the stability and digestibility of the cocoa products. It is, therefore, necessary to process cocoa beans to develop the characteristic color, taste, and flavor, and reduce the astringency and bitterness, which are desirable in cocoa products. Processing, however, affects the composition and quantities of the bioactive compounds, resulting in the modification of the health-promoting properties of cocoa beans and chocolate. In this advanced review, we sought to better understand the effect of cocoa’s transformational process into chocolate on polyphenols and methylxanthine and the mechanism of action of the original flavanols and methylxanthines. More data on the cocoa processing effect on cocoa bioactives are still needed for better understanding the effect of each processing step on the final polyphenolic and methylxanthine composition of chocolate and other cocoa products. Regarding the mechanisms of action, theobromine acts through the modulation of the fatty acid metabolism, mitochondrial function, and energy metabolism pathways, while flavanols mainly act though the protein kinases and antioxidant pathways. Both flavanols and theobromine seem to be involved in the nitric oxide and neurotrophin regulation. Theobroma cacao L.) belongs to the family Malvaceae and the genus Theobroma. The cocoa tree produces fruits, referred to as pods, along the trunk and branches. The pods are oval and contain the seeds (about 30–40 seeds), commonly known as cocoa beans, which are embedded in a sweet mucilaginous pulp. The pulp is rich in fermentable sugars and high in acidity (pH 3.0–3.5). Chocolate is the most popular cocoa-derived product, highly valued by consumers around the world [Cocoa  and methylxanthines (mainly theobromine) during processing that will affect the mechanism of action implicated in their biological activity. The research gaps are also identified to aid in the planning of future studies. Because this review aims to be an update of the information regarding the flavanols and methylxanthines of cocoa, most of the results reported up to 2020 will be briefly summarized and largely referred to comprehensive reviews; henceforth, we will mainly focus on recent data from the last couple of years, in which, despite the pandemic, research on this topic has been rather productive.The processing of cocoa beans can be categorized into primary and industrial processing. The primary processing of cocoa entails all the processes cocoa pods go through, from harvesting to obtaining the final dried beans . They plThe industrial processing of cocoa can also be sub-classified into secondary and tertiary processing. The secondary processing involves all the processes the dried fermented beans are taken through to obtain semi-finished products, such as cocoa liquor (cocoa mass), cocoa butter, cocoa powder, etc. The secondary processing includes cleaning, breaking and winnowing, sterilization, alkalization, roasting, nib grinding, and liquor processing . The terThe harvesting of ripe, matured cocoa pods initiates the primary processing of cocoa. For optimal processing and the production of high-quality beans for cocoa-based products, only matured, ripe, or at least semi-ripe, and disease-free pods are harvested. The Studies have reported on the direct influence of harvesting cocoa pods at an appropriate maturity stage on the flavor characteristics of the cocoa beans . The cocThe cocoa pulp is the substrate sequentially metabolized by microorganisms during the fermentation process. The properties of the substrate determine the type and quantities of the microbial development and metabolism during the fermentation, hence changes in the pulp may affect the production of alcohols by the yeasts and the subsequent production of acids by the lactic acid and acetic acid bacteria . Pod stoIn general, the pod breaking involves opening the harvested pods to extract the wet beans for fermentation, and it is important not to damage the beans in this process. Cutting the beans will allow insects or molds to enter the bean.Cocoa bean fermentation is crucial in making cocoa beans more valuable and stable. It also influences the marketability and acceptability of the beans. It is conducted for the development of the characteristic brown cocoa color and modification of the polyphenolic and pH, leading to a reduction in the astringency and bitterness of the final dried beans. The fermentation also generates the flavor precursors, namely the free amino acids and peptides, from the enzymatic degradation of the cocoa proteins, reducing sugars from the enzymatic degradation of the sucrose  from whiDuring the fermentation, the beans are removed from the pods and subjected to various activities of various microorganisms, which are prevalent within the surrounding environment. The changes in the cocoa beans produced by the fermentation occur in two stages: the microbial fermentation, which takes place in the pulp, and biochemical changes, which occur in the beans following the death of the embryo. Following the death of the embryo and the breakdown of the cell walls in the bean, endogenous seed enzymes  and substrates  interact and react in a specific manner ,61.The bioactive compounds in the beans are subjected to a biochemical modification through the polymerization and complexation with protein, hence decreasing the solubility and astringency . PolypheThe moisture content of the cocoa beans after fermentation is about 60%, and this needs to be reduced to around 7% by drying ,66 to prCocoa beans for processing are first evaluated for quality, which is important to the final product quality. The beans are then subjected to a cleaning process which involves the removal of all the extraneous materials from the cocoa beans. The process involves a sieving operation to remove all the extraneous materials, such as stones, strings, coins, wood pieces, soil particles, nails, etc. Cleaning before processing is essential to ensure the production of quality products devoid of extraneous materials and to also reduce the wear on machinery, as pieces of metal or stone can cause extensive abrasion on some of the equipment ,71.Processing cocoa beans into semi-finished products, such as cocoa liquor, powder, and butter, requires the use of the essential part of the beans: the nibs (cotyledon). Thus, the nibs need to be separated from the shells. Breaking and winnowing entail applying pressure on the cocoa beans to loosen the shells (breaking) and subsequently separating the shells from the nibs so that only the nibs remain (winnowing). A thorough separation of the shells from the nibs is necessary to ensure a high-quality product devoid of a bitter and unpleasant taste with a gritty texture. Breaking and winnowing can be performed after roasting the beans  or before roasting. When the latter is performed, the nibs can easily be treated with an alkali solution  .Cocoa beans are exposed to microbial contamination during the primary processes of fermentation, drying, bagging, and transportation. Cocoa beans or nibs are thus subjected to saturated steam under pressure for a sufficiently long time to reduce the microbial load . This prAlkalization, also known as Dutching, is an optional step in the processing chain where cocoa nibs are treated with an alkali solution, such as potassium bicarbonate or sodium bicarbonate, to increase the pH to 7–8 with the purpose of modifying the color and taste and improve the dispersibility of the powder solids in water ,45,54,74Alkalization can be performed in three main ways which include: nib alkalization, cake alkalization, and liquor alkalization ,76. Nib Cocoa bean roasting involves subjecting the dried fermented cocoa beans to high temperatures, usually between 120 and 150 °C ,77,78 foRoasting significantly affects both the amount and composition of the polyphenols in cocoa beans ,49,81. ICocoa beans can be roasted in three different ways, namely whole beans, nib, or liquor/mass roasting . Cocoa bCocoa nibs are milled into a low-viscous mass referred to as cocoa liquor or cocoa mass. The viscosity of the liquor produced is greatly influenced by the degree of roasting and the moisture content of the nib. Cocoa liquor consists of the cocoa solid particles suspended in the cocoa butter . The nibChocolates are semisolid suspensions of fine solid particles from sugar and cocoa  in a continuous fat phase . The conOne of the chocolate processing steps which could have a probable influence on the composition of the bioactive compound is conching. Conching consists of the mixing, shearing, and aeration of the chocolate mass during heating at a certain temperature  to produce liquid chocolate, where all the solid particles are coated with fat ,88. It iLimited studies have been conducted on the influence of conching on the polyphenolic and methylxanthine content of chocolates and their antioxidant properties, with varying opinions. Barišić et al.  noted thTempering is one of the most critical processing steps for making quality chocolate. It involves cooling while stirring the chocolate mass derived from the conching (from 40–50 to 18–28 °C) to obtain a stable form of the crystalline fat (polymorphic form V) responsible for the good melting properties and the glossy surface of good-quality chocolate ,95. HoweIn the last two decades, an emerging topic has been the study of the effect of flavonoids on MAPK and upstream/downstream-related proteins, receptors, or enzymes that control the cellular processes, such as proliferation, differentiation, apoptosis, and stress responses, under both normal and pathological conditions. MAPK signaling is activated in response to intra- and extracellular signals that activate the transmembrane glycoproteins of the tyrosine kinase receptor type, leading to the regulation of target genes. Three MAPK families have been reported in mammalian cells: extracellular signal-regulated kinase (ERK), c-Jun N terminal kinase/stress-activated protein kinase (JNK/SAPK), and p38 kinase ,7,8. TheThe specific effect of cocoa flavanols, catechins, and procyanidins on MAPKs and PI3K/Akt signaling pathways has been frequently reported in different cell types and tissues . PioneerCamellia fascicularis extract, one of whose major components is epicatechin, could markedly inhibit the phosphorylation of p65, ERK, and JNK, thereby suppressing the activation of the NF-κB and MAPK signaling