Aging affects all tissues and organs. Aging of the immune system results in the severe disruption of its functions, leading to an increased susceptibility to infections, an increase in autoimmune disorders and cancer incidence, and a decreased response to vaccines. Lymph nodes are precisely organized structures of the peripheral lymphoid organs and are the key sites coordinating innate and long-term adaptive immune responses to external antigens and vaccines. They are also involved in immune tolerance. The aging of lymph nodes results in decreased cell transport to and within the nodes, a disturbance in the structure and organization of nodal zones, incorrect location of individual immune cell types and impaired intercellular interactions, as well as changes in the production of adequate amounts of chemokines and cytokines necessary for immune cell proliferation, survival and function, impaired naïve T- and B-cell homeostasis, and a diminished long-term humoral response. Understanding the causes of these stromal and lymphoid microenvironment changes in the lymph nodes that cause the aging-related dysfunction of the immune system can help to improve long-term immune responses and the effectiveness of vaccines in the elderly. Aging is an inevitable biological phenomenon. Even during healthy aging, the functions of the immune system may be weakened by a process known as immunosenescence . ImmunosLymph nodes play a pivotal role in the innate and adaptive immune response to natural antigens and vaccines. Lymphatic vessels direct lymph from the tissues to the lymph nodes scattered throughout the body. As lymph passes through the lymph node parenchyma, antigens come into contact with the effector cells of the adaptive immune system, initiating a cascade of immune processes that enable the recognition and neutralization of foreign antigens and pathogens . Blood fThe number of lymph nodes in the human body ranges from 300 to 500, and their total weight is about 100 g. Studies have shown that the number of nodes decreases with age, and aging-associated degenerative features emerge in the lymph nodes, such as fibrosis, vitrification, lipomatosis, a reduction in the number of postcapillary vessels, and changes in the morphology and function of the specialized endothelial cells lining the venous capillaries . ConsequThus, aging-related lymph node structure disorganization and changes in the content of their immune cells seem to be major factors contributing to the aging of the immune system. This review discusses the current knowledge concerning age-related changes in lymph nodes and their impact on immune function.The primary function of the lymph node is to coordinate the immune response to antigens transferred from the peripheral tissues. Thanks to their highly specialized architecture, lymph nodes act as filters that drain infected areas or filter out antigens from body fluids. To fulfill their roles in innate and acquired immune responses, they must attract and recruit leukocytes from the blood and peripheral tissues. There are two routes for cell influx into the lymph nodes: specialized blood vessels, i.e., HEVs lined with specialized high endothelial venule cells and afferent lymphatic vessels. During inflammation, lymphocyte accumulation in the draining lymph nodes significantly increases, while their exit via the draining lymphatic vessels is temporarily blocked. These two inflammation-induced mechanisms increase the likelihood of antigen capture by a fraction of T cells expressing the antigen-specific receptor (TCR) on their surface . Lymph nLymph node degeneration is a widespread phenomenon, and its incidence increases with age . Indeed,It was initially believed that stromal cells only had a role in the architectural organization of lymph nodes; however, it is now known that they are involved in some aspects of innate and adaptive immune responses ,39,40. PThe structural and functional disorganization of the lymph nodes that occurs with aging may adversely affect these processes. Histological evaluation of the structure of mesenteric lymph nodes in the elderly has revealed general fibrosis, thickening of the capsule and trabeculae, and increased amounts of connective tissue around the blood vessels . The parLymphatic vessels regulate the transport of tissue fluid and facilitate the absorption of macromolecules from peripheral tissues. Proper recirculation of fluids and cells via the effective transportation of lymph is required to maintain an organism’s homeostasis. Lymphatic vessels are also key routes of immune cell transport from tissues to regional lymph nodes during an immune response . Under pCryptococcus neoformans, Mycobacterium smegmatis, and Staphylococcus aureus from the peripheral tissues to the draining lymph nodes, was impaired [Tissue swelling and an impaired response to pathogens are often observed in the elderly due to aging of the lymphatic system and altered lymph flow dynamics ,67. No dimpaired . In oldeimpaired . When chimpaired . The decimpaired ,74,75,76High endothelial venule cells are a critical subpopulation of endothelial cells lining the postcapillary HEVs  and act Analysis of aging-related changes in the nodal blood vessels showed a significant reduction in the number of HEVs in the paracortical zone of human lymph nodes and their degeneration level was substantial . On the No significant age-related differences have been found in the expression of the ICAM-1 and PECAM-1 adhesion proteins on mouse endothelial cells . HoweverTherefore, the decrease in the number of postcapillary vessels and changes in the morphology and functionality of high endothelial venule cells that occur with age reduce the migration of cells to aging nodes, contributing to their cellular disorganization. All these deficits make it difficult to initiate an early adaptive immune response and, thus, contribute to the susceptibility of the aged organism to infections .Marginal reticular cells (MRCs) represent a main element of the stroma. They are essential for the organization and function of secondary lymphoid organs (lymphoid tissue organizer)  and reta4β7 and α4β1 integrins and L-selectin, and thus, is involved in the homing of these cells to lymphoid tissues [Marginal reticular cells surround the lymphoid follicles composed of B lymphocytes and fill the spaces between the follicles in the lymph node ,80. They tissues .One hundred and twenty-two genes were differentially expressed between young and old adult MRCs . Upon anReticular cells producing the CXCL12 chemokine, marginal reticular cells being precursors of follicular dendritic cells and responsible for antigen transport, and follicular dendritic cells storing antigen and producing the CXCL13 chemokine re the stromal cells of follicle germinal centers ,89,90,91The aging of marginal reticular cells is responsible for defects in the MRC-to-FDC differentiation pathway . Indeed,Fibroblastic reticular cells constitute the main subpopulation of lymph node stromal cells and play a significant role in the initiation, organization, and control of the adaptive functions of immune cells ,101. FibLymphotoxin β receptor (LTβR) expressed on FRCs is crucial for their survival and maintenance . LymphotIn reaction to an infection, FRCs lengthen and expand, increasing the available space for proliferating lymphocytes ,106,107.Fibroblastic reticular cells are the primary source of lymph node collagen, an essential component of the extracellular matrix . At an aA reduced number of FRCs and their simultaneous densification causes disorganization of the FRC network in old lymph nodes. An altered FRC architecture at the border of the cortical (B cells) and paracortical (T cells) zones in the mesenteric lymph nodes has been detected in aged mice. The clear boundary between these two functional zones has been blurred. As a consequence, the architecture of the lymphoid follicles is disturbed. The stroma of the cortical and paracortical zones appears more compressed and less reticulated .During infection, FRCs numbers in old lymph nodes increases slightly and does not reach the level observed in young adult lymph nodes. The peak of FRC expansion is delayed in part because of their slower proliferation . Node fiFibroblastic reticular cells play an important role in maintaining the viability of naïve T cells by producing IL-7 and the CCL19 chemokine. Altered IL-7 expression by FRCs in aged mouse lymph nodes has been demonstrated and paralleled the decreased proliferation of the naïve lymphocyte population . MoreoveBased on the above information, it can be assumed that the aging of FRCs significantly impairs the immune response to the antigen.Naïve lymphocytes constantly patrol the body in search of antigens and trigger a rapid immune response. They enter lymph nodes by a complex process beginning with a series of molecular interactions requiring the addressins expressed on the high endothelial venule cells, which are recognized by L-selectin (CD62L) expressed on lymphocytes . IncreasImmunosenescence is associated with a gradual loss of naïve T cells and an increase in the number of memory and antigen-specific effector T cells that may eventually leave the lymph node and migrate to peripheral nonlymphoid organs. Studies in old rodents have shown disturbances in T lymphocyte movement, localization, and responses ,31,124 . ReducinThe surface area and volume of the cortical, paracortical, and medullary lymph node zones gradually decrease with age. The medullary cords become increasingly thinner, which is associated with a decrease in the T lymphocyte population ,34. ExamThe entry of naïve T cells into secondary lymphoid organs is a multistage process partly dependent on the interaction of the CCR7 receptor on their surface with the CCL19 and CCL21 chemokines expressed on the surface of high endothelial venule cells. In conjunction with CXCL13, these chemokines mediate the movement of lymphocytes in the lymph node and play an important role in directing T and B cells to the appropriate zones . In the The importance of the lymph node microenvironment for T lymphocyte survival and function is highlighted by experiments involving parabiosis. Upon joining the bloodstream of young and old mice, T-cell circulation in both animals was unaffected; however, the total number of T cells in the old lymph nodes did not increase, despite the high T-cell influx from the young animal. In addition, stromal cell and T-cell cellularity in the lymph nodes of the young parabiosed animals