Non-communicable diseases (NCDs), a leading cause of global morbidity and mortality, are key challenges to achieving the 2030 Sustainable Development Goals. Looking at trends over the years, the surge in NCDs is anticipated to continue, with the greatest impact on the poor and marginalized groups, mainly from low- and middle-income countries (LMICs) . During one should never let a crisis go to waste,” there is an opportunity to learn from COVID-19, specifically with regards to the prevention and control of NCDs. In this paper, we first highlight the challenges faced by PLWNCDs during the COVID-19 pandemic, then discuss how primary health care (PHC) can act as a critical foundation for strategies to meet the health needs of the PLWNCDs during current and future outbreaks and emergencies.Recalling the old truism constructed by Winston Churchill, “As NCDs and COVID-19 are highly correlated, they cannot be addressed in siloes. Further, during outbreaks, health systems have dual responsibilities to respond to acute system demand as well as continuing to provide essential health services. However, a rapid assessment by the World Health Organization (WHO) on the impact of COVID-19 on NCD resources and services revealed a considerable disruption to NCD services in many LMICs due of a lack of budget allocation for NCDs by governments or relocation of funds from NCDs to COVID-19 management . AdditioDespite the importance of prevention and control of NCDs during the pandemic , preventEmerging evidence from LMICs also shows that PLWNCDs, particularly from marginalized populations, experience myriad challenges in accessing health services, and procuring medication for pre-existing conditions, missed follow-up visits, and experienced worsening of their pre-existing conditions . The locRecognizing the global burden and impact of NCDs on individuals and societies, WHO developed the Global Strategy for Prevention and Control of NCDs 2013-2020) and Package of Essential Noncommunicable (PEN) Disease Interventions for integration and management of NCDs into PHC in low-resource settings, which has been endorsed by 193 member states [-2020 andDespite the need to establish a strong PHC at the community/population level, LMICs, often with the assistance of donor nations/organizations, have focused on establishing teaching hospitals, medical and nursing schools, and disease-specific vertical programs ,15. LMICDuring and beyond the pandemic, continuity of comprehensive care for PLWNCDs can be delivered through a strong PHC system by engaging community health workers in promoting self-management of NCDs, expanding digital innovation at the PHC level, and introducing policies, advocacy, and research to broaden the scope and our knowledge of NCDs management through PHC. Strong PHC systems are essential to maintaining essential health care services in communities, but the workforce shortages and absenteeism have hindered the provision of care through PHC. Specifically, in LMICs, the availability of a health workforce at the PHC level is substantially below the level recommended by WHO . Mixed iAs treatment of NCDs can be expensive, it may pose major economic challenges to health care systems in many LMICs. Hence, comprehensive self-management that can reduce health care expenses , should Although telemedicine existed pre-pandemic, it received significant attention in the COVID-19 era as an effective alternative for health service delivery when face-to-face consultations are not feasible . Some LMIn general, and specifically during this pandemic, emergency management policies were often centered on hospitals rather than PHC. This highlights the need to incorporate PHC in all policies, strategies, and services developed to manage emergencies. During the current and future pandemics, PHC could be leveraged as a critical foundation and the first line of defense for direct surveillance and management of outbreaks through community testing, contact tracing, outbreak communication, isolation, and other public health and social measures that have been crucial in slowing down disease transmission as well as a service delivery mechanism for the vulnerable population such as PLWNCDS. Policymakers and health care leaders also need to prioritize investment in human health resources in PHC as well as the essential diagnostic and medical supplies required for PHC to deliver comprehensive PHC services.Researchers working in LMICs have the opportunity to undertake studies on: (i) documenting their experience of implementing PEN package at PHC during the pandemic (ii) design and evaluate the acceptability and effectiveness of digital health technologies in the management of NCDs within PHC, and (ii) design and test models of care with PHC at the frontline of holistic care for PLWNCDs.The COVID-19 pandemic has impacted the lives of all, including PLWNCDs. The public health actions implemented by the governments of LMICs during the COVID-19 pandemic have been largely directed towards strengthening secondary and tertiary care and containment strategies for COVID-19 while continuity of care for PLWNCDs did not receive enough attention. PHC could be strengthened to blunt the impact of the current and future pandemics and emergencies on public health by providing continuity of care and essential health services to vulnerable and disadvantage groups. Some ideas to strengthen PHC includes delivering comprehensive preventive and treatment services linked to other levels of care, innovating PHC delivery through the use of digital technology, mobilization of CHWs to provide to localized health care both during the COVID-19 pandemic and beyond.


Adipose-derived stem cells (ASCs) isolated from domestic animals fulfill the qualitative criteria of mesenchymal stem cells, including the capacity to differentiate along multiple lineage pathways and to self-renew, as well as immunomodulatory capacities. Recent findings on human diseases derived from studying large animal models, have provided evidence that administration of autologous or allogenic ASCs can improve the process of healing. In a narrow group of large animals used in bioresearch studies, pigs and horses have been shown to be the best suited models for study of the wound healing process, cardiovascular and musculoskeletal disorders. To this end, current literature demonstrates that ASC-based therapies bring considerable benefits to animal health in both spontaneously occurring and experimentally induced clinical cases. The purpose of this review is to provide an overview of the diversity, isolation, and characterization of ASCs from livestock. Particular attention has been paid to the functional characteristics of the cells that facilitate their therapeutic application in large animal models of human disease. In this regard, we describe outcomes of ASCs utilization in translational research with pig and horse models of disease. Furthermore, we evaluate the current status of ASC-based therapy in veterinary practice, particularly in the rapidly developing field of equine regenerative medicine. In conclusion, this review presents arguments that support the relevance of animal ASCs in the field of regenerative medicine and it provides insights into the future perspectives of ASC utilization in animal husbandry. Mesenchymal stem cells (MSCs) can be isolated from a large variety of tissue sources, among which bone marrow mesenchymal stem cells (BMSCs), first identified in 1968 by Friedenstein et al. . DiscoveASCs have received considerable attention over the past decades, mainly because of their therapeutic potential in different areas of applied science –13. AlthThis review combines basic and applied science to discuss ASCs in the context of veterinary medicine. We describe the recent advances in studies of the source, isolation, and characterization of ASCs from livestock. Particular attention is directed toward the functional characteristics of cells that facilitate their application in large animal models for improving repair of multiple tissues in both humans and animals. In this review, we also provide an overview of the translational studies that demonstrate application of ASCs in some important pig models. Moreover, we evaluated the current status of ASC-based therapy in animals, particularly in rapidly developing equine regenerative medicine.The most abundant type of adipose tissue in adult mammals is white adipose tissue (WAT), which serves multiple functions, including energy storage and endocrine activity . WAT is In the current literature, there are limited comparative studies referring to cell yield or isolation method efficiency between different fat depots or different mammalian species Table . One exaw/v, 0.25%) and collagenase type I  that was used for ASC isolation from abdominal fat of cattle ) and pro-inflammatory  genes at 28 days post-treatment. However, at the protein level, a significant decrease in TNFα was found in the wounds