Interest in home-based stroke rehabilitation mechatronics, which includes both robots and sensor mechanisms, has increased over the past 12 years. The COVID-19 pandemic has exacerbated the existing lack of access to rehabilitation for stroke survivors post-discharge. Home-based stroke rehabilitation devices could improve access to rehabilitation for stroke survivors, but the home environment presents unique challenges compared to clinics. The present study undertakes a scoping review of designs for at-home upper limb stroke rehabilitation mechatronic devices to identify important design principles and areas for improvement. Online databases were used to identify papers published 2010–2021 describing novel rehabilitation device designs, from which 59 publications were selected describing 38 unique designs. The devices were categorized and listed according to their target anatomy, possible therapy tasks, structure, and features. Twenty-two devices targeted proximal (shoulder and elbow) anatomy, 13 targeted distal (wrist and hand) anatomy, and three targeted the whole arm and hand. Devices with a greater number of actuators in the design were more expensive, with a small number of devices using a mix of actuated and unactuated degrees of freedom to target more complex anatomy while reducing the cost. Twenty-six of the device designs did not specify their target users’ function or impairment, nor did they specify a target therapy activity, task, or exercise. Twenty-three of the devices were capable of reaching tasks, 6 of which included grasping capabilities. Compliant structures were the most common approach of including safety features in the design. Only three devices were designed to detect compensation, or undesirable posture, during therapy activities. Six of the 38 device designs mention consulting stakeholders during the design process, only two of which consulted patients specifically. Without stakeholder involvement, these designs risk being disconnected from user needs and rehabilitation best practices. Devices that combine actuated and unactuated degrees of freedom allow a greater variety and complexity of tasks while not significantly increasing their cost. Future home-based upper limb stroke rehabilitation mechatronic designs should provide information on patient posture during task execution, design with specific patient capabilities and needs in mind, and clearly link the features of the design to users’ needs.The online version contains supplementary material available at 10.1186/s12938-023-01133-8. Stroke is the third most common cause of disability in the world, with 25.7 million stroke survivors worldwide . The totAccess to rehabilitation services is more difficult for people who live far from clinics, in rural or under-resourced areas. Additionally, the recent COVID-19 pandemic has reduced access further: policies to reduce transmission through physical and social distancing make rehabilitation activities, often requiring close contact between patients and therapists, difficult or even impossible for outpatients. The healthcare system must adapt to this challenge; and one promising avenue is the use of rehabilitation mechatronics, such as robot-assisted rehabilitation therapy, in the home environment. Mechatronic devices in this work refers to mechanisms with which a patient can physically interact that incorporate sensors in their design and may also include actuators. Robots are a particular subset of mechatronic device: a mechanism with sensors and actuators joined by a control loop.MIT-MANUS was introduced [MIT-MANUS, often cited as the seminal rehabilitation robot, occupied a desk-sized workstation and allowed a patient to participate in planar arm exercises under the supervision of a single therapist or technician. Even in the early days of development, the patent for the device suggested future modules for the wrist and hand, and the home environment being the eventual goal [MIT-MANUS was later commercialized as the InMotion ARM (www.bioniklabs.com), with the additional modules becoming the InMotion ARM/HAND. Contrary to the aspirations of the patent, the InMotion ARM has remained a clinic-based device. Over time more complex rehabilitation robots were developed. In the mid-2000s, the ARMin robot [ArmeoPower (www.hocoma.com), a clinic-based device.Mechatronic rehabilitation devices have been in development since the late 1970s. One of the earliest examples was a large, hydraulically powered arm which required an entire room and a team of therapists and technicians to operate , 13. In troduced . The MITual goal . The MITin robot , 17 was in robot , and wasMIT-MANUS, the effectiveness of robotic rehabilitation for stroke has been of significant research interest. The initial study of the MIT-MANUS [Starting with the development of the IT-MANUS  showed pIT-MANUS –22 and kIT-MANUS –25. RoboIT-MANUS .ArmAssist (www.armassist.eu). Compared to the clinic-based devices, home-based devices face unique challenges in their development and adoption. The most significant challenges are: safety, cost, space requirements, and independent ease-of-use [While clinic-based rehabilitation robots are becoming more commonplace, home-based rehabilitation robots are not as widespread. A survey of upper limb rehabilitation robots in 2014 predicted that home-based devices would become more prevalent as demand for such devices increased . Accordie-of-use .Currently, the majority of stroke rehabilitation is provided in hospital settings. The intensity of therapy decreases significantly as individuals with stroke are discharged to the community . In CanaProviding home-based rehabilitation to stroke survivors offers many advantages. For the stroke survivors themselves, the home environment is comfortable, familiar, and closer to family and friends. For the healthcare system, delivering therapy in stroke survivors’ homes results in a lower likelihood of patient readmission . DeliverThe