decreased but was restored after the separation of the animals . A decreIn summary, changes in the lymphoid microenvironment with age, including deregulated steady-state and antigen-induced chemokine expression, contribute to decreased T-cell recruitment, limited access to factors necessary for survival, a disturbed distribution within the node resulting in limited access to antigens, and a reduced response to infection . Generation of permanent protective immunity requires the production of long-lived plasma cells capable of switching the classes of synthesized antibodies with high affinity for the antigen . In the B lymphocytes expressing the CXCR5 receptor on their surface penetrate the lymph node mainly through postcapillary venules in the paracortical lymph node zone. They are then attracted to lymphoid follicles by CXCL13 produced by lymphoid follicle stromal cells, reticular cells, and dendritic cells . After rDuring the primary B-cell response, antibodies with low antigen affinity are produced relatively quickly ,135. TheThe development of an immune response in the lymphatic follicle germinal centers is a regulated, multifactorial process that requires spatial organization and the cooperation of stromal cells and cells directly involved in the innate and adaptive response . The intThe formation of follicles is dependent on the CXCL13 chemokine and CXCR5 receptor expressed on B cells. In aging mice, a significant increase in CXCL13 protein secretion by marginal reticular cells and follicular dendritic cells and decreased CCL19 mRNA levels are observed, which is likely one reason for the disruption in the proper compartmentalization of lymph nodes . Moreovehi Ki67hi proliferating B cells and CD4+ PD1hi Tfh cells and an increased number of follicular CD4+ FoxP3hi and Lag3hi suppressor T cells were observed in the germinal centers of the lymph nodes of old monkeys. These data suggest a disrupted reciprocal regulation between B and Tfh lymphocytes [A decreased number of CD20phocytes . The abiphocytes ,143,144.phocytes .hi macrophages, myeloperoxidase-expressing neutrophils (MPOhi), and CD68hi monocytes than those of young animals. Myeloperoxidase is involved in the production of hypochlorous acid, a chemical compound with strong bactericidal and antiviral properties [hi monocytes and macrophages exhibit phagocytic functions and secrete IL-1β, CXCL9, CXCL10, and the ligands for CXCR3, a receptor highly expressed on T-cells present in germinal centers. These proinflammatory cells probably affect the activity of germinal centers by modulating the function and the local movement of B and T cells [Follicular CD4+ regulatory T lymphocytes are located in the lymphoid follicle at the border of the B- and T-cell zones and control and limit the response of germinal centers to antigen ,146. Theoperties . Follicu T cells .Such morphological and functional changes coincide and, in part, result from the disturbed structure of follicular dendritic cells, fibroblastic reticular cells, and other stromal cells, creating an unfavorable microenvironment .Chikungunya virus showed high antibody titers with a weak neutralizing function compared to the antibodies induced in young adult mice [The production of antigen-specific antibodies by memory B lymphocytes and plasma cells occurs in the germinal centers of the follicles . In old ult mice . Defectsult mice ,152. In ult mice ,154,155 Neutrophils are the main effector cells of innate immunity against extracellular pathogens, acting through phagocytosis, the release of cytotoxic proteins, the production of reactive oxygen species, and the release of neutrophil extracellular traps. In addition to the desired anti-microbial effects, the long-term action of neutrophils can result in tissue damage, as observed in chronic inflammatory diseases. Similar side effects arising from the improper functioning of neutrophils can likely occur in the lymph nodes ,157.Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes, Yersinia pestis, and BCG, infection with Toxoplasma gondii and Leishmania major [Neutrophils reach the lymph nodes by afferent lymphatic vessels and the bloodstream by HEVs through chemotaxis . Neutropia major ,163,164,ia major . In miceia major . These oia major . Howeveria major ,168. Conia major . In addiia major .An increase in the percentage of mature, old neutrophils has been observed in the lymph nodes of healthy old mice compared to young adults . These cAn increased number of neutrophils invading the T- and B-cell zones in the absence of accompanying diseases has been observed in the lymphoid organs of old female mice . Likely,The summary of aging-related changes in the lymph node immune cells is shown in Lymph nodes are secondary lymphoid organs that produce immune cells and respond immediately to foreign antigens, including vaccines. The structure of the lymph nodes ensures an efficient uptake, processing, and response to antigens present in the blood and lymph. This process aims to induce a long-term adaptive immune response in the host organism. The generation of permanent protective immunity requires the production of long-lived plasma cells secreting high-affinity class-switched antibodies . These cAging causes progressive disruption of the lymph nodes as their number and size are reduced, and structure becomes disorganized. The most affected are the germinal centers ,37,179. The importance of properly functioning lymph nodes in the course of severe infections was shown in COVID-19 patients. In those who did not survive the disease, the lymph nodes were devoid of germinal centers, follicular T helper lymphocytes did not differentiate properly, activated B cells were present outside of the germinal center microenvironment, and long-lived memory B cells with a high affinity for the antigen had not been produced . StructuTo sum up, immunosenescence leads to a weakened response to viral and bacterial infections and vaccines and an increased incidence of cancer and autoimmune diseases. The mechanisms responsible for the aging of lymph nodes have not been fully explained. Aging-related morphological and molecular changes in human and rodent lymph nodes affect the functioning of immune cells, which ultimately results in a diminished immune response. Understanding the molecular causes of aging-related changes can help identify new treatments to improve nodal health and, thus, improve immune responses and vaccine effectiveness in the elderly.


Self-generated auditory input is perceived less loudly than the same sounds generated externally. The existence of this phenomenon, called Sensory Attenuation (SA), has been studied for decades and is often explained by motor-based forward models. Recent developments in the research of SA, however, challenge these models. We review the current state of knowledge regarding theoretical implications about the significance of Sensory Attenuation and its role in human behavior and functioning. Focusing on behavioral and electrophysiological results in the auditory domain, we provide an overview of the characteristics and limitations of existing SA paradigms and highlight the problem of isolating SA from other predictive mechanisms. Finally, we explore different hypotheses attempting to explain heterogeneous empirical findings, and the impact of the Predictive Coding Framework in this research area. Sensory Attenuation (SA) describes the phenomenon that self-initiated sensory input is perceived with a lesser intensity than the same sensations generated externally  of a stimulus rendering it valuable in further processing Friston, . Therefootherness, as is present when hearing ones’ own voice on tape, rather than attenuated processing.In contrast to forward models, predictive coding does not conceive SA as a result of reafference cancellation. Rather, attenuation of expected signals is a logical conclusion from the imperative to minimize surprise and allocate attention and processing resources to unexpected stimuli since those are most effective in model updating. Importantly, this framework stresses the usefulness of predictive information on self-generated movements in creating a sense of agency  stimulus onset delays of up to 1,000 ms, suggesting that SA is not dependent on temporal predictability alone Lange, .Recent studies tried to further disentangle the individual contributions of temporal control and temporal predictability to SA. Kaiser and Schütz-Bosbach  demonstrIdentity prediction describes the ability to predict the identity of the stimulus, based on self-initiated behavior (motor-based identity prediction) or other cues . It describes the individual’s awareness of control over self-initiated actions (Jeannerod, A widely accepted connection between SA and SoA, however, has not been established yet. While SA appears to take place in low-level processing and in the first 200 ms after stimulus onset, SoA requires a higher and potentially later level of processing (Dewey and Knoblich, In a study by Timm et al. , SoA was vice versa (Burin et al., Other studies showed that, although sounds were always generated by the participants themselves, there were differences in SA depending on their belief in agency. Desantis et al. , for exaFocusing on auditory studies, this review summarized recent developments in SA research and discussed the strengths and weaknesses of two major theoretical frameworks, forward models and predictive processing. Results of current studies examining the confounding effects of temporality indicate that while temporal predictability and control indeed influence attenuation effects, other mechanisms must be included to explain SA (Kaiser and Schütz-Bosbach, Classical forward models depend on motor commands to predict and subsequently attenuate sensory inputs, thereby giving the agent the possibility to differentiate between self- and other generated stimuli, and thus facilitating a sense of agency. These models cannot account for several phenomena of SA that were observed independent from motor behavior, the strong role of attention in SA, as well as the influence of agency beliefs on SA prior to stimulus onset. Predictive processing, on the other hand, states that we constantly make use of prior information, either self- or externally-generated, in order to create predictions about upcoming changes in sensory input in the form of a generative model (Friston et al., FK, NK, and GH wrote 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.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.