treated with ASC/CM and EC/CM. Overall, despite the fact that the general findings of these studies remain partially inconclusive and reinforce the need for further research using this particular wound model, there is strong evidence that employing CM provides a promising method to bypass the need to deliver ASCs to improve the healing outcome   . Endomet[Table ] , 147. Eq[Table ] –150. Endl tissue . This prl tissue . These ul tissue . This apThis review demonstrates the current status of knowledge in terms of isolation techniques, culture, and multilevel characteristics of ASCs from farm animals, with particular attention focused on pigs and horses. Moreover, we provide a perspective on the general principles of ASC-based therapy in pig and horse models of human diseases, as well as highlighting the importance of using animal ASCs in veterinary practice. Although employing large animals for research on ASC therapeutic application generates higher costs due to animal size and husbandry needs compared to smaller laboratory animal models, their importance in the field of human diseases is evident as they have greater predictive ability. Thus, the ability to apply human-like settings to animal models increases the chances of bench findings translating to effective treatments.It is important to recognize and appreciate the fact that the exploration of cellular therapies with the use of large animals can be valuable in establishing alternative medical approaches needed in both preclinical animal models of human diseases and for treating a wide range of conditions that affect animals. As we have discussed, the multitude of different protocols for ASC isolation and the diversity of their delivery routes provide evidence of how much interest in ASC-based therapy in farm animals exists today. However, there are still many issues that need to be addressed when considering ASC-based therapy. First of all, the mechanisms of action through which ASCs enhance healing or attenuate disease are incompletely understood. Although the beneficial properties of ASCs are shown to be related to their immune suppression, anti-inflammatory, and pro-angiogenic roles, knowledge about the specific pathways through which ASCs achieve their pro-repair/pro-regenerative goals needs substantial research effort. Second, further investigations are required to standardize the protocols of the cell acquisition and therapy model in order to ensure safety, efficacy, and consistency for ASC therapy in animal patients. Currently, there are a multitude of different protocols with regard to patient vs. donor source, cell isolation technique, cell culture technique, MSC activation status, MSC dose, and route of administration, making it difficult to compare and choose the most optimal direction of ASC therapeutic development. The selection of the best suited method would guarantee good cell survival, wide distribution, and successful homing of cells in injured tissues, and finally, it must lead to satisfactory therapeutic outcome. Thirdly, in contrast to the slower translation of cellular therapies in human medicine, in the veterinary field such treatments have been rapidly commercialized from experimental models to mainstream clinical practice. Hence, the use of ASCs in veterinary practice requires strict regulatory procedures to ensure efficacy and safety of stem cell-based product applications.There is no doubt that the use of ASC therapy in veterinary practice has incredible potential in advancing cure options for domestic animals. However, we should be aware of the limitations regarding these therapies, and more in-depth research is necessary to fully understand the potential of ASCs.


Matching local feature points is an important but crucial step for various optical image processing applications, such as image registration, image mosaicking, and structure-from-motion (SfM). Three significant issues associated with this subject have been the focus for years, including the robustness of the image features detected, the number of matches obtained, and the efficiency of the data processing. This paper proposes a systematic algorithm that incorporates the synthetic-colored enhanced accelerated binary robust invariant scalar keypoints (SC-EABRISK) method and the affine transformation with bounding box (ATBB) procedure to address these three issues. The SC-EABRISK approach selects the most representative feature points from an image and rearranges their descriptors by adding color information for more precise image matching. The ATBB procedure, meanwhile, is an outreach that implements geometric mapping to retrieve more matches from the feature points ignored during SC-EABRISK processing. The experimental results obtained using benchmark imagery datasets, close-range photos (CRPs), and aerial and satellite images indicate that the developed algorithm can perform up to 20 times faster than the previous EABRISK method, achieve thousands of matches, and improve the matching precision by more than 90%. Consequently, SC-EABRISK with the ATBB algorithm can address image matching efficiently and precisely. Digital image matching is a technique that searches for homologous feature points, also named matches or correspondences, between two or more images. The generation of spatial products and the wide variety of environmental applications using remote sensing images require such a technique to achieve their goals. For example, image registration ,2,3,4, oClassic automatic image matching techniques can be classified into three categories: area-based matching techniques (ABMs), feature-based matching techniques (FBMs), and hybrid methods . ABMs, aMore recently, deep learning (DL)-based approaches developed in the field of artificial intelligence (AI) have had great impacts on image matching ,27,28,29Although DL-based methods can achieve very precise results, their requirements, i.e., a large amount of training data and an extensive period for data training, are critical concerns. For example, prior knowledge, such as ground truth and pre-trained CNN features, must be available to implement data training ,35,36,37Image matching exploiting FBMs, also known as local feature matching, undergoes three steps: feature detection, feature description, and feature matching . The feaTsai and Lin  comparedCurrently, most image matching algorithms convert an optical image into a grayscale image and utilize pixel intensities to match different images; color information, namely the red, green, and blue frequency bands, is not involved. A few methods, such as the colored SIFT (CSIFT)  and coloFor stereomatching that has two images only, the DL-based approaches may not be suitable to address the issue because the ground truth is not known and the number of training datasets is not sufficient. In most past studies, FBMs are crucial in solving this issue. To further improve the performance of stereomatching, this paper develops an integrated approach with two steps to achieve substantial precise matches and balance the image matching efficiency. The first step exploits the EABRISK method as the fundamental by considering its data processing efficiency and the matching result obtained. Different from the EABRISK method using the grayscale image, this research further adds color information into the feature descriptors to increase the distinctiveness and robustness for image matching. Instead of applying the spectrum model to normalize color spaces, this study utilizes R-G-B images and simulates the human retina mechanism to achieve the purpose. The second phase aims to increase the number of matches for stereomatching by geometric mapping since FBMs can usually yield sparse results. By this means, the feature point detected has an opportunity to find its correspondence to increase the number of matches. The rest of this paper is organized as follows. Building on BRISK-based methods, this paper proposes an integrated remote sensing image matching algorithm to achieve as many feature correspondences as possible while balancing the data processing time via a two-step process. The EABRISK algorithm developed by Cheng and Matsuoka  was inteThe ISR approach simulates the function of the human retina  and the As feature points of very high similarity cause ambiguities in determining the most likely match, the ITSM strategy attempts to address these ambiguities to achieve more matches by selecting the most likely match based on the minimal Hamming distance within a group of possible matches of very high similarity. For the case of stereomatching, the most likely match is further determined by the use of forward and backward processes and cross-checking for its consistency, thus reducing the ambiguities. Consequently, the ITSM strategy can retrieve the missing matches from those of very high similarity and increase the number of feature correspondences. Through the interoperability of ISR and ITSM, the EABRISK algorithm can address