pathways, which may induce the secretion of pro-inflammatory cytokines [Because pure phenolic compounds are unlikely to avoid metabolism before reaching the cells, the study of cocoa flavanols metabolites has been an emerging topic during the last decade, in particular colonic microbiota metabolites from catechin and epicatechin. Thus, it has been later reported that microbial phenolic metabolites from cocoa flavanols improved the glucose-stimulated insulin secretion via ERKs and PKC pathways . More reytokines .Recent data also claim flavanols, through MAPK and related pathways, are potent inhibitors of neuroinflammation . A recenAlthough polyphenols exert their antioxidant capacity mainly through the direct neutralization of free radicals and chelating metals, such as Fe2+ and Cu+ ,120, theIn particular, cocoa and its flavonoid compounds exert their protective effect against oxidative stress by targeting the transcription factor Nrf2 and Keap1, which participate in the regulation of the ARE. Thus, the regulation of Keap1 can lead to the nuclear accumulation of Nrf2 and the subsequent ARE activation . The firLater, results on mouse cortical neuron cultures suggested that a combination of epicatechin and quercetin activated the Akt- and Ca(2+)-mediated signaling pathways that converge on nitric oxide synthase (NOS) and CREB; this effect results in synergistic improvements in the neuronal mitochondrial performance which confer the profound protection against ischemic injury . RamírezCognitive function is defined as the mental performance that enables information processing, applying knowledge, and changing preferences . CognitiPerhaps the first approach in the field was the finding of the uptake and metabolism of epicatechin and its access to the brain after oral ingestion ; then, tEver since these comprehensive reviews, some new studies have mostly confirmed or substantiated the beneficial effect of cocoa flavanols on cognitive function. Epicatechin supplementation prevented short-term recognition memory impairment in high-fat diet-induced obese mice . In a huNonetheless, cocoa/flavanol/chocolate treatment has also proved ineffective for cognitive function in some recent studies. In an eight-week RCT (FlaSeCo study), the short-term use of dark chocolate naturally high in flavanols showed no benefit in the studied cognitive parameters in cognitively healthy older adults . In addiPerhaps the best established benefit of cocoa flavanols on health is their positive effect on cardiovascular function; in fact, the European Food Safety Authority (EFSA) has published two claims in support of the bioactivity of cocoa flavanols: cocoa flavanols help maintain normal blood pressure  and endoAn overall agreement on the beneficial effects of cocoa flavanols on cardiovascular function has been proclaimed since the pioneer studies from two decades ago ,174,175,Within the very last years, some new data have been added to the general knowledge; thus, an acute crossover RCT was conducted in 20 healthy males, adding further evidence that epicatechin is a causal vasoactive molecule within flavanol-containing foods/beverages. Interestingly, the data revealed that intake levels as low as 0.5 mg/kg body weight are capable of inducing acute improvements in vascular function, evaluated as the FMD, in healthy volunteers . In the However, not all the studies have shown beneficial effects; thus, a recent meta-analysis showed a significant inverse association between cocoa consumption and systolic/diastolic blood pressure, but the analysis could not conclude any beneficial effect of cocoa consumption on blood pressure in normotensive/elevated blood pressure subjects . MoreoveMethylxanthines show important biological activities that have several benefits for human health, acting against respiratory and cardiovascular diseases, cancer, obesity and diabetes, human infertility, neurological, and neurodegenerative diseases ,199. TheMany reported effects of theobromine are related to its role as a phosphodiesterase inhibitor. In high concentrations, which cannot be reached by nutritional intake but through pharmaceutical administration, theobromine and other methylxanthines lead to the inhibition of cyclic nucleotide phosphodiesterases and high-affinity ATP-dependent cyclic nucleotide transporters. This inhibition results in an increase in the cellular cyclic AMP levels and mobilization of intracellular calcium and, as a consequence, a modulation of the gamma-aminobutyric acid (GABA) receptors . Still, Two years later, a study reported that theobromine presented anti-proliferative activity against colorectal cancer cells HT-29 by modulating the gene expression associated with cell growth pathways. In fact, the Bax/Bcl-2 ratio was strongly upregulated in cells exposed to theobromine, significantly decreasing the cell proliferation . The folTheobromine downregulated the sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase (FASN), and upregulated the PPARα and CPT1a mRNA and protein levels in cultured hepatocytes and improved non-alcoholic fatty liver disease by inhibiting lipogenesis and fatty acid uptake and promoting fatty acid oxidation in the liver, which might be associated with its suppression of the mTOR signaling pathway . Recent One of the first reports showed that the acute consumption of high-flavanol/high-theobromine chocolate increased the plasma epicatechin and theobromine concentrations and decreased the arterial stiffness, with no effect on the endothelial function and a marginal increase in the diastolic blood pressure. However, the chronic intake increased the plasma theobromine, though it did not have positive impacts on the endothelial function, arterial stiffness, or blood pressure in pregnant women at risk of preeclampsia . On the Other authors observed a reduction in the brain oxidative stress, inflammatory intermediaries (tumor necrosis factor α (TNF-α), interleukin-1β, and -6, NF-κB), markers of cell damage (lactate dehydrogenase and caspase-3), acetylcholinesterase activity, and improvement in γ-aminobutyric acid quantity in rats that were given theobromine for 14 days daily after cerebral hypoperfusion . SimilarUntil recently, cocoa’s effects on cognitive function were plainly associated with the polyphenolic fraction, especially flavanols . In factThe first encouraging results were published still in the last century. Pioneer studies showed that theobromine ingestion caused an increase in the brain levels of A1-adenosine receptors . No moreSomewhat later, a study using a fat-enriched diet to induce a long-term deterioration in cognitive and memory functions showed that theobromine, at realistic concentrations in drinking water, restored the A1 receptor levels and improved the cognitive functions and Aβ levels . Still, Regarding other biological effects recently attributed to theobromine, it is worth mentioning that methylxanthine plays a relevant role in some effects related to cocoa intake, such as the lower proportion of IgA-coated bacteria. Moreover, theobromine modifies the gut microbiota, although other cocoa compounds could also act on intestinal bacteria, attenuating or enhancing the theobromine effects . FinallyCocoa bean processing is important as it improves both the economic and technological values of the beans. The primary and secondary processing of cocoa develops the characteristic flavor and color desired in chocolate and other cocoa-related products. However, processing, including chocolate production, affects both the composition and quantities of the flavanols and methylxanthines, mainly the theobromine. Cocoa bean processing mainly results in the reduction in the flavanols and theobromine content of cocoa beans and cocoa-related products. This modifies the taste and flavor as well as the health-promoting properties of cocoa beans and chocolates. Most of the work conducted on the influence of processing on the flavanols and methylxanthine contents in cocoa have focused mainly on the primary processes, with few processing steps during the industrial processing . No studies have reported on the impact of cocoa nib grinding, liquor pressing, and chocolate tempering on the composition of the bioactive compounds. Limited studies have been reported on the influence of conching. Considering the increased consumer interest in cocoa and cocoa-related products due to the presence of bioactive compounds, and the effect processing might have on their bioactivity and mechanisms of action, a holistic study of the entire processing steps (from beans to chocolates and other related products) and its impact on the bioactive compounds would have significant technological and commercial implications. Again, most of the studies reviewed here deal with cocoa beans, cocoa shells, cocoa powder, or black high-cocoa chocolates in which mainly flavanols and theobromine coexist. In this sense, it is challenging, in most cases, to attribute the activity and the mechanisms of action to one fraction or the other. However, we can conclude that theobromine seems to be effective, mainly through the regulation of the fatty acid metabolism, mitochondrial function, and energy metabolism pathways. Flavanols, however, seem to work through the protein kinases MAPKs and PI3K/Akt signaling pathways but also by regulating oxidative stress via targeting the transcription factor Nrf2 and Keap1, which participate in the activation of the antioxidant response element. Both flavanols and theobromine might be responsible for the nitric oxide regulatory effect of cocoa and dark chocolate for the neurological activity through this pathway and the regulation of neurotrophic factors and neuroplasticity pathways.Taking all of the above into account, it would be interesting to investigate the effects that the transformation of cocoa into chocolate produces on the original cocoa bioactive compounds and on the molecular mechanisms associated with their intake. On the other hand, there is a clear need to search for a final product that eliminates, if not completely, most of the sugar content that chocolates currently have on the market. This would allow for enhancing the health benefits associated with the consumption of chocolate by eliminating the risk associated with the consumption of added sugars and by selectively increasing the bioactive compounds of interest by modifying the technological food processes.