Variational auto-encoders (VAE) have recently been successfully applied in the intelligent fault diagnosis of rolling bearings due to its self-learning ability and robustness. However, the hyper-parameters of VAEs depend, to a significant extent, on artificial settings, which is regarded as a common and key problem in existing deep learning models. Additionally, its anti-noise capability may face a decline when VAE is used to analyze bearing vibration data under loud environmental noise. Therefore, in order to improve the anti-noise performance of the VAE model and adaptively select its parameters, this paper proposes an optimized stacked variational denoising autoencoder (OSVDAE) for the reliable fault diagnosis of bearings. Within the proposed method, a robust network, named variational denoising auto-encoder (VDAE), is, first, designed by integrating VAE and a denoising auto-encoder (DAE). Subsequently, a stacked variational denoising auto-encoder (SVDAE) architecture is constructed to extract the robust and discriminative latent fault features via stacking VDAE networks layer on layer, wherein the important parameters of the SVDAE model are automatically determined by employing a novel meta-heuristic intelligent optimizer known as the seagull optimization algorithm (SOA). Finally, the extracted latent features are imported into a softmax classifier to obtain the results of fault recognition in rolling bearings. Experiments are conducted to validate the effectiveness of the proposed method. The results of analysis indicate that the proposed method not only can achieve a high identification accuracy for different bearing health conditions, but also outperforms some representative deep learning methods. Mechanical equipment is widely used in all walks of life in modern society, where rolling bearings are the most common component of mechanical equipment. Due to the continuous influence of alternating impact force and load, rolling bearings are easily subject to varying degrees of fault, in different positions. Once bearings are damaged, it will inevitably cause mechanical equipment to stop work, bringing about economic loss and even causing personnel casualties . TherefoWith the rapid development of technologies such as sensors and industrial internet, the concept of intelligent diagnosis provides a new pathway for feature learning and the intelligent recognition of bearing faults ,4. Many To avoid the above problems and forgo the dependence on artificial feature extraction, increasingly, many deep learning methods  , convolu(1)A novel deep learning model, named stacked variational denoising autoencoder (SVDAE), is proposed, which can effectively process bearing vibration data under noisy environment and obtain high-quality deep features.(2)A new intelligent optimizer, named seagull optimization algorithm (SOA), is introduced to automatically determine the important parameters of SVDAE, which can avoid the empiricism and triviality of repeatedly manually adjusting parameters in deep learning methods.(3)A data-driven fault diagnosis scheme based on an optimized stacked variational denoising autoencoder is proposed for bearing fault identification, which can improve the accuracy of bearing fault diagnosis.(4)The effectiveness and superiority of the proposed method are demonstrated by experiments and comparisons between bearing fault diagnoses.In this study, to improve the anti-noise ability of VAE and adaptively select its network parameters, a new deep learning model, named optimized stacked variational denoising autoencoder (OSVDAE), is proposed for bearing fault diagnosis that can mine more representative fault information hidden in the raw bearing vibration data and establish accurately mapped relationships between it and the operating state of equipment. Specifically, the proposed OSVDAE method mainly consists of two stages . The major differences between our study and previous fault diagnosis studies can be summed up in two points. On the one hand, in the feature learning stage, considering a stacked denoising auto-encoder (SDAE) can not only improve the anti-noise ability of the auto-encoder, but also automatically learn more representative and discriminative fault feature information through stacking multiple denoising auto-encoder networks. Therefore, by integrating the advantages of SDAE and VAE, a stacked variational denoising autoencoder (SVDAE) is proposed for the feature learning of bearing faults. On the other hand, in the parameter optimization stage, a recently proposed intelligent optimizer, the seagull optimization algorithm (SOA) , which hThe rest of this paper is organized as follows. In this section, the basic theory of VAE is firstly described, then we used a summary table to conduct the literature review on VAE in fault diagnosis.z, with a Gaussian distribution can be obtained, the parameters of which  can be automatically learned by a network training process, such that new input data can be generated by the decoding for z. To make the generated data highly similar to the original data, here, maximized marginal distribution is conducted byx, by the latent variable, z; z.VAE is regarded as a new unsupervised learning algorithm with an encoder, sampling and a decoder that has a fast convergence rate and little overfitting. N, J is the dimension of the latent variable z,j-th element of L denotes the amount of sampling from z under the rules of Supposing that we have an approximation posterior, terature .Since the VAE method’s appearance, many studies on VAE in fault diagnosis have been presented in the literature. (1)To improve the anti-noise capability of VAE model, a new deep learning model, named stacked variational denoising auto-encoder (SVDAE), is constructed by integrating stacked denoising techniques and a variational auto-encoder.(2)To avoid the dependence of human experience of parameter selection of the existing VAE model, we adopted a novel optimizer, the seagull optimization algorithm (SOA), using its fast operation to adaptively select the parameters of SVDAE.(3)To improve the accuracy of fault diagnosis, an intelligent diagnosis scheme based on optimized stacked variational denoising autoencoder (OSVDAE) is proposed that can effectively identify bearing faults under constant and variable speeds.From to the literature survey, it can be seen that the studies mentioned above can solve the problems in fault diagnosis to a certain extent, but most of the above methods handle fault diagnosis problem at constant speed and select the parameters of the VAE model according to human experience. Additionally, the robustness of the above algorithm against noise is rarely studied. That is, the existing literature generally focuses on the application of VAE research to fault diagnosis under steady speeds, but little consideration is given to the concentrated surveying of parameter selection and the anti-noise capabilities of VAE models. Differently from these previous studies, this study mainly focuses to self-adaptive parameter selection and improving the anti-noise performance of a VAE model at constant speed and variable speed. Concretely, the novelty and contribution of this study can be summarized in three aspects:In this section, the basic theory of variational denoising auto-encoder (VDAE) is firstly presented, then a stacked variational denoising auto-encoder (SVDAE) is constructed on the basis of VDAE, and we use a novel meta-heuristic optimizer, the seagull optimization algorithm (SOA), to select the parameters of SVDAE. Finally, an intelligent bearing fault diagnosis scheme, based on optimized stacked variational denoising autoencoder (OSVDAE) is proposed.N,z, are connected with the decoder to generate the new data, y, which is highly similar to the original data, x.Due to unstable working conditions and complex operating environments, when a local fault appears in rolling bearings, the resulting bearing vibration signal contains a mass of noise interference, which indicates that the obtained identification accuracy will be not too high if traditional AE is used to process the noisy bearing vibration data. Denoising auto-encoder (DAE) is an improved version of AE, which can enhance the generalization ability and robustness of the AE model and prevent over-fitting problems by adding noise into the input data. Hence, considering the merits of both DAE and VAE, in this section, the concept of variational denoising auto-encoder (VDAE) is presented by integrating a denoising module into the original VAE architecture, which can extract the robust features from the noisy vibration signal. j-th class fault, x represents the input sample, K is the number of fault categories, Stacked auto-encoder (SAE) is a deep network structure composed of multiple standard AE stacking, which can learn fault characteristics in depth and reduce the dimensionality of input data. Hence, inspired by SAE and VDAE, in this section, a stacked variational denoising auto-encoder (SVDAE) is constructed to extract the latent variables layer by layer. Compared with single VDAE models, SDVAE can extract more robust and more representative latent features due to its deep network structure. Specifically, the training process of the SVDAE model is divided into two stages . N, learning rate a, number of nodes in the first hidden layer l1, number of nodes in the second hidden layer l2 and number of nodes in the third hidden layer l3) of the SVDAE model, which can improve its identification accuracy and avoid the problem of artificial empirical selection of the SVDAE model’s parameters. (1)N = 100, maximum number of iterations N denotes the epochs number of the SVDAE model, l1, l2 and l3 are the number of nodes of the hidden layers of VDAE1, VDAE2 and VDAE3, respectively.Load sample data, use Equation (8) to initialize the population of seagulls and set the initial parameters of the SOA. Specifically, set the population size of seagulls (2)Calculate the objective function of each seagull and determine the current best position of the seagulls. In this step, the identification accuracy (3)x denotes the current iteration number. A represents the movement behavior of seagulls in a given search space and meets A, which is linearly decreased from B is a random number and satisfies k denotes a random number between 0 and According to Equation (10), calculate the distance (4)Calculate the objective value of the current seagull and save the global best position of the seagulls. If (5)m = m + 1, repeat the steps (2)~(5) until the stop condition is satisfied.Judge if the stop condition is met. Specifically, judge whether the number of iterations is reached or the expected identification accuracy is achieved. If it reaches maximum number of iterations, output the best position (6)Use the optimized SVDAE model to automatically learn the discriminative fault feature information from the collected bearing vibration signal.When the SVDAE model is used to analyze the collected bearing vibration data, its performance may be affected by the hyper-parameter settings of SVDAE. That is, improper network model parameters will result in low recognition accuracy. If artificial adjustment methods are adopted to select the parameters of SVDAE, it will be tedious and complex, while high accuracy cannot be fully guaranteed. This indicates that an intelligent algorithm is urgently needed to determine the parameters of SVDAE. The seagull optimization algorithm (SOA) is a novel meta-heuristic optimizer proposed by Dhiman and Kumar, in 2019 . CompareTo make it easier for the reader to understand, we plotted the block diagram of OSVDAE, as shown in To extract more robust fault features from bearing vibration data and improve fault identification accuracy, this paper proposes a bearing fault diagnosis scheme based on optimized stacked variational denoising autoencoder (OSVDAE) with the seagull optimization algorithm (SOA), which can avoid the problem of complexity and the triviality of manually adjusting the parameters of the SVDAE model. Step 1: Vibration Data Collection. Bearings’ vibration data are collected by using a data acquisition card and an accelerometer mounted on an experimental platform. Additionally, a fast Fourier transform (FFT) of the collected bearing vibration data is conducted to obtain the frequency spectrum data, then their frequency spectra are randomly selected as training samples or testing samples.Step 2: Deep Feature Learning. The training samples are input into the constructed OSVDAE model to train the stacked encoding network layer-by-layer, which is aimed at obtaining the representative latent fault features. Meanwhile, the SOA method is employed to automatically determine the important parameters of the OSVDAE model.Step 3: Fault Pattern Identification. The testing samples are fed into the well-trained OSVDAE model to automatically identify bearing faults and provide the final intelligent bearing fault diagnosis.Experimental data are provided by the Bearing Data Center of Case Western Reserve University (CWRU). The experimental apparatus mainly consists of a motor, testing bearing, a torque transducer, a dynamometer and control electronics. The proposed method is used to process the above collected bearing experimental data, where the key parameters of the SVDAE model are automatically determined by the SOA method. To show the advancement of the proposed method and enhance the reliability of the diagnosis results, the same experimental data from above are analyzed by the traditional VAE and three representative deep learning models . Due to the randomness of sample selection, each algorithm is executed 10 times to observe their identification results. According to previous studies, their model parameters are specifically summarized as follows: (1) In the traditional deep VAE , the netTo study the impact of training sample size on the diagnosis ability of different deep learning methods, the total training sample size is respectively set to 50, 100, 150, 200, 250, 300, 350, 400, 450 and 500, where the number of training samples of each bearing condition is 10% of the total size of the training sample data. The identification results of different methods are plotted in To further consolidate the diagnosis results, we analyze the impact of noise on the recognition performance