image matching effectively .Converting an optical image into a single grayscale channel is the most widely adopted approach for performing image matching, but the R-G-B color information is neutralized. According to , howeverAs presented in In terms of the nearest-neighbor strategy, this study gathers four feature points from the four channels based on their image coordinates in which their row and column count are identical. This strategy simplifies the image coordinates to integers to acquire the maximum number of SC keypoints; otherwise, subpixel-level coordinates with complex decimals may reduce the number of SC keypoints. For example, four sets of image coordinates—, , , —available in the four channels can be gathered as an SC keypoint when simplifying their image coordinates to integers.After determining the most representative keypoints, the proposed method further reforms the feature descriptors by adding the color information. Since each individual most representative keypoint is composed of four channels, four sets of 64-byte feature descriptors are available. According to Hendrickson , cells iSince the EABRISK algorithm evaluates feature similarities from the outermost ring to the innermost ring as a way to imitate human visual accommodation, the outermost ring should contain a mixture of information that has the least visual impact. As shown in One of the disadvantages of matching local feature points is that the number of matches may not be as large as expected. This can occur due to either: (1) the recognition and extraction of only certain feature points  by the future detection algorithm or (2) the lack of identical keypoints between the two images. Although many image processing algorithms require only a portion of matches to address the demands of the system, more matches are often needed to improve the precision or reliability of the outcomes. For example, in affine image registration, at least three matches are required to solve for six parameters mathematically. With the inclusion of extra matches, the least squares method helps to improve the precision of the six parameters. The consideration of the spatial distribution of the matches within the images is also important because matches that form weak geometric networks may produce unstable solutions. For instance, if only three matches are used for affine image registration, they must not be collinear; otherwise, the six affine parameters cannot be determined. With more matches available, there is a higher probability of achieving a better geometric network. Such a concern is also pertinent to the eight-point  and fivea, b, c, d, e, f), as described in As the SC-EABRISK algorithm selects the most representative keypoints to perform image matching, it is apparent that the number of matches obtained must be reduced. To compensate for this detriment, the proposed method further exploits geometric mapping to retrieve feasible matches from the keypoints that are not used during the SC-EABRISK image matching stage. An important reason for addressing geometric mapping is to avoid spending extra data processing time to maintain the efficiency of the entire process. For a given stereo pair involving a master image and a target image after SC-EABRISK processing, the results—the seed matches—are utilized as control points (CPs) to determine the geometric relationship between the two images. The proposed method in this study uses affine transformation according to Equation  as the gWhen mapping unused keypoints, the proposed method incorporates all keypoints emerging from the four channels in both the master and target images to obtain the greatest number of correspondences possible. As shown in Detecting and removing mismatches (outliers) is typically the last step for most FBMs, after which correct matches (inliers) can be obtained and preserved. Instead of manual outlier removal, automatic algorithms based on sample consensus are usually applied to determine the greatest number of correct matches (NCMs).Random sample consensus (RANSAC), proposed by Fischler and Bolle , may be Locally optimized RANSAC (LO-RANSAC) is an extension that further optimizes the current best fitting model iteratively to recognize additionally probable outliers from the RANSAC result , allowinIn addition to the above methods, advanced approaches known as universal sample consensus (USAC) approaches are demonstrating impressive effectiveness in solving this task . Graph-Consensus ; it progThe performance of the proposed SC-EABRISK with the ATBB method is assessed via four indicators: the NCMs obtained, matching precision (MP), recall, and effectiveness. In many image matching studies, the NCM, derived from outlier removal, is a straightforward indicator for evaluating the algorithm. MP, defined by Equation , is the The experimental results present and analyze the performance and generalizability of the proposed algorithm by using three kinds of imagery datasets. The first dataset contains eight benchmark images (four pairs) accessed from the INRIA Rhone-Alpes research center to test the preliminary ability of the proposed method. The second dataset involves close-range photos (CRPs) that frequently address remote sensing issues such as 3D modeling. The third dataset presents aerial and satellite image pairs that aim for remote sensing tasks such as large-scale environmental monitoring. Although the image dimensions are a factor that affects the result of the image matching, this paper instead focuses on the number of features extracted and synthesized for image matching and analysis. In addition, this research also compares the image matching results with two relevant approaches building on ORB—learned arrangements of three patch codes (LATCH)  and boosFour image pairs were randomly selected from the six benchmark datasets involving 48 images. To assess the performance of the proposed method, this paper compares the results derived from the EABRIAK, SC-EABRIAK with ATBB, BEBLID, and LATCH algorithms separately and investigates their differences in terms of NCMs, MP, recall, and effectiveness. Since CRPs are the most widely used imagery dataset for performing SfM-based 3D reconstruction, applying the proposed algorithm to CRPs is also important. Although there is no clear definition of CRPs, this paper classifies them as ground-based and drone images because the distances between the scene object and the camera in these images are much shorter than in aerial and satellite imagery. The first case presents a pair of drone images capturing buildings devastated by the Kumamoto earthquake in Japan in 2016. A surveying team from Chiba University collected disaster images a few days after the earthquake to reconstruct the site on a computer for spatial and environmental analyses. The second example includes two ground-based CRPs accessed from images courtesy of Carl Olsson for a standard SfM problem. In both cases, local feature matching plays an essential role in establishing the spatial relationships among images, namely the estimation of ROPs.In addition to the above experiments and analyses, this paper also applied the proposed method to a pair of orthoaerial images with 80% overlap to examine its performance in the case of image registration, because such a task requires feature correspondences for CPs to estimate the spatial relationship between the two images. A pair of IKONOS satellite images with different illumination conditions were also utilized to examine the performance of the developed method.Automatic remote sensing optical image matching is fundamental and crucial for many spatial applications. In addition to the reliability and robustness of the local features themselves, the efficiency of the data processing step has gained more attention in recent years . This paHowever, the displacements of possibly identical keypoints caused by subpixel-level BRISK detection and extraction in the four images prevent direct color synthesis. To achieve this objective, the proposed method groups four points with very close pixel coordinates emerging in the grayscale and R-G-B images as the most representative keypoints. Thereafter, color synthesis for the feature descriptors is addressed by these four group points from four color images. Compared with color-invariant methods ,58, the There are two significant limitations to the proposed method. First, the number of SC keypoints may be very low in some specific cases, e.g., This paper proposes an integrated approach for improving the efficiency and performance of image matching based on BRISKs. In addition to using grayscale images, the proposed method adds color information extracted from R-G-B images to enhance the distinctiveness and robustness of the feature descriptors and improve the precision of the image matching. To suitably utilize the color information, the proposed method selects the keypoints that emerge in the four color spaces simultaneously and