Even worse, the heavy misuse of antibiotics undoubtedly also contributes to the emergence of multidrug-resistant (MDR) bacteria, and results in a potential global health crisis. To tackle the resistance problems, countries have gradually restricted or banned the use of antibiotics in feed in recent years .Antimicrobial peptides, as small molecule peptides produced by the host to resist the infections of external pathogens, are one of the most promising antibiotic alternatives based on their membrane disruption mechanisms and immunomodulatory effects  Gram-negative bacteria and reduce their minimum inhibitory concentrations below the interpretative susceptibility breakpoints.Currently, numerous chemical modifications have been proposed to improve the metabolic stability of AMPs, among which, peptidomimetic approaches can reduce proteolytic susceptibility by removing the peptide-like characters of AMPs thereby resulting in the inability of proteases to recognize and degrade the resulting mimic molecules  and so on. Currently, the exact antibacterial mechanisms of polyphenolic compounds are still unclear, but some studies have demonstrated that polyphenolic compounds can cause disruption in bacteria cell membranes, for instance, Zhang et al. confirmed that the compound phenolic acid  could cause bacterial flagellar abscission, cell membrane structure damage, and finally lead to the leakage of intracellular macromolecules, and bacterial death.Plant polyphenolic compounds, as a large family of phytochemicals widely distributed in the plant kingdom, have won the favor of many researchers because of their variety of biological functions including anti-carcinogenic, anti-inflammatory, and anti-oxidant properties. Moreover, some phenolic compounds have been proven to be effective in inhibiting various pathogenic bacteria, such as Lu et al. comprehensively analyzed the main components of oregano essential oil (OEO) and found carvacrol and thymol are the major ingredients responsible for its bactericidal activity. Moreover, carvacrol/thymol could synergize with 405 nm blue light (BL) to kill multidrug-resistant Pseudomonas aeruginosa, greatly improving their antibacterial potential. These findings offered a unique opportunity to standardize OEO products in the basis of the amount of carvacrol and thymol.In addition to polyphenolic compounds, natural plant essential oils (EOs) also have been well-known as potential microbicides. However, bactericidal efficacies of EOs are controversial, mainly because the amount of active ingredients in individual EOs varies with sources and extraction process. Yin et al. demonstrated that dietary Lycium barbarum polysaccharides (LBPs) supplementation could improve growth performance, antioxidant capacity and immunity, and reduced diarrhea incidence in weaned piglets. Koorakula et al. systematically studied the impacts of a commercial phytogenic feed additives (PFAs) product on the gut microbiome and resistome of broiler chickens. The results revealed that PFA treatments increased the abundance of Firmicutes such as Lactobacillus, reduced the abundance of Escherichia, whilst resulted in a decrease in abundance of antibiotic resistance gene. Taken together, phytochemicals have very broad application prospects as feed additives to replace antibiotics in animal production.Due to their excellent properties as antibiotic alternatives, various phytochemicals have been used in animal production as feed additive to improve animal health and growth performance  and the Natural Science Foundation of Heilongjiang Province (YQ2020C009).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


China’s manufacturing industry has been confronted with the issue of extensive development with high input, high consumption, and high emissions for a long time, and its green development is the key to reaching carbon neutrality in China. Under the digital economy, business model innovation is the fundamental means of the green development of manufacturing enterprises. Four representative listed companies in China’s manufacturing were selected as typical cases for the case study. Through open, axial, and selective coding that is based on proceduralized grounded theory, this study profoundly explores business model innovation paths of the manufacturing industry oriented towards green development in the digital economy following the research logic of “green development orientation–business model innovation process–business model innovation result”. Moreover, this study further compares the differences among paths and discusses each path’s effectiveness and applicable conditions. Results show that: (1) Four green business model innovation paths are revealed based on the four green development orientations: efficiency-oriented path, value-oriented path, user-oriented path, and ecology-oriented path. (2) Different enterprises pursue distinct business model innovation paths. The scientific premise for enterprises to opt for the optimal innovation path is the matching of upgrading demands, existing conditions, and path characteristics. Ultimately, the following policy implications are offered: First, promote the green innovation of business models in the manufacturing industry. Second, consider enterprises’ heterogeneity and implement differentiated support policies. This study can serve as theoretical support and decision-making reference for business model innovation and green development in manufacturing enterprises. As a major carbon emitter, China is facing the dual pressure of low-carbon transition and an economic downturn brought on by the COVID-19 epidemic. Therefore, achieving green development—namely, innovation and development patterns that scientifically balance the ecological environment and economic growth—becomes a significant topic during the crisis . As the In recent years, China has gradually become an important leader and driver of the global digital economy . Under tIn general, existing studies on business model innovation in the academic circle have focused on the following. (1) they explore the influencing factors or driving forces of business model innovation based on the internal and external aspects of enterprises ,15,16. FThe aforementioned research perspective has formed diverse valuable research results. However, three deficiencies remain. First, existing studies pay more attention to the influencing factors and evaluation of business model innovation ,32,33, wBased on the above analysis, this study takes a number of typical Chinese manufacturing enterprises as the research object and selects the green development pioneers who embedded digital technology into their business model for green business model innovation as samples. This study systematically analyzes business model innovation paths of manufacturing oriented towards green development of manufacturing under a digital economy through multi-case research and three-level coding and additionally performs a comparative study on the paths. This paper aims to fill the existing research gaps, enrich the business model innovation and green development theory, and serve as practical guidance and theoretical reference for manufacturing enterprises and the government.This study is organized as follows. With regard to the so-called enterprise business model, scholars have conducted research in light of value chains, enterprise systems, organizational management, and the science of strategy ,40,41,42The digital economy is the increasing application and integration of digital technology in the whole economy and society . DigitalBusiness model innovation is an important “window of opportunity” for our manufacturing industry transformation and upgrading . Under tTo sum up, although digit and green have become two important directions of manufacturing enterprises’ business model innovation, academic research is still lacking. In essence, the premise of green development is sustainable economic development. We must innovate the business model, balance the relationship between green development and enterprise profit, and unify ecology and marketization in order to realize green development truly. Most of the existing research only explores the business model innovation of Chinese manufacturing enterprises from the perspective of higher competitive advantages and enterprise performance, ignoring the combination of China’s current green development situation. It is necessary to extend the connotation of green development in business model innovation, seek a business model innovation path that takes into account enterprises’ profit growth and green development, and guide the green transformation of manufacturing enterprises. These are the core issues to be solved in this study.Through the above review of the literature, this study intends to consider that the business model innovation process oriented towards green development in the digital economy is as follows: On the basis of the green development orientation that corresponds to the upgrading pressure, manufacturing enterprises utilize digital technology and digital platforms to innovate the logic of original value creation and to achieve green business model innovation finally. Based on this process, to further explore the specific green business model innovation paths of manufacturing, whether differences exist between these paths, and what application conditions are required for each path, this paper constructs an analytical framework based on the basic logic of “green development orientation–business model innovation process–business model innovation result”  The purpose of this study is to analyze the business model path for green development under the digital economy, which belongs to the “how—question”. Exploratory case analysis lies in the “discovery logic” rather than the “verification logic” , which cThe sample selection for the case study is based on the following considerations. (1) Universality and heterogeneity of cases. The issue of the business model innovation path for enterprises requires cases with widespread or variable consumer types, production characteristics, and establishment periods. (2) Availability and adequacy of data. The annual reports and other public information of four companies listed as case companies are available. Their development model has also captured widespread attention from the media and research institutions, and a large amount of news, the literature, and additional relevant information has been published. (3) Representativeness and typicality. All four companies exhibit strong industry representation and leadership. Hence, they are robust benchmarks in their fields. Moreover, the case companies have a good demonstration role in the green development of China’s manufacturing industry. All four companies fully implement the national green and low-carbon development strategy, adhere to green innovation to help the development of companies, and achieve the coordinated development of economic and environmental benefits. (4) The principle of the matching between the case object and the research questions. Samples were selected to fit the themes of the “digital economy and green development” and “business model innovation.” The case enterprise started the digital transformation earlier, and on this basis, it has successfully implemented the green business model innovation to achieve green development and thus has rich experience in innovation and development. In summary, the case enterprise information is as In order to improve the reliability of the research, according to the idea of continuous analysis of grounded theory, the case enterprises are divided into a modeling group and a testing group. In accordance with the principles of the availability of information, the typicality and heterogeneity of the selected cases, and the matching of the research problems, five cases of Changan Automobile Group, Shenyang Machine Tool, Xi’an Shaangu Power, Qingdao Red Collar Group and Haier Group were selected to test the saturation of the theoretical model.As a representative enterprise in its field, the growth and innovation mode of Xiaomi Corporation, Goldwind Company, Qumei Group, and Baosteel Group have captured widespread attention in the industry and academia, thereby making various publicly available interviews, surveys, books, reports, and other materials abundant to cover research needs sufficiently. The specific sources of the case materials in this paper as In this study, data coding is carried out according to programmed grounded theory. In order to avoid the influence of the coders’ individual