Online mental health service (OMHS) platforms have contributed significantly to the public’s mental health during the COVID-19 pandemic in China. However, it remains unclear why the public used OMHS platforms for psychological help-seeking (PHS) behavior and how PHS behavior varied across different stages of the COVID-19 pandemic. Based on the ecological PHS behavior data from two OMHS platforms, we extracted population, psychological problems, and influential factors of PHS behavior by text mining and time series analysis methods. Seven top-ranked psychological problems  and seven influential factors  were found. The online PHS behaviors related to different psychological problems and influential factors remained a growing trend before 2020 and have been increasing significantly due to the COVID-19 outbreak. Four main stages were found during the pandemic according to the changes in the online PHS population: sharp growth, significant decline, slight rebound, and slow decline. This study identified large-scale, spontaneous PHS behaviors among the online public during the COVID-19 pandemic and the various psychological problems and influential factors that varied across different stages of the pandemic, suggesting that the government and health practitioners should adopt effective policies and strategies to prevent and intervene in mental health problems for the online public. Coronavirus disease 2019 (COVID-19) has caused more than 195 million cases and 4.18 million deaths worldwide to date ,4.Facing the mental illnesses and psychological problems of the general public, online mental health services (OMHS) have become an alternative to offline services in the special context of the COVID-19 pandemic. OMHS are conducive to saving time. More importantly, they have the advantage of allowing the patient and the practitioner to avoid face-to-face contact, which is critical to successfully curbing the spread of the coronavirus . MoreoveThere are two kinds of methods that can be used to investigate the impact of COVID-19 on the public’s mental health and that have been used in existing studies. The first method is the questionnaire survey. All of the studies and systematic reviews and meta-analyses mentioned above used self-report questionnaires ,6. DespiThe second approach is text mining technology. The majority of previous studies crawled posts from social media platforms, e.g., Tweets and Weibo, then utilized sentiment analysis or topic modeling to explore the emotions and topics that appeared in the posts ,9,10,11.Online platforms specific to PHS have contributed significantly to the COVID-19 pandemic in China and are more suitable than social media platforms for the exploration of the temporal dynamics of mental illnesses and psychological problems during the COVID-19 pandemic. These platforms can be roughly divided into two types, both of which could be complementary to each other: (1) OMHS platforms that were active before the emergence of the COVID-19. Researchers can compare PHS behavior, psychological symptoms, etc., before, during, and after the COVID-19 pandemic by using the data from these platforms. (2) OMHS platforms that were established to specifically deal with the pandemic, e.g., the MOE-CCNU Mental Health Service Platform . On thesThe above studies suggest that there are few studies on the psychological and behavioral patterns of online psychological help seekers using OMHS before and during the pandemic. Therefore, one research question being asked during the present research is to understand the reasons why online psychological help-seekers conduct PHS behavior and its patterns before and during the COVID-19 pandemic. Another research question that will be considered in the present research is the examination of the extent to which the temporal patterns between the COVID-19 pandemic and the behavior of online psychological help-seekers concerning psychological problems interact with each other. Specifically, previous studies focused on the psychological impact of the public in the early stages of the COVID-19 pandemic ,14, whilhttps://www.xinli001.com/, accessed on 30 July 2021), on which nearly 20 million have asked for psychological help. In the Q&A section of the platform, psychological help-seekers are able to post about their psychological distress and problems and are able to seek psychological services and support from the platform’s psychological counselors anonymously. The post may include several optional components such as the title of the post, age, gender of the help-seeker, course of the psychological problem, inner feelings, duration of the problem, and the label . We utilized “Bazhuayu” , a web scraping software, to crawl 54,797 psychological help-seeking questions, of which 3263 posts referred to the COVID-19 pandemic. It was possible for each post to contain the following three components: the title of the description, the description of the psychological problem, and the asking time.The first data source is a famous Chinese online counseling platform “One Psychology”  to construct the latent semantic model for large scale PHS texts in order to obtain domain lexicons for psychological problems and related influential factors. Specifically, the cosine similarity between the words in the model vocabulary and the predefined lexicon was calculated based on the model. We recruited two graduate students to set the cosine similarity thresholds to remove words in the PHS texts that were irrelevant to the predefined vocabulary, to check the retained words manually, and then to build the domain lexicons of psychological problems, psychological problems, and influential factors.Secondly, we constructed the domain lexicons for the OMHS communities. Using the Jieba tool  and the Baidu stop-word list, the text from mental health questions was cut, and stop words were deleted. According to the neural embedding-based latent semantic analysis method, the texts were used as the training corpus. To implement this method, we used the word embedding method from the Word2vec in Gensim software . There was a positive relationship between the monthly trends of PHS behavior in the OMHS community and those on the MOE-CCNU Mental Health Service Platform .To further explore and validate the correlation between the COVID-19 pandemic and the temporal dynamics of the PHS population, we used the time series analysis method to recognize the temporal patterns of the number of PHS posts in the OMHS community and platform during the COVID-19 pandemic see . Concernp < 0.001), while the number of posts was negatively correlated with the number of new confirmed cases . During the significant decline period, the number of posts was positively correlated with new confirmed cases , while the number of posts was negatively correlated with the cumulative number of confirmed cases  and the cumulative number of deaths . During the slight rebound period and the slow decline period, there was no significant correlation between the number of COVID-19 cases and the number of posts. The results show that there were stronger correlations between cumulative data  and the number of posts compared to the correlations between new increased data  and the number of posts, especially during the early stages of the COVID-19 outbreak.To validate the close relationship between the pandemic and the temporal dynamics of the PHS population, we further conducted correlation analysis of the temporal patterns between the COVID-19 cases and online PHS posts across different stages. To investigate the temporal dynamics of the behavior of the PHS population during the COVID-19 pandemic, we analyzed the monthly patterns of the number of online PHS posts during the pandemic see . In thisAs shown in As shown in The present study investigated the population, psychological problems, influential factors, and the temporal patterns of online psychological help-seekers in the context of the COVID-19 pandemic. One of the two major findings concerns what and why online psychological help-seekers conducted PHS behaviors before and during the COVID-19 pandemic. Previous studies found that negative emotions and social interaction problems due to the lockdown were the main issues during the COVID-19 pandemic , e.g., aConsidering the temporal patterns of online psychological help-seeking behavior during the COVID-19 pandemic, it is worthy to mention the following findings: First of all, the present study found that online PHS behavior related to different psychological problems and influential factors continued in an early growth trend and increased with the COVID-19 outbreak. The population of people experiencing psychological problems related to PHS behavior due to negative emotions  was the biggest while severe mental disorders  were the fastest-growing problem. This finding proves that the external environment changed greatly during the COVID-19 pandemic, and the increase of online PHS behavior was a common phenomenon.https://www.jiandanxinli.com/public/2020/, accessed on 29 September 2021) reported that visitors in their early adulthood (21–35 years old) accounted for 77.57% of their users. Compared to developmental adaptive problems, the relatively serious psychological problems related to PHS behavior increased faster, reaching more than 4 times those of the previous level, which indicates that some severe mental disorders were triggered by the COVID-19 pandemic [Specifically, 1. during the COVID-19 pandemic in 2020, the number of online PHS increased by 179% compared to in 2019, and the GAGR was 3.315 times that during 2016 to 2019. Explicit danger such COVID-19 paired with uncertainty is known to be associated with increased negative emotions and anxiety . A survepandemic . One of pandemic ,37. Our Secondly, the present study found that the dynamics of the online PHS population using OMHS platforms can be divided into four stages by considering the temporal patterns of online PHS during the pandemic: sharp growth, significant decline, slight rebound, and slow decline. 