of the proposed method. Concretely, Gaussian white noise of different signal-to-noise ratios (SNR) is added into the original vibration data to investigate and compare the results of the various deep learning methods. To more deeply investigate the diagnostic results of the proposed method, the five-fold cross-validation of different deep learning methods is conducted. Concretely, the collected dataset (600 samples) is equally divided into five parts , where four parts  are alternately selected as the training samples and the remaining part  is regarded as the testing samples. That is, five trials of different methods are performed. The average identification accuracies of the five trials are regarded as the final diagnoses. In this case, an experimental bearing dataset from the laboratory is used to evaluate the performance of the proposed method. The experimental equipment mainly consists of a motor, drive belt, loading equipment, a bearing test module, an electrical control system and a computer monitoring system, which can be seen in The proposed method was adopted to identify the above bearing fault conditions. According to the process of the proposed method, the SOA method is firstly used to automatically determine the important parameters of the SVDAE model. The optimized results are shown in To verify the advantages of the proposed method, the same bearing data are also processed using four typical deep learning methods . Moreover, to improve the reliability of the diagnostic results, 10 trials of each method are carried out for a fair comparison. Note that, in all compared methods, the number of iterations and the learning rate are the same as that of the proposed method. The VAE, SDAE and DBN models all have five layers , their network structures are 2048–512–64–32–6, 2048–200–100–80–6, and 2048–200–100–80–6, respectively. The network structure of CNN is set to the same as in case 1. To consolidate the diagnostic results of the proposed method, the identification results of various methods under different training samples are calculated, as shown in To investigate the robustness of the proposed method for bearing vibration signals in a noisy environment, we adopt different methods to process the above bearing condition data containing different noise levels . To more deeply show the diagnostic results of the proposed method, we conducted five-fold cross-validation on the proposed method and four comparison methods . Similarly, the collected dataset are equally divided into five parts, whereby four parts  are alternately selected as the training set and the remaining part  is regarded as the testing set. That is, each method conducts five trials. The average accuracy of five trials of each method is regarded as their final diagnosis results (see (1)In this paper, through the fusion of stacked denoising techniques, VAE and an optimization algorithm, the proposed method could improve the anti-noise performance of the VAE model and adaptively select its parameters. However, the over-fitting problem of the proposed method was not considered completely. That is, the overfitting problem of the network model is one limitation of this study. Therefore, to solve this problem, in a future work, considering the advantages of the existing available advanced AE It is difficult to obtain sufficient bearing fault data in actual production, which easily leads to imbalanced samples from training. This indicates that bearing fault diagnosis, under data imbalance, is a difficult problem. That is, another limitation of this study is the uncertainty of implementing unbalanced bearing fault diagnosis. Therefore, to solve the unbalanced fault diagnosis problem, in a future work, we intend to integrate the synthetic minority over-sampling technique or bagging method into SVDAE to improve the generalization performance of the network model. Additionally, some loss items  can also be added into the SVDAE model to solve the unbalanced fault diagnosis problem of rolling bearings, which is our future research direction.(3)When multi-sensor experimental data are collected, including vibration and acoustic signals, the utilization of multi-sensor information is very critical for the reliable fault diagnosis of bearings. This paper mainly solves the bearing fault diagnosis problem of single-sensor data, whereas the effectiveness of the proposed method is unknown for multi-sensor data processing. That is, the indeterminacy of the proposed method in multi-sensor fault diagnosis is regarded as one limitation of this study. Therefore, in our future work, we will refer to the coupling notion of a deep coupling auto-encoder (DCAE) , by whic(4)In the experimental case 2 of this paper, bearing vibration data were actually collected on different dates. As the room temperature was different on different dates, the collected bearing vibration data was collected in different room temperatures. This indicates that the proposed method can identify bearing faults under different room temperatures. In other words, when bearing vibration data of different room temperatures are analyzed, it is generally not required to re-train the proposed model. However, due to the limitations of the experimental conditions, when the experiments of this paper were conducted, the room temperatures were not recorded, which is regarded as one deficiency of this study. Therefore, in our future work, we will adopt a thermodetector to record the room temperature in which bearing data is collected and confirm the identification accuracy of the proposed method as a function of room temperature.(5)In two experimental cases of this paper, the robustness and parameter selection of the proposed SVDAE were studied intensively, but the internal working mechanism of the SVDAE was not investigated in detail. Therefore, in our future work, we will adopt some representative feature visualization techniques , principal component analysis (PCA), local preserving projection (LPP) and local sensitive discriminant analysis (LSDA)) to clearly describe the clustering of output features of the different layers of SVDAE. Meanwhile, in a future work, the discrimination degree of the output features of the proposed method will be quantitatively evaluated by using sensitive indexes .Based on the comparisons and analysis of fault diagnosis results obtained by different methods under two sets of experimental bearing data, we can draw a definite conclusion that the proposed method has an accurate classification result and has better identification accuracy than several typical deep learning methods mentioned in this paper; this is probably due to the stacked denoising techniques and the parameter optimization process introduced into the original VAE model, which are also the advantages of the proposed method. The proposed method can provide a reference for algorithm the improvement and future study of the VAE model in bearing fault diagnosis. Despite this, this paper nonetheless leaves some work to be done on the proposed method in the future. Some limitations and specific future works of the proposed method are envisaged as follows:(1)A novel deep learning model, named stacked variational denoising auto-encoder (SVDAE), was presented to extract the inherent fault features from the original bearing vibration data and provided better robustness than the original VAE.(2)A new meta-heuristic intelligent optimizer, termed the seagull optimization algorithm (SOA), was employed to automatically select the hyper-parameters of SVDAE model, which improved the feature learning ability and avoided the dependence upon human experience for parameter selection in deep learning.(3)An intelligent diagnostic framework based on optimized stacked variational denoising autoencoder (OSVDAE) was proposed for reliably diagnosing bearing faults that does not require artificial, features-based expert knowledge and so is appropriate for ordinary technicians.(4)The experimental results and comparison analysis of bearing fault diagnosis showed the effectiveness and superiority of the proposed method.This paper proposed a novel bearing fault diagnosis scheme based on optimized stacked variational denoising autoencoder (OSVDAE). Two experimental examples were adopted to demonstrate the effectiveness of the proposed method in identifying bearing faults. The experimental comparison results showed that the proposed method could obtain a high identification accuracy of 99% or above, which was greater than those of the traditional VAE and several representative deep learning models . Additionally, the proposed method showed certain robustness for bearing fault signals in noisy environments. The main contributions and novelties of this paper are as follows:Due to the limitations of the research conditions, this paper mainly focused on solving the problem of bearing fault diagnosis, whereas other key parts  of mechanical equipment are also prone to breaking down. Hence, in future work, the problem of reliable fault diagnosis in other key parts  will be analyzed using the proposed method.


Biomass polyphenols are bio-active macromolecules with distinct chemical structures in a variety of biomass. In recent years, the study of biomass polyphenols and their application in food and medicine fields has become a research hotspot, which predominantly focuses on the preparation, purification, structural identifications, and measurements of biological activities. Many studies describe methodologies for extraction and application of polyphenols, but comprehensive work to review its physiological activities like drugs and health products are lacking. This paper comprehensively unlocks the bioactivities of antioxidant, antibacterial, antitumor, anticancer, neuroprotection, control of blood sugar, regulation of blood fat, and promotion of gastrointestinal health functions of polyphenols from different biomass sources. This review will serve as an illuminating resource for the global scientific community, especially for those who are actively working to promote the advances of the polyphenols research field. The growth and development of biomass are sustained by the regulation of metabolism and resistance against different biological stresses. The endogenous metabolites of biomass are composed of primary and secondary metabolites. In the different biomass, the major constituents are cellulose, hemicellulose, lignin, which can be applied to prepare various value-added products and bio-materials . Apart fThere has been a long history of utilization of biomass polyphenols, which have been used in tanning and as medicines starting from ancient times . The natBiomass polyphenols are a class of natural compounds widely distributed in biomass with an abundance second to lignin, cellulose, and hemicellulose. Polyphenols are predominantly accumulated in the leaves, vascular tissues, bark, immature fruits, seed coat, and disinfected tissues of biomass. China is rich in biomass polyphenol resources varieties , includivia consuming oxygen in the environment  hydrolyzed tannins  and 2) condensed tannins (polyflavanol polyphenols or proanthocyanidins) . Hydrolyironment .More than 8,000 different kinds of polyphenols and their derivatives have been identified in the biomass kingdom . The namPolyphenols are usually ingested as mixtures of different compounds that are immersed in a complex food substrate. The material then undergoes digestion, which exerts changes in structure and activity, before the mixture eventually reaches and acts upon target organs. After ingestion, absorption from the digestive tract usually requires intestinal enzymes, such as lactase rhizopericoside hydrolase and cytosolute β-glucosidase, to hydrolyze glycoside binders and produce the corresponding aglycones . These aDue to the diversity of biomass polyphenols, a variety of biological activities has been reported, including antioxidant , anti-inRedox is an essential class of metabolic reaction that occurs in living organisms. However, when the electron flow becomes decoupled, the generation of harmful free radicals results in detrimental outcomes . Free raBiomass polyphenols have strong activity due to their ability to delocalize uncoupled electrons, which can scavenge free radicals, chelate metal ions and inhibiting oxidase activity, and protect endogenous antioxidant enzymes in the body . Most navia regulating the activities of cellular enzymes. Biomass polyphenols have been widely used in various fields due to their strong antioxidant activities. In conclusion, biomass polyphenols show prominent antioxidant performance and free radical scavenging capabilities, which is of great significance to broadening their fields of research and various applications.via multiple modes of action, which include alteration of the bacterial membrane permeabilization, inhibition of the bacterial DNA gyrase, interference with the energy metabolism, and perturbation of the functions of bacterial porins . The medium dose of GJE treatment showed the most effective inhibition of neuronal necrosis in different brain regions of the rat model of chronic cerebral ischemia  and peroxisome proliferator-activated receptor-γ (PPARγ) signaling pathways. via the IRS-1/PI3K/Akt pathway, which in turn inhibited Tau hyperphosphorylation and ultimately improved cognitive function in AD rats. in vitro. High doses of PGL inhibited intestinal lipase activity while promoting the expression of tight junction proteins, thereby inhibiting lipid absorption and reducing blood serum total cholesterol (TC) and triglyceride (TG) levels to prevent intestinal mucosal damage due to lipid overload.via multiple modes of action. In addition, several common fruit and vegetable polyphenols, such as pomegranate polyphenols, tea polyphenols, hawthorn polyphenols, and apple polyphenols, exert similar effects on downregulating TG, TC, and LDL-C levels while upregulating the level of high-density lipoprotein cholesterol. Currently, the study on the mechanisms of glucose- and lipid-lowering capabilities of biomass polyphenols has attracted much more attention but still requires further investigations.Green tea polyphenols, grape polyphenols, citrus juice polyphenols, and sand buckthorn leaf polyphenols play similar roles in lowering blood sugar Intestinal barriers refer to the intact structure