subjectivity, reduce the errors in the case study and improve the sensitivity of the theory, this study formed a coding team to complete the coding process, and the members adopted the form of “back-to-back” independent coding analysis, comparison and discussion until a consensus was reached. The coding process is as follows, open coding, spindle coding, selective coding, and theoretical saturation testing.Open coding involves repeatedly refining the original material, extracting information regarding the research object, and conceptualizing and classifying it. This paper focuses on the “Business model innovation of manufacturing enterprises orientated to green development under the digital economy” to conduct open coding. First, the words and sentences related to this content in the material are marked and preliminarily simplified into concepts. This step is followed by “categorization,” in which concepts that seem related to the same phenomenon are grouped into subcategories. The final four cases resulted in 61 subcategories  as the green development orientation. Based on this orientation, the efficiency-oriented path is meant for enterprises to achieve intelligent transformation through the gradual automation and digitization of the production process to resolve efficiency issues and enhance product quality. Efficiency-oriented enterprises implement automation equipment, accelerate digital construction, and connect diverse plant equipment to the Internet for data collection. These measures make the advantages of automated manufacturing superimposed with networking and digitization, give full play to the role of digital technology in controlling and enabling industrial development, and implement the automation of the production process. Furthermore, enterprises transform into intelligence, reconfigure critical resources, and optimize specific processes. Based on the data self-service platform to achieve intelligent analysis and application of production data, such as state perception, intelligent decision-making, advanced warning, and intelligent visualization. This path ultimately achieves an upgrade in the efficiency of the whole industrial chain under upgrading technology levels , reducesThis path has two key nodes. (1) Automation of production processes. Enterprises effectively integrate production lines, processes, and procedures and use automation technologies and artificial intelligence to establish an automated production line group that runs through the whole process from raw materials into the factory to finished products. To optimize its production process, the Baosteel Group executes the “machine substitution” strategy and introduces new technologies, such as industrial robots, unmanned cranes, and artificial intelligence. On the one hand, it has developed a unified standard for operation mode, operation process, and information processing to achieve the acquisition of product lifecycle data. On the other hand, it unifies data structure so that the upper and lower process data in the workshop can flow and cooperate and thus implement the full automation of the production process gradually. Based on this, the automation level of the Baosteel Group has reached a new height and is close to the advanced international level, making the production process more safe and efficient and realizing the improvement of the production line quality index, cost index, and energy consumption index. This indicates that manufacturing enterprises should carry out the automatic transformation on the basis of the standardization and standardization of their production process so as to improve the working efficiency and solve the problem of industrial manufacturing safety production.(2) Intelligent transformation. Together, intelligent machines and human experts form a human–machine integrated intelligent system, which will drive manufacturing development to a new level. During the product process, the system will carry on independent analysis, reasoning, and decision-making for the simulation of the process. It continuously improves its own intelligence through data accumulation, thereby providing strong support for energy conservation and environmental protection, product quality improvement, cost control, and efficiency enhancement. Intelligence is the direction of development for manufacturing automation, which updates the concept of manufacturing automation and extends it to flexibility, intelligence, and a high degree of integration. The Baosteel Group is currently in this process, and the main action strategy is to establish a human–machine integrated intelligent system and implement intelligent analysis and application of data continuously. As an example, the development of an energy efficiency diagnostic model for steel furnaces, the online, real-time monitoring of pollution factors, and the comparison of energy consumption and pollutant emissions with standard lines for early warning in order to maximize energy efficiency and minimize pollutant emissions. In addition, a higher level of intelligence is also available in the form of virtual reality platforms. This application simulates the performance of products, equipment, and plants in real-life situations, thereby enabling enterprises to inspect in a virtual environment before proceeding into production and then optimizing the entire process in parallel based on the test results to reduce resource waste and environmental pollution. This manifests that enterprises should take digital transformation as the starting point to complete the construction of a series of platforms and systems, such as an integrated control platform, AR/VR system, integrated decision IOC and intelligent diagnosis to strengthen their ability to intelligent data analysis, and build visual, transparent, and intelligent manufacturing.Based on the above analysis and discussion, combined with coding materials, this paper proposes Proposition 1:Proposition 1. Based on efficiency orientation, production process automation and intelligent manufacturing represent an important green business model innovation trend. Manufacturing enterprises digitalize and automate the production process by introducing digital technology and implementing autonomous control and dynamic production to optimize production and reduce consumption and emissions. Then, they further analyze and apply the production data intelligently to achieve intelligent transformation, improving the accuracy of decision-making to save energy, reduce emissions and enhance the quality of products. Such innovation increases the efficiency of resource utilization in the production process and reduces environmental pollution so as to promote the green development of manufacturing.Enterprises are under pressure to upgrade their value proposition, accordingly taking value enhancement  as the green development orientation. Based on this orientation, the value-oriented path is meant for enterprises to transform from merely supplying products to supplying additional services for products, which eventually provide total solution services to achieve servitization transformation. Value-oriented enterprises primarily reinforce digital technology research and development and patent construction to shape the unique core capabilities  constantly. With their core capabilities, they further explore high-value-added markets (market innovation) and provide additional services for products. Lastly, enterprises are capable of developing resource service platforms to rapidly supply digital services , such asThis path has three key nodes. (1) Core competence shaping. Enterprises continue to develop critical core technologies to shape a unique competitive advantage. With a focus on technological innovation, enterprises shape the ability to increase value for customers, thereby laying the foundation for subsequent servitization. For instance, the Goldwind Company continued to invest in scientific research over the years and insisted on independent research and development and innovation of wind power technology, which laid a leading edge for its long-term sustainable development. As the technology continues to break through, the technology level and products of Goldwind Company have also taken a leading position in the world. Digital technology runs through their industrial chain and has intelligent operation and management capabilities for labor scheduling, cost and risk control, energy efficiency prediction, asset management, and economical operation, forming the core advantages and competitiveness of the enterprise. This indicates that the premise of enterprise servitization is to develop distinctive core competence of delivering irreplaceable services.(2) Additional services for products. To change the homogenization of market products and the continuous decline of core business profits, enterprises desire to expand various payment services while selling products and achieve the service of core technology. Accordingly, enterprises adopt sustainable considerations to address customer needs, broaden their business scope, and provide professional services supported by core technologies. For example, the Goldwind Company provides maintenance, wind turbine design, old equipment technology system upgrade, and other services. At this time, the service model of Goldwind Company mainly provides product-centric services to increase the added value of products and accumulate technical service experience and related markets.(3) Servitization transformation, from manufacturer to servitization provider. The development of servitization in manufacturing aims to generate value-added and create sustainable value. Providing total solutions meet this demand. As a result, manufacturing enterprises further improve the degree of service, that is, from providing additional services for products to providing integrated to meet the value of customers at a high level of the total solution services. In the course of its development, the Goldwind Company has invariably insisted on becoming the “leader” of integrated wind power solutions that strives to create greater value for users in all aspects of wind power development and operation. Therefore, Goldwind deepens the intelligent and digital operation and maintenance into the whole value chain of operation and maintenance services, providing customers with comprehensive digital and high-level solution services instead of homogenized and replaceable services. For instance, the Goldwind Company created the online Smart Operation System- SOAM™, which integrates unified IT tools with advanced applications, such as centralized power prediction, intelligent fault diagnosis, and health status warning, and provides customers with professional and convenient integrated energy optimization solutions. With the servitization transformation, Goldwind’s main business has shifted to providing functions rather than ownership, identifying business areas with long-term value, and helping other related enterprises to optimize their energy operations and achieve energy saving and emission reduction. This proves that servitization transformation can lead to the green development of the entire upstream and downstream industry chain, co-establish a high-quality ecosystem, and mitigate social and environmental risks.Based on the above analysis and discussion, combined with coding materials, this paper proposes Proposition 2:Proposition 2. Based on value orientation, providing total solutions and developing platform-based digital services represent a significant green business model innovation trend. Manufacturing enterprises independently R&D critical core technologies to expand their service businesses with unique competence. Afterward, through the digital platform, they integrate various resources to form a resource service platform, provide integrated digital solutions, help customers expand their value space, and achieve service transformation. Such innovation enhances the value proposition of enterprises by identifying the business areas with long-term value and leads the entire industry to create a higher level of sustainable value so as to promote the green development of the manufacturing industry.Enterprises are under pressure to upgrade their user relationships, accordingly taking user relationship enhancement  as the green development orientation. Based on this orientation, the user-oriented path is meant for enterprises to entitle users to participate in the manufacturing, implement personalized customization based on agile manufacturing, emphasize experiential user consumption, and shape a differentiated