Evidence indicates that pharmacotherapy is the mainstay of treatment, both in early and chronic psychosis. Despite clinical improvement, many people with psychosis develop disabilities related to domains of negative, physical health and mood symptoms, cognitive dysfunction, and socioeconomic disadvantages, through all stages of psychoses. This implies a key need for psychosocial interventions. Initiation of combined drug and psychosocial treatments plays a significant part in the early phase of psychosis . SeveralThis collection of articles aimed to bring together various psychosocial interventions across the course and chronicity of psychotic illnesses. The objective was to understand the innovations and adaptations of interventions both in the early phase as well as the chronic phase of the illness. It was also felt necessary to appreciate the application of these multi-module interventions in real-world settings. This volume brings together various interventions from different parts of the globe.There is a noteworthy relationship between symptoms, cognition, social functions, and employment –7. SeverPichler et al. investigating the long-term employment status of individuals with mental illnesses, who have received IPS, make important observations. In the randomized controlled ZhEPP trial, 250 Swiss disability pensioners with mental illnesses were randomly allocated into either IPS intervention or treatment as usual group (TAU). The trial demonstrated that IPS was better than standard approaches for pensioners with mental illnesses to get jobs in the competitive employment space. Six years after the start of the trial, Pichler et al., interviewed 114 individuals on their employment status, job tenure, workload, and salaries. The IPS group had higher employment rates (40%) when compared to TAU (28%), at 24 months. However, no differences between the groups were noted at 72-month follow-up assessments. These findings imply the need for longitudinal studies to examine the adaptation and sustainability of interventions like IPS.Fibbins et al. report on the feasibility of integrating an exercise clinic, within a mental health service for people with serious mental disorders in Sydney, Australia. Using a single-site, open-trial methodology, an accredited exercise physiologist delivered individually tailored physical activity interventions in a part-time exercise physiology clinic. Outcome measures included body mass index, cardiovascular indicators, and a self-report physical activity. An average of 1 weekly exercise session was delivered to a total of 84 mental health service users. The study demonstrated a statistically significant increase in physical activity and a decrease in inactivity. The researchers concluded that exercise clinics were feasible within mental health services. They recommended that such a service if incorporated within a routine care service, would help address barriers like staff culture, finance, and resources to integrating physical activity as part of standard care.Less than half of people with mental illnesses engage in the recommended 150 min of moderate-vigorous physical activity per week and most have low levels of cardiorespiratory fitness . The higYoga, as an adjunct intervention, has been shown to significantly improve the severity of psychopathology and functioning in patients with schizophrenia , 16. SpeSchulze et al. have explored the experiences of participants in the Yoga-based Group Intervention (YoGI) for in-patients with schizophrenia spectrum disorders (SSD) in Germany using qualitative methods. Interviews with in-patients explored the personal experiences of taking part in YoGI. The transcribed interview data were coded and analyzed using an inductive thematic approach. The respondents experienced interconnectedness, were mindful of their limitations, and were able to adapt to the practice. The persistent practice of the asanas resulted in an experience of confidence and relaxation. Increased awareness of self resulted in the participants becoming aware of imminent as well as reduced severity of symptoms. The researchers opined that YoGI showed several promising benefits for in-patients with SSD and recommended that future studies should focus on sustainability and transfer of methods to routine use.However, few studies have qualitatively examined the patient perspectives on the experiences of Yoga. Clubhouses are programs that help people with mental illness establish a daily routine, social and affective connectedness, in a context other than the usual medical care settings. People are treated as individuals, than “patients” . SignifiYan et al. undertook a systematic review and a meta-analysis of the clubhouse model of psychiatric rehabilitation in China. They investigated the role of the model in promoting symptom remission and functional recovery of persons with schizophrenia. Data extracted from 7 databases were subjected to quality assessment, data synthesis, and subgroup analysis. Both randomized and non-randomized studies were included. The overall results showed that psychopathology, social and occupational functioning and quality of life improved significantly and a reduction in family burden was noted. The researchers recommended that the clubhouse model may be useful to meet the urgent need for improving mental health services in China. The results however need to be viewed with caution on account of the limited sample size.Cognitive dysfunctions are central features of psychotic disorders. They often occur in the prodromal period of psychosis and continue through the course of illness , 24. TheChong et al. using a naturalistic design, discuss the application of cognitive remediation training (CRT) in patients with first-episode psychoses population in Singapore. Participants were part of the Singapore Early Intervention Psychoses program. They underwent 24 CRT sessions, using Cogpack and Neuropsychological Educational Approach to Remediation. Pre- and post-assessments were done using the Montreal Cognitive Assessment and Brief Assessment of Cognition in Schizophrenia. The participants significantly improved in several cognitive domains such as verbal memory, digit sequencing, and symbol coding. The study showed that CRT interventions were helpful in early psychosis.Harris et al.), aimed to assess if functional outcomes improved. Neuropsychological Educational Approach to Remediation (NEAR) and the Social Cognition and Interaction Training (SCIT) treatments were delivered by trained therapists to participants randomized to either NEAR+ SCIT or NEAR + treatment as usual (TAU) groups. The trial was conducted over 20 weeks in five youth mental health services. Although the COVID pandemic restricted the follow-up, this research conducted in a naturalistic service setting, indicated that the group receiving a combined NEAR + SCIT approach showed a trend toward improved functioning.Using a combined social cognitive remediation treatment with a neurocognitive remediation therapy, for young people with schizophrenia, bipolar disorder, or depression, the ADVANTAGE trial , for family caregivers of persons with mental illnesses, is an evidence-based family intervention that encourages mutual support and learning between families. MFT is provided as part of the Singapore EPIP services. The experiences of families that were part of Multi-Family Therapy (MFT) have been reported by Several reviews and reports have shown that over two-thirds of persons suffering from chronic psychoses do not have access to specialized mental health treatments , 31, espBird et al. describe the prevailing psychosocial interventions in the existing services in two LMICs-India and Pakistan. The situational analysis revealed that a wide variety of psychosocial interventions were delivered to persons with psychosis in mental health facilities in a collaborative and integrated manner. These interventions were perceived positively by the respondents, who included patients, their family members, and mental health professionals. The data also revealed several real-world and systemic barriers to the services.Based on the findings of a situational analysis, via a tablet, computer, or smartphone is a psychosocial intervention, to enable the therapeutic effectiveness of usual meetings between patients and clinicians. Earlier RCTs, using DIALOG+, in both high and low-income countries, have demonstrated improvement in quality of life and reduction in symptoms  intends to improve a range of functioning in multiple domains . StudiesChen et al. aimed to test the potential of the use of Animal-assisted therapy (AAT). Using an RCT design, the study assessed the efficacy of AAT psychological intervention with dogs in a clinical setting. Patients with chronic schizophrenia who were middle-aged and older participated in a 12-week program. The outcome measures included the severity of symptoms and stress levels of the patients. Using a robust methodology, the researcher reported a reduction in psychiatric symptoms and stress. The study demonstrated the usefulness of AAT as an adjunct therapy to usual treatment programs.Lee et al. argue that co-production is a moral obligation. The authors urge that co-production needs to be an integral part of any recovery-oriented interventions in the mental health care system.Mental health service users do better when their choices and preferences are integrated into decisions for their management . An infoA person with lived experience supporting others with mental illness is an established peer support intervention. The earliest investigation, UPSIDES-RCT a, parallel-group, multicentre, randomized controlled trial was designed to test the effectiveness of using peer support to develop empowering mental health services (UPSIDES) at several levels .Sims et al.), aimed to understand if interventions by peer volunteers were acceptable and feasible. Persons diagnosed with schizophrenia, their family caregivers, and mental health professionals responded to questions on the usefulness of peer support interventions and the various areas that peers could provide the services. The majority of the participants welcomed peer support interventions. The areas of interventions suggested included practical help for persons with schizophrenia, to improve their mental health and their daily routines. There was an emphasis on independent living, social relationships, and meeting medication and treatment-related goals. Highlighting the potential acceptability of peer volunteer programs, the authors emphasized the need to test the effectiveness of implementing a peer support program as a necessary component of a mental health service.Will such intervention be feasible in low and middle-income countries? A cross-sectional survey in an outpatient mental health clinic in Chennai, South India . Bird et al.) within LMICs reflected on the existing practices in the two settings. It explored contact with services, access to new cases, follow-up patterns, the multidisciplinary approach, and the contribution of users and family members to the program. The emphasis of the situational analysis focused on an exploration of the barriers and facilitators, including organizational readiness for a new intervention.Two