1. According to the five stages of grief, when an individual experiences some inevitable trauma, a sudden and unfortunate blow, or the loss of a loved one, the individual likely expresses denial and anger first, then depression, and finally acceptance . From thThirdly, the online PHS population was positively associated with the increased confirmed cases of COVID-19 at the early stages of the pandemic, while it was not significant in the post-pandemic era. These results indicated that the PHS behavior of online psychological help-seekers may have experienced different stages during the COVID-19 pandemic. The present study found that the temporal patterns of different psychological problems and influential factors related to online PHS behavior are different during different stages of the COVID-19 pandemic. Although the PHS behavior mostly reached its peak in the early stage of the pandemic, their temporal patterns are not the same. The number of negative emotions related to PHS behavior peaked in the sharp growth period, to the love, psychotherapy, work, interpersonal relationship, and family, while suicidal intentions and psychotherapy related to online PHS behavior peaked in the significant decline period. When the COVID-19 pandemic was controlled, the number of help-seekers gradually decreased and finally remained stable. During the COVID-19 outbreak, researchers indicated that the mere exposure to information about COVID-19 was associated with higher anxiety levels , and symThe present study has the following strengths: First of all, this study has extensively studied the population, psychological problems, and influential factors of the PHS behavior of the online public related to the COVID-19 pandemic. As far as we know, this is the first study that has focused on the associations between the COVID-19 pandemic and online psychological help-seeker behavior. Since OMHS platforms have become the main service channel for online psychological help-seekers under the current pandemic, our research has developed previous research results on psychological help-seeking behavior ,14, helpSecondly, compared to traditional research, the data in this study have the advantages of having good usability and strong authenticity. As for the data usability, this study uses the longitudinal behavior data on online psychological help-seeking using OMHS platforms over five years to support the acquisition of a high-precision timeline for the amount of online psychological help-seeking behavior, psychological problems, and influential factors. Moreover, these ecological data have advantages over traditional questionnaire methods in terms of data scale, acquisition cost, and ease of access. As for the data authenticity, this study ensures the authenticity of the large-scale online PHS data related to the COVID-19 pandemic. On the one hand, previous studies pointed out that questionnaires may cause potential problems such as memory and social desirability bias . On the Thirdly, the domain topic modeling method used in our study has advantages over the classical topic modeling method used to characterize topics in a fine-grained granularity. This study utilized the text topic mining method based on neural embedding, which is able to extract the topics of psychological problems and influential factors; while the traditional topic model method cannot classify and extract heterogeneous topics.Fourthly, this study deepens our understanding of online PHS behavior in the middle and late stages of the COVID-19 pandemic. The present study considered the COVID-19 pandemic as several development stages, allowing us to provide a full picture of the population, psychological problems, and influential factors of online PHS behavior. This could remedy the shortcomings of most previous studies, which examined mental illness and help-seeking behavior only in the early stages of the COVID-19 outbreak ,34,37,41Last but not least, OMHSs have become one of the most important channels that the public uses for psychological help. The present study shows that investigating the psychological problems and influential factors of the online public is an efficient alternative to offline investigation. Therefore, our study validates that OMHSs can not only provide extensive psychological support for the public but that they have also become a window for researchers and organizations to continuously observe, track, and intervene in the mental health status of the public.The present study is not without limitations. Firstly, culture may affect the impact of the COVID-19 pandemic on emotional expression and issues of concern that are shared by the online public. The present study only investigated Chinese PHS behavior during the COVID-19 pandemic and lacks support for data from different countries and cultures. Hence, these findings should be cautiously interpreted in terms of their generalizability. Future studies should aim to replicate the present findings by comprising different countries and cultures.Secondly, although the present study aims to investigate the relationship between the COVID-19 pandemic and the online PHS behavior of the public as a whole, there is still a lack of understanding of differences between different ages, genders, and other important variables. As far as we know, psychological help-seekers on all OMHS platforms are anonymous. When they post PHS information, demographic information such as gender, age, and occupation are not required. Although most help seekers do not expose demographic information on the platform explicitly, we can use machine learning technology to predict this information in subsequent studies.In general, there are several important implications to understanding PHS behavior during the COVID-19 pandemic in China. One implication is that the changes to a population, psychological problems, and influential factors of online PHS behavior can help psychological counselors and psychotherapists grasp the transformation of help-seekers and develop strategies to service these help-seekers in the context of a major public health emergency. Another implication is that online platforms are important tools for individuals who have mental illness and psychological problems to seek psychological help during the COVID-19 pandemic. Therefore, governments and health systems should increase their attention and provide adequate financial and policy support for the online psychological services during this period.Specifically, as for online psychological service agencies, they should first focus on the problems of online psychological help-seekers such as depression and anxiety, suffering, social phobia, lack of interest, suicidal tendencies, worry (afraid), and anger, and then cultivate an online psychological assistance force related to these problems and take on targeted interventions for online psychological help-seekers in different stages of the COVID-19 pandemic. That is, in the sharp growth period of the COVID-19 out-break, interventions should focus on stress response and emotional problems, while in the significant decline period, psychotherapy and interventions for severe psychological problems should be added.As for the government and institutions, they can use online media to raise public awareness for the prevention of psychological problems and guide the public to consciously use online psychological assistance services. In response to influential factors such as love, marriage, psychotherapy, work, interpersonal relationships, personal characteristics, and family, the government should promote the resumption of work and support the opening of psychotherapy institutions to support people in crisis. Meanwhile, the government should help people with psychological distress to repair any interpersonal, marital, and family relationships that were destroyed during the COVID-19 pandemic through schools, universities, and community organizations. Moreover, the government and online psychological services should additionally increase psychological assistance resources related to suicidal tendencies and depression and should develop contingency plans to fully meet the demands of the mass increase of people in crisis during the COVID-19 pandemic. Meanwhile, the government should take administrative measures to support the resumption of work and production, safeguard people’s work, and rebuild their interpersonal interactions. In addition, appropriate publicity strategies should be adopted during the COVID-19 outbreak to avoid potential adverse effects on the public’s mental health by not over-publicizing the cumulative number of cases.Overall, the present study investigated online PHS behavior before and during the COVID-19 pandemic in China. Specifically, the present study identified the population, psychological problems, and influential factors related to the temporal patterns of online PHS behavior in different stages of the COVID-19 pandemic and examined the associations between PHS behavior and the increasing number of confirmed COVID-19 cases. We found that PHS behavior increased sharply after the declaration of the COVID-19 outbreak. Negative emotions may be the main issue for help-seekers. At different stages of the COVID-19 pandemic, the types of psychological problems and influential factors varied. Psychological counselors and psychotherapists could use the data presented here to grasp the transformation of such changes to provide targeted and higher quality services in different stages of the COVID-19 pandemic. Governments and public health systems should pay more attention to online psychological assistance in the context of the COVID-19 pandemic.


The cranial nerves, which represent extensions of the functional structures of the brain, traverse the head and neck. They are connected to various cranial structures and are associated with several diseases. An in-depth understanding of their complex anatomy and normal imaging appearance allows the examiner to identify and characterize abnormalities with greater precision. One important tool for evaluating the cranial nerves is contrast-enhanced magnetic resonance imaging, especially three-dimensional steady-state free precession sequences, which provide high soft-tissue and spatial resolution, despite the slenderness of the nerves. In most cases, imaging findings are nonspecific. Therefore, to narrow the differential diagnosis, it is necessary to take a full patient anamnesis, perform a focused physical examination and order laboratory tests. In this pictorial essay we review, illustrate and discuss, from a pathophysiological perspective, congenital, traumatic, and vascular diseases of the cranial nerves. The cranial nerves originate from the encephalon as twelve pairs, representing extensions of the functional structures of the brain and traversing the head and neck. They are numbered from I to XII in the craniocaudal direction. Cranial nerve I (the olfactory nerve) and cranial nerve II (the optic nerve) arise respectively from the cerebral hemispheres and the diencephalon, whereas cranial nerves III to XII all emerge from the brainstem. The cranial nerves pass through cranial bone foramina, exhibiting complex anatomy on their way, are enveloped by the leptomeninges, and are myelinated by Schwann cells, except for cranial nerves I and II, which are encased in olfactory ensheathing cells and oligodendrocytes, respectively.Although radiological findings are nonspecific in many cranial nerve pathologies, magnetic resonance imaging (MRI) with heavily T2-weighted three-dimensional (3D) steady-state free precession (SSFP) sequences, which have high spatial resolution and provide good contrast between cerebrospinal fluid and the cisternal segments of the cranial nerves, and contrast-enhanced T1-weighted sequences, facilitates the depiction of abnormalities. Computed tomography (CT) scans with bone window settings are also quite useful for detecting cranial nerve pathologies, such as: agenesis/hypoplasia of the facial nerve canal and the geniculate ganglion fossa; fractures that extend through the skull base foramina in the context of trauma; enlargement or erosion of the skull base foramina caused