and function of the intestine to prevent harmful substances such as bacteria and toxins from passing through the intestinal mucosa and entering other tissues, organs, and blood circulation in the human body. The normal intestinal mucosal barriers are composed of a mechanical barrier, a chemical barrier, an immune barrier, and a biological barrier, and the integrity of each intestinal barrier is indispensable to human health. The intestinal barriers maintain the normal intestinal permeability and regulate the transportation and absorption of nutrients  and other food-related compounds (such as polyphenols). In addition, intestinal barriers regulate the composition of bacteria from the lumen to the blood flow of transfer . The intvia collaborating with the intestinal microbiota. Biomass polyphenols influence the activities of intestinal microflora, repair gastrointestinal mucosal damage, optimize the intestinal structure, and interact with other macromolecules to affect gastrointestinal function. via the biliary duct and re-absorbed throughout the enterohepatic recirculation. In animal studies, the addition of polyphenols to diets reduced high-fat diet-induced obesity and modulated the gut microbiota by increasing the growth of short-chain fatty acid-producing bacteria and decreasing the growth of lipopolysaccharide-producing bacteria. More clinical trials are required to investigate the application of dietary polyphenols as nutritional or functional foods in the prevention and treatment of obesity in humans, and studies that aim at elucidating the mode of action of specific bacteria strains in mediating dietary polyphenols would be necessary.Gastrointestinal dysfunction is one of the major factors that contribute to type II diabetes, cardiovascular disease, insomnia, obesity, and other disorders . TherefoAlthough polyphenols have been considered as chemical impurities, recent studies and findings underlined its biological activities in terms of exerting antioxidant, antibacterial, antitumor, neuroprotection, regulation of blood lipid, and promotion of gastrointestinal health functions. This thus attracts more attention from researchers worldwide to further investigate the pharmacological applications of biomass polyphenols and use them as one of the major components in natural products-derived drugs. More interestingly, given that biomass polyphenols are enriched in daily food, this further highlights the essential contribution of polyphenols to human life and makes biomass polyphenols one of the research hotspots. A range of studies has demonstrated efficient extraction of polyphenols from tea, grape, pomegranate, rapeseed, and other raw materials, which are coincidentally used in medical treatments and as functional food supplements. Many diseases are associated with antioxidants, but given the purity of the extract and the complexity of the structure, polyphenols are currently only used as supplements for the treatment of diseases, and research into their use as medicines for the treatment of diseases still requires innovative extraction techniques and in-depth research into anti-disease mechanisms, to explore their therapeutic potential. Hence, the mechanisms of polyphenols’ pharmacological actions still require further investigation. It is hoped that with the increasing attention from researchers on natural drugs and the progress of scientific technology, more methods of rapid separation and preparation of polyphenols can be developed, and the underlying pharmacological mechanisms of polyphenols will be further elucidated to provide the material basis for further pharmacological examination and clinical investigation.


Multi-materials of metal-polymer and metal-composite hybrid structures (MMHSs) are highly demanded in several fields including land, air and sea transportation, infrastructure construction, and healthcare. The adoption of MMHSs in transportation industries represents a pivotal opportunity to reduce the product’s weight without compromising structural performance. This enables a dramatic reduction in fuel consumption for vehicles driven by internal combustion engines as well as an increase in fuel efficiency for electric vehicles. The main challenge for manufacturing MMHSs lies in the lack of robust joining solutions. Conventional joining processes, e.g., mechanical fastening and adhesive bonding involve several issues. Several emerging technologies have been developed for MMHSs’ manufacturing. Different from recently published review articles where the focus is only on specific categories of joining processes, this review is aimed at providing a broader and systematic view of the emerging opportunities for hybrid thin-walled structure manufacturing. The present review paper discusses the main limitations of conventional joining processes and describes the joining mechanisms, the main differences, advantages, and limitations of new joining processes. Three reference clusters were identified: fast mechanical joining processes, thermomechanical interlocking processes, and thermomechanical joining processes. This new classification is aimed at providing a compass to better orient within the broad horizon of new joining processes for MMHSs with an outlook for future trends. The use of high-performance materials such as techno-polymers and fiber-reinforced thermoplastic are opening new possibilities in terms of the “Circular Economy” concepts. Fiber-reinforced thermoplastics are distinguished by their intrinsic recyclability and re-processability. Indeed, the ability to reshape the part using thermoforming may result in a substantial reduction in material waste. Thermoplastic composites are increasingly being used to replace thermosetting composites in many commercial applications because of their advantages mentioned above. Besides, the automobile and aviation industries are sought to replace metal components with thermoplastic composites to minimize vehicle weight. As a result, thermoplastic composites are used as composite stiffeners to strengthen components, resulting in a greater strength-to-weight ratio, lighter and tougher structures, and improved fatigue properties. Thermoplastic composite stiffeners are more resistant to corrosion as compared to thermoset ones. Besides, they are produced through Out-of-Autoclave (OoA) processing, which saves cycle times and energy greatly.Thermoplastic composites and high-performance thermoplastics are usually joined to metallic parts in complex assemblies (such as a vehicle body). Thus, hybrid metal-composite and metal-plastic systems are involved in many applications. The chemical composition, mechanical properties, and physical features of the dissimilar materials often make combining metals-polymer and metal-composite relatively difficult. The commonly used joining technologies, typically, adhesive bonding and mechanical fastening, involve a lot of shortcomings and drawbacks. For example, pretreatments are needed for adhesive bonding to remove surface oil, grease, powder, and surface oxide. This requires the use of inefficient and environmentally destructive processes. Adhesive bonding also requires advanced instruments such as fixtures and jigs  to keep the components together during the healing process. Furthermore, adhesive bonding is susceptible to long-term instability as well as serious environmental vulnerability and shows high sensitivity to the loading direction ,2. BesidMechanical fastening procedures usually require spot contacts, which result in stress concentration and fiber interruption in composites. The adoption of inserted third parts (such as bolts or rivets) in mechanical fastening cause overweighting and increased costs. Besides, bolt-nut connections may involve problems concerning loosening fastening force owing to uneven stress distribution and concentration at threads ,4. FinalRecently, alternative solutions have been proposed to overcome the above-mentioned limitations. Advanced mechanical joining processes represent a suitable solution. These processes, which include mechanical clinching and self-pierce riveting, do not require pre-drilled holes; thus, they enable a sensible reduction of the overall joining time.Thermomechanical interlocking is another viable solution for hybrid metal-composite structures. These processes include friction self-riveting , frictioThe third category of joining processes for hybrid metal-composite structures is thermomechanical joining processes (TMJPs) enabled by micromechanical interlocking, adhesion, or chemical bonds at the joint interface. The formation of the joints is often supported by more than one joining mechanism. Some examples of TMJPs are direct laser joining ,18,19,20The growing adoption of hybrid structures would benefit from a systematic view of the newly developed manufacturing processes. This could enable an easier and more appropriate selection of the processes for a given demand. In recent years, many literature reviews have been presented with the aim of “put in order” the available processes. In 2009, Amancio-Filho and dos Santos  performeThe main purpose of this study is to provide a comprehensive overview of available joining processes for metal-composite and metal-polymer hybrid structures. This would lead to a better selection of the suitable joining process to meet the given application demand. Thus, a critical overview of advanced joining processes for metal-composite hybrid structures developed recently on the aspect of principles, applications, advantages, and limitations of the joining processes is performed.This review proposes a new classification of the joining solutions based on the main similarities among the processes. This classification includes traditional joining processes  and advanced joining processes, which include advanced mechanical fastening, thermomechanical interlocking, and thermomechanical joining, as depicted in These processes involve macro-mechanical interlock between the two (or even three) components. The interlock is achieved through the plastic deformation of the joining partners or the local fracture of the composite without the need of pre-drilled holes. This group mainly includes mechanical clinching and self-pierce riveting. Additionally, in the case of clinching, an external fastening element is needed.Mechanical clinching is a joining method in which two or more sheet materials are locally deformed to create a geometrical interlocking by a punch and a die. The advantage of mechanical clinching is that it can be achieved by only deforming the material to be jointed without using any external element such as rivet, screw, and adhesive. Due to these characteristics, mechanical clinching has been used to join ductile metals and polymers with various thicknesses ,45,46,47Many studies ,58,59 han) and interlocking length (ts), as shown in In mechanical clinching process design, the failure mode analysis of the joint is important because it indicates the weaker part of the joint. Mechanical clinching is mainly used in the civil construction and automotive industries  as varioNeugebauer et al.  introducSelf-piercing riveting (SPR) is a single-step joining technique, using a semi-tubular rivet to fasten the sheet materials. The SPR process is generally carried out in four steps : clampinAs the name suggests, a semi-tubular rivet is pressed into the sheets clamped together between a holder and die and pierces through the upper sheets. At the flaring step, the lower sheet flows into the die cavity, and the rivet flares outward to form a mechanical interlock between the upper and lower sheet. As SPR eliminates the requirement for pre-drilled or punched holes and the associate accurate alignment before joining, it allows the joints to be fabricated rapidly in a single operation. As the process relies on a mechanical interlock rather than fusion, it can be used to combine dissimilar materials without overheating. It is especially suitable for dissimilar material combinations that involve zinc-coated, organic-coated, or pre-painted steels, aluminum alloys, polymers, and composites. The unique advantages of SPR have led to a significant increase in practical applications in the automotive industry. The joint quality of SPR is typically determined by the rivet head height, the interlock distance, and the minimum remaining bottom materials’ thickness, as shown in Many process parameters can influence the quality and strength of SPR joints, such as rivet, die, and setting force. Nowadays, the rivet with a countersunk head is normally used in the SPR process. The geometry of rivet is designed by considering various factors such as the materials to be joined, die shape, and rivet hardness ,81. DepeHou et al.  showed tThermomechanical interlocking processes involve a high degree of thermo-mechanical deformation to generate hooks, interlocks, and to undercut the mechanically interlocking/fastening of the two components. The adoption of a heating source during the process reduces the forming forces and improves the formability of the materials involved. Currently, thermomechanical interlocking processes include friction riveting, friction self-riveting, injection clinching joining, friction-based filling stacking, friction stir lap welding, and fused deposition modeling-based joining.In friction riveting , a rotatFriction riveting is suitable to connect polymer or polymer composites to different metals for a variety of applications in aerospace, automobile, and civil engineering . The proFriction self-riveting is another thermomechanical interlocking process that exploits the micro or macro holes on a metal sheet . This prInjection clinching joining was used to produce spot joints between a metal with a pre-drilled hole and a polymer-based component . The polFriction-based filling stacking  was deveA variant of the process that involves the direct deposition of polymeric material through fused deposition modeling (FDM) has been recently developed to avoid the use of a pre-prepared stud . In fuseFriction stir lap welding, which was originally developed for welding hard-to-weld metals , has been extended to various combinations of materials . Different joining mechanisms may be involved such as the adhesion of a polymer to the fibers of the second, as shown in Thermomechanical joining processes (TMJPs) do not