studies reported in this Research Topic, bring to light the role of the mental health setting as critical consideration when delivering a new intervention. Any new psychosocial intervention needs to consider both the enthusiasm of the professionals as well as barriers in the designing phase. The situational analysis (Fibbins et al. demonstrated the feasibility of implementation of an exercise physiology clinic for users within the service. They opined that such services would increase the levels of physical activity and reduce inactive times for persons with chronic mental illness. They also reiterated the need for a collaborative approach in implementing an exercise clinic and taking into consideration the individual needs of the patients.This Research Topic has highlighted the wide range of interventions that have been an intervention. Consistent with a recent systematic review, combined with a theory-driven logic model approach, the interventions described in this collection of articles, can be seen to align with four fundamental requirements that include the provision of information and skills, promotion of a working alliance, role modeling recovery and increase in choices . While mAll authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Eating disorders (EDs) are disabling mental disorders  to this collection focused on clinical samples of patients with EDs.Muzi et al. evaluated the mediating role of personality variables on pre-treatment ED symptomatic impairment and treatment outcome. Their results exhibited that Clusters A and B of the Shedler Westen Assessment Procedure-200  by providing evidence that mothers display higher avoidance and seeking information than fathers. Interestingly, lower illness duration predicted higher collusion with the illness in both parents. Cooperativeness, self-directedness, and harm avoidance positively predicted collusion, parental coercion, and seeking information strategies with some differences between fathers and mothers. In sum, illness duration and personality traits of parents affected the type of parental coping strategies developed to face AN in adolescents. Also about the role of parents, Basile et al. reported that safety/protection, care/nurturance, and emotional expression were the most frequently reported unmet needs within the childhood memories of patients, in particular, with regard to the maternal figure. Besides, mothers were described as more abandoning, but at the same time mostly enmeshed in the relationship with their daughters. Conversely, patients perceived their fathers as more emotionally inhibited and neglecting.Three studies provide data on the role of the parents' personality traits and attachment in the EDs. Ramos et al. explored the clinical utility of considering the illness duration at presentation for treatment in AN and clinical impairment as markers of severity. Clinical impairment seems to be the strongest predictor of poor outcome in terms of eating psychopathology, depressive symptoms, emotion dysregulation, and symptom distress. Weineck et al. evaluated the discrepancy between explicit feelings of power and implicit power motives and its relationship to anxiety. Patients with AN displayed significantly lower explicit feelings of power, however, they showed similar implicit power motives compared to healthy controls (HC). The authors consider that the discrepancy between explicit feelings of power and implicit power motives is related to anxiety and may represent a risk factor to the illness maintenance in AN. Mikhaylova and Dokuka conducted interesting research using a concentric circle methodology analyzing 50 ego networks constructed with data drawn from interviews with Russian-speaking bloggers previously diagnosed with AN that write about this condition. The authors reported that young women with AN tend to have a limited number of social ties, and prefer not to connect with family members. Finally, Leslie et al. evaluated differences in the neural correlates of Theory of mind pathways in young women with AN, and young women weight-restored (WR) from AN, as compared to HC. Their results suggest that the neural processing of theory of mind remains more intact in young women with AN than previously thought.Four studies investigated samples of patients suffering from AN. Gagliardini et al. explored the role of mentalization in EDs. Through a latent profile analysis, the authors found four different profiles in relation to impairments in the dimensions of mentalization: (1) affective/self/automatic imbalances, characterized by the prevalence of affective mentalization that overwhelms the capacity to reflect on mental states with an imbalance on the self-dimension; (2) external imbalance, characterized by excessive focus on the external cues of mentalization; (3) cognitive/self/automatic imbalances, characterized by over-involvement on the cognitive and self-facets of mentalization, with an impairment in adopting the other mind viewpoint; and (4) cognitive/other/automatic imbalances, indicating those patients who have similar impairments compared to profile 3 but with deficits in self-reflection and an excessive focus on others. These profiles were heterogeneous in terms of EDs represented in each group and were related to significant differences on specific domains such as empathy, attachment style, emotion dysregulation, reflective function, and, interpersonal reactivity.A stimulating study by French and Chen measured respiratory sinus arrhythmia (RSA), skin conductance (SC), and self-reported emotions at baseline and after film clips that elicited either a neutral, sad, happy, or fearful emotional state. They found that ED groups compared to individuals without EDs generally reported more negative emotions (e.g sadness and anxiety) but were not more emotionally reactive to the film stimuli, which lacked ED-specific content. That is, those with AN reported more fear, those with binge eating disorder (BED) reported more frustration, and those with BED and with bulimia nervosa (BN) reported more tension than healthy controls. Furthermore, patients with BN and BED showed decreased urges to binge during all film clips compared to baseline, suggesting that non-ED specific emotion-eliciting stimuli may at least temporarily decrease urges to binge, even while inducing negative affect.Another interesting article in our Research Topic concerns the role of emotions and psychophysiological responses across the main EDs diagnosis. Springmann et al. expand the discussion of gender and ED. They suggest that understanding the role of gender for ED relies on adequate methodological and theoretical access to the construct of gender.Gender is a relevant factor in the etiology of ED and the prevalence of the ED show that women are excessively affected, compare to men  of eating among 341 college campus students. Their findings showed that LOC of eating occurred for individuals with higher ED psychopathology who experienced depressive symptoms. Moreover, self-criticism was a mediator between emotion regulation and disorder eating, which was significantly associated with LOC eating via increased negative urgency.Concerning non-clinical samples, Aouad et al. investigated the relationship between defense-style (coping strategies) and ED outcomes over a 5-years period. They found that immaturity and neuroticism but not maturity were the defense-style variables that predicted psychological distress over a 5-years period, while psychological distress predicted only neurotic defense styles. These results may suggest that without treatment, mature, immature and neurotic defense-styles may largely remain immutable to significant shifts over time.Santo André et al. explored how a group of classical ballet dancers perceived their eating attitudes and their bodies, looking for possible EDs symptoms and body image (dis)satisfaction. The constant restrictive diets and other weight-loss strategies to achieve a leaner body were associated with ED symptoms and body dissatisfaction. Remarkably, 50% of the sample were dissatisfied with their current body shape, and for 57% of them the desired body shape was a leaner figure than the one they considered healthy.It is well-known that participating in specific activities like dance could be an ED risk factor. Strahler et al. found increased difficulties in regulating their emotions and more insecure attachment pattern among people with higher pathological orthorexic eating. According to the authors differentiating between pathological  and healthy  orthorexic eating behaviors can be helpful for the diagnosis of orthorexia nervosa.Finally, a study explored the psychological correlates of excessive healthy and orthorexic eating in a convenience sample of 399 adults. Pellegrini et al. proposed a reflection on the functioning of EDs that include the impact of early relational trauma on emotion regulation strategies, the role of attachment relationships in the development and maintenance of these disorders, the narrative construction of the self and the symptom, and connections with somatic memories. For a better understanding of eating disorders, they propose the model of Multiple Access Psychotherapy (MAP). MAP focuses on the self-referential modalities through which the individual tends to build the representation of the self and of oneself in the world, adapting the own preferred “access route” to deal with suffering.As an ideal conclusion of the present Research Topic, the article by The present Research Topic was designed to promote a scientific discussion around, and e fforts to address the complex issue of the psychosocial risk factors of EDs. Relevant manuscripts were collected to increase our knowledge on several aspects of these risk factors in EDs. A major part of clinical research is currently directed toward trying to identify the underlying factors of different psychological disorders, moving beyond any reductionist approach. The identification of such factors provide crucial information for the development of effective prevention and treatment programs.All the manuscripts in this Research Topic provided a broad description and explanation of the psychosocial risk factors in ED, and sought to provide practical and useful information on their evaluation and usefulness in different treatment options. We believe that identifying risk factors in EDs still represents a challenge for all health and mental health professionals.Overall, we hope that this Research Topic dedicated to the psychosocial risk factors in EDs will contribute to further improvements in the field, providing interesting insights and help clinician and researchers to grasp the complexity of this topic.MA wrote the first draft of the manuscript. CS-G, GLC, AC, GN, and GT provided critical revision of the manuscript and important intellectual contributions. All authors read and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Concrete is one of the most widespread materials in the civil engineering field due to its versatility for both structural and non-structural applications depending on the density range, competitiveness in terms of durability and manufacturing costs, as well as ease in finding raw constituent elements. For this