uses them as the most representative keypoints. For each of these representative keypoints, the 64-byte feature descriptors are rearranged following the mechanism underlying the human retina in terms of cell distribution and color recognition, and each keypoint in its corresponding color space contributes a portion of descriptors to form the SC feature descriptors. Every group containing four keypoints derived from the four color images is synthesized as an individual keypoint; thereafter, the EABRISK algorithm, which imitates visual accommodation, is applied to the SC feature descriptors for image matching, and thus, the SC-EABRISK algorithm aims to match the most representative keypoints and their more robust SC feature descriptors. The subsequent ATBB procedure further utilizes the results derived from the SC-EABRISK phase to extensively geometrically map the unused keypoints to find their likely correspondences. Both forward and backward geometric mapping thus involve all keypoints in the master and target images and the ATBB procedure allows the acquisition of a greater number of NCMs simply and effectively without additional TC.The experimental results using benchmark imagery datasets, CRPs, and aerial and satellite images ensure the generalizability and practicability of the developed SC-EABRISK with ATBB method because the images were captured by different platforms and cameras. In terms of performance evaluation, this paper employed four indicators, the NCMs, MP, recall, and effectiveness, to assess the proposed method. Since the most representative keypoints are selected, the SC-EABRISK algorithm has a reduced number of NCMs and recall values, but the increased MPs and effectiveness values imply that image matching can be performed more precisely and efficiently. Following ATBB processing, the four indicators are significantly improved, indicating that most of the detected keypoints and their correspondences are found successfully. Therefore, all experimental outcomes indicate that the proposed method balances the NCMs and the TC, a profound issue when addressing image matching by previously proposed FBMs. Although the proposed method still presents some limitations, it is expected to improve the capacities of FBMs, leading to better spatial products and applications, such as image registration, SfM, and 3D reconstruction. For future works, the proposed SC-EABRISK algorithm may be extended to multispectral and hyperspectral satellite image matching by involving additional bands to make the feature descriptors more robust and distinctive. In addition, the image matching results may serve as training data for DL-based approaches to match additional images in the future.


If we only contemplate customized incubation services and growth of tenants, they are positively correlative. On the other hand, if referring to the role of social networking services in this process, we disclosed that not only customized incubation services positively impact behavior of social networking services, but also behavior of social networking services positively facilitates the growth of tenants; at the same time, the customized incubation services exhibit no direct impact on the growth of tenants otherwise. It witnesses that the behavior of social networking services fully mediates the relationship between customized services and the growth of tenants. As a result, we should promote incubation services to be deeply embedded in social networking services; incubator management should even improve the capability to deal with big data embedded in social networking services. In additional, entrepreneurial ecosystems should be also embedded in social networks intensively.The third-generation incubator is generally characterized by embedment of social networking and customized incubation services are closely embedded in the social networking. How the social networking play their role in the process that customized incubation services facilitate the growth of tenant? In order to disclose whether social networking services (SNS) mediate the impact of customized incubation services on the growth of tenants, this article focuses on the whole process where customized services facilitate the growth of tenants by means of social networking services. First, it employs situational theory and contingency theory to analysis why customized services result in behavior of social networking services; second, it explores why behavior of social networking services facilitates the growth of tenants based on co-production theory and social network theory; next, it conduct a study on the direct relationship between customized services and growth of tenants anchoring on the theory of co-production, customer satisfaction, and dynamic environment. Based on these theories, it develops the overall theoretical model of mediating effect. Following that, it conducts empirical test: it has first ascertained whether there is a positive relationship between customized services and growth of tenants. Then, three paths of the theoretical model have been measured by means of the structural model. At the same time, the  Social networks are essentially information networks. People use the social networking services not only for viewing and obtaining information, but also for creating and maintaining social relationships. Social networking services have fundamentally changed how people communicate with each other. More importantly, they have made it extremely easy to establish relationships among individuals as well as between individuals and organizations. Social networking services are also referred to as social networking site or SNS or social media. These terms are used interchangeably in this article.There is no generally accepted definition of “social networking services.” While according to Wikipedia, a social networking service is an online platform, which people use to build social networks or social relationship with other people who share similar personal or career interests, activities, backgrounds, or real-life connections. There is a variety of social networking services available online. However, most incorporate common features are: (1) Social networking services are Web 2.0, Internet-based applications, (2) User-generated content (UGC) is the lifeblood of social networking services, (3) Users create service-specific profiles for the site or app that are designed and maintained by the social networking services (SNS) organization, and (4) Social networking services facilitate the development of online social networks by connecting profile of a user with those of other individuals or groupsThe first-generation business incubators mainly provide physical room to their tenants. The second-generation incubators mainly provide intangible valued services such as financial services, entrepreneurial mentoring, and technical assistance. The third-generation incubators focus on providing multiple accesses to external resources and knowledge . Owing tCustomized services are accompanied by wide information dissemination, large-scale exploratory learning, and cross-fertilization of online and offline behaviors. Hence, an intuitionistic phenomenon is that customized services are deeply embedded in social networking services. For example, social networking is employed a primary tool to propagate potential as well as financial demand of tenant; at the same time, tenants search possible investors mainly by means of social networking. Entrepreneurial mentor could have been advanced promptly once their communication has been set in the context of social networking. Technology assistance might have been more convenient, if the technology transfer, especially explicit knowledge, has matched the social networking.Comparing with the first-generation and second-generation incubator, the third-generation incubator would mainly offer the accesses to heterogeneous networks. It is called a kind of networked incubation. Those networks facilitate tenants to contact with service providers directly, so that to express their demands and gain specific services. As we know, the foundation of being able to express demands and gaining services is the convenient flow of information. In the case that SNS is on hand, whether the appeal to customized incubation services unconsciously drive the process of co-production conducted by SNS remains unclear. In face of the context of customized incubation services, behaviors of SNS tightly embedded in those services as well as the growth of tenant, we could not help speculating what role the SNS has played in the process that customized incubation services might facilitate the growth of tenant? If the customized incubation services have impacted the growth of tenant by means of social networking, why the customized incubation services result in the behavior of SNS? At the same time, why the behavior of SNS impact the growth of tenant? When researchers, management, as well as policymaker