require substantial deformation of the components. They use an external energy source  to heat the joint interface until it reaches the desired joining temperature range. An application of compression is often desirable to achieve higher bonding strength. The sequence of a TMJP is schematically illustrated in The surface conditions of the joining partners including the nature of the polymer (polymer matrix), the chemical composition of the metal surface, and the morphology of the metal surface.The joining parameters used during the operation.The joint strength can be affected by many factors including but not limited to:Depending on the equipment adopted, these processes can be used to produce spot and continuous connections.Micromechanical interlocking, physical interactions and chemical bonds may be used to connect metal to a composite component. The formation of the joints is often supported by more than one mechanism. Micromechanical interlocking can be achieved by localized deformation of the metal that flows around the carbon fibers ,94 or thThe atomic-level interaction between metal and polymer at the joint interface can be classified into two categories: physical interactions and chemical bonding. Physical interactions include the generation of Van der Waals force and hydrogen bonding. Van der Waals force is the weakest force among the atoms in direct contact at the joint interface and it is the results of London interaction, Keesom interaction, or Debye interaction. Hydrogen bonds can be produced at the joint interface when hydrogen atoms on the polymer faying surface interact with the metal surface. Compared to chemical bonds, hydrogen bonds are also much weaker. Chemical bonding at the polymer-metal interface involves the formation of covalent bonds. The atomic/electronic level interaction between metal and polymer during joining has not been fully understood. This is because the interaction occurred at elevated temperatures at the buried joint interface. It is hard to in situ detect the buried chemical information during dissimilar material joining, and it is also extremely difficult to analyze the interfacial chemical information of the as-joined hybrid structures at the atomic or electronic level.Recent investigations ,96 showeThe importance of carbonyl groups for promoting metal-polymer bonding was further highlighted through a systematic analysis of available literature. The results were summarized in Various surface modification methods are under development in this field to enhance the bonding between metal and polymer. The surface modification of the polymer side is to add oxygen atoms or ions on polymer chains to promote the generation of chemical bonds between metal and polymer during TMJP. In contrast, the objective of pretreatment on a metal surface is often to generate micro holes or textures for generating micromechanical interlocking between the joining partners at the joint interface.TMJPs can complete rapidly while adhesive bonding needs a long curing time.No autoclave is necessary.No additional thermoset interlayer. This may solve numerous issues, including weight increase, cost, and storage.Thermoplastics are commonly tougher as compared to thermosets.Damaged thermoplastic joints could be restored by applying TMJP without the need to disassembling the structure.Although similarity exists between TMJP and adhesive bonding, these two processes are different in principle. TMJPs are developed to generate a bonding at the interface between a thermoplastic polymer and a metal under the activation of heating and compression pressure. TMJPs aim to form strong chemical bonds between the polymer matrix and metal in addition to developing micromechanical interlocking and physical interaction at the joint interface. In contrast, adhesive bonding between a metal and a polymer component is achieved by adding a viscous liquid polymer at the interface and developing the bonding through the evaporation of a solvent or through curing via heat, time, or pressure. Therefore, the adhesive bonding is formed between a metal and a thermoset. Compared to adhesive bonding, TMJPs has the following advantages:Although promising, TMJP needs to overcome many challenges to enable its high-volume engineering applications. Since the thermoplastic material needs to be heated to flow to achieve the bonding during TMJP, sufficient heat is necessary to molten the polymer at the joint interface. An overheating at the joint interface will cause a significant polymer degradation and therefore it needs to be avoided. Therefore, correct TMJP parameters are critical for producing high-quality dissimilar material joints. This dramatically complicates the TMJP process design and requires a deep understanding of the materials to be joined and their response at elevated temperatures.These concerns are evidenced by numerous experimental studies which showed that the processing temperature played a key role in affecting the strength of the joints made by TMJPs. Joining at a temperature lower than the target temperature results in inadequate energy to activate the joining. Overheating, on the other hand, can cause negative effects such as formation of voids, higher thermal shrinkage, and significant polymer thermal degradation. This may have a major effect on the joints’ mechanical and chemical properties. Besides, joining at higher temperatures may lead to energy waste and prolonged processing time. The flowability of the polymer to be jointed is mainly determined by the temperature at the joint interface. The temperature should be adequate to melt the polymer for the complete filling of any spaces between the metal and polymer see b,c. Howea limited dimension of the heating source on the metal component surface;the presence of clamping equipment that promotes localized heat exchanges andthe limited contact interface between the metal and the underlying polymer/composite.During the TMJP, the temperature distribution at the metal-composite interface is not uniform. Some setup of the joining processes may lead to uneven temperature distribution, as depicted in This leads to uneven joining conditions at the metal-composite interface ,121. To However, since numerous process parameters are involved, the optimization of these processes based on a full experimental approach would be costly and time-consuming. Additionally, this would lead to local maxima rather than the effective optimization of the process. Thus, a viable solution for process design is represented by the development of models that, once validated over a wide processing space, would provide accurate predictions of the processing conditions . The process design and optimization could be performed by validated simulation campaigns using these validated numerical  and MachWith the wide adoption of hybrid metal-composite structures, developing advanced joining methods suitable for hybrid structures has become a major challenge. Traditional joining methods, such as mechanical fastening and adhesive bonding, exhibit significant drawbacks. Fast mechanical joining, thermomechanical interlocking, and thermomechanical joining techniques have shown their capability to produce high-performance joints with reduced manufacturing time. The advantages provided by these processes could potentially make it possible to overcome almost all the limitations involved in traditional mechanical fastening and adhesive bonding techniques. These processes provide advantages of higher efficiency, easier standardization, easier automation, short joining time, and less environmental effect than adhesive bonding. Furthermore, the TMJPs do not need to destroy the external surface of the polymer-based joining partner, resulting in a relatively smooth surface. This feature is attractive for many engineering applications compared to mechanical fastening methods, which typically need to produce a through-hole on the parts to be joined. A common benefit of most of the new joining processes mentioned above is that they do not need an additional connecting part, which helps to reduce weight. A comparison among the three classes of advanced joining processes is summarized in Besides, many of the presented processes have been developed only recently, and consequently, they are still far from being optimized. This makes it harder for a direct comparison among the processes. When dealing with metal-composite laminates’ joining, advanced mechanical fastening processes may cause severe composite damage . This is more often observed in clinched connections; however, hole-clinching, and self-pierce riveting were less affected by this issue. The metal formability may also represent an issue when using mechanical fastening processes. However, recent studies showed that heat-assisted systems  , are helAdvanced joining processes share a common demand: the necessity to develop reliable models for the prediction of the process-induced defects as well as the mechanical behavior of the joints. So far, the process design has been mainly based on extensive and time-consuming experimental campaigns that generally lead to local optima and do not provide significant transferable knowledge, as the strength of the joints are related to the processing parameters using “black-box” models. On the other hand, the development of numerical models of the processes would enable a better understanding of the phenomena involved. At the same time, it could represent a precious tool for determining the influence of process parameters on the quality of the connections.For advanced mechanical fastening processes, the process-induced deformation determines the dimension of the undercut and the thickness of the necks. These have been extensively studied through numerical simulations when dealing with metal joining . HoweverThese models would enable the prediction of the dimension of macro-interlocks. Besides, the prediction of the temperature field could predict the onset of temperature-induced defects, which include a variation of crystallinity, development of porosities, and even thermal degradation of the polymer. However, the development of suitable and reliable numerical models is even more complex since the high amount of deformation, which is typically involved in these processes. Besides, it would also require a comprehensive characterization of the polymer (or composite) to determine the temperature-dependent mechanical behavior. This would enable to determine the material flow during the joining process more accurately.Thermomechanical joining processes would also benefit from the adoption of numerical models for a better understanding of the influence of the process conditions on the quality of the joints . The quaEven though a direct comparison is hard to be performed, the main pros and cons of each process are summarized in Thermomechanical interlocking behaves like an alternative to conventional riveting processes (except friction stir welding). The formation of thermomechanical interlocking is based on the mechanical interlock between the metal and the composite employing a stud/rivet. This is formed or joined by employing a thermomechanical process that enables to fill the cavities pre-drilled on the metallic sheet through an external stud (as in friction-based filling stacking), a deposited material, or the thermomechanical upsetting of the protrusion (as for injection clinching joining). All these processes, (except for friction stir welding) produce spot connections that are prone to introduce high-stress concentration.Thermomechanical joining processes are based on the bonding of the thermoplastic matrix Advanced mechanical fastening: the joining is achieved through mechanical interlocking, which is produced through plastic deformation  of the joining partners. These processes produce a significant alteration at both sides of the connection  Some processes do not require hole drilling as well as external connecting elements.Thermomechanical interlocking: the joining is mainly developed through macro-mechanical interlocking and high thermoplastic deformation of the joining partners. These joining processes damaged the appearance of at least one joining partner due to the high degree of thermoplastic deformation as well as the adoption of protruding elements in many cases. These joining processes can be used to produce either spot or continuous joints.Thermomechanical joining processes: the joining is achieved through the application of heating (different heating media are available) and compression pressure at the joint interface. Different joining mechanisms can be activated including chemical bonding, physical bonding, and micro-mechanical interlocking. These processes can guarantee better joint appearance since high degree of plastic deformation of the joining partners can be avoided during the joining. These processes can also be used to produce either continuous or spot joints.Hybrid metal-polymer and metal-composite structures represent the key solution in the automotive and aircraft industries to reduce product weight. Many efforts are being conducted to provide alternative solutions to established joining techniques. Emerging joining technologies are gaining great attention as they would provide many advantages over conventional mechanical fastening and adhesive bonding, including inherent simplicity, high joint strength, short joining time, no embedded materials, and high automation and standardization viability. However, a systematic view of this process was still missing. This review article would be beneficial for both process developments and for process selections for metal-polymer and metal-composite structures. Based on their characteristics, advanced joining processes have been classified into three main categories:After a description of the processes, and their peculiarities, an analysis of the main advantages, shared issues, as well as current limitations in process design and simulation were provided. Due to their complexity and relatively recent development, a shared need to almost all these processes is the development of a robust design and process simulation tools. This would greatly advance the understanding of the process, and promote process development and optimization. Finally, an outlook on current trends and future developments has been provided.