by slow- or fast-growing cranial nerve tumors, respectively; and cranial nerve compression secondary to conditions that result in bone expansion and subsequent foraminal narrowing, including fibrous dysplasia.Complete patient anamnesis, a focused physical examination and laboratory tests are crucial for making the clinical-radiological correlation, allowing radiologists to narrow the differential diagnosis. In this pictorial review, we briefly assess the normal anatomy of the cranial nerves, as well as illustrate and discuss some of the congenital, traumatic, and vascular diseases that affect them.I - Olfactory nerve (sensory function): passes below each frontal lobe via the olfactory sulci and transmits impulses from the olfactory epithelium to the brain.II - Optic nerve (sensory function): emerges from each globe as a thick fiber bundle that passes through the optic canal, and merges with the other optic nerve to form the optic chiasm.III - Oculomotor nerve (motor and parasympathetic functions): arises from the interpeduncular fossa of the midbrain; passes along the lateral wall of the cavernous sinus and through the superior orbital fissure; innervates the levator palpebrae superioris and most extraocular muscles ; and has parasympathetic functions, controlling the ciliary and sphincter pupillae muscles.IV - Trochlear nerve (motor function): arises from the dorsal surface of the midbrain just below the inferior colliculus, surrounds the contralateral surface of the midbrain, passes along the lateral wall of the cavernous sinus and through the superior orbital fissure, and innervates the superior oblique muscles.V - Trigeminal nerve (motor and sensory functions): arises from the anterolateral surface of the pons, passes below the tentorium cerebelli, arriving at Meckel’s cave, where it splits into the ophthalmic, maxillary, and mandibular nerves, which pass through the superior orbital fissure, foramen rotundum, and foramen ovale, respectively, to exit the skull; enables mastication, carries proprioceptive and nociceptive afferents to the face and mouth, and innervates the tensor tympani, tensor veli palatini, and mylohyoid muscles, as well as the anterior belly of the digastric muscle.VI - Abducens nerve (motor function): arises from the pontomedullary junction, near the midline; crosses the petrous apex within Dorello’s canal; ascends to pass through the cavernous sinus near the internal carotid arteries; exits through the superior orbital fissure and innervates the lateral rectus muscle.VII - Facial nerve : arises from the pons at the cerebellopontine angle; enters the internal auditory canals from an anterosuperior direction; passes through the temporal bones; exits through the stylomastoid foramen; controls facial expressions and taste sensation from the anterior two-thirds of the tongue and oral cavity; and regulates the function of the salivary glands (except the parotid gland), as well as that of the lacrimal, nasal, and palatine glands.VIII - Vestibulocochlear nerve (sensory function): arise from the pons at the cerebellopontine angle; enters the internal auditory canals together with the facial nerve; splits into the cochlear nerve, in an anterior inferior direction, and the superior and inferior vestibular nerves, in a posterior direction; and carries afferents related to hearing and balance.IX - Glossopharyngeal nerve : arises from the medulla oblongata in the postolivary sulcus via a series of vertical rootlets lateral to the olivary body, above and along with those of the tenth and eleventh cranial nerves; carries sensory afferents to the oropharynx, posterior third of the tongue, carotid sinus, carotid body, and tympanic membrane; supplies motor innervation to the stylopharyngeus muscle; and provides parasympathetic innervation to the parotid gland.X - Vagus nerve : the longest of the cranial nerves, arising from the medulla oblongata via rootlets in the postolivary sulcus; exiting the posterior cranial fossa through the jugular foramen; descending in the carotid sheath posterior to the internal jugular vein and internal/common carotid arteries; and dividing into its pharyngeal, thoracic, and abdominal branches.XI - Spinal accessory nerve (motor function): arises from caudal region of the nucleus ambiguus via rootlets in the postolivary sulcus, below and along with those of the ninth and tenth cranial nerves, joining the latter, from which it is indistinguishable.XII - Hypoglossal nerve (motor function): arises from the medulla via a series of vertical rootlets in the preolivary sulcus; enters the hypoglossal canal of the occipital bone; descends to the neck near the carotid sheath; passes lateral to the hyoglossus muscle to enter the tongue from below; and innervates all intrinsic and extrinsic muscles of the tongue, except the palatoglossus muscle, which is innervated by the tenth cranial nerve.. As shown in .The septo-optic dysplasia spectrum comprises a heterogeneous group of rare disorders and malformations of the midline, including optic nerve hypoplasia and hypothalamic-pituitary dysfunction. Most patients have low visual acuity and nystagmus. Abnormalities include corpus callosum dysgenesis, absent septum pellucidum, cerebellar hypoplasia, and fornix aplasia . Most ca.Absence or hypoplasia of the abducens nerve, as an isolated finding, is rare. There have been few reported cases of disturbances other than absence of abduction of the eye, which usually occurs in individuals with Duane or Moebius syndrome, as depicted in Duane syndrome is a congenital condition, characterized by non-progressive, horizontal eye movement. It is caused by failure of the abducens nucleus and nerve to fully innervate the lateral rectus muscle. Individuals with Moebius syndrome can have craniofacial, cardiovascular and musculoskeletal defects, with or without other cranial nerve palsies, as well as abnormalities of the chest wall, spine, limbs, and soft tissues. Typical features of the syndrome include the following: facial diplegia of the upper and lower facial muscles; impaired abduction of both eyes; craniofacial and limb malformations; hypoglossia; and long tract signs. Findings on CT and MRI ; optic nerve hypoplasia; other eye movement disorders ; trigeminal neuropathies with oculoauriculovertebral dysplasia and hemifacial microsomia (Goldenhar syndrome); syndromes associated with inner ear malformations and vestibulocochlear nerve agenesis or hypoplasia ; and less common combinations of syndromes .There are many other congenital conditions involving the cranial nerves. Possible mechanisms of cranial nerve trauma include stretching, impingement, and transection. Such trauma may be iatrogenic and sometimes requires surgical repair. A combination of CT and MRI is usually required for a thorough assessment, and neuropathies resulting from recent trauma can show enhancement on contrast-enhanced T1-weighted images. Of all the cranial nerves, the third is the most commonly injured, such injury typically being due to contusion (at the petroclinoid ligament), tearing, or complete avulsion (at the interpeduncular fossa).Traumatic lesions of the cranial nerves are variable, depending on the length, course, and vascular supply of the nerve in question, as well its relationships with the surrounding bony and dural structures, as illustrated in Traumatic olfactory dysfunction occurs in 5% of cases of head trauma. During blunt trauma, movement of the brain relative to the cribriform plate causes shearing of olfactory nerve fibers.Isolated lesions of the abducens nerve due to trauma are rare and are usually associated with cranial or cervical fracture. The main sites are dural entry points at the petrous apex. As depicted in .Facial nerve palsy is a common complication of temporal bone fractures . The sit.Vascular diseases can result in injury to the cranial nerves. Such injury can be caused by neurovascular compression, ischemic events, and hemorrhagic mechanisms, as well as by vascular malformations or neoplasms. The size of an aneurysm and its relationship to adjacent structures can be determined by CT angiography and magnetic resonance angiography  cranial nerves are close to the extracranial segment of the internal carotid artery in the upper cervical parapharyngeal space. Therefore, compression by the expanded artery may cause cranial nerve palsies. Involvement of the upper cranial nerves may occur when the dissection extends through the petrous and cavernous segments. Interruption of blood supply is another cause of cranial nerve palsy. The ninth and twelfth cranial nerves are supplied by the ascending pharyngeal artery, whereas the fifth and the seventh cranial nerves are supplied by the middle meningeal artery, branches of the external carotid artery.A tear in the intima of the carotid artery (carotid artery dissection) allows blood to flow into the subintimal and medial layers of the artery wall. In most cases, carotid artery dissection occurs spontaneously, although it may also occur after trauma or secondary to arteriopathy. In 30% of cases, there is pseudoaneurysmal dilatation , usually. Other classifications consider the etiology (traumatic or spontaneous) and hemodynamics (high or low flow) of the fistula. As can be seen in Abnormal communication between the carotid artery and the cavernous sinus (carotid-cavernous fistula) may be classified anatomically as direct (type A); as a dural shunt (indirect) between the meningeal branches of the intracavernous internal carotid artery and the cavernous sinus (type B); as a dural shunt between the meningeal branches of the external carotid artery and the cavernous sinus (type C); or as a dural shunt between the meningeal branches of the intracavernous branches of the internal carotid artery, meningeal branches of the external carotid artery and the cavernous sinus (type D), which manifests as unilateral dysfunction of the ninth through twelfth cranial nerves, and Villaret’s syndrome, which is distinguished from Collet-Sicard syndrome by the fact that it is accompanied by Horner’s syndrome (Cerebral venous thrombosis may present a wide spectrum of signs and symptoms. Although uncommon, such thrombosis is associated with various types of cranial nerve palsy and should therefore be considered in their differential diagnosis, especially in patients with hypercoagulable conditions. Several cranial nerve syndromes have been attributed to extension of the clot into contiguous venous tributaries, with subsequent paralysis of the adjacent nerves. The involvement of the jugular foramen may cause syndromes of lower cranial nerves, characterized by several eponyms, such as Collet-Sicard syndromesyndrome .The cranial nerves are connected to several different structures of the head and neck, and they can be affected by a variety of pathologies. Despite the fact that MRI provides excellent soft-tissue resolution and represents a very important tool to evaluate these structures, the imaging findings are nonspecific in most cases. Knowledge of anatomy and correlating imaging findings with clinical data are essential to reaching an accurate diagnosis.