recent COVID-19 pandemic has demonstrated another advantage of home-based rehabilitation mechatronics: they allow therapy to continue for patients when physical distancing measures are in place. The majority of stroke survivors are older adults with a variety of underlying health conditions , which mWhile there are many advantages to providing home-based therapy, there are challenges to implementation. Home-based programs need frequent, high-repetition activities to be most effective: at least 45 min per day, 2–5 days per week . Home-baThe requirements for the design of home-based rehabilitation mechatronic devices have been the subject of some research. Sivan et al. , 37 founThe design of a home-based rehabilitation mechatronic device must relate the properties of the device to the contextual factors within which it will be situated. An important distinction between home-based and in-clinic devices is that the personal and environment factors are better managed in the clinic: the environment itself is controlled, trained staff are available to assist the patient, and the patient is directly instructed in the activity. Therefore, while in-clinic devices can focus largely on a patient’s body function and anatomy in their design, home-based devices must weigh the personal and environmental factors more heavily in their design process. Consider how the Device Property “ease of setup” differs between a clinic and a home environment. In a clinic, a trained therapist or technician can set up or configure the device, therefore the bar for what is ‘easy’ differs from the home environment where the stroke survivor may have to set up the device themselves with an impaired arm, or other issues.The objective of this review is to investigate the capabilities of upper limb rehabilitation mechatronic devices designed for home use that have been developed in the past 12 years and identify the remaining challenges to further development. The reason for considering mechatronic devices more broadly rather than robots specifically is that not all stroke patients require the added assistance or resistance of an actuated device. Therefore, creative solutions that balance the cost of adding additional features versus the specific needs of the end-user are worth considering in the review.While in-clinic devices have demonstrated that robot rehabilitation can be an efficacious treatment, the effectiveness of a treatment depends on its ability to meet user needs in a given environment . Home-baPrevious reviews have either considered rehabilitation devices intended for both in-clinic and at-home use , 41, or The contributions of this article are as follows. First, it summarizes the state of the art in home-based upper limb stroke rehabilitation mechatronic devices reported on over the past 12 years. Second, it compares existing devices based on their capabilities relative to stakeholder needs. Finally, it summarizes the limitations of existing devices and provides recommendations for the development of future devices reflected by user needs.The scope of the review was limited to mechatronic devices, mechanisms with which a patient can physically interact that incorporate sensors in their design and may also include actuators, collectively referred to as ‘devices’, specifically designed to provide exercise therapies for upper limb rehabilitation in a stroke survivor’s home. The devices must be purpose-built to facilitate therapeutic activities, not an assistive device that aids a person in their activities of daily life (ADL), nor an assessment system that solely measures a person’s function. Rehabilitation games created on existing platforms such as video game systems, a camera system, or cell phones were excluded. Papers describing incomplete designs, such as the design of an actuator for an unrealized future device, were also excluded.Haptic Theradrive, ArmeoSenso, Smart Glove, and ArmAssist are the only commercialized devices on the final list.Three databases were searched: IEEEXplore, ScienceDirect, and PubMed. Searches were performed using a combination of the following keywords: “upper extremity”, arm, “upper limb”, stroke, rehabilitation, therapy, training, robot (and variations such as robotic) and home. Records were limited to the period between January 1, 2010 and December 3, 2021, when the final search occurred. This time period was chosen because the field of rehabilitation mechatronics is developing rapidly, therefore a 12-year period was considered sufficient to capture the state of the art. Papers were first filtered by title and abstract, then further filtered by full-text content. The flow diagram of the study is shown in Fig. The database search yielded 354 results. After reviewing titles and abstracts and removing duplicates, the results were narrowed down to 110 publications. In full-text review, 8 were excluded for describing assistive devices, 5 were excluded for describing in-clinic devices, 17 were excluded for involving devices that were designed before 2010 or unmodified camera or video game systems, 4 were excluded for describing incomplete or unrealized designs, 5 were excluded for only using virtual reality headsets, and 28 were excluded for being off-topic, such as describing a non-robotic rehabilitation therapy program. Upon reviewing the references of the included publications, 16 additional publications were added by the authors that did not appear in the search but were relevant to the review, bringing the total number of publications to 59.Figure ArmeoSenso attaches sensors at multiple points along the arm, so it does not fit the definition of an endpoint device, yet lacks any skeletal structure to qualify it as an exoskeleton. Therefore, exoskeleton devices are a subset of “joint-based” devices. Examples of devices in each category included in the review are given in Fig. The devices were summarized by their functionality, including the anatomy targeted, the number of