Although all countries have taken corresponding measures, the coronavirus disease 2019 (COVID-19) is still ravaging the world. To consolidate the existing anti-epidemic results and further strengthen the prevention and control measures against the new coronavirus, we are now actively pioneering a novel research idea of regulating the intestinal microbiota through tea polyphenols for reference. Although studies have long revealed the regulatory effect of tea polyphenols on the intestinal microbiota to various gastrointestinal inflammations, little is known about the prevention and intervention of COVID-19. This review summarizes the possible mechanism of the influence of tea polyphenols on COVID-19 mediated by the intestinal microbiota. In this review, the latest studies of tea polyphenols exhibiting their own antibacterial and anti-inflammatory activities and protective effects on the intestinal mucosal barrier are combed through and summarized. Among them, (−)-epigallocatechin-3-gallate (EGCG), one of the main monomers of catechins, may be activated as nuclear factor erythroid 2 p45-related factor 2 (Nrf2). The agent inhibits the expression of ACE2 (a cellular receptor for SARS-CoV-2) and TMPRSS2 to inhibit SARS-CoV-2 infection, inhibiting the life cycle of SARS-CoV-2. Thus, preliminary reasoning and judgments have been made about the possible mechanism of the effect of tea polyphenols on the COVID-19 control and prevention mediated by the microbiota. These results may be of great significance to the future exploration of specialized research in this field. COVID-19 remains an important public health issue of great concern at home and abroad, and it is still in the state of a global pandemic . The socThe most common clinical symptoms of patients with new coronary pneumonia are fever, dry cough, and dyspnea, but gastrointestinal symptoms cannot be ignored . The surIn this environment, this article aims to seek a new method for the prevention and intervention of COVID-19, that is, the utilization of tea polyphenols to regulate the intestinal microbiota ,8. The rMantlevirus, Coronaviridae, and Orthocoronavirinae subfamily. It is the largest known RNA virus of humans [Under such a circumstance where the novel crown epidemic has lasted for more than one year, people’s understanding of the genus of coronaviruses, including the novel crown virus, has reached a new level . Coronavf humans . This maf humans . It genef humans . Most cof humans . With thf humans .COVID-19 has brought great challenges and threats to human life . The cauOnce a virus infects a cell, it first penetrates the cell membrane of the host cell, and then un-shells, synthesizes and assembles macromolecules. Finally, the progeny virions are released outside the cells. Prior to this, the first step in initiating infection is the specific binding of the viral envelope protein to the viral receptor on the cell surface, allowing the virus to be adsorbed on the cell surface . AccordiCOVID-19 mainly affects the lungs, causing interstitial pneumonia and respiratory distress syndrome, and meanwhile, it also affects other organs ,35. MostThe gut microbiota influences the development and function of the immune system, which in turn regulates gut microbiota diversity. An effective vaccine should be able to elicit a protective immune response against a given viral preparation, while gut microbiota composition and diversity directly or indirectly modulate the immune response to the vaccine. A healthy gut microbiota is a key factor in maintaining gut homeostasis, which is critical for optimal vaccine performance. Nutrient imbalances and gut dysbiosis negatively impact host health, immunity, and gut barrier, and their synergistic interactions may affect vaccine efficacy.With the spread of the new coronavirus around the world, variant strains are also emerging. Among them, the Delta strain has quickly become the dominant strain due to its strong transmission, high viral load, and strong pathogenicity. It has brought new challenges to the global epidemic prevention and control. The current study found that the new coronavirus Delta strain has a higher viral load than Beta and other variant strains, and the lower cycle threshold and longer virus release period of this strain significantly enhanced its transmissibility when tested by polymerase chain reaction (PCR). The Delta strain showed higher replication efficiency in airway organoids and the human airway epithelial system, and the spike-affinity-increasing ACE2 receptor protein enhanced viral adhesion and made it easier to enter the body. The spike protein is the “key” that the virus uses to penetrate the door of human cells, and it is also the target of most vaccines. It is precisely because of these mutant characteristics of the Omicron variant that it increases the risk of secondary infection of the human body with the new coronavirus. Some experts believe that because AIDS will weaken the human body’s immunity, the variant of the Omicron virus is more likely to infect people with weakened immunity, which in turn can cause other diseases, which can be called the “AIDS” of the new coronavirus. Therefore, stricter protection and control strategies are needed, and new and effective prevention and control methods are more actively developed.The intestinal microbiota is an important part of the physiological functions of animal body digestion, metabolism, and vitamin synthesis . With thPlant polyphenols, also known as plant tannins, are secondary metabolites with polyphenolic hydroxyl structure . They arLactobacillus plantarum ZLP001 could strengthen the intestinal barrier by enhancing the defense function of intestinal epithelial cells and regulating the intestinal microbiota [Escherichia coli, Lactobacillus, and Enterococcus in the intestine [The metabolism and absorption of plant polyphenols are inseparable from the participation of intestinal microbiota, and their metabolites can exert more beneficial effects on the intestinal microbiota and the body . Wang Jicrobiota . The resntestine . Other rStudies have reported that rosemary extract has a significant inhibitory effect on inflammation . As an aEGCG, a catechin monomer, is the main component of green tea polyphenols. It is a polyphenol compound that has been studied extensively . It has EGCG can inhibit the initiation and assembly activation process of NLRP3 inflammasome;As an inhibitor of NLRP3 inflammasome activation, EGCG inhibits the LPS initiation phase and assembly activation pathway in macrophages, mitigates cell scorching, and inhibits NLRP3 inflammasome activation by blocking the spatial location of mitochondrial translocation and ASC speck formation during inflammasome activation;EGCG can improve the activation level of inflammasomes in mouse-derived macrophages induced by a high-fat diet.The 5NLRP3 inflammasome is the core of the inflammatory response. The main mechanisms of EGCG inhibiting inflammation are:In a clinical trial of catechin antiviral efficacy, it was found that, when taking catechin/theanine capsules for 5 months, the probability of clinical influenza infection was significantly lower than that of the placebo control group, and the time for patients to get rid of clinically confirmed infection was also shorter, significantly shorter than the control group, suggesting that taking catechin/theanine can effectively prevent influenza virus infection. Studies have confirmed that tea polyphenols can inhibit the secretion of hepatitis B virus surface antigen (HBs Ag) and hepatitis B virus e antigen (HBe Ag) and can significantly reduce the expression of HBV-DNA in the supernatant of the cell culture system, indicating that tea polyphenols have the potential to be developed into an anti-HBV drug. In clinical trials, EGCG showed a good effect in reducing HIV infection, and the polyphenols were well tolerated without adverse reactions.Moreover, plant polyphenols can fight tumors by influencing tumor cell signal transduction, inducing tumor cell differentiation and apoptosis, regulating related enzyme activities and tumor cell cycle, and inhibiting tumor cell proliferation. Through the PI3K-AKT signaling pathway, EGCG do COX-2wn-regulates cyclooxygenase-2 (COX-2), activates caspase-3 and caspase-9, induces the apoptosis of liver cancer cells, inhibits the activity of matrix metalloproteinase (MMP)-2 and MMP-9, promotes the apoptosis of B-lymphoma cells, downregulates the expression levels of PI3K and AKT/NF-κB, and makes the liver cancer cell SMMC7721 stagnate in the S phase .Research found that under the synergistic effect of quercetin, resveratrol, ethanol, and grape polyphenols, polyphenols can significantly inhibit nitric oxide synthase, which plays an important role in protecting human health . Others The dietary intervention of ingesting foods high in plant polyphenols in an appropriate amount and time can regulate the intestinal microbiota to a certain extent . For exaStudies on the “microbiota–gut–brain axis” show that intestinal microbes affect the body’s immune system and nervous system, thereby altering brain functions and interfering with the pathological development of the central nervous system (CNS). Environmental factors such as an unbalanced diet, abuse of antibiotics, and lifestyle changes can change the composition of the intestinal microbiota and even lead to their collapse, leading to increased intestinal permeability, blood–brain barrier permeability, and inflammation of the peripheral and central nervous system, and ultimately cause neurological diseases . TherefoEscherichia coli, thus keeping the intestinal micro-ecosystem healthy and stable.The various medical functions of tea have been widely reported, and some studies have explored the regulatory effects of tea on intestinal microbiota. Currently, the research directions mainly focus on two aspects; one is the inhibitory effect on the intestinal