brand image with scenario-based innovation. On the one hand, user-oriented enterprises’ manufacturing and delivery must acquire and satisfy the preferences of consumers; on the other hand, they must produce economically and sustainably to achieve rapid integration and timely response of resources. With the support of digital technology, the enterprise online, through the construction of a user touchpoint platform, gains a comprehensive insight into consumer demands, generates user participation and design, and uses big data analysis to capture personalized market demands and achieve an accurate allocation of resources. Moreover, enterprises offline implement scenario innovation, embed multi-scenario elements to promote experiential consumption, and further strengthen the interaction between enterprise and consumers online and offline to shape a brand concept that is in tune with the spirit of the audience. This path ultimately shortens the distance between enterprises and consumers, improves the relationship between enterprises and consumers, and achieves accurate resource allocation to prevent resource mismatch and resource backlog ,75 As s.This path has three significant nodes: (1) To achieve customized production. Consumers have tended to pursue personalized spiritual satisfaction in recent years. At the same time, digital technology reduces conversion expenses and substantially affects the stability and sustainability of client resources. Therefore, enterprises should implement a user-centered pattern to develop their sustainable competitive advantage and reduce waste triggered by the misallocation of resources. For example, using the “DESIGN IN” model through the user design platform or brand interactive community on the demand side, consumers can participate in the product design process, alleviating market information asymmetry and reducing communication costs. This model meets users’ individual needs, facilitates word-of-mouth communication, and contributes to the development of corporate brands. It is worth noting that personalized customization necessitates that manufacturing enterprises increase their market adaptability to shorten the product development cycle and eliminate inventory. Consequently, flexible manufacturing has become an inevitable choice for manufacturing enterprises to improve the dynamic adaptation between product supply and demand. For instance, Qumei Group has improved its manufacturing level on the supply side through digital management and modular production, increased the flexible delivery capacity of personalized consumption trends, and captured the forward-looking market. In short, the original homogeneous product competition is not conducive to economic growth and results in a waste of resources, so enterprises should use digital technology to shorten the product manufacturing cycle and enhance the rapid response capability of manufacturing so that personalized and flexible production becomes an essential strategy at the enterprise production level.(2) Scenario innovation. Offline scenario innovation is reflected in three touchpoints: digital touchpoint , physical touchpoint , and interpersonal touchpoint (add experience-centered interaction with consumers). Using “You + Living Hall” of Qumei Group as an example, the experiential consumption of leisure, entertainment, and shopping is realized through the home scenario layout, and it further accomplishes the visceral interaction between consumers. It also incorporates digital technologies such as virtual reality and artificial intelligence, enabling consumers to perceive information online while enhancing the consumer experience and promoting business sustainability. This implies that guided by data and taking experience as the starting point, Qumei Group has added more products and consumption scenarios around users’ needs, gradually connecting the links of users’ lives with each Qumei scenario and establishing a strong connection. In conclusion, in the current era of green development, the products and services produced must have not only economic value but also spiritual cores, such as experience and emotional value. As a result, enterprises should adapt to the live scene, integrate scientific and technological elements, and highlight the comprehensive experience of consumers through cross-border industrial integration, so as to actualize the value resonance with consumers.(3) Combining offline and online innovation. The traditional storefront model is being replaced by online and offline commerce integration. The advantages of online commerce integration include commercial flow, information flow, and capital flow, which can reduce intermediate links and provide enterprises with timely access to data and information to optimize the allocation of resources. Offline commerce integration has advantages in logistics, service, and experience, and the arrangement of offline scenarios is crucial for stimulating consumer demand, increasing user experience, and fostering consumer loyalty. By combining the benefits of online business flow, information flow, and capital flow with the benefits of offline logistics, service, and experience, the advantages can be amplified geometrically, bringing greater benefits to the economy, society, and the environment.Based on the above analysis and discussion, combined with coding materials, this paper proposes Proposition 3:Proposition 3. Based on user orientation, product customization and experience-centered scenario innovation represent a significant green business model innovation trend. Manufacturing enterprises leverage digital platforms to engage users in manufacturing, utilize big data to excavate the user’s expectations, and enhance manufacturing responsiveness, so as to meet the individualized needs of users. Then, they develop experiential consumption through scenario innovations such as cross-border integration and digitalization of shops, and finally, achieve integrated development online and offline. Such innovation ameliorates the market situation of a large number of homogenized products, increases the viscosity of users, and achieves accurate allocation of resources to reduce resource wastes so as to promote the green development of manufacturing.Enterprises are under pressure to expand their boundaries, accordingly taking ecological synergy  as the green development orientation. Based on this orientation, the ecology-oriented path is meant for enterprises to produce smart connected products, achieve cross-departmental collaboration by constructing a business ecosystem to enrich enterprise product categories, and finally establish smart connected product systems by ecological platforms. Ecology-oriented enterprises develop information resources sharing platforms and construct a business ecosystem comprised of associated industries and accessory product suppliers in a nested, value-added manner to diversify their product offerings, increase their control over pivotal resources, and expand their boundaries. Afterward, through large-scale and highly integrated connections between intelligent products, the product and business scope of enterprises is extended to a set of associated smart and connected scenario products and services. Furthermore, through multi-scenario linkage, the intelligent connection of all things is realized. This path ultimately achieves resource connection and sharing with external stakeholders, interconnects previously isolated resources to perform well together as a system, and generates considerably better resource value and functionality  As show.This path has two significant nodes: (1) Product intelligence. Enterprises enhance the digital and intelligent levels of their products to make them more user-friendly and expand their functionality and value. By embedding different IT technologies , physical products transform into intelligent products that comprise hardware, sensors, and communication components. Intelligent products enable identifying user behavior and generating user behavior data and utilize intelligent computing capabilities  to record, calculate, and even think autonomously. For instance, the acceleration sensor in the bracelet of Xiaomi Corporation counts steps by measuring the amount of change in direction and acceleration. Then, the smart module in the bracelet processes the data through intelligent computing capabilities to match the exercise types of users and supply a more scientific exercise program for the user. This predicts that product intelligence is a development trend for the transformation and upgrading of traditional manufacturing industries, such as mobile phones, wearable devices, and home appliances. Through the development of digital technologies such as the Internet of Things (IoT), enterprises can optimize the original functions of products, strengthen the connection between products and users to improve the added value of products, and increase their market control.2, temperature, and humidity detected by the air detector, and the system creates a comfortable indoor environment by linking air conditioners, air purifiers, and humidifiers to form a new systematic function. This indicates that the smart-connected components of smart-connected products not only optimize the product functions but also integrate individual, discrete products into customized, integrated system solutions to meet the broader potential needs of users. The smart connected product is no longer an entity with a single function but a platform bearing multiple functional modules, which constantly reshapes the internal product boundary and expands the enterprise boundary through product interactive connection.(2) Construction of the smart connected product systems by the ecological platform. In the process of smart product development, enterprises use a unified IoT smart chip to promote the generation of standardized data to determine the interactive linkage of products so as to create a systematic product ecological environment for users. For instance, Xiaomi Corporation has launched a smart home system: based on PM2.5, PM10, COHowever, due to the diversification of consumer demands, the resources of an individual enterprise often fail to meet the construction of smart connected product systems through manufacturing or purchasing. Enterprises usually pursue a business ecosystem of cross-sectoral collaboration to share resources, knowledge, wealth, and value creation and achieve the synergy of ecosystem resources. For instance, the Xiaomi Corporation has launched the Xiaomi Eco Cloud, which enables data interaction and sharing among different products. Other enterprises can access their clouds to the Xiaomi loT platform through the Eco Cloud and incorporate it into the “Mi Home App” to achieve unified control so that their resources and external resources can implement synergetic development. This approach consolidates information from different products and enterprises across organizational boundaries to further increase the value of data reuse and amplify the role of resources. In addition, data sharing based on a cloud platform will not significantly increase the cost of organization operation, which can effectively avoid the internal production cost of organizations will continue to increase with the expansion of borders. This reveals that enterprises are able to take advantage of the general ecological platform as the data path points to achieve product links and data sharing. By constructing cross-industry and cross-field hyperlinks, the integrated communication and collaborative utilization of multi-source heterogeneous information flow are able to be actualized so as to establish a large-scale, cross-boundary, hyperlink, and highly integrated production system.Based on the above analysis and discussion, combined with coding materials, this paper proposes Proposition 4:Proposition 4. Based on ecology orientation, Providing smart connected products and building business ecosystems represents a significant green business model innovation trend. Manufacturing enterprises use digital technologies, such as the IoT, to generate the intelligence and interconnection of products and improve their added value. Afterward, by building a generally shared platform to achieve a business ecosystem across the organizational boundaries of multiple stakeholders, they gradually construct smart connected product systems to form intelligent life scenario products, such as smart homes. Such innovation optimizes product attributes and creates a business ecosystem to generate large-scale, cross-border collaborative innovation and data sharing, making the resource create higher value and function so as to promote the green development of the manufacturing industry.The so-called business model innovation path is a general term for the direction, starting point, focus, process, and methodological means to achieve business model innovation. The coding process and the explanatory argumentation of typical cases take the basic elements of the business model innovation path as the main line of research and analysis and the focus of the investigation. Therefore, the four business model innovation paths in the previous section are compared comprehensively around the essential elements of the paths, such as the starting point, the direction and focus, the innovation process, effectiveness, innovation risk, and applicable condition as .The comparison between the paths and the case studies of the four manufacturing enterprises indicates that differentiated optimal innovation paths exist for various enterprises. First, around the critical aspects of innovation, such as production processes, technology development, market response, and product development, enterprises select their innovation starting point based on upgrading needs. Second, innovation focus and innovation process differ significantly between paths, thereby further resulting in varying effectiveness and applicable condition. Therefore, enterprises should combine their existing resources and capabilities to achieve an optimal match with differentiated innovation paths in accordance with the upgrading pressures they face.This paper has performed an exploratory study by means of a multi-case study method and the encoding technique of proceduralized grounded theory. The main research findings are presented as follows.