contemplate the customized incubation services extensively embedded in the SNS, they could not help speculating the theoretical logics underpinned those three behaviors. The motivation of this article is just here to make clear the theories, which could account for the role of SNS when customized incubation services are conducted to facilitate the growth of tenant.Then, the study questions are as follows: did customized services result to behavior orientation of social network services? Did behavior orientation of social network services facilitate the growth of tenants? Extant study shows that customized services have a positive effect on the growth of tenants , thus diAs the article highlights the role of social networking in the casual relationship between customized services and growth of tenant, its theoretical contributions are: (1) Developing theory that behaviors orientation of social networking services facilitates the growth of tenant and (2) Developing the theoretic model of mediating role of behaviors orientation of social networking services.The rest of this article is organized as follows. Section “Theoretical Analysis and Hypotheses” describes theory analysis and hypotheses. Section “Methodology” describes data, measurement, and methodology. Section “Data Analysis and Hypothesis Testing” describes conclusion and management implications.The relationship of customized services and behaviors orientation of social networking services is developed based on situational theory. According to the theory, learning and development only occur in communities of practice. This concept implies that people who engage in common endeavors must not simply learn, but create a community environment that facilitates creative learning , p. 22. Customized incubation services differ from universal incubation services; they are processes of providing idiosyncratic services to satisfy specific needs. Such processes consist of three independent subprocesses: defining the needs of tenants, establishing cooperative relationships, and realizing incubation services.According to situational theory , partiesFirst, social networking services create situations that facilitate information dissemination. Social networking services enable users to directly transmit information using functions embedded in social media software such as passive connecting with others, exhibiting contents, responding to others, and comment at any time. So, parties involved in co-operation could disseminate real-time information through a variety of terminal devices.Second, social networking services create situations that spark multiple cooperative relationships. Study shows that facilitators of cooperation are diversity of parties ; common Third, social networks create situations that help financial services, entrepreneurial mentoring, and technical support to go smooth.In the opinion of real options , financiEntrepreneurial mentoring service either provide direct management consulting services such as mentoring on operation management, human resources management, and financial management or just play a broker to help tenants to gain access to external resource and knowledge. As social networking services could connect different boundaries of entrepreneurship ecology and create sparse, diversified social networks , they caTechnical support is essentially knowledge transfer . Social According to contingency theory, to drive the growth of tenants, parties of co-production should adjust their behaviors with dynamic environment . Since sThus, we could speculate:Hypothesis 1: Customized services result to behavior orientation of social networking services positively.According to co-production theory by On the other hand, social networking services facilitate incubator management to act as a broker. By means of multiple external networks developed by social networking services, tenants could spread information on their credibility . Social At the same time, social networking services also weaken the constraints of social norms and enterprise culture on entrepreneurship. Tenants located on incubator typically pursue knowledge commercialization by means of new technologies, new business models, and new products . This brNext, we focus on community-level social capital, which comprises bonding social capital, bridging social capital , as wellBonding social capital refers to close relationships between network nodes. These relationships originate from mutual trust and commitment. In turn, mutual trust and commitment intensify the close relationships between them. In additional, word-of-mouth effect of social networking services removes the opportunists from the cooperative networks, so the balance of game is to further keep mutual commitments. As mutual commitments intensify the close relationships, social networking services could strength bonding social capital .Bridging social capital refers to the connections with external community. It is an important channel for information flow between heterogeneous nodes. As social networking services have the function by means of which tenants could connect with external nodes passively, tenants could develop more connections with external community  and thenLinking social capital refers to those connections between distinct hierarchies in a community. The transhierarchical relationships allow tenants to connect with government agencies, incubator management, client firms, and other entrepreneurs, which facilitate tenants to obtain useful information and resources outside the formal hierarchies. Since social networking services could develop a kind of virtual community, which is a non-hierarchy organization, social networking services should be an effective measure to develop transhierarchical connections. The relationships embedded in transhierarchical connections help to smooth away organization gap, orientation of bureaucracy, as well as differentiation of identification . Thus, sWe could speculate:Hypothesis 2: The behavior orientation of social networking services could promote the growth of tenants.Customized service is a kind of demand-driven processes including three subprocesses—information dissemination of demand, sparking of specific relationships, and realization of services. Customized service focuses on demands of customer-oriented, which is other from supply oriented logic  and its Next, as the heterogeneity of needs increases, customized services become more effective. Owing to distinct technologies, entrepreneurs, and external environments, demands of tenants are highly heterogeneous. Even we divide customized services into three subcategories: financial services, entrepreneurial mentoring, and technical assistance, the heterogeneous of demand is still obvious. Study shows that services, which could meet the idiosyncratic needs of consumers, lead to higher customer satisfaction . Then, cThird, owing to distinct resource endowments, technology, and life cycle , tenantsThus, we could speculate:Hypothesis 3: Customized services positively promote the growth of tenants.Customized services can directly promote the growth of tenants. In another way, customized services lead to the behavior orientation of social networking services; at the same time, behavior orientation of social networking services facilitates the growth of tenants.Then, we could speculate:Hypothesis 4: Social networking services mediate the relationship between customized services and the growth of tenants.The research model is shown in 2; accordingly, 40 incubators are selected from each region randomly. The samples are selected from state-level incubator because the operations of those incubators are in good manner; data compiled are complete and statistical methods of data are plausible.Incubator is a part of national innovation systems and it is subjected to regional economic development. In order to test of research model, it is necessary to smooth away sample biases of regions. So, this study investigated state-level business incubators located in the five regions according to the general administrative division of China: Northeast, North, East, Central, South, and West. A total of 200 incubators were selected from the list of incubators on the website of the Torch High-Tech Industrial Development Center of the Ministry of Science and TechnologyAdditional, Torch High-Tech Industrial Development Center agreed to backup the surveys as we have cooperated with the Strategy Research Institute of Wuhan East Lake High-Tech Development Zone for a long time, while the Wuhan East Lake High-Tech Development Zone and the Torch High-Tech Industrial Development Center have official collaboration. So, we were granted timely access to the annual statistical reports from official agencies responding to investigation about China incubator. Those information and data could be an alternative to those from surveys.In the name of the Torch High-Tech Industrial Development Center, we distributed 