reason, the mechanical behavior of concrete and, even more, reinforced concrete (RC) has been a research theme tackled by many researchers through different approaches for years. Although the relevant literature is full of papers on this topic, ranging from experimental works to theoretical contributions, an accurate and comprehensive description of the actual mechanical behavior exhibited by concrete and reinforced concrete at service and ultimate conditions still remains a challenge in the field of structural engineering. This is due to several intricate and interconnected phenomena involved, such as tensile cracking, compression crushing, strain softening, interaction between aggregates and matrix, interaction between concrete and reinforcement, stiffness degradation, energy dissipation, and ductility exhibited under cycling loading.Following these research motivations, this Special Issue collects 15 papers focused on the mechanical behavior of concrete materials and structures, including both experimental findings and numerical analyses using both conventional and advanced methodologies. In the Editors’ opinion, each article contains clear scientific novelty from various standpoints , thus representing a major contribution to the understanding of the mechanical behavior of concrete materials and structures. The Editors hope that this article collection can somehow contribute, even if modestly, to the continuous research for a more thorough and reliable understanding of the mechanical behavior of ordinary and prestressed concretes, as well as special concretes, including high-strength, recycled, and fiber-reinforced concretes, for both structural and non-structural applications, and for the development of related numerical/analytical predictive models.Among the experimental contributions, Ni et al.  presenteThree contributions were focused on recycled concretes, from either an experimental or numerical perspective. Garbaya et al.  incorporThe mechanical behavior of concrete was analyzed not only under static loading. The dynamic characteristics of concrete were experimentally investigated by Sun et al.  through Another aspect playing a key role in structural serviceability analyses of RC structures is the concrete shrinkage. Dey et al.  presenteThe influence of multi-walled and single-walled carbon nanotubes (CNTs) on the carbonation, compressive and flexural strength, electrical resistance, and porosity of special mortars was experimentally analyzed by Lee et al. . Based oAn increasing number of researchers have recently advanced the use of machine learning methodologies for predicting the mechanical characteristics of concrete based on training sets of data. For estimating the compressive strength of ultra-high-strength concrete (UHSC), Shen et al.  used sofBernardo et al.  addresseThe deflection behavior of horizontal structural members was the object of the investigation of D’Antino and Pisani . The recOne of the most complex phenomena to simulate in concrete structures is fracture behavior, due to the heterogeneous microstructure and interaction between aggregates and matrix. In this context, Tawfik et al.  employedIt is well known that durability of existing concrete structures was not always regarded as a crucial performance requirement in the past, and periodical maintenance plans have not been performed over the years. As a consequence, many damage phenomena have been recently observed in existing concrete structures dated from around 50 years ago; in some extreme cases, these damage mechanisms have led to complete structural collapse, as recently observed for bridges. One of the most serious factors negatively affecting the durability of concrete structures is the corrosion of steel reinforcement. In this context, De Domenico et al.  developeFinally, the review paper by Dong et al.  illustra


Ankle fracture-dislocations are one of the most severe types of ankle injuries. Compared to the simple ankle fractures, ankle fracture-dislocations are usually more severely traumatized and can cause worse functional outcomes. The purpose of this study was to review the previous literatures to understand the anatomy, mechanisms, treatment, and functional outcomes associated with ankle fracture-dislocations.The available literatures from January 1985 to December 2021 in three main medical databases were searched and analyzed. The detailed information was extracted for each article, such as researchers, age, gender, groups, type of study, type of center research, level of evidence, significant findings, study aim, cause of injury, time from injury to surgery, type of fracture, direction of dislocation, follow-up, postoperative complications and functional evaluation scores.A total of 15 studies  met the inclusion criteria. Only one study was a prospective randomized trial. The top-ranked cause of injury was high-energy injury (21.3%). Moreover, the most frequent type of fracture in ankle dislocations was supination-external rotation (SER) ankle fracture (43.8%), while the most common directions of dislocation were lateral (50%) and posterior (38.9%).Collectively, most ankle fracture-dislocations are caused by high-energy injuries and usually have poor functional outcomes. The mechanism of injury can be dissected by the ankle anatomy and Lauge-Hansen's classification. The treatment of ankle fracture-dislocations still requires more detailed and rational solutions due to the urgency of occurrence, the severity of injury, and the postoperative complications. Ankle fractures are one of the most widespread fractures in adults, with a morbidity of 174 per 100,000 per years . HoweverThe patients who experience the ankle fracture-dislocations tend to have poorer functional outcomes –6. This The electronic literatures were searched from PubMed, Web of science and Scopus databases using the search terms of “ankle fracture-dislocations”, “dislocated ankle fractures”, “fracture-dislocation of the ankles” and “Malleolar fracture dislocation”. The overall search procedures, including literatures search, data extraction and quality evaluation were performed by the two independent reviewers. The referenced papers included in reviewed articles were also examined, and the final search was performed on 5 January 2022.Studies were excluded if they were case reports, case series, conference abstracts. Moreover, the manuscripts were unable to be reviewed if it cannot be presented in a type of full-text. A fracture-dislocation was diagnosed when radiographs demonstrated ankle fractures with the presence of separation of the talus relative to the tibia on either the anteroposterior or lateral view. The search was performed by each reviewer independently with any disagreements in article eligibility resolved by the consensus discussion among all authors. Moreover, studies on the ankle fracture-dislocations that were written in English and presented as full-text were included in this review. Studies that were not written in English, not related to the topic of ankle fracture-dislocations, pure ankle dislocations, included only specific types of ankle fracture-dislocations, such as the “Logsplitter” injury , and lacAll data were collected by the two reviewers according to the uniform criteria. We documented the first author, title, published journal, year, type of study, design, and level of evidence of each study. The demographic data were recorded and extracted, including the groups, sample size, gender and age. The detailed data includes time from injury to surgery, operative time, fracture classification, surgical technique, clinical outcomes and postoperative complications. Moreover, the postoperative complications mainly included infection, posttraumatic arthritis, delayed union, nonunion, malunion and so on. The level of evidence was evaluated based on the guidelines of the Oxford Centre for Evidence-Based Medicine .The overall data in this current review were exhibited as the count (percentage) or mean ± standard deviation (SD). The pooled means were calculated for the mean age, time from injury to surgery and length of follow-up.The results of search strategy and study selection criteria are shown in A total of 1,089 patients were enrolled in 15 included studies. As shown in As exhibited in the As shown in the As shown in Based on the key findings of our systematic review of ankle fracture-dislocations, most studies have focused on the treatment and functional outcomes. In order to explore the injury in depth, we decided to look at the anatomy as well as the pathological mechanisms of the ankle joint and further discuss the treatment as well as the prognosis by analyzing the pattern of injury. The purpose of this systematic review is to provide a more scientific and comprehensive understanding of ankle fracture-dislocations to guide treatment selection and subsequent related studies from the following aspects., posterior inferior tibiofibular ligament (PITFL) and interosseous tibiofibular ligament (IOL). Functionally speaking, the role of the AITFL is to tighten the fibula to the tibia and limit the excessive motion of fibula and external rotation of talus , 33. A cThe PITFL is generally considered to have two parts . Importantly, partial analyses indicate that transverse ligament is an important structure independent of the posterior inferior tibiofibular ligament . Its fibThe IOL is considered to be the distal continuation of interosseous membrane of tibiofibular joint, which mainly inhibits the lateral translation of fibula , 38. SevIn terms of the injury pattern of ankle fracture-dislocations, strong violence causes the fracture and ligament damage and eventually results in the loss of alignment of the articular surfaces.The Lauge-Hansen's classification is the basis of ankle fracture mechanism and four types of ankle fracture-dislocations according to classification are exhibited in In addition, it is clear that the AITFL will be the first to rupture. Since PITFL is a relatively strong ligament, its injury often takes the form of an avulsion posterior ankle fracture. Its deeper layer, the transverse ligament, forms a posterior labrum that limits the posterior displacement of talus, this results in a relatively rare posterior dislocation of talus. When the talus is extremely externally rotated, the injury to PTFL can occur and are essentially only seen in cases of ankle dislocation . The SERAs one of the most severely injured and intricate types of ankle fractures, a recent study has confirmed that trimalleolar fractures have a higher risk of dislocation . BiomechThe PER fractures are severe ankle injuries and account for approximately 14%–22% of all ankle fractures , 50. A rThe other two uncommon types reveal relatively significant differences in dislocation rates. The probability of dislocation is 76% for the pronation-adduction (PAD) ankle fracture versus 5% for supination-adduction (SAD) ankle fracture (The ankle fracture-dislocations are consisted of the fractures with total dislocation and subluxation. According to the relationship between direction of talus displacement and ankle mortise, ankle dislocations are classified into five types, including the anterior, posterior, medial, lateral, superior or the combination of