Proteinuria is common in the setting of HIV infection, and may reflect comorbid kidney disease, treatment-related nephrotoxicity, and HIV-related glomerular diseases. The mechanisms of podocyte and tubulointerstial injury in HIV-associated nephropathy (HIVAN) have been the subject of intense investigation over the past four decades. The pathologic contributions of viral gene expression, dysregulated innate immune signaling, and ancestry-driven genetic risk modifiers have been explored in sophisticated cellular and whole animal models of disease. These studies provide evidence that injury-induced podocyte dedifferentiation, hyperplasia, cytoskeletal dysregulation, and apoptosis may cause the loss of glomerular filtration barrier integrity and slit diaphragm performance that facilitates proteinuria and tuft collapse in HIVAN. Although the incidence of HIVAN has declined with the introduction of antiretroviral therapy, the collapsing FSGS lesion has been observed in the context of other viral infections and chronic autoimmune disorders, and with the use of interferon-based therapies in genetically susceptible populations. This highlights the fact that the lesion is not specific to HIVAN and that the role of the immune system in aggravating podocyte injury warrants further exploration. This review will summarize our progress in characterizing the molecular mechanisms of podocyte dysfunction in HIVAN and other forms of HIV-associated kidney disease. In the four decades since the first cases of AIDS were reported in 1981, an estimated 77.5 million people have been infected with HIV and more than 34 million people have died from complications of HIV infection , 3. HIIVThe epidemiology of HIVAN suggested that both viral and host factors play a central role in pathogenesis. The development of HIVAN in HIV-transgenic mouse models has allowed for extensive investigation into the mechanisms of glomerular injury, proteinuria, and kidney failure in HIVAN, which will be the primary focus of this review.The emergence of HIVAN in the setting of AIDS and the decline in incidence of ESKD with the introduction of ART is consistent with a direct role for HIV in the pathogenesis of HIVAN. Early reports demonstrated the presence of HIV nucleic acids in renal epithelial cells –7; howevPodocytes are an essential cellular component of the tripartite glomerular filtration barrier . PodocytThe collapsing FSGS lesion of HIVAN is characterized by podocyte dedifferentiation and hyperplasia, loss of podocyte maturity markers, foot process effacement and podocyte detachment, podocyte apoptosis, and heavy proteinuria –33. The Nef is one of four accesory proteins  expressed by HIV . DespiteThe HIV accessory protein Viral Protein R (Vpr) has also been identified as a significant contributor to kidney injury in HIVAN. Like Nef, podocyte-restricted expression of Vpr in murine models established on the susceptible FVB/N background was sufficient to produce glomerular collapse and tubulointerstitial disease , 56, 57.The HIV regulatory protein Tat may also contribute to podocyte dysfunction in HIVAN. Tat is essential for HIV gene transactivation . In primAPOL1 gene provided evidence of a genetic contribution to the racial disparity  and other circulating mediators of innate immunity signaling appear to drive cription , 83. In r injury . This fiof HIVAN . Notablyof HIVAN –88. SmalCOVID-19 , 2.HIV infection, by a variety of intracellular and systemic influences on podocyte physiology, perturbs cellular fate commitment, gene expression, and viability to promote development of the collapsing FSGS lesion of HIVAN. A nuanced understanding of the processes that drive podocyte injury in HIVAN may uncover novel therapeutic targets for treatment of other glomerular diseases. Prompted by epidemiologic studies demonstrating accelerated progression of kidney disease in the setting of HIV and diabetes , MallipaA lack of animal models has slowed progress toward elucidating the pathogenesis of immune complex glomerular disease in PLWH. This has been compounded by the diverse spectrum of glomerular lesions that occur in this setting and that have been considered together in most clinical studies. Small but rigorous human studies have suggested a role for immune complexes directed against HIV antigens in the pathogenesis of immune complex kidney disease . BecauseKidney injury due to the antiretroviral agent tenofovir disoproxil fumarate (TDF) may also present with proteinuria, although this is typically low molecular weight proteinuria rather than albuminuria. Tenofovir is a nucleotide analog that is chemically related to the older antiviral agents cidofovir and adefovir, both of which are known to exhibit dose-limiting proximal tubular toxicity. The first approved tenofovir prodrug, TDF, has been associated with proximal tubulopathy and non-albumin proteinuria. Although the mechanism of proximal tubular cell injury has not been fully elucidated, it is thought to involve mitochondrial dysfunction as a result of the weak inhibition of mitochondrial DNA polymerase gamma , 96. TenDespite some risk of nephrotoxicity with tenofovir and other antiretroviral agents, the use of ART for treatment and prevention of HIV infection is currently the most effective way to mitigate the myriad pathogenic effects of HIV on the kidneys. While the incidence of advanced kidney disease due to HIVAN has decreased with the use of ART, HIVAN remains a valuable model for the study of podocyte injury and APOL1-induced glomerular disease.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.GH was supported by the NIH/NIDDK (K08DK111940), the American Society of Nephrology and the Harold Amos Medical Faculty Development Program, the Northwestern University George M. O'Brien Kidney Research Award, the Doris Duke Charitable Foundation, and the Duke Claude D. Pepper Older Americans Independence Center. CW was supported by the NIH/NIDDK (R01DK112258 and P01DK056492).GH is also a consultant for Reata Pharmaceuticals, Travere Pharmaceuticals, Otsuka Pharmaceuticals and Goldfinch Bio. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Long noncoding RNAs (lncRNAs) exert an increasingly important effect on genome instability and the prognosis of cancer patients. The present research established a computational framework originating from the mutation assumption combining lncRNA expression profile and somatic mutation profile in the genome of renal cancer to assess the effect of lncRNAs on the gene instability of renal cancer. A total of 45 differentially expressed lncRNAs were evaluated to be genome-instability-associated from the high and low cumulative somatic mutations groups. Then we established a prognosis model based on three genome-instability-associated lncRNAs -GlncScore. The GlncScore was then verified in testing cohort and the total TCGA renal cancer cohort. The GlncScore was evaluated to have an accurate prediction for the survival of patients. Furthermore, GlncScore was associated with somatic mutation patterns, indicating its capacity of reflecting genome instability in renal cancer. In conclusion, this study evaluated the effect of lncRNAs on genome instability of renal cancer and provided new hidden cancer biomarkers related to genome instability in renal cancer. Renal cancer (RC) occupies approximately 3% of all adult malignancies as the twelfth most common cancer across the world , 2. NephLong noncoding RNAs (lncRNAs) have been great players in almost every extent of gene function and control . RecentlAs we have known, the genome instability is not only a marker of cancer but also an important prognostic factor because it is related to tumor progression and survival. lncRNA NORAD has been shown to contribute to genome stability through the ability modulation of an RNA-binding protein for assembling a higher-order ribonucleoprotein complex . It has P < 0.05) between the GU and GS groups.The clinical characteristics, RNA-seq expression information, and somatic mutation data of RC patients were obtained from The Cancer Genome Atlas (TCGA) database. We obtained the mutation frequency of each patient and defined patients with the top 25% highest mutation frequency as the high mutation group (GU group) and patients with the lowest 25% mutation frequency as the low mutation group (GS group). lncRNAs related to genome instability were defined as the differentially expressed lncRNAs  modified The relationship between the paired expression of genome-instability-related lncRNAs and mRNAs was measured by computing the Pearson correlation coefficients, and the top 10 mRNAs were regarded as coexpressed genome-instability-related lncRNA-related partners. For predicting the hidden roles of genome-instability-associated lncRNAs, obviously enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were determined by performing functional improvement analysis of coexpressed lncRNA-related mRNA partners. ClusterProfiler package in R software was employed to make the function enrichment analysis.The Research on a Genome-Instability-Originated lncRNA Signature for Survival Forecast. We used the genome-instability-derived lncRNAs to develop a model for survival prediction. The outcome was set as the overall survival which was defined as the survival from date of inclusion until the death of patients. All patients with RC were randomly divided into training group and test group. The training set is mainly adopted for the identification of the prognostic lncRNA and the construction of predictive risk model; the test set is mainly adopted for the verification of the prognostic risk model.R version 4.0.3 was employed to make all statistical analyses. The correlation between the expression extent of lncRNA related to genomic instability and entire survival was evaluated with univariate and multivariate Cox proportional hazards regression analysis. On the basis of the parameters of multiple regression analysis and the expression extent of lncRNAs related to prognostic genomic instability, genomic-instability-derived lncRNA features (GlncScore) were constructed for result forecast. Taking the median score of the patients in the training set as the critical value of risk, the patients fall into high-risk group with high GlncScore or low-risk group with low GlncScore. The survival rate and median survival rate of every prognostic risk group were calculated with Kaplan-Meier approach, and the diversity in survival rate between the high-risk group and the low-risk group with a significant level of 5% was evaluated with the log-rank test. A time-related receiver operating characteristic curve (ROC) was adopted to assess the performance of GlncScore.According to the cell mutation of patients with renal clear cell carcinoma from TCGA database, the comparison of expression differences of lncRNAs between GU group and GS group was made in descending order. Finally, 45 lncRNAs were found to have significant differences in expression: 15 upregulated lncRNAs and 30 downregulated lncRNAs in GU group . A totalWe used gene enrichment analysis to predict the hidden roles of 45 lncRNAs associated with genome instability. By measuring the association between 45 differentially expressed lncRNAs and protein coding genes, we got the top 10 most closely related lncRNAs and mRNAs for the construction of the lncRNA-mRNA coexpression network . FurtherP < 0.05; P ＜ 0.05) was retained. Finally, we constructed a genome-instability-originated lncRNAs signature (GlncScore) to evaluate the prognostic risk of patients with renal cancer by combining the correlation coefficient of multivariate Cox analysis and the expression extent of three independent prognostic lncRNAs. The formula of the GlncScore is as follows:For the further study of the prognostic effect of the above candidate lncRNAs, 692 patients with renal cancer from TCGA database were divided into training group and test group, with 346 patients in training group. The baseline characteristics of the training and test groups were well balanced as shown in Supplementary P < 0.05, log-rank test; On the basis of the median value of risk score, patients fell into high-risk group  and low-risk group . Kaplan-Meier analysis showed that the survival outcomes of patients in the low-risk group are greatly better than those of patients in the high-risk group , tumor rejection, radiofrequency ablation, cryoablation, arterial chemoembolization, laser ablation, and ultrasound energy accumulation. The purpose of minimally invasive treatment is to preserve normal kidney tissue as much as possible and minimize complications.The incidence