200 surveys through e-mail, WeChat, and an online chat APP (QQ). The survey states that this study aimed at assistance of policymaking explicitly and it was endorsed by the Strategy Research Institute of the Wuhan East Lake High-Tech Development Zone, so we collected 142 complete responses, 37 incomplete responses, and 21 surveys have no responses at last. We also distributed surveys face-to-face by means of annual meeting and special conference and collected 54 responses. Thus, the total valid samples are 196. Mathematical and psychological theories and empirical analyses have witnessed that 7-point Likert scale is plausible to measure the extent of human behavior and psychological inclination . The meaTo measure customized services, which others perform for tenants, we adopted the 7-point Likert scale item, which has been employed by On the other way, the articles “Networked Incubators”  and “StiAdditionally, growth of tenants has been still estimated by 7-point Likert scale in an article published on “Journal of Engineering and Technology Management” . Other tThe reliability of the variables was analyzed using reliability and composite reliability analysis . The valValidity analysis includes: (1) Face validity: this refers to whether the words that described the items are accurate and appropriate. Science those items were adapted from existing literatures, they are of good face validity, (2) Convergent validity: this refers to whether items are highly correlated when they measure the same variable. The convergent validity of the items can be evaluated by analyzing their standardized loading and average variance extracted (AVE) of items. The items exhibit good convergent validity, if their standardized factor loading is greater than 0.70 and the AVE of variables is greater than 0.50. All the items in the theoretical model have a minimum loading of 0.869 and are significant. This confirms that the model meets the baseline of goodness of fit statistics. Furthermore, the reliability of the items is greater than 0.5, the composite reliability of the items is greater than 0.7, and the AVE of the variables is greater than 0.5. This confirms that the theoretical model has an appropriate structural fitness , 2. TablFirst, we should ascertain whether there are positive relationship between customized services and growth of tenants. The scatter diagram of the two variables shows that they are positively correlated . So, we If coefficients of path a and b  are botht-test, the t-value is 3.460 when degree of freedom is 60 and significance level is 0.001. The degree of freedom of the mediation model is 62, while the t-values of coefficient of path a and path b are 5.63 and 9.24, respectively . While we focus on the relationship among customized services, behavior orientation of social networking services, and growth of tenants, we found that customized services facilitate the growth of tenants via behavior of social networking services; at the same time, customized services had no direct impact on the growth of tenants. We could draw the conclusion that behavior of social networking services could fully mediate the relationship between customized services and growth of tenants. As shown in M = 0.56 × 0.68.This study focuses on the relationship between customized services, behavior orientation of social networking services, and growth of tenants. Our conclusions can be summarized as follows: customized services directly facilitate the growth of tenants  Incubation services must be deeply embedded in social networking services.The mediating effect of behavior of social networking services indicates that social networks are most important measures to facilitate customized services. It is necessary to develop and improve infrastructure of mobile network, which could set the baseline of social networking services. We should promote all the co-production to embed in social networking services extensively . First, (2) Incubator management should improve the capability to deal with big data embedded in social networking services.Social networking services are accompanied by emerging big data. If incubator management could make use of big data to guide the customized services, it could gain competitive advantage . So, it (3) Entrepreneurial ecosystems should be intensively embedded in social networks.Entrepreneurial ecosystems represent a diverse set of interdependent actors within a geographic region that influence the formation and eventual trajectory of the entire group of actors and potentially the economy as a whole. Entrepreneurial ecosystems evolve through a set of interdependent components, which interact to generate new venture creation over time . As entrThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Hubei University. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.LZ developed the research model, conducted the analysis, co-drafted the manuscript, collected the data, and edited the manuscript. YZ co-drafted the manuscript and responded to the reviews. Both authors contributed to the article and approved the submitted version.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.


Firmicutes, Actinobacteria, and Bacteroidetes, colonize the surface of the respiratory mucosa of healthy people. They interact and coexist with the local mucosal immune system of the human airway, maintaining the immune stability and balance of the respiratory system. While suffering from chronic respiratory diseases, the microbial population in the airway changes and the proportion of Proteobacteria is increased in patients with asthma. The abundance of the microbial population in patients with chronic obstructive pulmonary disease (COPD) is decreased, and conversely, the proportion of Firmicutes and Proteobacteria increased. The diversity of airway microorganisms in cystic fibrosis (CF) patients is decreased, while pathogenic bacteria and conditional pathogenic bacteria are proliferated in large numbers. The proportion of Firmicutes and Proteobacteria is increased in patients with upper airway cough syndrome (UACS), which replaces the dominance of Streptococcus and Neisseria in the pharynx of a normal population. Therefore, a clear understanding of the immune process of the airway flora and the immune dysfunction of the flora on the pathogenesis of chronic respiratory diseases can provide new ideas for the prevention and treatment of human respiratory diseases.Large quantities of bacteria, including  The human body carries a huge group of microbial populations, which constitutes a complex and delicate ecosystem. The complex interaction between microbes and the human immune system determines the health of the human body. The airway is an open cavity connecting the human body with the outside world. It is always invaded by external microbes, so it has strong local immunity. For example, the airway contains not only motile cilia, strong secretory goblet cells, and secretory IgA on the mucosal surface but also abundant mucosal-associated lymphoid tissue under the mucosa, which is sufficient to cope with the invasion of external pathogens . Once thFirmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, and Fusobacteria [Large quantities of bacteria colonize the surface of the respiratory mucosa of healthy people, of which the main groups are bacteria . Bacteribacteria . This isbacteria , 14. Howbacteria .Streptococcus pneumoniae and Chlamydia pneumoniae infections were common during acute asthma attacks [Proteobacteria in the flora was significantly different from that of healthy people [Moraxella catarrhalis, Haemophilus influenzae, or Streptococcus pneumoniae, were increased significantly, which were related to the severity and acute exacerbation of asthma [Proteobacteria, including Haemophilus influenzae, Pseudomonas aeruginosa, Klebsiella pneumonia, and other respiratory pathogens, in respiratory specimens of asthma patients was higher than that of the normal population. The increase in these pathogens was also found in patients with irregular inhaled hormone therapy, suggesting that this feature of respiratory flora was a characteristic of asthma itself and not simply a result of immunosuppression caused by inhaled hormones. In contrast, the proportion of Prevotella of Bacteroidetes in the airways of asthma patients was lower than that of the normal population [Asthma is a kind of disease that is well-recognized as immune dysfunction of the respiratory system, which is defined as a clinical syndrome of intermittent respiratory symptoms caused by viral upper respiratory infections, environmental allergens, or other stimuli, characterized by nonspecific bronchial hyperresponsiveness and airway inflammation , 17. Due attacks . Analysiy people . Throughf asthma , 22. Thepulation –25.Haemophilus influenzae and Haemophilus parainfluenza were impaired in response to dexamethasone, which was found in some patients with hormone-resistant asthma [The distribution of