these directions. The anterior ankle dislocation is generally where the foot remains stable, the ankle is forced into dorsiflexion, and there is a backward force on the lower leg. Due to the anterior dislocation of the talus, the dorsalis pedis artery may be damaged as a result , 55–57. Ankle fracture-dislocations may increase the risk of the injury to soft tissues surrounding ankle and overlying skin and consequently result in severe complications. The main indication for conducting a non-surgical closed reduction is ankle subluxation . Non-disExternal fixation is mainly the application of gypsum or splinting after the closed reduction. The ankle is usually immobilized in a neutral position to maintain the ankle stability and avoid contracture of Achilles tendon, and the care must be taken to avoid the skin compression when using the plaster fixation, especially in the elderly who can develop the severe skin ulcers as a result . In addiThe surgical timing for ankle fractures is not yet definitive. Generally, the ankle will begin to swell continuously within 48 h after the fracture occurs, especially if the ankle is dislocated. Most surgeons are concerned about the skin complications associated with early surgery on an overly swollen ankle –68. CurrThe purpose of ankle fracture surgery is to restore the fibula length and maintain the stable anatomical reduction. The treatment of open ankle fracture-dislocations focuses on avoiding the infection, reducing the rate of complications, promoting the bone healing and restoring the good function . The mosAnkle fracture-dislocations represent a more significant injury to the bony and soft-tissue structures of ankle joint. Thus, we need to focus on the treatment of periarticular ligament injuries in addition to ORIF routinely. Based on the previous analysis of the mechanism of injury, the ankle fracture-dislocations are usually combined with the syndesmotic injuries. Moreover, the instability of the syndesmotic complex may result in the long-term dysfunction and osteoarthritis . AlthougJudging by the mechanism of injury, the ankle fracture-dislocations are likely to be accompanied with the injury to medial deltoid ligament. It is worth being vigilant that 58.3% of acute ankle fractures were associated with the medial triangular ligament injury . ApproxiWith the increasing demand for functional movement in modern society, more and more orthopaedic surgeons are currently concerned about the functional outcomes of ankle fracture-dislocations. A study on the prognosis of ankle fracture-dislocation found that the functional outcomes were worse in the open ankle fracture-dislocations. Talar cartilage injury after dislocation tends to be prone to arthrosis, and its prevalence increases with age . HoweverAnkle fracture-dislocations are mostly due to the high-energy violence and can be accompanied with varying amount of bone and soft tissue injury. Dislocation often leads to worse functional outcomes in ankle fractures. According to Lauge-Hansen's classification, the injury of the deep deltoid ligament is closely related to the injury mechanism of SER and PER ankle fractures. Conservative treatment is not recommended in the event of fracture-dislocation. In addition to conventional ORIF, syndesmotic fixation is also important while additional deltoid ligament repair is unnecessary. Collectively, the ankle fracture-dislocations still require a more comprehensive and clearer treatment guideline in the future, as well as the prognostic evaluation system.


Dental implant restoration is the preferred choice for patients with dentition defects or edentulous patients, and obtaining stable osseointegration is the determining factor for successful implant healing. The risk of implant failure during the healing stage is still an urgent problem in clinical practice due to differences in bone quality at different implant sites and the impact of some systemic diseases on bone tissue metabolism. Low-intensity pulsed ultrasound (LIPUS) is a noninvasive physical intervention method widely recognized in the treatment of bone fracture and joint damage repair. Moreover, many studies indicated that LIPUS could effectively promote the osseointegration of dental implants and improve the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). This review is aimed at investigating the research progress on the use of LIPUS in dental implant medicine from three aspects: (1) discuss the promoting effects of LIPUS on osseointegration and peri-implant bone regeneration, (2) summarize the effects and associated mechanisms of LIPUS on the biological functions of BMSCs, and (3) introduce the application and prospects of LIPUS in the clinical work of dental implantation. Although many challenges need to be overcome in the future, LIPUS is bound to be an efficient and convenient therapeutic method to improve the dental implantation success rate and expand clinical implant indications. With the advancement of dental implant science, implant restoration has become the preferred treatment approach for patients with dentition defects or edentulous to restore oral function and aesthetics . OsseoinGood bone quality and adequate bone mass can ensure that dental implants are placed at the ideal site, leading to a good functional and aesthetic outcome. However, periodontal disease, trauma, and bone tissue atrophy or resorption often cause alveolar bone insufficiency, and thus, different degrees of peri-implant bone defects appear after the implants are placed. Therefore, bone augmentation surgery, such as guided bone regeneration (GBR), is required to cover the exposed surface of the implant . HoweverFurthermore, systemic diseases, such as diabetes mellitus and osteoporosis, are considered important risk factors that impact the success rate of dental implant treatment. These diseases are usually accompanied by different degrees of bone remodeling disorders, which can interfere with the osseointegration of implants during the healing period. Although diabetes mellitus with good blood glucose control and osteoporosis under systemic medication is no longer absolute contraindications for implant surgery because of the progress in implant surface treatment technology , several2 to produce many biological effects, including promoting protein synthesis, improving cell proliferation, and increasing cellular secondary messenger calcium uptake . T. T2 inteIn addition, Abdulhameed et al. observed an increase in the thickness of the buccal bone plate in the implantation area stimulated by LIPUS, with a statistically significant difference compared with the control group of patients who underwent conventional healing . MoreoveLIPUS has the advantages of low toxicity, low immunogenicity, noninvasiveness, high targeting selectivity, and repeatability , 23, 69.As novel physiotherapy, LIPUS has been widely used in bone tissue, cartilage tissue, and soft tissue repair and reconstruction, and many studies have used it to promote the regeneration of oral and maxillofacial tissue. In the field of dental implantology, the application of LIPUS is still in its infancy. The existing studies provided a certain research foundation concerning the mechanism and clinical function of LIPUS, but further discussion is still needed.In this review, based on the existing studies, it was found that LIPUS had an apparent promoting effect on dental implant osseointegration, suggesting that LIPUS could shorten the healing cycle after implant surgery and accelerate peri-implant bone reconstruction. Bone-derived cell adhesion, proliferation, migration, and differentiation on the surface of implants play a key role in the osseointegration process. This review systematically summarized the current role of LIPUS in the biological functions of the cells and related mechanisms. In addition, this review also addressed the application prospects of LIPUS in clinical dental implantation. Despite facing many challenges, based on the experience of LIPUS application in the treatment of bone tissue diseases, such as fracture and bone defect, the potential value of LIPUS in clinical dental implantation may be far beyond the existing reports.in vitro, we suggested that a transformation from a small-animal model to a large-animal model be considered for in vivo validation experiments. A model of jaw bone implantation with weight-bearing stress can be established, and the observation period can be further extended to more convincingly detect the effect of LIPUS. In addition, we also suggest exploring the therapeutic effect of LIPUS on the osseointegration of implants in abnormal microenvironments, such as in diabetes or osteoporosis, and clarifying the intervention effect of LIPUS on implants with poor initial stability or a poor healing state, so as to provide a new theoretical basis for improving the success rate of dental implantation and expanding the clinical indications.Based on the in-depth exploration of the mechanism of LIPUS


Adolescents of underserved communities face multiple health system barriers to access HPV vaccination. The Horizon 2020 project RIVER-EU will implement interventions to address these barriers in the migrant community in Greece, the Turkish and Moroccan communities in the Netherlands, the Ukrainian community in Poland and the Roma community in Slovakia. The objective of this study was to identify promising evidence-based interventions that potentially meet the specific contextual needs of the target groups, as a basis for assessing their transferability.Based on the PIET-T models of transferability, we developed a methodology to assess the needs-based usefulness of an intervention for a target context. Criteria of intervention usefulness addressed specific aspects of the health issue, population, intervention content, outcomes, up-to-datedness, applicability, quality and usefulness of the evidence-base. Guided by methodological workshops, country members with their local advisory boards performed a rating of 32 interventions identified from a systematic literature search.Through independent assessment in each country, 5 of 32 interventions were selected as useful, with overlap: 2 interventions were selected by all countries, and 1 by 2 countries. In all countries, trained community members to support HPV vaccination were seen as promising. In Greece and the Netherlands, an educational programme in schools was included. Further, the Netherlands chose an intervention addressing providers’ HPV vaccine communication, and Slovakia a multilevel intervention.The feedback of the country members on the assessment emphasised the structured way to face complexity of understanding the potential usefulness of an intervention from the perspective of the target country. Critical discussions on the interventions enabled to specify needs for further clarification, for adaptations, and alternatives to consider for transferability analyses.Identifying potentially useful health system approaches to vaccination in specific contexts is a complex step that goes beyond analysing quality of primary evidence.Our methodology for intervention selection emphasises the consideration of the unique needs of target communities to address health system barriers to vaccination.