of kidney cancer is still increasing by 3% every year in the world. Because there is no early diagnosis and warning method, about half of newly diagnosed patients develop locally advanced kidney cancer or metastatic kidney cancer, while metastatic kidney cancer only takes an average of 10 months as the lifetime. The insensitivity of conventional radiotherapy and chemotherapy to kidney cancer results in the lack of means to prevent the recurrence and metastasis of kidney cancer; it also hinders the realization of the goal of improving the quality of life of advanced kidney cancer and prolonging the survival period of advanced kidney cancer. Sorafenib, a targeted drug for the treatment of advanced renal cell carcinoma, was first approved by the U.S. FDA in 2005, followed by sunitinib, axitinib, pazopanib, temsirolimus, everolimus, and benzalkonium chloride. Varizumab has been approved for the market, opening a new chapter for the treatment of advanced kidney cancer. The key to the treatment of kidney cancer with targeted drugs lies in how to adjust the dose of the drugs and at the same time discovering, reducing, and dealing with the side effects caused by targeted drug treatments, especially in the first month of treatment, are very important. Kidney cancer has a variety of immune correlations, and the clinical efficacy of multiple immunotherapies for renal cancer has been widely used. The immunotherapy of kidney cancer covers immune targeted therapy, combined immune targeted therapy, and immunotherapy combined with immune checkpoint blocking, kidney cancer vaccines, cytokines, and adoptive cells. IL-2 treatment of kidney cancer CAIX has become a screening indicator, which opens up a new direction for selective immunotherapy of kidney cancer. At the same time, in the in-depth study of the interaction of renal cancer immunotherapy, CTLA-4, and immune checkpoint antibody PD-1, new immunotherapeutic factors have brought new hope to clinical immunotherapy of renal cancer. However, the judgment of the efficacy of combined immunotherapy for kidney cancer may be due to the different responses of patients to immunotherapy and individual differences. More evidence-based medicine research is needed. With further research on the molecular level of cancer cells, the development of new vaccines for dendritic cells and tumor antigen preparations will open up new ways for the treatment of patients with advanced renal cancer. In short, it emphasizes regular physical examination, early diagnosis, and early surgical treatment of susceptible people. The diagnosis and treatment of kidney cancer with integrated traditional Chinese and Western medicine are advocated, so Chinese medicine can also play a certain clinical role. The survival rate and quality of life of kidney cancer patients in China will definitely improve.Individualized treatment of cancer is the trend of cancer treatment . It is vRecently, increasing attentions have been paid to the role of lncRNAs as cancer biomarkers . IdentiflncRNAs are a class of noncoding RNA molecules with transcripts between 200 nt and 100 kb in length. Most of them are produced by RNA polymerase II transcription. Their subcellular locations are diverse and are distributed in the nucleus, cytoplasm, and organelles. In most of the cases, lncRNAs are longer and have an mRNA-like structure, some have a poly(A) tail, and some do not have a poly(A) tail and have dynamic expression and different splicing methods during the differentiation process. By comparison with the coding gene, the expression level of lncRNA is lower. The expression level of lncRNA between different tissues is not the same, which is not only tissue-specific; at the same time, lncRNA also has temporal and spatial specificity; that is, the expression level of lncRNA in the same tissue or organ at different growth stages can also change. lncRNAs not only exert a significant effect on the pathogenesis of tumors but also exert a great effect on cardiovascular, autoimmune, infectious, and neurological diseases. This study has confirmed that lncRNAs have the following functions: ① Recruiting chromatin remodeling complexes to specific genomic sites and making them catalytically active. ② Transcription of the transcription factor in the upstream promoter area of the protein-encoding gene, involved in the expression of neighboring protein-encoding genes. ③ Inhibiting RNA polymerase II, forming complementary double strands with the transcript of the gene encoding protein, being involved in the shearing of mRNA, and then generating various forms of shearing or generating endogenous sRNA under the action of Dicer enzyme to control gene expression level. ④ Binding to a specific protein regulating the activity of the corresponding protein or changing the cytoplasmic localization of the protein. ⑤ Transcription as the precursor of small molecule RNA, such as miRNAs and piRNA. Abnormal expression of lncRNA can promote the occurrence of many diseases including tumors.With the maturity and application of high-throughput detection technology and the rapid development of bioinformatics, the expression regulation functions of lncRNAs have been discovered one after another, which not only enriches the complexity of the genome but also makes us realize some abnormalities of lncRNA in renal cancer. The expression situation makes our research on the link between lncRNA and kidney cancer more in-depth. However, the biological understanding of lncRNA in renal cell carcinoma is still slow, and its function and mechanism are still unclear. Moreover, there are few lncRNAs closely related to renal cell carcinoma. In the future, the mechanism of their effect on the occurrence and development of renal cell carcinoma shall be explored further. Existing studies have found the mechanism of abnormal expression of lncRNA in renal cell carcinoma and the mechanism of the influence of abnormal expression of lncRNA on the occurrence, development, metastasis, and invasion of renal cell carcinoma, laying the foundation for our next treatment of renal cell carcinoma. We believe that, with the deepening of research, lncRNAs studies will open a new chapter in the molecular targeted therapy and drug development of renal cancer. lncRNAs can take part in controlling gene expressions at the levels of transcription, posttranscription, and epigenetics, thereby affecting the growth, development, aging, death, and other life processes of the body. Recently, researches have found that lncRNAs have a function similar to oncogenes or tumor suppressor genes and are closely associated with the proliferation, invasion, metastasis, and prognosis of renal cancer cells. This article discusses the research progress of lncRNA in renal cancer and provides a new direction for finding molecular markers and drug targets for renal cancer.There were several limitations in the current research. First, the GlncScore is on the basis of the computational framework; further experimental research would be needed to understand its regulatory mechanism. Second, the GlncScore should be verified externally to ensure the practicability and repeatability of the model. Third, the influence of different treatment approaches on the predictive accuracy of the model was not evaluated; the future study should perform subgroup analysis based on the treatment the patients received.This study identified the lncRNA features derived from genomic instability as an independent prognostic marker for stratifying the risk subgroups of renal cancer patients. Through further prospective verification, GlncScore may be of great significance to the genomic instability and customized decision-making of renal cancer patients –20.


Mitochondria are known to generate approximately 90% of cellular reactive oxygen species (ROS). The imbalance between mitochondrial reactive oxygen species (mtROS) production and removal due to overproduction of ROS and/or decreased antioxidants defense activity results in oxidative stress (OS), which leads to oxidative damage that affects several cellular components such as lipids, DNA, and proteins. Since the kidney is a highly energetic organ, it is more vulnerable to damage caused by OS and thus its contribution to the development and progression of chronic kidney disease (CKD). This article aims to review the contribution of mtROS and OS to CKD progression and kidney function deterioration. By definition, OS is an imbalance between reactive oxygen species (ROS) production and removal due to overproduction of ROS and/or decreased antioxidant defense activity  and hydroxyl ions (OH−)  is reduced to H2O  during the oxidative phosphorylation process, during which molecular oxygen  in the mitochondrial matrix  at the Q binding site, which is located at the junction of the membrane arm and matrix arm   Hirst, . Additioi) and outer (Qo) pools of ubiquinone oriented toward the matrix and the intermembrane space, respectively  in mitochondria , which oxidizes the glycerol 3-phosphate and reduces Q to QHAnother site where electrons could escape and form ROS in mitochondria is the electron-transferring flavoprotein–ubiquinone oxidoreductase (ETF-QOR)  subunit of ketoglutarate dehydrogenase enzyme complex (KGDHC) may be a significant source of mtROS because the flavin of Dld is abundant in mitochondria and has a sufficiently negative redox potential to allow superoxide production , dihydroorotate dehydrogenase, and p66shc/cytochrome As mentioned above, cellular components other than mitochondria are also capable of producing ROS in the kidney. NADPH oxidases (NOX) are accepted as a major source of ROS generation in diabetic nephropathy and CKD alongside mitochondria  in the intermembrane space and manganese SOD (Mn-SOD) in the matrix  and thioredoxin (TrxS–) are then reduced by glutathione reductase and thioredoxin reductase, respectively, using NADPH as a substrate  or lipophilic   patients, ROS were increased significantly than in healthy subjects; this increase was associated with high levels of the OS marker 8-hydroxy-2′-deoxyguanosine (8-OHdG) , which causes nitrosative stress. The ONOO− formed can oxidize lipids, DNA, and proteins, resulting in modulations of cell signaling and oxidative damage leading to cell necrosis and apoptosis  results in the formation of hypochlorous acid (HOCl), thereby contributing to chlorinated stress  to produce peroxynitrite , MDA, 8-OHdG, and advanced oxidation protein products (AOPPs).Advanced glycosylation end products are a heterogeneous group of protein and lipids to which sugar residues are covalently bound. Advanced glycosylation end product generation is increased during hyperglycemic conditions such as diabetes mellitus  possesses the ability to convert HAnother marker is the MDA, which is a lipid peroxidation byproduct. It was reported to be increased in CKD, especially in HD patients, and negatively correlated with the GFR  has been shown to be a strong and independent predictor  (Cachofeiro et al., In CKD patients, CVD is the major cause of mortality (Ling and Kuo, Oxidized low-density lipoproteins are important players in the initiation and progression of atherosclerotic changes (Duni et al., Amyloidosis is a group of complex diseases caused by extracellular deposition of pathological insoluble fibrillary proteins in organs and tissues, and it may result in severe organ dysfunction (Vaxman and Gertz, In OS conditions, ROS contribute to the formation of oxidized amino acids, which directly changes the function of proteins (Meenakshi Sundaram et al., Anemia is considered as a common complication in CKD patients. Its severity increases as the kidney disease progresses Smith, . The maiIron deficiency anemia enhances the susceptibility of eryptosis and increases the risk of OS, which in turn targets the erythrocytes in CKD through increased peroxidation, subsequently leading to modifications in cellular structures and function (Ling and Kuo, Overproduction of mitochondrial ROS and the altered antioxidant system play a crucial role in the pathogenesis and the development of CKD through the enhancement of OS in the kidney, thus leading to a dysfunction in cell components and organelles especially mitochondria, resulting in more mtROS production, inflammation persistence, and CKD aggravation. Further investigations of mtROS mechanisms in CKD patients may help in the development of pharmacological strategies targeting mtROS for therapy.HT and HY wrote the paper. CW, RL, WX, and YL revised the paper. HT, HY, and YL designed the outline of the paper. 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.


Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of end-stage liver disease, leading to a rapidly growing global public health burden. The term “gut microbiome (GM)” refers to the approximately 100 trillion microbial cells that inhabit the host’s gastrointestinal tract. There is increasing evidence that GM is involved in the pathogenesis of NAFLD and may be a potential target for intervention. To explore GM-based strategies for precise diagnosis and treatment of NAFLD, great efforts have been made to develop a comprehensive and in-depth understanding of the host–microbe interaction. This review evaluates this interaction critically, mainly considering the intricate regulation of the metabolism, immunity, and inflammatory status during the evolution of the disease pathogenesis, revealing roles for the GM in NAFLD by examining advances in potential mechanisms, diagnostics, and modulation strategies.Synopsis: Considering the intricate metabolic and immune/inflammatory homeostasis regulation, we evaluate the latest understanding of the host–microbe interaction and reveal roles for the gastrointestinal microbiome in NAFLD. Strategies targeting the gastrointestinal microbiome for the diagnosis and treatment of NAFLD are proposed. Non-alcoholic fatty liver disease (NAFLD) describes a collection of hepatic clinicopathological syndromes that range from simple hepatic steatosis, non-alcoholic steatohepatitis (NASH) to fat-related fibrosis and cirrhosis . CharactThe human gastrointestinal microbiome (GM) refers to the assemblage of microorganisms  that inhabit the gastrointestinal tract . The resIn the present review, we dissect the role of the GM and their inflammatory mediators on immune regulation in NAFLD. Specifically, we focus on the characteristic changes of the GM in patients with NAFLD, including diversity and uniformity/homogeneity, and the developed non-invasive diagnostic strategies. In addition, the mechanism by which the GM regulates metabolic and immune homeostasis during the onset and progression of NAFLD and advances in modulating the GM to treat NAFLD are also highlighted.Many studies have demonstrated cross-talk between the GM and multiple organs of the host, which affects local and systemic metabolism and immune homeostasis . The intThe intestinal barrier in the gut–liver axis includes physical, immune, and biochemical components, plays an important role in the gut–liver axis . The gutGastrointestinal microbiome dysbiosis can disrupt these barriers, increasing mucosal permeability. Dietary factors can not only alter the intestinal microbiome composition, but also play a vital role in the maintenance of the intestinal barrier. The pathological state of the intestinal barrier induced by a high fat diet (HFD) results in intestinal bacterial translocation and endotoxin entering the portal venous system . As feedLachnospiraceae, Ruminococcaceae, Lactobacillaceae, and Peptostreptococcaceae, which are SCFA-producing and 7α-dehydroxylating bacteria , Ruminococcus, Faecalibacterium, and Eubacterium (producing butyrate), can induce SCFA production  are generated mainly from the fermentation of polysaccharides by the GM, and play a pivotal role in energy metabolism and inflammation regulation . The difoduction .via ATP citrate lyase. The hepatic metabolism of fructose promotes the transcription of genes related to hepatic lipid synthesis, and the metabolite acetate provides the raw material for this process. In addition, SCFAs can induce differentiation of T-cells into Th1 or Th17 cells, depending on the cytokine milieu and the epigenetic activity of histone deacetylases. IL-17 secreted by Th17 cells might play a pro-HCC role by promoting tumor angiogenesis , thus promoting liver lipid accumulation and cell proliferation, leading to the occurrence of NAFLD-HCC  did not improve NASH, it significantly improved liver fibrosis compared with that in the control group  can convert choline to TMA and then to trimethylamine-N-oxide (TMAO) in the liver, which reduces the bioavailability of choline  the disease .Bacteroides (Phenylacetic acid (PA) is mainly produced by the metabolism of aromatic amino acids  by teroides . A multiteroides . These cIndole, one of the products of tryptophan metabolism by the GM, is generally considered to have anti-inflammatory effects . ClinicaAt present, no effective or targeted drug for NAFLD has been approved for marketing. Lifestyle change is still the main intervention for NAFLD; however, the effect and patients’ compliance are poor. The close relationship between the GM and NAFLD has been confirmed. Intestinal dysbacteriosis and disturbance of metabolites  and the subsequent metabolic, immune, and inflammatory homeostasis damage might be critical factors for NAFLD development. Thus, targeting the GM is a growing and promising field aiming to slow down and even reverse NAFLD . MoreoveAlong with the lifestyle changes , NAFLD and its related diseases have become a global epidemic . It is eWith the rapid development of next-generation sequencing technology, metagenomics, and non-targeted metabolomics, we have made considerable progress in analyzing the composition and key metabolites of the GM, which has been considered as a potential and valuable non-invasive biomarker to diagnose NAFLD . HoweverThe complexity of NAFLD means that there is still no feasible method to reverse the disease process or prevent its occurrence. The clinical significance of specific GMs and metabolite changes associated with NAFLD remains unclear. The strategy of targeting the GM to reverse the adverse changes of NAFLD has several limitations. Each patient might be associated with different diseases, including obesity and diabetes, and might harbor different predisposing factors, such as genes, diet, and metabolic phenotypes . A key bAll authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.This work was supported by the National Natural Science Foundation of China (31960236 and 31770536). Lanzhou Chengguan District Science and technology planning project (2020SHFZ0029); Lanzhou talent innovation and Entrepreneurship Project (2019-RC-34); Fund of the first hospital of Lanzhou University (ldyyyn2019-75).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.


End concrete cover separation is one of the most common failure modes for RC beams strengthened with external FRP reinforcement. The premature failure mode significantly restricts the application of FRP materials and could incur serious safety problems. In this paper, an innovative stress field-based analytical approach is proposed to assess the failure strength of end concrete cover separation and the conventional plane-section analysis is extended to evaluate the corresponding carrying capacity of FRP-strengthened RC beams. First, the dowel action of reinforcement and the induced concrete splitting, reflecting the interaction between concrete, steel and FRP, are considered in establishing the geometrical relationships of stress field for cracked concrete block. Then, the cracking angle and innovative failure criterion, considering the arrangement of steel and FRP reinforcement and cracking status of concrete and its softening effect, are derived to predict the occurrence of concrete cover separation and related mixed modes of debonding failure. Subsequently, an extended sectional analytical approach, in which the components of effective tensile strain of FRP resulted from flexural and shear actions are both considered, is presented to evaluate the carrying capacity of strengthened beams. Finally, the proposed calculational model is effectively validated by experimental results available in the literature. Due to the pronounced advantages, such as high strength, light weight, electromagnetic transparency, non-corrosive, and nonconductive properties, externally bonded (EB) fiber-reinforced polymer (FRP) and near-surface-mounted (NSM) FRP have become the prevailing techniques over the last three decades for flexural strengthening of existing reinforced concrete (RC) members ,2,3,4. EConcrete cover separation at the end of FRP reinforcement has been found to be the common failure mode in the retrofitting techniques using EB and NSM FRP methods and has obtained increasing research attention ,11,12,13Many analytical models and numerical techniques have been also presented to evaluate the failure strength of concrete cover separation ,43,44,45In addition, the fracture moment Consequently, the resultant force tion (5) ,30,31,32Equation (4) illustrates that the effective tensile strain of FRP reinforcement figured out by concrete tooth model is highly sensitive to crack spacing; therefore, crack spacing is the most critical factor to predict the failure strength of concrete cover separation. Consequently, the modified concrete tooth models by refining the calculation of crack spacing were subsequently presented ,32. AccoConcrete tooth model and the other mentioned analytical models have been so widely employed due to its simplicity and convenience in analysis and design. However, the great simplifications render the pronounced drawbacks in accuracy and application scopes. Thus, the more sophisticated numerical techniques have been used to improve the accuracy of prediction of concrete cover separation. Hawileh et al.  presenteGreat efforts on experiments and on analytical and numerical approaches have been made to investigate the concrete cover separation of RC members strengthened by external FRP reinforcement , whereas a full understanding of this failure mode is still lacked, and the precise and reliable calculation approach is still in demand. In this paper, a novel stress field-based analytical approach is presented to evaluate the failure strength of concrete cover separation induced at the end of external FRP reinforcement and the corresponding carrying capacity of FRP-strengthened RC beams that failed in concrete cover separation. First, dowel action of steel and FRP reinforcement and the induced concrete splitting, which reflect the interaction between concrete, steel and FRP reinforcement and are commonly ignored in existing investigations, are considered to be the critical factors to result in concrete cover separation and properly incorporated into the establishment of fundamental geometrical relationships of stress field for cracked concrete block. Then the influential factors such as transverse strain and splitting crack of concrete interacted with surrounding steel and FRP reinforcement are comprehensively taken account for the calculation of effective compressive strength of concrete in stress field. Accordingly, the cracking angle to identify the stress field, and the innovative failure criterion are derived to predict the occurrence of concrete cover separation and the related mixed modes of debonding failure; the arrangement details of steel and FRP reinforcement and the cracking status of surrounding concrete and its softening effect are properly considered in the derivation. Subsequently, the indispensable shear component in the effective tensile strain of FRP is taken into account by a simplified stress field approach to evaluate the carrying capacity of strengthened RC beams that failed in end concrete cover separation. Finally, the proposed calculational model is effectively validated by the experimental results available in the literature. Before the establishment of analytical model, it is fundamental to understand the mechanical state and failure mechanism of separation of concrete cover at FRP reinforcement end. According to many experimental investigations ,34,46,47More specifically, if the applied shear stress exceeds the bond strength between FRP and concrete, the crack creates at the FRP/concrete interface, which is known as interfacial debonding ,6,7,21. If FRP reinforcement is not attached, the horizontal splitting cracks can be also generated because the bond action between steel reinforcement and concrete ,49,50 anThis study mainly focuses on the end concrete cover separation of FRP-strengthened RC beams. Thus, the dominant dowel action of steel and FRP reinforcement and the induced concrete splitting would be considered, and the failure mechanism of concrete cover separation generated at the maximum moment region and the relevant bond action of steel reinforcement is not further discussed.Concrete cover between internal steel reinforcement and external FRP reinforcement is divided into discrete blocks by inclined separation cracks along the strengthened RC beam. Based on the conventional assumptions and simplifications, the stress field approach schematically shown in To derive the failure criterion and failure strength of end concrete cover