(1) Based on the green development orientation, the four green business model innovation paths, including the efficiency-oriented path, value-oriented path, user-oriented path, and ecology-oriented path, are revealed. They utilized digital technology to change the content and logic of the original business model of enterprises, implement tangible value appreciation or intangible value development, and create economic and environmentally sustainable value. Specifically, the efficiency-oriented path leans toward efficiency improvement, which maximizes the efficiency of energy and resource utilization and minimizes pollutant emissions in the production process by transforming the production process from automation to intelligence and reducing production costs. The value-oriented path leans toward value enhancement, which enables enterprises to reposition themselves in the industry or value network with servitization transformation, develop digital services to break away from the contradiction between business growth and resource overload, and lead the sustainable development of the industry. The user-oriented path leans toward the user relationship deepening, which creates a locked-in user effect with personalized customization and scenario-based innovation to eliminate homogeneous competition in the industry, thereby increasing the viscosity of users and achieving precise resource allocation to prevent resource mismatch and waste. The ecology-oriented path leans toward ecological synergy, which constructs smart connected product systems with a business ecosystem of cross-department collaboration through a digital platform, and expands enterprise boundaries, thereby maximizing the resource portfolio value.(2) With regard to the basic elements of the paths, such as the starting point, the direction and focus, the innovation process, effectiveness, innovation risk, and applicable condition, this paper compares the four green business model innovation paths comprehensively, identifies the differences among the four paths, and discusses the effectiveness and applicable condition of each path. Further analysis demonstrates that the business model innovation path has differentiated characteristics, and the optimal business model innovation path of an enterprise is determined by the matching relationship among innovation path characteristics. Their business model upgrade demands and their existing conditions.The research in this paper has enabled a richer research perspective on the fundamental path and path selection of business model innovation oriented towards green development in traditional manufacturing enterprises, whose theoretical insights are mainly embodied in three aspects.(1)In this study, the multi-case study method has reinforced the universality of the research findings, which in turn has compensated for the inadequacy of the fact that most of the existing studies on the business model innovation path of manufacturing are single case studies. The four core categories of efficiency orientation, value orientation, user orientation, and ecological orientation are derived to illustrate the differentiated green development orientation of manufacturing under the background of the digital economy and green development. Furthermore, the four green business model innovation paths are presented and compared in this foundation, which extends the relevant theories on the types and choices of green business model innovation paths. Moreover, it compensates for the inadequacies of the current relevant research, such as a single perspective and vague definition of paths.(2)The relationship between the digital economy and green development has been deepened. This study combines the digital economy and green development and integrates their synergistic relationship into the business model, which is a further improvement of the relationship between the digital economy and green development discussed in the existing literature. Existing studies have shown that there is a two-way relationship between the digital economy and green development, but most of them are macro-oriented and lack consideration of the relationship between the two from the perspective of the business model. Through the case study, this paper finds that the business model innovation process under the guidance of green development of enterprises cannot be separated from digital technology, and the business model innovation under the digital economy can promote the sustainable development of the economy and reduce the related negative environmental externalities.(3)This paper expands the theory of business model innovation. On the one hand, it enriches the connotation of business model innovation theory. Most of the existing research on business model innovation focuses on economic influence. This paper takes into account the challenges brought by environmental change and resource scarcity, emphasizes the important position of green development orientation in the process of business model innovation, and seeks business model innovation paths that take into account both Economic benefit and environmental efficiency. On the other hand, it expands the application situation of business model innovation theory. Based on the “China story” under the background of the digital economy and green development, this study takes a number of Chinese local manufacturing enterprises as typical cases to reveal the common experience of manufacturing enterprises’ business model innovation and provides specific path suggestions for Chinese manufacturing enterprises in the critical period of transformation how to achieve business model innovation.Manufacturing enterprises need to choose an appropriate green business model innovation path based on their actual situation. This paper puts forward the following management implications for manufacturing enterprises to implement business model innovation.(1) Enterprises with large-scale automation capabilities, comparatively mature and stable markets, and the desire to reduce costs and increase efficiency can opt for the efficiency-oriented path. Enterprises can use digital simulation, virtual reality, and other technologies to digitize difficult-to-materialize technologies and processes, automate production, and enable intelligent data analysis and application. In the innovation process, enterprises should pour attention to top-to-bottom strategic planning and introduce appropriate technologies based on their own development needs to avoid misunderstanding efficiency and only pursue advanced technology.(2) Enterprises with core technology research and development capabilities, high technical barriers in the industry, and the desire to realize the upgrading of the industry value chain positioning can opt for the value-oriented path. Enterprises can develop digital services through digital technology and form a digital service platform to realize business value-added. In the innovation process, enterprises should focus on core technology development and service expansion and provide diversified, differentiated, and personalized integrated services for users. This approach avoids the frustration of transformation that resulted from the severe homogenization of industry products and services.(3) Enterprises with products relevant to the daily lives of the general public and the desire to lock in consumer resources can opt for the user-oriented path. Enterprises can achieve close interaction with the demand side through digital platforms to realize user value co-creation so that users’ individual needs and emotional needs can be fully expressed. In the innovation process, enterprises should prioritize in-depth interaction with users, comprehend user needs through big data analysis, and organize production with a user-centric focus. Simultaneously, they should develop a flexible supply chain, alter their business processes, and enhance their adaptability to adjust to the complex environment of internal and external changes.(4) Enterprises with core products with the foundation of embedded intelligent modules and the desire to extend product boundaries further can opt for the ecology-oriented path. Enterprises can produce intelligent products and form a business ecosystem through digital interconnection, gradually building a system of intelligent, interconnected products. In the process of innovation, enterprises should focus on the cohesion of smart product modules and inspire data sharing between products. At the same time, in the process of ecosystem construction, enterprises should consider products comprehensively to avoid the problems of product positioning and product management by excessively concentrated or scattered investment in the ecological chain.Based on the case analysis and findings, this paper puts forward the following suggestions on how to promote the green development of the manufacturing industry.(1)Actively guide the manufacturing industry to implement innovative green business models. The government encourages enterprises to use market-based methods to achieve relevant green business model innovations, gives full play to the incentive role of fiscal policies, and reasonably amplifies the signaling role of government subsidies. For example, the government can provide substantial rewards and honorary support to enterprises that carry out green business model innovations, adjusts the ratio of ex-post to ex-ante subsidies, and explores diverse forms of subsidies and recognition.(2)Give full consideration to the heterogeneity of enterprises and implement differentiated support policies. The competent authorities should implement differentiated innovation support policies according to the technical level of the industry, the attributes of the industry’s production, the attributes of the industry’s market, and the product types of the enterprise. For example, the steel industry can promote its automation and intelligent development, the consumer goods manufacturing industry can promote its personalized customization, and the high-end equipment manufacturing industry can promote its service-oriented transformation. By conducting pilot evaluations in specific industries, local conditions can be adapted.First, the qualitative research method itself has some limitations. For example, there may be some inevitable subjectivity in the coding process, which needs to be empirically tested by large samples. Second, green development and technological innovation in the case show an interactive driving phenomenon. Hence, future studies may investigate the interaction mechanism between technological innovation and green development. Finally, digital change and green development concepts will continue to affect the path of business model innovation, thereby necessitating the tracking of new cases and practices in the future.