Dear readers,Pulsed-field ablation (PFA) for cardiac arrhythmias was recently developed to incorporate a novel, non-thermal energy source for ablation. The procedure consists of applying rapid electrical pulses to the target area, resulting in apoptosis, without the use of thermal energy. Moreover, it is cardiac-specific and was demonstrated to spare collateral structures such as the esophagus and phrenic nerve. Single-arm studies were conducted in Europe and demonstrated its safety and efficacy, leading to the commercial release of PFA catheters there. In the United States, the technology remains investigational, awaiting the completion of randomized clinical trials that are currently ongoing.The Journal of Innovations in Cardiac Rhythm Management contains an interesting article investigating this aspect of PFA, titled “Open-chest Pulsed Electric Field Ablation of Cardiac Ganglionated Plexi in Acute Canine Models.”1 In it, the authors demonstrated that the epicardial ablation of ganglionated plexi using pulsed-field energy results in altered markers of cardiac autonomic tone.Despite the large number of clinical and pre-clinical studies investigating PFA, some aspects of its mechanism of action remain poorly understood. One particular area is its effect on cardiac ganglionated plexi. This issue of The ablation of ganglionated plexi has the potential to improve the success rate of catheter ablation if used as an adjunctive treatment to pulmonary vein isolation in selected patients; thus, it is possible that this study by van Zyl et al. may have important clinical implications in the future. However, it also has limitations, the most important of which is the fact that it was acute and thus lacks data concerning the chronic effect of PFA on the autonomic nervous system. It is well known that PFA can cause reversible stunning of the phrenic nerve when it is inadvertently ablated during pulmonary vein isolation. As a result, it is important to prove in longer-term studies that ablation of the ganglionated plexi is irreversible before it can be tested in human studies.I hope that you find the content of this issue educational.Sincerely,md, fhrs, faccMoussa Mansour, Editor in ChiefThe Journal of Innovations in Cardiac Rhythm ManagementMMansour@InnovationsInCRM.comDirector, Atrial Fibrillation ProgramJeremy Ruskin and Dan Starks Endowed Chair in CardiologyMassachusetts General HospitalBoston, MA 02114


Drug addiction is a chronic psychiatric disorder characterized by compulsive drug-seeking and drug-using behavior, and a tremendous socioeconomic burden to society. Current pharmacological and psychosocial methods have shown limited treatment effects for substance abuse. Deep Brain Stimulation (DBS) is a novel treatment for psychiatric disease and has gradually gained popularity in the treatment of addiction. Addiction is characterized by neuroplastic changes in the nucleus accumbens (NAc), a key structure in the brain reward system, and DBS in this region has shown promising treatment effects. In this paper, the research progress on DBS for drug addiction has been reviewed. Specifically, we discuss the mechanism of NAc DBS for addiction treatment and summarize the results of clinical trials on DBS treatment for addiction to psychoactive substances such as nicotine, alcohol, cocaine, opioids and methamphetamine/amphetamine. In addition, the treatment effects of DBS in other brain regions, such as the substantia nigra pars reticulata (SNr) and insula are discussed. Addiction is a brain disease manifested by compulsive substance use despite harmful consequences. Drug addiction is one of the most serious and global public health problems. According to a recent survey, smoking, alcohol abuse and illegal drug use cause 11.8 million deaths each year, which is more than all cancer deaths . It was With the development of neurosurgery, Deep Brain Stimulation (DBS) technology has gradually gained popularity in treating addiction. DBS uses 3D imaging technology to accurately target specific areas of the brain, such as the subthalamic nucleus (STN) and the nucleus accumbens (NAc), using intracranially implanted electrodes connected to pectorally implanted batteries and pulse generators (IPG). During stimulation, DBS electrodes influence neural activity through high-intensity pulses to achieve the desired therapeutic effect. DBS technology was originally used for the treatment of movement disorders starting in the 1980's, and has achieved satisfactory results in the treatment of progressive dyskinesias . By 2019Compared with traditional brain neurosurgery, DBS has the characteristics of reversibility and controllability, and is regarded as a safe alternative treatment compared to pharmacological treatment for neurological and psychiatric conditions. So far, the Food and Drug Administration (FDA) has approved DBS technology for Parkinson's disease (PD), obsessive-compulsive disorder (OCD), essential tremor (ET) and primary dystonia . In addiThe etiology and pathogenesis of drug addiction are related to altered functioning of multiple brain systems. These include altered glutamate, opioid, cannabinoid, gamma-aminobutyric acid, norepinephrine and serotonergic systems. In addition, the mesolimbic dopaminergic reward system plays a central role in the pathogenesis of addiction and hypofunction of this system is a key characteristic of drug addiction. It is widely accepted that the initial reinforcing effects of drugs of abuse are mediated by large and rapid increases in the level of dopamine (DA) in the NAc. However, prolonged use of these drugs leads to hypofunction of the dopamine system . It has Common addictive substances include nicotine, alcohol, cocaine, methamphetamine, marijuana, opioids, tranquilizers and sedatives , and theAddiction caused by these psychoactive substances is considered to be a relapse disorder with repeated stages. It is a cycle composed of three stages of “drug use,” “withdrawal” and “craving and relapse”, and aniAt present, the specific mechanism that underlie the therapeutic effects of DBS for the treatment of psychiatric disease has not been fully understood, but great progress has been made in the treatment for obsessive-compulsive disorder , 24, majDBS was initially thought to inhibit local neurons because the therapeutic effects of DBS in the subthalamic nucleus were similar to the effects of damage to the subthalamic nucleus , 29. HowNeuroplasticity is the basis of learning and long-term memory. DBS of the anterior thalamic nucleus and ventromedial pre-frontal cortex of rats can promote the proliferation of granule cells in hippocampal dentate gyrus and the increase of hippocampal synaptic density, respectively . TreatinAbnormal neural oscillations will affect the communication function of the brain. Rhythmic DBS interrupts the pathological neural oscillations in the target nucleus and connected circuit, and normalizes dysfunctional information flow to improve brain function . The impAddiction to psychoactive substances, also known as psychoactive substance use disorder, is characterized by repeated desire to continue taking the substance regardless of harmful consequences . AlthougNevertheless, the mechanism of NAc DBS treatment for addiction is still unclear. Some animal studies indicate that the reduction of addictive behavior depends on the normalization of activity in the NAc shell, a part of NAc responsible for the perception of the rewarding effects of drugs , 48. AddSince 2003, several clinical trials of DBS treatment in addiction to psychoactive substances such as tobacco, alcohol, cocaine, opioids and methamphetamine/amphetamine have been completed. The stimulation parameters, outcome, duration of follow-up and reported side effects have been summarized in The effect of DBS on smoking cessation was unexpectedly found in a study of DBS treatment for other neuropsychiatric disorders. Among patients with anxiety disorder, obsessive-compulsive disorder or Tourette syndrome with a long-term smoking history, three out of every 10 people were able to quit smoking after DBS, and the smoking addiction severity and cigarette consumption of the remaining seven participants also decreased significantly during 1-year, 2-year, and 30-month follow-up. Kuhn et al.  found thTo date, three studies investigated the effect of NAc DBS on alcohol use and found that alcohol intake or craving was reduced in all the studies , 45, 52.In 2016, Gonzales-Ferreira treated a cocaine addicted patient using DBS electrodes placed in the medial NAc adjacent to the bed nucleus of the stria terminalis (BNST) . Six monRecently, three studies investigated the effects of NAc DBS on opioid consumption or cravings –59 and rZhang et al.  found thDrug addiction is a chronic mental disorder characterized by compulsive drug-seeking and use behavior. Substance use disorders are a major socioeconomic burden to society. In recent decades, DBS has emerged as an effective way to treat addiction to psychoactive substances, providing a novel option for patients with high relapse risks after traditional treatments have failed.Although the NAc is the most widely used site for the stereotactic implantation of DBS electrodes for the treatment of addiction , 62, theIt should be mentioned that DBS is an invasive surgical intervention with potential risks, including hemorrhage and infection , 70. AltIn conclusion, the application of DBS treatment for drug addiction is challenging but promising. However, it should be mentioned that most results are obtained from case reports. Further double-blinded studies and clinical trials, potential synergy with other non-invasive interventions, and larger patient populations are needed for validating DBS as a standard treatment option for refractory substance use disorders.RC, JZ, and ST wrote the paper. JP, HL, YC, and SZ collected the literature. All authors contributed to the article and approved the submitted version.This work was supported by grants from the National Science Foundation of China (NSFC 81301144) and Research Learning and Innovative Experiment Project for University Students of University of South China .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.