separation, only the mechanical state of cracked concrete block at the end of FRP reinforcement needs to be appraised. Consequently, the fundamental hypotheses about mechanical and geometrical conditions are made to satisfy the requirements of stress field theory for concrete ,63,64,65Two adjacent inclined separation cracks are defined as the boundaries of concrete block. The tensile stress along the inclined cracks reaches the effective tensile strength of concrete, and the shear stress along the inclined cracks is ignored ,50,54.The first inclined separation crack straightly extends from the end of FRP reinforcement to the gravity center of the (outer) steel reinforcement; without considering crack spacing, the adjacent inclined and straight separation crack starts at the end of projection of the first inclined crack  steel reinforcement to the first inclined crack. The propagation length depends on the splitting degree and is assumed to be larger than the length of the upside of concrete block in this study.The dowel action is simplified as uniform load distributed on surrounding concrete block ,54,55,56Considering the plasticity and stress redistribution of concrete, the assumption and simplification of uniformly distributed tensile stress along inclined cracks and dowel action would generate the conservatively safe evaluation of failure strength of concrete cover separation, which is specifically validated and discussed in To establish the geometrical relationships of stress field for cracked concrete block, the mechanical state should be identified. First, the uniformly distributed tensile stress along the inclined separation cracks is defined as with 0.8 ,54,55,56Subsequently, it should be pointed out that the dowel actions of both steel and FRP reinforcement contribute to concrete cover separation according to experimental investigations . Howeverorcement  and thenIn this study, the distributed tensile stress on top surface of concrete block is ignored due to the development of splitting crack, and the dowel action Moreover, there exists shear stress acted on the top surface of concrete block surrounded by cracked concrete and steel bars, as schematically shown in The stress state of concrete block concerned in calculations is schematically in Replacing Defining the parameters β.Accordingly, Equation (10) can be further simplified into Equation (13) explicitly representing the relationship between cracking angle In addition, the relationship between cracking angle A parameter Consequently, through combining Equations (13) and (14), the relationship between geometrical parameter With the geometrical parameter rsection  can be dFurthermore, based on the geometrical relationship demonstrated in One of the critical failure conditions of concrete cover separation is concrete cracking along the inclined separation cracks at the end of FRP reinforcement. Thus, the transverse stress of micro concrete struts  adjacention (21) ,68:(21)εRelationship between the principal compressive strain ion (22) ,69:(22)εPlease note that the principal compressive strain concrete ,69. The ion (23) :(23)fcp0The effective compressive strength concrete ,63,64,65concrete ,63,64,65Consequently, the effective compressive strength of concrete in stress field is calculated by Equation (24):fficient ; ηε is tfficient ,63,64,65fficient ,77,78,79Equation (24) indicated that the generation and development of splitting crack would significantly reduce the effective compressive strength of concrete and affect the failure strength of concrete cover separation discussed as follows. To establish the failure criterion of concrete cover separation, stress state of a local part of micro concrete strut adjacent to the first inclined separation crack and external FRP reinforcement is shown in The principal tensile stress Case 1: Generally, the principal compressive stress concrete ,64. AccoIn contrast to most formulations of debonding failure strength, characterized by the individual material properties and geometries of concrete and external FRP reinforcement, the derived strength model additionally incorporates the influential factors such as interaction between concrete, steel and FRP reinforcement, cracking status of surrounding concrete and its softening effect, and arrangement details of internal steel reinforcement and external FRP reinforcement. Moreover, as the Mohr’s circle for stress of micro concrete in  devices ,81 are wOn the other hand, to ensure the occurrence of concrete cover separation, the maximum local shear stress orcement ,83, whiceriments ,10,16,47concrete ,83 in EqAnother possible mixed mode of cover separation and sliding failure is schematically shown in th 37.2° ,71. HencIn addition, according to the geometrical relationships of Mohr’s circle of stress shown in Based on Equation (28) and concrete ,63,64,65Case 2: By contrast, Case 2 does commonly occur due to the extremely low principal compressive stress of So far, the mechanical state of micro concrete strut adjacent to the first inclined separation crack shown in Select a cracking angle Specify the geometrical parameter Calculate the cracking strain of tensile concrete Select a splitting cracking width of Figure out the plasticity of concrete coefficient Check the correctness of principal compressive stress If Step 6 is false, adjust the value of If Step 6 is true, calculate the cracking angle If the computed cracking angle Check the computed cracking angle If Step 10 is false, repeat steps 1–8 and 10; andIf Step 10 is true, obtain the desired cracking angle Please note that under the condition of satisfying the requirements of failure strength listed in step 6 and the lower bound of splitting crack width of 0.015 Consequently, an analysis flowchart to estimate cracking angle As the cracking angle Referring to the aforementioned analytical approaches of local shear stress, the average shear stress For the scarcely occurring Case 2 with the average tensile stress With the estimated average shear stress The effective tensile strain of FRP corresponding to the occurrence of concrete cover separation is evaluated by Equation (31):It should be pointed out that the effective tensile strain of FRP corresponding to concrete cover separation is not identical to the one at the maximum bending moment section that failed in flexure, which is assumed to be sufficient and not the critical factor in this study. The location of end concrete cover separation renders the huge difficulties in precise evaluation of carrying capacity of RC beams strengthened with FRP reinforcement. Hence, most studies merely paid attention to assessing the effective tensile strain of FRP corresponding to concrete cover separation ,30,31,38For the intermediate crack-induced concrete cover separation, as shown in By contrast with the conventional sectional analysis performed at the critical section with the maximum bending moment, the presented analytical approach focuses on the section where the concrete cover is completely separated, namely the end of the first inclined separation crack . On the ion (32) ,84:(32)εSubsequently, the analyses of flexural and shear behavior of strengthened RC beams are respectively performed to specify the flexural strain Flexural strain The resultant force concrete , represeAccording to the common assumption that the plane section remains plane, the depth of compressive region Similarly, the compressive strain Consequently, the bending moment The shear force Considering the combination of steel and FRP longitudinal reinforcement, the calculational formulation based on the modified compression field theory (MCFT) ,62 and tThe development of angle of the MCFT ,62 and tthe MCFT , whereasthe MCFT ,18 reporry (CFT) , was modry (CFT) ,18 to es section ,18,87.Moreover, based on the solution of concrete plasticity , the uppTo facilitate calculation, the inclination angle of Considering crack spacing, the starting point of the second inclined separation crack, where the effective tensile strain of FRP at concrete cover separation is derived according to stress field approach, may be not coincident with the studied beam section, as the points A and A’ illustrated in The modification coefficient and (57) ,88,89,90h−c)bw/3 ,88,89,90Subsequently, the detailed process to assess the carrying capacity of strengthened RC beams that failed in concrete cover separation is illustrated as follows.Select a flexural strain Select a curvature Figure out the depth of compressive region Specify the reinforcement stresses of Compute the resultant force If If Compute the strain of FRP reinforcement If If Correspondingly, an analysis flowchart to assess the carrying capacity of strengthened RC beams is illustrated in To validate the proposed approach, the strengthened RC beams that failed in concrete cover separation with the desirable data in the available literature ,22,23,28With the proposed analytical model, the calculation of cracking angles of concrete blocks was first performed. The calculational results (Subsequently, incorporating the effective tensile strain of FRP reinforcement derived from the calculated cracking angles of concrete blocks, carrying capacities of the strengthened RC beams are assessed. In calculations, the effect of amplification coefficient of average crack spacing The statistical results in ferences ,92. SincA novel analytical approach based on concrete stress field was proposed to predict end concrete cover separation in RC beams strengthened with external FRP reinforcement. First, with the introduction of dowel action of steel and FRP reinforcement and the induced concrete splitting, which are the critical factors to reflect the interaction between concrete, steel and FRP reinforcement, the geometrical relationships of stress field for concrete were established through proper simplifications to configuration and mechanical state of cracked concrete block. Then, to assess the cracking angle and the correlated failure strength of concrete cover separation, the effective compressive strength of concrete in stress field was finely identified by incorporating the influential but prone to be neglected factors such as transverse strain, cracking status of surrounding concrete, and arrangement of internal steel reinforcement and external FRP reinforcement. Subsequently, an extended plane-section analytical approach, in which the components of effective tensile strain of FRP induced due to flexural and shear actions are both comprehensively considered according to the detailed location of concrete cover separation, is proposed to evaluate the carrying capacity of strengthened RC beams in a simple process. Finally, an excellent agreement between the predictions and experimental results was obtained to validate the proposed analytical approach; furthermore, the discussions and suggestions about the parameters concerned in the approach were proposed.The detailed conclusions of this study can be drawn as follows:By contrast with the conventional analytical models of concrete cover separation, merely focusing on the local response of concrete around FRP reinforcement, the proposed analytical approach based on stress field could comprehensively and properly consider the influence of the interaction between concrete, steel and FRP reinforcement, cracking status of surrounding concrete and its softening effect, and arrangement details of internal steel reinforcement and external FRP reinforcement on concrete cover separation; it is suited for practical design and analysis, and can be extended for external reinforcement with other composite materials.Dowel action of steel and FRP reinforcement, and the induced concrete splitting are the critical factors to establish the geometrical relationships of stress field for cracked concrete block and to derive the failure strength of concrete cover separation, and cannot be neglected.The assumption of the lower bound of splitting crack width of 0.015 The shear component in the effective tensile strain of FRP reinforcement cannot be ignored and was efficiently considered in the analysis of carrying capacity of strengthened RC beams that failed in end concrete cover separation.Crack spacing has a great effect on the assessment of carrying capacity of strengthened RC beams and, consequently, the coefficient incorporating the amplification factor of average crack spacing The proposed analytical approach obtained the satisfactory and conservatively safe prediction of the experimental results; by contrast, the commonly used concrete tooth model overestimated the failure strength of concrete cover separation, and generated unsafe prediction of carrying capacity of strengthened RC beams.