dysfunctional microbiota, and the other is the growth-promoting effect on beneficial microorganisms. Some studies have shown that black tea extracts and the intake of tightly pressed tea juice can increase trypsin activities, thus activating proteases in the small intestine and stomach to accelerate the decomposition and absorption of food . The maiHelicobacter pylori infection and promotes the regeneration of gastric epithelial cells [Tea polyphenols have a positive regulatory effect on the animal intestinal mucosal barrier . The intal cells . Lee et al cells . At presal cells . HoweverAt the same time, tea polyphenols have significant antibacterial and anti-inflammatory effects. The main mechanism of tea polyphenols exerting anti-inflammatory effects is to regulate the expression of inflammatory factors to achieve the purpose of inhibiting inflammation . In the In addition, as an activator of Nrf2, EGCG can inhibit the entry of SARS-CoV-2 into host cells and provide host cells with preparations against SARS-CoV-2 infection ,75. Nrf2Escherichia coli O157:H7. E. coli can cause diarrhea, damage mucosal epithelial cells, and invade mucosal epithelium to form local ulcers and inflammation when it is dysregulated [Bacillus dysenteriae and Escherichia coli, which have certain curative effects on dysentery. In addition, tea polyphenols in tea combine with proteins playing the role of tannin protein, thus relieving intestinal tension and calming intestinal peristalsis to achieve anti-inflammatory and anti-diarrheal effects. The addition of tea polyphenols can inhibit the growth of bacteria and prolong the shelf life of feed [Proteus vulgaris, Staphylococcus aureus, Lactobacillus, and intestinal pathogenic bacteria [Tea regulates intestinal microbiota via indirect and direct approaches: the indirect one is through the inhibition of various dysbiosis microorganisms in the intestinal tract; tea polyphenols and tea pigments and other active ingredients have a significant inhibitory effect on a variety of dysbiosis microorganisms, while the direct effect is that tea polyphenols and other active ingredients to protect and promote the growth of beneficial intestinal microbiota regulate the intestinal microecological balance. Studies have confirmed that the astringent component of tea, catechin, has a bactericidal effect on enterohemorrhagic egulated . Tea polegulated . Tea pol of feed . Meanwhi of feed . Studiesbacteria . Taking bacteria . At the bacteria .Gut microbiota can transform tea polyphenols into corresponding metabolites through different metabolic pathways, while these metabolites can exert a modulatory effect on intestinal microbiota by selective prebiotic and antibacterial activities . After oAccording to reports, the first patient with new coronary pneumonia in the United States experienced gastrointestinal symptoms such as diarrhea, nausea, and vomiting, and abdominal discomfort during the course of the disease . It has With in-depth research on the clinical symptoms, signs, and pathological changes of coronavirus disease, it has been gradually realized that the new coronavirus not only causes lung tissue damage but also involves multiple tissues and organs throughout the body, especially the gastrointestinal tract and immune system. It has been found that the imbalance of gut microbiota is associated with more and more diseases, from gastrointestinal diseases (such as inflammatory bowel disease) to metabolic disorders . In the The intestinal microecological balance is closely related to various diseases such as digestive system diseases and immune diseases. Tryptophan and its metabolite nicotinamide are key regulators of the intestinal microbiota and inflammation . The ACEIt is worth noting that there are many beneficial ways to regulate the imbalance of the intestinal microbiota, including fecal microbiota transplantation (FMT), probiotics application, and dietary intervention-using non-digestible dietary substrates such as prebiotics . In dietIn general, regulating the intestinal microbiota can still play a role in the prevention of COVID-19 to some extent. On the one hand, patients with COVID-19 have intestinal microbiota disorders and impaired barrier function and may have gastrointestinal symptoms, such as nausea, vomiting, and diarrhea, and gastrointestinal symptoms are the first manifestation of their symptoms . On the Evidence has indicated that intestinal microbes play a key role in the prevention and intervention of COVID-19. At the same time, the role of tea polyphenols in regulating intestinal microbiota has been confirmed by many studies, and we inferred that we can try to use tea polyphenols as a starting point to mediate the intestinal microbiota to prevent and intervene regarding COVID-19. At present, there is still room for development in the prevention and intervention of COVID-19 by regulating intestinal microbes. The intervention of tea polyphenols to improve the imbalance of intestinal microbes provides a new target for the prevention intervention of COVID-19. The regulation of intestinal flora by tea polyphenols can also create the advantage of intestinal homeostasis for optimal vaccine performance. However, compared with vaccines, polyphenol interventions are not targeted and only universal. It is hoped that through the study of specific dietary intervention mechanisms, the occurrence of COVID-19 virus infections can be reduced or prevented.


Heavy metal (HM) toxicity has become a global concern in recent years and is imposing a severe threat to the environment and human health. In the case of plants, a higher concentration of HMs, above a threshold, adversely affects cellular metabolism because of the generation of reactive oxygen species (ROS) which target the key biological molecules. Moreover, some of the HMs such as mercury and arsenic, among others, can directly alter the protein/enzyme activities by targeting their –SH group to further impede the cellular metabolism. Particularly, inhibition of photosynthesis has been reported under HM toxicity because HMs trigger the degradation of chlorophyll molecules by enhancing the chlorophyllase activity and by replacing the central Mg ion in the porphyrin ring which affects overall plant growth and yield. Consequently, plants utilize various strategies to mitigate the negative impact of HM toxicity by limiting the uptake of these HMs and their sequestration into the vacuoles with the help of various molecules including proteins such as phytochelatins, metallothionein, compatible solutes, and secondary metabolites. In this comprehensive review, we provided insights towards a wider aspect of HM toxicity, ranging from their negative impact on plant growth to the mechanisms employed by the plants to alleviate the HM toxicity and presented the molecular mechanism of HMs toxicity and sequestration in plants. Feeding an exponentially growing population in the era of global climate change is a serious challenge. Among different environmental factors, abiotic stressors are the major factors affecting crop yield and the livelihood of mankind . In partIncreased anthropogenic activities such as mining, modern agriculture practicing, fertilizer application, extensive use of groundwater for irrigation, sewage disposal, and industrialization have disturbed the distribution of these HMs, leading to their accumulation at specific sites ,5. AccumPlants growing in HM-contaminated soils show visible symptoms like stunted growth, chlorosis, root browning, and sometimes even death ,11. MorePlants growing in HM contaminated soils show visible symptoms as the uptake and accumulation of HMs in plant tissues alter the morphology and overall health of the plants .Raphanus sativus  r r249] rey of HMs . Furthery of HMs  and maizy of HMs , confirmOryza sativa, the application of epibrassinolide (EBL) helps to plant combat Cr-induced oxidative stress following the upregulation of the antioxidant mechanism at the molecular level. Nevertheless, GR activity was found to be elevated when Cr-treated seedlings were exposed to EBL, resulting in the improvement of the growth of seedlings [2O2 via elevating low molecular weight antioxidant ascorbic acid levels in Cr-treated seedlings [2+ chelation, reversed Cu-toxicity-induced root growth inhibition and the expression of genes related to the ROS-detoxification and cell wall modifications [Phytohormones play a decisive role in stress tolerance of plants grown in metal-polluted via activation of a signaling cascade and antioxidant defense mechanism . For inseedlings . From theedlings ,257,258 eedlings ,261,262.eedlings . Similarications . Moreoveications . Furtherications .HM toxicity is emerging as one of the most serious concerns across the globe. The toxic effects of HMs on plants depend on a variety of factors including type and concentration of HMs and plant species, plant growth stage, and exposure time. The negative effects of the HMs on the growth of the plants are the combined outcome of the changes in their anatomy and physiology. Tolerant plants retaliate to HM toxicity by activating a complex signaling network which often culminates into activation of a defense response that includes accumulation of (1) antioxidants for detoxification of excess ROS, (2) secondary metabolites for sequestration of HMs to vacuoles, and (3) compatible solutes for the osmoregulation along with regulation of metal transporters, among others. The information derived from the HM accumulator/hyperaccumulator plants can be used in the future to improve the ability of non-food plants to accumulate higher amounts of HMs in order to be used to mitigate the HM contamination in environmental matrices. Moreover, the information derived from the HM tolerant plants can be used to induce the mechanisms that result in reduced uptake and accumulation of HMs in food plants and thus their negative consequences for human health.