A structural scaffold embedding brain cells and vasculature is known as extracellular matrix (ECM). The physical appearance of ECM in the central nervous system (CNS) ranges from a diffused, homogeneous, amorphous, and nearly omnipresent matrix to highly organized distinct morphologies such as basement membranes and perineuronal nets (PNNs). ECM changes its composition and organization during development, adulthood, aging, and in several CNS pathologies. This spatiotemporal dynamic nature of the ECM and PNNs brings a unique versatility to their functions spanning from neurogenesis, cell migration and differentiation, axonal growth, and pathfinding cues, etc., in the developing brain, to stabilizing synapses, neuromodulation, and being an active partner of tetrapartite synapses in the adult brain. The malleability of ECM and PNNs is governed by both intrinsic and extrinsic factors. Glial cells are among the major extrinsic factors that facilitate the remodeling of ECM and PNN, thereby acting as key regulators of diverse functions of ECM and PNN in health and diseases. In this review, we discuss recent advances in our understanding of PNNs and how glial cells are central to ECM and PNN remodeling in normal and pathological states of the CNS. In 1895, Hens Gierke proposed the idea of a homogeneous and amorphous ground substance that embeds neuroglia and forms the structural architecture of the brain . Soon afA large fraction of ECM is homogeneous and amorphous; however, several morphologically distinct forms are distributed throughout the brain . A thin Recent studies suggest that the structural organization of ECM and PNNs, and therefore their functions, are regulated by intrinsic mechanisms- driven by neurons- as well as extrinsic- driven primarily by glial cells . CNS gliWhile astrocytes are mainly engaged with the synthesis and release of ECM and their proteolytic enzymes, it is microglia that contribute significantly to the continuous elimination of the ECM molecules due to their characteristic phagocytic property. Normally, the homeostatic states of ECM and PNNs are maintained by a constitutive expression of ECM and proteases by neurons and astrocytes, as well as clearance by microglia. However, as seen in several recent studies on epilepsy, Alzheimer’s disease (AD), Huntington’s disease (HD), neuropathic pain, etc., dysfunctional microglia leads to abnormal clearance or accumulation of the ECM and PNNs contributing to the pathology .In this review, we discuss the classic roles of and recent advances in the functions of ECM and PNNs, followed by the role of glial cells in ECM and PNN remodeling in healthy brain and pathologies. These roles suggest a pivotal contribution of glial cells to this remodeling process and thus encourage a discussion on a glia-centric approach to treatment strategies.Extracellular matrix is present in all tissues of the body as a structural framework of amorphous and diffused interstitial matrix; however, brain ECM is unique in its composition and organization. From a composition point of view, a major fraction of the brain ECM consists of glycosaminoglycans (GAGs), proteoglycans, and glycoproteins, with a negligible fraction of fibrous proteins which is contrary to the fibrous protein-rich ECM in a majority of other tissues . Anothervia which fluids and soluble molecules enter and leave the brain, BMs provide structural support by acting as an adhesive substrate for cells to anchor to and mediate signal transduction via integrin and other transmembrane matrix receptors  and brain vasculature (vascular BM) . Similareceptors . Meningeeceptors . The vaseceptors  and colleceptors . In seveeceptors . Extravaeceptors , 2017  . This foA large fraction of diffused interstitial matrix coats the synapses, forming a perisynaptic matrix, and is involved in synaptogenesis and plasticity often under the regulation of matrix remodeling enzymes . DepletiBesides PNNs, few other specialized phenotypes of the ECM are embedded largely within the diffused interstitial matrix. For example, perinodal ECM is a condensed form of ECM around the nodes of Ranvier  consistiHistorically, PNNs have been the most intriguing yet enigmatic ECM structures. PNNs are widely expressed in several brain regions including the cerebral cortex, amygdala, striatum, and hippocampus  as well The key role of anchoring the extracellular components of PNNs to the cell membrane is performed by HA-producing transmembrane enzymes, hyaluronic acid synthase (HAS 1-3) . HAS-assIn different regions of the developing mouse brain, traces of PNN appear at different ages and gradually achieve fully condensed arborization in several weeks. For example, immature PNNs can be identified in brainstem by postnatal day 4 ; howeverDespite a progressive condensation of CSPGs into PNNs in the developing brain, the total CSPG content remains largely unchanged- which complicates the question of mechanisms whereby PNN CSPGs are inhibitory to neuroplasticity . IntriguDevelopmental formation of PNNs is activity-dependent, and several brain regions including barrel cortex, thalamus, visual cortex, and vocal center in songbirds show underdeveloped PNNs if deprived of activity, suggesting a high malleability of PNNs . AlthougChondroitin sulfate proteoglycans are critical constituents of the PNNs and several signaling functions of CSPGs are independent of their phenotypic appearance as PNNs or interstitial matrix as evidenced in the following studies. In the extensively studied visual system, a high density of CSPGs repels the growing retinal axons to navigate them to their target areas in the developing brain. Conversely, depleting CSPGs with ChABC is disruptive to the axonal guidance and misleads the axons to non-target areas . Since aSubsequently, in adolescence, CSPGs are condensed as PNNs, which are largely known to lock the synapses to prevent further modifications and close the critical period of heightened neuroplasticity as discussed in the previous section. Intriguingly, the plasticity reinstates in the adult CNS when PNNs are disrupted. Mechanistically, disruption of PNN or its constituents triggers several short and long-term cellular and molecular changes which can promote neuroplasticity. For example, PNN depletion induces synaptic potentiation in otherwise plasticity-resistant CA2 synapses . BrevicaPerineuronal nets and interstitial matrix are by and large composed of the same set of ECM molecules; therefore several functions of PNNs can be considered independent of their structural integrity. However, there are several functions which require the organized PNN assembly with sulfated proteoglycans . Several+, K+, or Ca++ ions. During the fast-spiking activity of PV neurons, a dynamic exchange of Na+ and K+ ions with the stationary negative charges of the PNNs can aid the PV neuron activity  increases the membrane capacitance of the PV neurons leading to a reduction in spike firing activity and consequently reducing the overall inhibitory drive. Experimental disruption of PNNs mimics the increased capacitance and reduced firing activity of PV neurons as shown by PV neurons with disrupted PNNs in glioma , suggestThe necessity of PNNs in CNS functioning is profoundly evidenced in CNS disorders in which PNN disruption is commonly observed; experimental PNN disruption largely phenocopies the disease characteristics. In acquired forms of epilepsies triggered by injury, stroke, and brain tumors, elevated matrix remodeling proteases disrupt the PNNs . PNN disA similar dysfunction of PV neurons accompanied by disrupted PNNs is evidenced in animal models and human subjects of schizophrenia, bipolar disorder, and autism spectrum disorders , whereinIn summary, a large number of studies suggest that the physiological functions of the PNNs and their constituents broadly encompass developmental signaling, regulation of neuroplasticity, modulation of neuronal activity, extracellular ion homeostasis, and neuroprotection. In diseased states increased proteolytic cleavage of PNNs disrupts their structural integrity and reduces the overall abundance. Depending on the brain area/s involved, loss of PNNs can contribute to disease etiology predominantly by PV neuron dysfunction and altered E-I balance, loss of neuroprotection, altered ECS and ionic balance, and maladaptive neuroplasticity . The cauOne of the classic housekeeping functions of glial cells is the continuous secretion of ECM molecules to maintain the architecture and extracellular milieu of the CNS. In principle, both neurons and glial cells synthesize and secrete ECM molecules; however, glial cells- especially astrocytes and microglia- are the primary regulators of ECM wear and tear in CNS pathophysiology. In this section, we discuss the role of glial cells in the homeostatic regulation of ECM and PNN and consequently the functional outcome.Astrocytes, the most abundant CNS glia, are involved in a variety of functions including neuronal migration, secretion of growth factors and neuromodulatory molecules, synaptogenesis, synaptic pruning, and water, ion, and neurotransmitter homeostasis . In the Astrocytes are the predominant source of hyaluronan that constitutes the interstitial matrix and PNNs in the gray matter and surrounds the myelinated fibers in white matter . Since hBesides CSPGs, tenascins, and HA, which act as both structural and signaling molecules, astrocytes secrete several ECM glycoproteins known as matricellular proteins primarily for a signaling function. By adjusting the spatiotemporal expression of matricellular proteins such as hevin/SPARC , thromboFrom a structural point of view, astrocytes, in conjunction with capillary endothelial cells and pericytes, synthesize and assemble ECM components to form the BM . Subsequin vitro without astrocytes , and glycoprotein (fibronectin and vitronectin) are deposited around the lesion, primarily by reactive astrocytes forming the glial scar . CondensSince PNN disruption is commonly observed in several CNS disorders, it is a legitimate question whether astrocytes play any role in PNN disruption in such pathologies. The answer lies partly in the fact that astrocytes are