Psychiatric disorders affect more than 970 million people in the world , mitochondrial dysfunction, and energy impairment. In this sense, this Research Topic of Frontiers in Neuroscience aimed at bringing together clinical, preclinical, and literature reviews to provide insights into the role of immune and oxidative pathways on the etiology of psychiatric disorders and on the identification of novel molecular targets and pharmacological interventions.Sun et al. showed in a pre-clinical study that the exogenous administration of resolving D1 (RvD1) can prevent sevoflurane-induced cognitive decline by attenuating neuroinflammation in the hippocampus of diabetic rats. The authors showed that the RvD1 proresolution pathway might be impaired in the central nervous system of diabetic rats, which enhances the susceptibility to sevoflurane exposure and leads to exaggerated microglia activity and neuroinflammation that contribute to cognitive decline under type 2 diabetes mellitus conditions.As part of this research collection, Casaril et al. summarized in a mini-review the association between neuroinflammation, mitochondrial dysfunction, and bioenergetic failure in inflammation-associated depression. The authors reviewed clinical and pre-clinical evidence for mitochondrial dysfunction in inflammation-associated depression and how dopaminergic neurons might be particularly vulnerable in this condition. Importantly, the authors addressed sex differences and emphasize the importance of the appropriate inclusion of both sexes in future studies. Of note, the emerging field of immune-neuropsychiatry reinforces that the brain is neither inert nor immune-privileged and can be governed by peripheral immune mechanisms (Dantzer et al., In the second contribution, Reis and Castro-Faria-Neto discuss in a mini-review the possible mechanisms that trigger long-term cognitive decline developed because of systemic infectious diseases, such as malaria, sepsis, and SARS-Cov2. Mechanistically, activation of pattern recognition receptors, excitotoxicity, increased generation of ROS, and ferroptosis have been discussed. The authors also provide a detailed description of the crosstalk between neurons and glial cells in physiological and pathological conditions, emphasizing the impact on BBB integrity, and endothelial and synaptic function. However, there is no effective therapy to treat cognitive decline associated with infectious diseases. In the end, the authors emphasize the importance of conducting clinical studies in parallel with improving the experimental models or systems biology approaches to better elucidate the association between severe systemic infectious diseases and cognitive decline.Neuroinflammation and oxidative stress can also contribute to the development of cognitive decline. Zhu et al. describe the existence of distinct phenotypes of inflammation-associated macrophages and microglia in the postmortem dorsolateral prefrontal cortex of control subjects vs. people with schizophrenia through gene expression analysis. Various macrophage markers, but not microglial markers, were increased in patients with schizophrenia, which suggests that macrophages, rather than microglia, might play a bigger role in neuroinflammation in this disease. These promising results open a window for the use of single-nuclei RNA-seq to confirm the inflammatory status of macrophages and microglia in schizophrenia and to anatomically map these changes.In an original research article, Jang et al. explore the role of the kynurenine pathway and stress in alcohol use disorder and internet gaming disorder in young adults. The authors showed that subjects with addictive disorders showed higher stress levels and lower resilience levels than the healthy control group. Additionally, subjects with alcohol use disorder had higher plasma levels of kynurenine and kynurenine/tryptophan ratio as well as decreases in kynurenic acid and kynurenic acid/kynurenine ratio compared to healthy control subjects. Subjects with internet gaming disorder exhibited plasma levels of kynurenine and kynurenine/tryptophan ratio values intermediate between alcohol use disorder and healthy control subjects. The authors suggest that stress might affect the kynurenine pathway creating a vulnerable neuronal network, which might contribute to the development of addictive disorders.In another original research article, The exact mechanisms underlying the link between immune-inflammatory activation, oxidative stress, and psychiatric disorders are not fully elucidated and are likely to be complex and disease-specific. Therefore, many different lines of research should be pursued when searching for better treatments or gaining more knowledge about the etiology of psychiatric diseases. Contributing articles to this Research Topic have highlighted some of the biological pathways and potential pharmacological approaches for the treatment and understanding of psychiatric disorders.AC conceptualized and wrote the editorial.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Ischemic cardiomyopathy refers to systolic left ventricular dysfunction in the setting of obstructive coronary artery disease and represents the most common cause of heart failure worldwide. It is often the combination of an irreversible loss of viable mass following an acute myocardial infarction (AMI) with a dysfunctional, but still viable, myocardium in the context of a chronically reduced myocardial blood flow and reduced coronary reserve. Medical treatments aiming at modulating neurohumoral response and restoring blood flow to the ischemic cardiomyocytes were shown to dramatically abate the occurrence of ventricular dysfunction and adverse remodeling in ischemic cardiomyopathy.Novel therapeutic approaches, such as mechanical unloading and modulation of the inflammatory response, appear to be promising. Furthermore, the understanding of the mechanisms by which, despite optimal treatment, heart failure ensues after AMI, with or without adverse remodeling and systolic dysfunction, is a critical step in the search for novel ways to tackle heart failure risk beyond preservation of left ventricular volumes and systolic function.In this review article, we explore the principal pathophysiological mechanisms and pathways of heart failure in ischemic cardiomyopathy, therapeutic opportunities, and knowledge gaps in this area. Ischemic cardiomyopathy refers to systolic left ventricular (LV) dysfunction in the setting of obstructive coronary artery disease (CAD), and represents the most common cause of heart failure (HF) worldwide . Left veIn this review article, we explore the principal pathophysiological mechanisms and pathways of HF in ischemic cardiomyopathy, therapeutic opportunities, and knowledge gaps in this area.The infarct size following AMI is the most important predictor of LV dysfunction and remodeling after AMI , 12. LarThe degree of LV dysfunction during the acute phase of AMI is not only the result of the irreversibly myocardial loss but may be greater due to the contribution of myocardial “stunning,” regions of depressed cardiac function following the reperfusion of an occluded artery that gradually recover over the course of a days following a successful reperfusion . The undCoronary microvascular injury following the recanalization of an occluded epicardial coronary artery is another important determinant of the final infarct size, and a predictor of future adverse remodeling and outcomes , 18. ThiAll these mechanisms contribute to a worse prognosis by causing a larger infarct size, myocardial dysfunction, and adverse remodeling .After AMI, the loss of contractile myocytes and reduced stroke volume leads to LV dilatation. This phenomenon can be acutely beneficial by maintaining stroke volume through the Frank-Starling mechanism. However, the LV wall stress is proportional to the radius of the ventricular cavity and inversely correlated to LV wall thickness, as explained by Laplace law . Hence, Reduced cardiac output promotes the activation of renin–angiotensin–aldosterone system (RAAS). Angiotensin II alters gene expression contributing to myocyte growth, affects cardiac metabolism and energetics, and increases protein synthesis in both fibroblasts and myocytes, thus increasing extracellular matrix deposition and fibrosis .AMI is a trigger for the inflammatory response aimed at clearing necrotic debris, which is then followed by an anti-inflammatory reparative phase leading to myocardial scar formation. Perturbation of this balance may acutely worsen the infarct size and chronically contributes to adverse remodeling and post-AMI . While sLV dysfunction in the setting of CAD may also occur in patients without history of AMI. Repeated episodes of stunning as well as chronic low flow may induce metabolic and cellular adaptation leading to development of dedifferentiation of cardiomyocytes (hibernating myocardium) to prevent myocardial necrosis. Hibernating myocardium is viable myocardium, and therefore retains the ability to recover function upon revascularization . The mosBesides scar and stunning/hibernation, LV dysfunction in patients with CAD may also be the result of other contributing, pre-existent, or superimposed factors, such as ventricular interdependency, electromechanical desynchrony , prior scar, or other causes of cardiomyopathies  that may coexist and meaningfully contribute to LV remodeling, dysfunction, and HF syndrome.Several treatment options are currently available, and supported by strong evidence, in order to prevent or treat HF in ischemic cardiomyopathy. Prompt reperfusion of the infarct-related artery remains the mainstay treatment for AMI. As cardiomyocyte death per unit of time appears to be curvilinear with time from arterial occlusion, achievement of arterial patency in the first few hours after AMI allows for myocardial salvage and reduced infarct size, and subsequently might reduce the incidence of heart failure and other adverse outcomes , 30. ThrSubsequent management strategies focus on modulating and interrupting the mal-adaptive process that led to infarct expansion and replacement fibrosis deposition within the cardiac muscle. Contemporary state-of-the-art pharmacological treatment focuses on modulation of the renin–angiotensin–aldosterone and of beta-adrenergic receptors. Of note, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) were shown to reduce the development of myocardial fibrosis and hypertrophy, as well as LV adverse remodeling, hence reducing the onset of HF . Table 2p = 0.17), despite the trends toward lower number of events for the individual endpoints with sacubitril-valsartan . In. In64]. Pathophysiologic mechanisms leading to HF in patients with CAD may be in fact multifactorial and only partially explained by measures of LV systolic dysfunction at rest or changes in LV volumes. The acute myocardial damage is only one of the factors implicated in the determination of cardiac contractility, LV filling pressure, and cardiac output reserve. Post-infarction inflammatory, hemodynamic and neurohormonal response, chamber compliance, myocardial stiffness, cardiac pre-existing individual risk factors, and subclinical comorbidities all contribute at vary degree to determine cardiac function and decline in cardiorespiratory fitness , 67. ResIschemic cardiomyopathy is the most common cause of HF in the general population. Treatments aiming at modulating the neurohumoral response and, in selected cases, restoring blood flow to the ischemic cardiomyocytes were shown to dramatically abate the occurrence of HFrEF in ischemic cardiomyopathy. Novel therapeutic approaches, such as mechanical unloading and modulation of the inflammatory response, appear to be promising. Furthermore, the understanding of the mechanisms by which, despite optimal treatment, HF ensues after AMI, with or without adverse remodeling and systolic dysfunction, is a critical step in the search for novel ways to measure HF risk beyond preservation of LV volumes and LVEF, and for novel interventions to reduce the incidence of HF after AMI with subsequent consequences on morbidity and mortality. The scarcity of data exploring cardiac reserve and cardiorespiratory fitness following an AMI paves the way for more systematic investigations to provide novel pathophysiological insights and a better understanding of the problem.