Background: The ongoing global pandemic has become the world's leading health problem, causing massive public fear and concern. Reports suggest that athletes are seeking mental health support, showing the pressures of boredom, and tension associated with their anticipated social isolation. The current study seeks to evaluate the evidence regarding the effects of the coronavirus pandemic on occupational stress in professional athletes.Method: A scoping review was conducted. A comprehensive search involving Embase and PubMed databases was conducted using a combination of the following key words: COVID-19, SARS-CoV-2, coronavirus, and athletes. In this study, articles were retained if they were original studies reporting on the impact of the pandemic on professional athletes.Results: Nine studies were identified as they investigated the impact of the pandemic on athletes. Most were observational and cross-sectional, and one was longitudinal. Outcome measures mainly investigated were level of depression, anxiety, and stress. Dependent variables were physical activity, nutrition, mental state, sleep quality, individual well-being, social identity, exclusivity, negative affectivity, alcohol consumption, psychological distress, and gambling habits.Conclusions: This review highlights the need for proactive engagement with professional athletes, coaches, trainers, and sports councils to facilitate understanding and awareness-raising, process optimization, and delivery of consistent training and psychosocial aid and occupational therapy programs that maintain the health and well-being of athletes while minimizing occupational stress during a pandemic. The coronavirus pandemic in 2020 resulted in significant global challenges. Government agencies and public health organizations have adopted public health initiatives to minimize the peak infection rate, of which the most effective recommendation known to restrict and postpone the spread of the virus is social  distancing. Most countries have increasingly adopted community isolation measures to increase social distancing, such as mandatory lockdowns, isolation periods, and the closing of public areas . StudiesSocial distancing measures have resulted to a substantial rise in workplace stress, with many categories of workers affected . Work-reThe world of sports has not been exempted from the protective measures against pandemic, with athletes unable to practice or compete or participate in international competitions. Global health recommendations have led to the cancellations and postponements of numerous athletic events in order to social distance and in an attempt to limit the spread of the virus . InternaWith limitations to practice in competitions, the potential implications to athletes are numerous, as this may affect their health with lack of training and their income as matches are canceled. In addition, there may be an element of fear of athletes catching the virus, as there have been numerous high-profile cases of professional athletes testing positive for COVID-19 . The facThe current study seeks to evaluate the evidence regarding the effects of the coronavirus pandemic on occupational stress in professional athletes.The scoping review was conducted according to the standards and guidelines established in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) with the associated extension for Scoping Reviews .We conducted a systematic literature search of the Embase and PubMed databases using a combination of the following keywords: COVID-19, SARS-CoV-2, and athletes. Databases have been checked until the date of our literature searches (30 November 2020). Studies were included in this review if they were original studies focusing on the effect of the pandemic on professional athletes. In order to ensure completeness, we also checked for references to our full-text articles. References of the reported relevant reviews were also screened.Criteria for eligibility were (1) Population: professional athletes, (2) Intervention: COVID-19 pandemic, (3) Comparator: not available, and (4) Outcomes: any qualitative or quantitative findings published in the literature related to psychological health. No restrictions were placed on study design, age, or injury type.Exclusion criteria were studies not related to the COVID-19 pandemic, not reporting outcomes, and not in English.Three reviewers  engaged in the database screening process and the analysis of the full text for eligibility. Disagreements between the three reviewers were resolved through dialogue and consultation with the two senior authors .In line with scoping review practice, included studies have not been assessed in terms of quality .The results of the screening process are shown in the PRISMA diagram in Original research articles were cross-sectional studies . No confIn a 2-month prospective longitudinal study at the German professional men's soccer league, coronavirus infection rate could be kept low through strict hygiene measures including regular PCR testing .In South Africa, a cohort of elite and semi-elite athletes out of 15 sports reported self-reported pandemic psychological effects on physical, nutritional, and psychological health  (In Turkey, depression and anxiety symptoms were lower in athletes compared to non-athletes but were comparable in team athletes and individual athletes .In Italy, professional athletes and team sports athletes demonstrated a higher athletic identity during the lockdown era . CognitiIn Sweden, self-reported pandemic psychological influences have been widespread among elite soccer, ice hockey, and handball athletes, as well as worries about one's sport and one's own career linked to the crisis situation. Depression and anxiety were not significantly higher than predicted but correlated with coronavirus-related worry definitions. Fear of increased gambling during the crisis could not be explicitly shown, but at-risk gambling in male athletes was widespread and also related to a rise in pandemic gambling.In the USA, during pandemic school closures and sport cancellations, lower levels of physical activity and quality of life and increased symptoms of anxiety and depression have been identified in female athletes, team sports players, and areas with a higher percentage of poverty . Due to In Spanish handball players, reduced training intensity, and volume were associated with reduced sleep quality and increased sleep hours during the isolation period .In Brazilian soccer players, over normal off-season, 63 days of quarantine affected several physical performance tests .Although results varied slightly between different sports and geographical regions, the general consensus from studies , 19, 20 Studies investigating the impact of the coronavirus pandemic on public health have found a high level of psychological distress . PsycholThe evaluated investigations included stressors such as fear of being infected, lack of access to training facilities, lack of ability to continue practicing their skills, canceled matches, lack of social support, and lack of or reduced income. These stressors may lead to outcomes such as disturbed sleep, eating disorders, obsessive-compulsive disorders, family conflicts, and unhealthy coping mechanisms such as smoking and increased alcohol intake. The COVID-19 pandemic impacting the training schedules of athletes has affected their sleeping habits and caused unhealthy habits and coping mechanisms such as increasing their carbohydrate intake and preferring sedentary behavior above active behavior . This evAnother issue that could occur as a result of the constraints imposed is of a financial nature. Competitions, matches, and leagues were canceled due to the outbreak, and this could be the only source of income for certain athletes. While professional athletes in leading leagues do not face the same financial restrictions, cancelations of many sporting events worldwide would impact many teams globally . This prThese outcomes further have consequences on general and cardiovascular health, causing a vicious cycle of events. The potential inability of these athletes to manage their stress and coping mechanisms may lead to long-term depression and other detrimental health effects . AlthougMental health cannot be separated from physical health, as mental health symptoms and associated systemic disorders increase the risk of physical injury and delay recovery. Physical activity has beneficial effects for both the prevention and treatment of different diseases and psychiatric diseases such as depressive and anxiety disorders . PsycholIn the context of the COVID-19 pandemic and professional athletes, the strengths of this analysis include its exploration of peer-reviewed articles. Its drawbacks must, however, also be recognized. In accordance with the scoping analysis procedure, the included articles were not evaluated for accuracy. Study bias may also have been introduced by removing gray literature and non-English language texts. Future studies would benefit from a researching a broader range of bibliographic databases.As exposed in this scoping review, several studies on the impact of the coronavirus pandemic on athletes indicate that this pandemic may act as a triggering life event that would increase occupational stress to afflict mental health and well-being. Afflicted mental health and well-being could also impact their cardiovascular health, which in turn could adversely impact further their mental health. Research on mental and cardiovascular health shall further investigate the identified risk effects brought on from a combination of stressors directly associated with COVID-19 exposure, isolation, lack of physical exercise, reduced income, and fear of unemployment in athletes. Such stressors and their impact on athletes' healthcare should be tackled by psychosocial aid and occupational therapy programs to better deal with the coronavirus pandemic.OB and LC conceptualized the review and initiated the draft of the manuscript. RH, MA, and DS screened the articles, contributed to the abstraction, and reviewed the manuscript. HA and KD contributed to the abstraction and validation of data and preparation of the manuscript. All authors critically reviewed and revised the final version of the manuscript and contributed significantly to the conceptualization and reporting of the review.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.


Furthermore, current limitations and future perspective in the development of smart wetting surfaces are also given. This review aims to offer deep insights into the recent developments and responsive mechanisms in smart biomimetic surfaces with switchable wettability under external various stimuli, so as to provide a guidance for the design of smart surfaces and expand the scope of both fundamental research and practical applications.In order to satisfy the needs of different applications and more complex intelligent devices, smart control of surface wettability will be necessary and desirable, which gradually become a hot spot and focus in the field of interface wetting. Herein, we review interfacial wetting states related to switchable wettability on superwettable materials, including several classical wetting models and liquid adhesive behaviors based on the surface of natural creatures with special wettability. This review mainly focuses on the recent developments of the smart surfaces with switchable wettability and the corresponding regulatory mechanisms under external stimuli, which is mainly governed by the transformation of surface chemical composition and geometrical structures. Among that, various external stimuli such as physical stimulation , chemical stimulation  and dual or multi-triggered stimulation have been sought out to realize the regulation of surface wettability. Moreover, we also summarize the applications of smart surfaces in different fields, such as oil/water separation, programmable transportation, anti-biofouling, detection and delivery, smart soft robotic