a major source of PNN-disrupting MMPs in both homeostatic and diseased states. After brain injury and trauma, PNN disruption is accompanied by upregulation of MMP-2 and MMP-3 levels by reactive astrocytes . MMP-9 aMicroglia are the resident immune cells in the brain and are known for their classic phagocytic function of eliminating entire cells or subcellular structures- mainly synapses- in healthy and diseased states . The devPioneering studies in the recent past implicate microglia equally well in the regulation of homeostatic functions such as ECM and PNN remodeling, eventually governing synaptic plasticity. The classic example is a reversible increase in the abundance and condensation of cortical PNNs  and incrA similar role of microglia has recently been reported in the spinal cord dorsal horn wherein peripheral nerve injury promotes microglial degradation and endocytosis of PNNs around projection neurons. PNN depletion activates the projection neurons to induce pain-related behavior . DespiteDespite a wide range of upstream cellular and molecular events, the mechanisms of ECM and PNN remodeling largely converge onto the metalloproteinases, which serve as an immediate effector to decisively control the ECM and PNN remodeling. Metalloproteinases are zinc-containing endopeptidases, normally expressed by neurons, astrocytes, microglia, and endothelial cells. However, under pathological conditions such as ischemic stroke and brain tumors, non-resident immune cells and tumor cells can also produce metalloproteinases . ProteolMetalloproteinases consist of two families: MMP and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs). In principle, out of 24 MMPs, MMP-1–3, 7–17, 24, and 28 are expressed in the brain under specific pathophysiological circumstances; however, a vast majority of them remain largely undetectable in a normal physiological state . Based oMatrix metalloproteinases and ADAMTSs can collectively cleave all elements of the ECM and PNNs as well as several growth factors and membrane proteins  which is a serine protease and classically known to dissolve blood clots. tPA can degrade PNN directly as its substrate or epilepsy . Howeverepilepsy .Extracellular matrix forms the structural scaffold of the brain architecture and serves both structural and signaling functions in the developing and adult brain. PNNs are a highly organized form of ECM and confer several functions including neuroplasticity, ionic homeostasis, neuroprotection, and regulation of neuronal activity. A growing body of evidence causally links PNN disruption with the pathophysiology of several CNS disorders such as epilepsy. Glial cells, predominantly astrocytes, are one of the major sources of ECM molecules in developing and adult CNS, thereby directly influencing brain development and functions. Glial cells also release matrix cleaving proteases which are the main effectors of ECM and PNN remodeling during development, adulthood, aging, and diseases. By regulating the spatiotemporal expression of ECM molecules as well as the ECM remodeling proteases, glial cells play a central role in ECM homeostasis in CNS physiology and pathology. Owing to their multifaceted roles in ECM homeostasis, glial cells appear to be promising targets for therapeutic interventions. However, more studies are required to understand the mechanistic insight of glial regulation of ECM and PNNs to pinpoint the molecular pathways and target molecules.BT: literature search, data curation, and manuscript writing, editing, and communication. LC and CP: literature search, data curation, and manuscript editing. HS: literature search, manuscript editing, and funding acquisition. All authors contributed to the article and approved the submitted version.


Green technology innovation is an effective way through which to achieve carbon neutrality and sustainable development. Based on provincial panel data of 30 provinces in China from 2005 to 2018, this work examines the tripartite relationship among green technology innovation, resource misallocation, and carbon emission performance by constructing panel regression models and a dynamic threshold panel model. The research results show that green technology innovation significantly improves carbon emission performance. Further analysis shows that both capital and labour misallocation have a negative impact on carbon emission performance and hinder the contribution of green technology innovation to the improvement of carbon emission performance. The regression results show that there is a threshold effect of green technology innovation on carbon emission performance: as the degree of resource misallocation increases, the positive impact of green technology innovation on carbon emission performance gradually decreases. This study provides an important reference for policy-makers in implementing policies to improve carbon emission performance. Policy-makers should continue to promote the level of green technology innovation and improve the efficiency of labour and capital allocation. Climate change has become the most serious challenge to global sustainable development . The masGreen technology innovation and rational resource allocation are the key approaches to solving carbon emissions and environmental problems . Green tAccording to neoclassical economic growth theory, economic growth depends on the advancement of technological factors and the increase in the input of labour and capital factors . Due to The literature on green technology innovation, resource misallocation, and carbon emissions is relatively abundant; however, previous studies lacked a systematic incorporation of green technology innovation, resource misallocation, and carbon emission performance into the same analytical framework. Does green technology innovation help improve carbon emission performance? What effect does resource misallocation have on carbon emission performance? Is there a threshold effect on the impact of green technology innovation on carbon emission performance?To answer the above questions, this work systematically studies green technology innovation, resource misallocation, and carbon emission performance using Chinese provincial panel data from 2005 to 2018. Based on existing research, this paper includes the following three main innovations. First, we put green technology innovation, resource misallocation, and carbon emission performance into the same analytical framework to better study their tripartite relationship. Second, through a moderating effect model, we separately examine the moderating effects of capital and labour misallocation on the impact of green technology innovation on carbon emission performance. Third, a dynamic threshold model is used to test the impact of green technology innovation on carbon emissions through the use of capital misallocation and labour misallocation threshold variables.The remainder of the article is organized as follows. Section “Literature review” reviews the relevant literature. Section “Methodology and data” presents the model and data. Section “Empirical results and discussion” presents mainly the empirical results and discussion. The conclusions are presented in the final section.With the development of science and technology, green technology has gone through various: terminal treatment technology, waste-free technology, clean technology, renewable energy technology, and pollution prevention technology . At presHowever, other viewpoints hold that the effects of green technology innovation on carbon emissions and the environment are not significant. Through a study of 71 economies, In an economy where resources can flow freely enough to achieve Pareto optimality, efficient resource allocation is said to exist, and resource misallocation denotes a deviation from this ideal state . ResourcLabour is an important production factor, and the labour market is a market involving two-way choices. Workers choose high-quality enterprises based on their own experience, education, expertise, preferences, and career ideals. Companies usually select excellent employees based on their differentiated characteristics. Therefore, due to information asymmetry, differences in the capabilities of firms and workers can lead to labour misallocation . MoreoveIn summary, capital misallocation and labour misallocation have caused many problems, such as aggravating the imbalance of regional and industrial development, reducing total factor productivity, bringing about excess capacity, economic losses, and environmental pollution, hindering the smooth economic cycle, and restricting economic development .As a key factor in climate change, carbon emissions have attracted extensive attention. At present, studies on carbon emissions focus mainly on the measurement method, influencing factors, and efficiency of carbon emissions, as well as the trading of carbon emission rights . MoreoveIn general, scholars have carried out a series of studies on green technology innovation, carbon emissions, resource misallocation, and environmental pollution . HoweverThis paper focuses on the tripartite relationship among green technology innovation, resource misallocation, and carbon emission performance. Therefore, an econometric model is constructed as shown in i and t denote province and time, respectively; and where To analyse the threshold effect between green technology innovation and carbon emission performance under different degrees of capital misallocation and labour misallocation, we refer to the research of where Referring to Green technology innovation can apply green technology to all stages of production, giving play to the spillover effects of innovation and the environment . This pakr) and labour factor (lr) as in Equation (6) as follows:Resource misallocation not only reduces total factor productivity but also affects carbon emission performance. Referring to the theoretical framework of scholars such as where itY. The capital and labour factor inputs are represented by itK and itL, respectively, where the former is represented by the fixed capital stock of each province, and the latter is represented by the average annual employment