different bacterial communities is also related to the features of asthma. Airway microbes and asthma patients also have certain effects on the responsiveness of glucocorticoids. In vitro studies have shown that monocytes and macrophages cocultured with t asthma . Studiest asthma , 28. Thet asthma .These studies indicated that changes in respiratory flora would increase types of pathogenic bacteria but reduce types of normal flora and biomass in asthma patients, suggesting that the immune dysregulation of the respiratory flora may be one of the causes of asthma attacks.COPD is a highly heterogeneous disease that seriously affects human health. It is characterized by persistent airflow obstruction and increasing airway chronic inflammatory response to harmful particles or gases. Exposure to noxious smoke and particles is a major driver for the progression of COPD. At the same time, other factors also play a part, such as genetic predisposition, nutritional status, and respiratory infection . The rolProteobacteria such as Pseudomonadaceae, Burkholderiaceae, and Enterobacteriaceae was increased, and the relative abundance of Firmicutes was decreased [Firmicutes and Actinobacteria were the dominant flora in the lungs of COPD patients. By sampling and sequencing the BALF of patients with moderate and severe COPD, Pragman et al. found that the structure of the flora in the lungs of these two groups of patients was changed and that Firmicutes, Proteobacteria, and Actinobacteria were abundant in the lower airways of these patients [Unlike the early changes in the microbiota of patients with asthma, there is no significant difference in respiratory flora between mild and moderate COPD patients and normal people . Changesecreased . Howeverpatients . Microbipatients .Firmicutes before the colonization of the dominant bacteria. This finding also supported the clinical features of acute exacerbation in both types. Taking into account the different microbial modes, different therapeutic measures are required. Although the composition of respiratory flora in patients with COPD has been clear through microbiological analysis, the role of respiratory flora in the pathogenesis of the disease remains to be further explored.Microbiological studies showed that, at the acute exacerbation stage of COPD, there was no significant difference in respiratory microbes compared with the stationary phase . The resCF is a familial autosomal recessive inherited congenital disease, which is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), resulting in the structural and functional alterations of the transmembrane protein in pulmonary CF, thereby causing chronic pulmonary infection and pulmonary function deterioration in patients, leading to early deaths . CF is cPseudomonas aeruginosa and Burkholderiaceae. Although antibiotic treatment and species richness declined slightly, the microbial community structure hardly changed. Moreover, the microbial composition in acute exacerbation was highly similar to that in the stationary phase, suggesting that exacerbations may be due to the spread of infection in the lungs, rather than changes in the composition of the microbial community.Fodor et al. used massive pyrosequencing technology to identify changes in the airway microbial community structure of 23 CF patients during CF exacerbations and stabilities and obtained more than 350,000 sequences, representing nearly 170 distinct microbial floras . ApproxiPseudomonas aeruginosa, Haemophilus influenzae, and Staphylococcus aureus. Meanwhile, other strains such as Burkholderia, Stenotrophomonas maltophilia, and Achromobacteria xyloxydans were also present in elderly patients [Bacteroidetes and Fusobacteria were the dominant strains in healthy individuals while Actinobacteria accounted for a larger proportion in CF patients. The structure of pulmonary florae was destroyed, pathogenic bacteria and conditional pathogens were multiplied, and florae were out of balance, which may be one of the causes of CF.The research through in vitro bacterial culture of the patients' sputa revealed that the predominant pathogenic bacteria were patients , 43. TheUACS, formerly known as postnasal drip syndrome (PNDS), is a syndrome of chronic cough caused by the reflux of allergic or nonallergic inflammatory secretions from the nasal cavity and nasopharynx into the pharynx . It can Firmicutes and Proteobacteria are the dominant flora in UACS that are different from the normal flora. Among these, Lactobacillus of Firmicutes and Pseudomonas aeruginosa of Proteobacteria have significantly increased and replaced the dominant position of original Streptococcus and Neisseria in the pharynx of normal people. Moreover, TRPV1 and TGF-β2 were increased significantly in UACS patients [β1 and β2 in mammary secretions of dairy cows infected with Pseudomonas aeruginosa compared to those uninfected, demonstrating the correlation between Pseudomonas aeruginosa and TGF-β1 and β2. Meanwhile, Pseudomonas aeruginosa could also stimulate airway inflammation through a variety of known inflammatory pathways, leading to an increase in the prevalence of UACS [There is a slight difference in the types of pharyngeal flora between healthy people and patients with UACS. patients . TRPV1 ipatients . TRPV1 i of UACS .Fungal colonization in the human body refers to the presence of a large number of fungi growing in the form of spores at a site where the human body communicates with the outside world, such as the alimentary canal, the upper airway, and urogenital tract, but without local tissues damage or symptoms . ColonizCandida and Aspergillus in the upper airway are very common [Candida was the most common fungus colonizing in the lower airway, among which the infection rate of Candida albicans was the highest (37.91%), followed by Aspergillus (16.99%) [Aspergillus fumigatus and Candida albicans being the most common [Contamination and colonization with y common . The res(16.99%) . Systemit common .Glucocorticoid has a potent anti-inflammatory and immunosuppression function, which eliminates most pathogenic bacteria and improves the airway microenvironment by effectively reducing the levels of proinflammatory cytokines and airway inflammation. Inhaled corticosteroids, without obvious systemic side effects, can easily form an effective concentration in the airway and work directly, which is quickly destroyed by enzymes in alveoli and inactivated by the liver after entering the blood circulation.α and leukotrienes by promoting the production of enzyme-linked protein I, resulting in the decrease of phospholipase A2-α; (2) inhibiting the production of inflammatory protein and its phospholipase A2-α by inactivating MAPK; (3) inhibiting the expression of cytokines, chemokines, cell adhesion factors, and their receptors by activating NF-κB pathway [Candida infection in the oral and pharyngeal [pneumonia and mycobacterial disease). Thus, rationally controlling the time of using hormones may reduce the incidence of adverse reactions.Glucocorticoids can enter into the nucleus by binding with glucocorticoid receptor in the cytoplasm through the cell membrane and form hormone-hormone receptor complex, which combines with special DNA sequence to produce biological effect through the following three ways: (1) inhibiting the release of inflammatory factors such as TNF- pathway . Glucoco pathway . Howeveraryngeal . Furtherfirmicutes and Bacteroidetes was increased in normal obese children [In addition, previous studies have proved that the diversity of oral microflora was decreased, while the proportion of children . Becausechildren .Although ICSs have been widely used in the clinical treatment of respiratory diseases because of the strong anti-inflammatory activities, they could not effectively improve the inflammatory response of airway remodeling and proliferation. Most clinical reports have shown that excessive inhalation of ICSs may cause drug dependence or resistance and other adverse reactions, especially in children with asthma in the early stage, which will affect children's immune system and result in hormone-dependent. Therefore, exploring new anti-inflammatory drugs to combine or even replace hormones is the leading direction of drug development.Lactobacillus rhamnosus and Lactobacillus plantarum. This supplement inhibits the expression of inflammatory factors in the lung by activating TLR3 and RIG-1 signaling pathways in alveolar macrophages to promote IFN-β and also regulates lung flora and intestinal flora to alleviate respiratory syncytial virus (RSV) infection. Over-the-counter probiotics have been used in clinical trials to investigate their potential effects in various disease conditions, but it is required more stringent quality control to ensure the purity and efficacy of products. The challenge of detecting unwanted microbial contaminants is that the sensitivity of detection may be reduced in the presence of the required probiotic