The surgical approaches to the cerebello-mesencephalic region remain challenging. In this article, we present the extreme lateral supracerebellar infratentorial (ELSI) approach to treat a large hemorrhagic pilocytic astrocytoma of the SCP. (2) Methods: An 11-year-old boy, known for neurofibromatosis Type I, presented to the emergency department of our institution with symptoms and signs of intracranial hypertension. The cerebral magnetic resonance imaging (MRI) revealed a large hemorrhagic lesion centered on the SCP provoking obstructive hydrocephalus. Following an emergency endoscopic third ventriculocisternostomy (ETV), he underwent a tumor resection via an endoscope-assisted ELSI approach. (3) Results: ELSI approach allows for a wide exposure with direct access to lesions of the SCP. The post-operative course was uneventful, and the patient was discharged home on post-operative day 5. Post-operative MRI revealed a near total resection with a small residual tumor within the mesencephalon. (4) Conclusion: ELSI approach offers an excellent exposure with the surgical angles necessary for median and paramedian lesions. The park-bench position with appropriate head flexion and rotation offers a gravity-assisted relaxation of the tentorial and petrosal cerebellar surfaces. The endoscope can be an adjunct to illuminate the blind areas of the surgical corridor for an improved tumor resection without significant cerebellar retraction. Pilocytic astrocytomas (PAs) are the most frequent primary intracranial tumor in children and the majority of them arise from the cerebellum. Their optimal management includes gross-total resection (GTR), which is associated with an excellent progression free survival . HoweverThe paramedian variant of the supracerebellar infratentorial approach was described by Yasargil and Voigt for the resection of a cavernous malformation of the parahippocampal gyrus ,6. The eNowadays, ELSI is considered a versatile approach that is used to access pathologies in the posterior incisura space and cerebello-mesencephalic fissure, namely in pineal region, posterior thalami, dorsal midbrain and pons, quadrigeminal and ambient cisterns ,9,10. OpIn this paper, we present our experience using endoscope-assisted ELSI approach to resect a large hemorrhagic PA of the SCP.An 11-year-old boy, known for Neurofibromatosis (NF) Type I presented to the emergency department of our institution with symptoms and signs of intracranial hypertension. On neurological examination, he presented drowsiness and a partial left VI cranial nerve palsy. A cerebral magnetic resonance imaging (MRI) revealed a large hemorrhagic lesion centered on the left SCP associated with an obstruction of the aqueduct of Sylvius and resultant obstructive hydrocephalus . The dif. FollowiA hockey-stick incision extending from the inion to the spinous process of C2 was performed. The suboccipital muscles are dissected layer by layer using monopolar electrocautery. The atlanto-occipital membrane is opened with care utilizing micro-scissors. The foramen magnum is afterwards opened using Kerrison punch. A suboccipital craniotomy with a lateral extension  is performed. The entire left transverse sinus, the transverse-sigmoid junction, and the proximal part of the sigmoid sinus are exposed.A small durotomy is performed at the inferior edge of the craniotomy and cerebro-spinal fluid (CSF) is aspirated from the lateral cerebello-medullary cistern to relax the cerebellum. The dura is then widely opened about 5–8 mm inferior to the transverse sinus and medial to the sigmoid sinus in a curvilinear fashion. Three dura retraction sutures are placed below the transverse sinus, at the transverse-sigmoid junction, and medial to the sigmoid sinus. Arachnoid dissection is performed to free the tentorial surface of the cerebellum. Bridging veins, including the precentral cerebellar and superior vermian vein are preserved if they do not interfere with the surgical corridor. On the tentorial surface of the cerebellum three fissures are encountered in the way towards the SCP and can be used as anatomical landmarks. Superficial to deep they are the preculminate sulcus , precentral cerebellar sulcus  is achieved, no further treatment is deemed necessary ,14. GTR Hemorrhagic presentation of Pas is rare, and it is observed more commonly in adults and few anecdotal reports in children till date ,15. SeveSCP, or brachium conjunctivum, is a paired bundles of white matter fibers that connects the cerebellum to the midbrain and it is associated with coordination of muscle activity and cognitive function . The SCPThe SCP represents the main outflow of the cerebellum, and it contains efferent fibers from the dentate nucleus, medial emboliform, and globose nuclei to the contralateral ventrolateral thalamus and red nucleus . As thesIt is worth mentioning that fastigial efferent fibers, although they do not emerge via the SCP, form the uncinate fasciculus of Russell around the SCP as they cross to the contralateral side, to reach the vestibular nuclei. Another group of fibers of the uncinate fasciculus, ascend ipsilaterally to terminate according to a somatotopic distribution in the VL et VPL. A smaller group of fibers instead, descend to the ipsilateral side to end in the vestibular nuclei and reticular formation .Keeping in consideration these anatomical and functional connections of the deep cerebellar nuclei via the SCP, lesions of the SCP may result in variable clinical symptoms, as listed before . The clinical course of SCP injury remains peculiar. Kim et al., investigated the state of the SCP using diffusion tensor tractography (DTI) in a 6-year-old girl treated surgically for PA of the left cerebellar hemisphere . Pre-opeFrom a surgical standpoint, the SCP is located near the cerebello-mesencephalic sulcus at the dorsolateral midbrain, corresponding to the junction of the quadrigeminal and ambient cisterns. Anatomical relationships in this region consists anteriorly in the pineal body rostrally, the quadrigeminal plate, the trochlear nerve and the lingula of the vermis on the midline . It is rTraditionally, the supracerebellar infratentorial approach, with it is a variant of the median or paramedian approach, have been utilized for lesions in the cerebello-mesencephalic fissure and posterior incisural space, including pathologies localized on the SCP. However, other approaches have been reported in the literature, such as the occipital transtentorial, and ELSI approach ,10,11,24Endoscopic assistance in microsurgical procedures was first reported by Hopf and Perneczky as an adjunct to the microscopic manipulations . BeltagyThe ELSI approach offers a wide exposure with multiple surgical angles for median and paramedian lesions located in the posterior incisural space arising from the superior cerebellar peduncle without placing at risk critical neurovascular structures. ELSI in park-bench position with appropriate head flexion and rotation offers a gravity-aided relaxation of the tentorial and petrosal cerebellar surfaces. Additionally, posterior third ventriculostomy can be safely performed to obtain additional brain relaxation. The endoscope is an adjunct to illuminate the blind areas of the surgical corridor to improve tumor resection without significant cerebellar retraction.