of each province. In addition, on this basis, Kiβ of the capital factor and Liβ of the labour factor in region i. On this basis, the indicators are substituted into Equation (9) to calculate the relative distortion coefficients This work further assumes that each province has a C-D production function with constant returns to scale, as shown in iK represents the capital stock of region i, K represents the total capital stock of the whole country, and i to the national capital stock. i. iY accounts for the share of the total national output value Y. Taking the capital factor as an example, i should use under the ideal situation of efficient capital allocation. From the calculation formula of the relative distortion coefficient, it can be seen that if iD exceeds the theoretical value, and the capital is overallocated; otherwise, the actual capital used in area i is insufficient.where per capita GDP to represent the economic development level of each province  from 2005 to 2018. The data sources are the The estimated results of the effect of green technology innovation on carbon emission performance are reported in As mentioned above, this study analyses mainly capital misallocation and labour misallocation. The samples selected in this paper have the data structure characteristics of “large N and short T.” Considering endogeneity and heteroskedasticity problems, system generalized method of moments estimation is used to analyse the impact of resource misallocation on carbon emission performance. To ensure the validity of the analysis results, we examine the effects of capital misallocation and labour misallocation on carbon emission performance. The regression results in Capital and labour resources play an important role in green technology breakthroughs and green product marketization. If elemental resources are misallocated, and then green technology innovation faces difficulty in promoting carbon emission performance. To explore the effect of the role of resource misallocation in the impact of green technology innovation on carbon emission performance, this study uses three moderating variables to test the moderating role of resource misallocation in this relationship. These variables are the interaction term of green technology innovation and capital misallocation, that of green technology innovation and labour misallocation, and that of green technology innovation, capital misallocation, and labour misallocation. The regression results in The previous empirical results show that resource misallocation has a negative moderating effect on the relationship between the promotion of green technology innovation and carbon emission performance. Is there any heterogeneity in the impact of green technology innovation on carbon emission performance under different resource misallocation levels? To answer this question, a dynamic GMM threshold panel model is adopted to examine the nonlinear effects of green technology innovation on carbon emission performance at different levels of capital misallocation and labour misallocation. The GMM method is used to construct moment estimation conditions, and the threshold model is embedded in the GMM model. The threshold value is determined by the grid search algorithm, thereby obtaining a dynamic GMM panel . The tesrk) and labour misallocation (rl). According to the Wald statistics and their p values, all the dynamic threshold models with different threshold variables exhibit significant threshold effects at the 1% significance level. Therefore, threshold effects exist. Furthermore, the impact of green technology innovation on carbon emission performance exhibits a nonlinear feature due to resource misallocation.First, we use capital misallocation as a threshold variable to investigate the impact of green technology innovation on carbon emission performance under different levels of capital misallocation. We find that with the increase in the level of capital misallocation, the regression coefficient of green technology innovation increases, indicating that the higher the degree of capital misallocation is, the greater the negative effect of green technology innovation on carbon emission performance. Then, we use labour misallocation as a threshold variable with which to examine the impact of green technology innovation on carbon emission performance under different levels of labour misallocation. We find that as the degree of labour misallocation increases, the regression coefficient of green technology innovation also increases, indicating that the higher the labour misallocation is, the greater the negative effect of green technology innovation on carbon emission performance. The above empirical results further confirm that both capital misallocation and labour misallocation have inhibitory effects, hindering the effect of the promotion of green technology innovation on carbon emission performance. This finding may be due to the fact that resource misallocation hinders the realization of green technology innovation. On the one hand, green technology innovation requires considerable financial support. However, capital misallocation causes funds to flow into sectors or industries with low productivity, thereby affecting the rational allocation of funds . On the To verify the validity of the above empirical results, this paper uses DIF-GMM model estimation and replaces the explanatory variables to test the robustness of the results. We use the number of green utility model patents granted to represent green technology innovation. The test results are shown in To improve carbon emission performance, it is very important to enhance green innovation capabilities. Considering that resources are the basis of green technology innovation, resource misallocation influences the effect of the promotion of green technology innovation on carbon emission performance. Based on provincial panel data of China from 2005 to 2018, this study systematically incorporates green technology innovation, resource misallocation and carbon emission performance into the same analytical framework by using panel regression models and a dynamic threshold panel model. The research conclusions are as follows. (1) Green technology innovation plays a significant role in promoting carbon emission performance. However, capital misallocation and labour misallocation are not conducive to improving carbon emission performance. (2) Resource misallocation plays a negative moderating role in the impact of green technology innovation on the improvement of carbon emission performance. The conclusions remain valid regardless of whether capital and labour misallocation are considered individually or together. (3) Under the effect of resource misallocation, green technology innovation has a nonlinear promotion effect on carbon emission performance. Based on the above conclusions, this study puts forward the policy recommendations presented below.First, the government should continue to strengthen green technology innovation and improve the innovation guarantee system. Moreover, the government should actively lead the green development of emerging industries, advocate the use of green and low-carbon energy in various departments, and accelerate the development of green products. Energy-saving and environmental protection industries and cleaner production industries should be developed, and traditional manufacturing industries should be encouraged to accelerate their green transformation and upgrading.Second, the market-oriented reform of factors should be deepened, and the optimal allocation of factor resources should be realized. The government should relax its excessive regulation of resources, reduce excessive intervention in the factor market, and release more market vitality. In addition, the rational allocation of factor resources in different departments and regions should be properly guided. Furthermore, it is necessary to improve the green industry financial system, expand multiple financing channels, adjust the profit and loss of funds through the financial system, guide the flow of funds through the price of funds, and improve capital allocation efficiency.Third, it is very meaningful to solve labour misallocation by strengthening human capital investment; actively cultivating professional and high-tech talent; improving household registration, land systems and social security systems; removing barriers to labour mobility across departments; and reducing labour mobility costs.Finally, the government should strengthen its antimonopoly policies, investigate and punish acts of unfair competition in accordance with the law, eliminate local protection and market segmentation, accelerate the establishment of a unified national market system and rules, improve resource allocation efficiency, and promote high-quality economic development.Although this study analyses the tripartite relationship among green technology innovation, resource misallocation, and carbon emission performance, some limitations exist. Future research can be further expanded in the following aspects. First, based on data availability, more detailed city-level data can be used for analysis. Second, the impact of land misallocation and data misallocation on environmental and carbon performance can be further analysed. Third, green technology innovation, resource misallocation, and environmental indicators can be measured through the use of other methods.https://data.stats.gov.cn/.Publicly available datasets were analyzed in this study. This data can be found at: MD: writing—original draft, software, methodology, and project administration. QZ: conceptualization, funding acquisition, supervision, and writing—review and editing. YZ: conceptualization, writing—review and editing, supervision, and validation. FL: data curation, formal analysis, writing—original draft, and visualization. All authors contributed to the article and approved the submitted version.This work was financially supported by the Major Program of National Social Science Foundation of China (21&ZD151).The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.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.