microorganisms. One of the strategies under study was to reduce or eliminate the growth of bacteria in the product for improving the sensitivity of detecting the contaminating microbes. FDA scientists developed and used recombinant phage lysine as a reagent to improve LBP purity detection through “mock” purity assays (“test-tube” studies) where Lactobacillus jensenii represented the probiotic's product strain. However, the type of strains, dosage, and course of probiotic can affect the outcome of clinical application, and even the same flora will have different effects at different ages. Therefore, the prevention and treatment of respiratory infection with probiotics deserves further research.Probiotic refers to live biotherapeutic products (LBP) containing enough viable organisms with well-defined composition. It can change the composition of the flora at a certain site of the host through colonization, thereby improving the microecological balance of the host and playing a beneficial role . On the Candida albicans and Staphylococcus aureus, which was correlated with the concentration of baicalin, that is, the DNA synthesis of Candida albicans was decreased with the increase of drug concentration [Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa [Streptococcus pneumoniae, Staphylococcus aureus, etc.) activities of the agents, but few considered the antibacterial effect in vivo. And due to the complexity of pharmacodynamics, it is difficult to draw the conclusion whether antibacterial effects of drugs or anti-inflammatory effects play the decisive role in airway inflammation.Natural products or traditional Chinese medicine have been reported to improve airway immunity, ameliorate the function of the blood-air barrier, inhibit inflammation, and reduce growth of pathogenic bacteria due to its advantages of multicomponent, multichannel, and multitarget , which hntration , 67. Cryntration . The Yinruginosa . Xiaocharuginosa . It can There is still a lack of robust research on pharmacological mechanisms. Therefore, further efforts are needed to elucidate the underlying mechanism in germ-free mice.Changes in the immunity of respiratory flora play an important role in the development of multiple chronic respiratory diseases. In recent years, with the application of various new techniques in the detection of microbes in respiratory specimens, growing evidence showed that respiratory microbial population and its related local mucosal immunity were associated with the clinical manifestations, acute exacerbation, and prognosis of chronic respiratory immune disorders, such as asthma and COPD. Through studying the microbiological basis of the progression of human respiratory diseases, we can make a better understanding of the local immunological mechanism of the progression of these diseases, facilitate the judgment of disease types, predict the responsiveness to treatment, and evaluate the therapeutic effect. It provided a new idea for the clinical diagnosis, treatment, prediction, and prognosis of respiratory diseases.


The potential for further refinement of the AOP and its components is discussed in relation to available nanosafety knowledge and data. Overall, this perspective provides a basis for development of AOP-aligned alternative methods-based integrated testing strategies for assessment of nanoparticle-induced lung cancer.Lung cancer, one of the most common and deadly forms of cancer, is in some cases associated with exposure to certain types of particles. With the rise of nanotechnology, there is concern that some engineered nanoparticles may be among such particles. In the absence of epidemiological evidence, assessment of nanoparticle carcinogenicity is currently performed on a time-consuming case-by-case basis, relying mainly on animal experiments. Non-animal alternatives exist, including a few validated cell-based methods accepted for regulatory risk assessment of nanoparticles. Furthermore, new approach methodologies (NAMs), focused on carcinogenic mechanisms and capable of handling the increasing numbers of nanoparticles, have been developed. However, such alternative methods are mainly applied as weight-of-evidence linked to generally required animal data, since challenges remain regarding interpretation of the results. These challenges may be more easily overcome by the novel Adverse Outcome Pathway (AOP) framework, which provides a basis for validation and uptake of alternative mechanism-focused methods in risk assessment. Here, we propose an AOP for lung cancer induced by nanosized foreign matter, anchored to a selection of 18 standardized methods and NAMs for  Promising molecular biology tools such as high-throughput screening of perturbed key molecular players in toxicity pathways and high-content omics profiling are popular but hindered for uptake in safety assessment procedures due to the perceived risk of over-interpretation of the outcome without consideration of the broader biological context and the relevance for human carcinogenicity  IARC, , 2014. DC) IARC, . Thus, tty IARC, .in vitro assays, including specifications for applicability to nanoparticles  is fairly far developed and coupled to a battery of more or less standardized assays, including alternative non-animal methods, which have been specifically adapted for testing of nanoparticles , (ii) its key focus on mechanistic information, and (iii) its governance by the OECD leading to broad support from large regulatory bodies  leading to adverse outcome (AO). In addition, key event relationships (KERs) allow for inclusion of information regarding the required threshold of perturbation for transitioning from one KE to the next  offer the much-needed biological context for 2 was recently reviewed leading to a suggested AOP for TiO2-induced lung cancer  have been classified as (possibly) carcinogenic  in vitro and in vivo  nanoparticles.The MIE, KEs, and AO in the suggested AOP were aligned with relevant existing KEs in the AOP-Wiki, as well as selected evidence for their association with exposure to nanoparticles . The tab2 nanoparticle-induced lung cancer , where particle overload cannot be a problem. In comparison, 1.3 excess lung cancer cases per 100,000 exposed are expected based on chronic inhalation studies in rats  whereas in vitro studies often report mass of nanoparticles per unit volume (μg/ml). In order to enable comparisons between models, it is helpful to consider cellular target dose as compared to tissue burden. The nominal concentration in the medium of in vitro studies can differ substantially from the cell dose since different nanoparticle characteristics affect their ability to reach the cells at the bottom of the culture dish  model to estimate the movement of particles to the cells RT-PCR. In addition, novel high-throughput and targeted transcriptomic techniques are increasingly becoming available for assessment of transcriptional changes in relevant gene sets and biological pathways  assessment of repairable DNA damage or related DNA repair mechanisms, and (ii) assessment of irreparable DNA damage, i.e., inheritable chromosome damage and mutations. Here, we refer to the former as genotoxicity assays, which are anchored with KE1B and KE2  nanoparticles, but the extent to which it interferes with the assay remains to be elucidated  assay (OECD TG 476), and the cII loci assay (FE1-MML)  487; Magdolenova et al., 2 nanoparticles, and thus anchored with KE4  which provides findable, accessible, interoperable, and reusable (FAIR) data from several European projects (Jeliazkova et al., The nanosafety community has over the past decade focused extensively on enabling harmonized data management of the widely diverse data types generated within the field, and has recently led to the establishment of the Nanosafety Data Interface (In addition to iterative implementation of knowledge surrounding specific case study stressors, such as here covered by nanosized particles, the development of AOPs also benefits from efforts within other fields, even if challenges remain regarding how to adapt cross-field information to nanoparticles. For example, a recent effort to translate classical genotoxicity MoAs into the AOP framework can be expected to support refinement of the proposed AOP (Sasaki et al., Overall, the putative AOP, in its current form, supports systematic and structured integration and evaluation of mechanistic data derived from alternative ways of assessing primary and secondary genotoxicity, supporting safety assessments and prioritization of nanoparticles in need of further testing (Nymark et al., The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.PN conceptualized the idea and wrote the first draft of the manuscript. HK, SH, and UV contributed to development of the putative AOP and to the writing of the manuscript. All authors contributed to the article and approved the submitted version.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.