degrees of freedom (DOF) offered, the motions allowed, the actuators used in the design (if present), measurement capabilities, and the type of interaction provided. Within each group the devices are arranged by order of their original publication date. The interaction type is divided into two categories: endpoint, referring to devices that interact with the user through a handle or other single point on the body; and joint-based, referring to devices that attach to multiple points across joints on the body. While previous reviews of rehabilitation robots have used the categories “endpoint” and “exoskeleton” , we use PaRRo [hCAAR [Quantitative measures of the devices’ characteristics, such as force/torque, workspace dimensions, and cost, are not presented in Table PaRRo  and the o [hCAAR , have diThe following motions were identified for the devices presented in Table BULReD [Reaching tasks were the most common: 23 out of the 38 devices were designed to perform a reaching task (24 including the devices designed for elbow motion). Of those devices, only six also included grasping, and only two, BULReD  and the BULReD , includeGT System and ArmAssist, therefore they are shown at the borders of the regions.To help visualize the variety of types and anatomy presented in Table ArmeoSenso, HomeRehabMaster, and GT System, measure trunk orientation.Approximately half of the devices measure the spatial position of the user’s hand, six measure the position of a subset of arm joints, and three measure the position of all arm joints. Three devices, the eWrist [Sixteen of the devices measure the force or torque of the user’s interaction. Five of those measure grasping or fingertip force, and nine measure bulk hand force or torque . One device, the eWrist , measureHomeRehabMaster [Out of the 38 devices, 21 proposed a method of assessing patient motor function automatically, 10 of which used multiple forms of assessment. The different methods proposed were: joint range of motion or reachable workspace (11 devices); kinematic performance, such as tracking error, movement time, or maximum jerk (11 devices); required assistance force or patient voluntary force (5 devices); compensation frequency, such as the number of times a patient leans forward excessively (3 devices); game success rate, such as the number of times a patient achieves a desired position or action (3 devices); and virtual reproduction of an existing assessment, specifically a subset of upper limb actions involved in the Fugl-Meyer assessment .PWRR [Of the 26 actuated devices, all but two used electric motors, and 18 used DC motors specifically. Electric motors, and DC motors in particular, are well-understood from a dynamic modelling perspective, straightforward to control, compact, and can easily be purchased in a variety of sizes, so their popularity in this application is unsurprising. The only non-electric actuated devices found in this review were the soft robotic glove designed by Polygerinos et al.  and the PWRR , both ofULERD elbow exoskeleton was 16 N m [Ambidexter was capable of 8.4 N m [For the devices that reported force or torque capability, the magnitude varies greatly. Devices targeting reaching motions or proximal anatomy were capable of larger forces and torques than those targeting finer tasks and distal anatomy. For example, the maximum torque of the s 16 N m , while t 8.4 N m .Haptic Theradrive [BULReD [ATD (10–16 N) [hCAAR (28 N) [PaRRo (30 N) [HOTAR was not specified directly, but in experiments it did not exceed a force of 15 N [BULReD was designed for bimanual reaching, it is reasonable that its force capabilities are larger: involving the unimpaired arm in the task increases the force capability of the patient. The Haptic Theradrive is an outlier compared to the other unimanual reaching devices, explained by the authors as a budget-related issue: they obtained an aftermarket treadmill motor for a low price that exceeded their requirements [The strongest devices were the eradrive  and the  [BULReD , both of10–16 N) , the hCAR (28 N) , and theo (30 N) . The for of 15 N . Since tirements .GT System at approximately 1000 USD [Haptic Theradrive [Ambidexter [PaRRo [RobHand [hCAAR [RobHand [Although 24 out of the 38 devices presented mentioned that ‘low cost’ was an important design consideration, only 8 provided a cost estimate. The lowest cost device was that developed by Mohammadan et al., which cost approximately 1000 Malaysian Ringgit  , and one, the abMaster , was desThis is one area in which mixed actuated and unactuated designs can be used. Almost all of the devices presented were either entirely actuated or entirely unactuated, therefore there is a gap where selectively actuated devices can be developed. Generally speaking, stroke survivors demonstrate obvious impaired motor function on one side of the body, so they primarily need assistance forces on that side. Therefore, designers can expand the capabilities of a device by mixing an actuated design on the patient’s affected side with an unactuated design on the unaffected side. This would allow bimanual therapy, or other activities with more degrees of freedom, without increasing the device cost as much as a fully actuated system. However, more research is needed on the effectiveness of bilateral arm training to determine if this capability is worth the tradeoffs for at-home rehabilitation.PVSED [Safety is important for any device that a stroke survivor is expected to use unsupervised or remotely supervised. The choice of actuator has significant implications on the safety, performance, and weight of the devices, and therefore represents a challenge in the design. Rigidly connecting the user to a motor creates the potential for injury, especially for stroke survivors with weakened joints and muscles and reduced proprioception. Most of the devices presented use rigid structures to transmit force, with the following exceptions. The PVSED  introducPVSED  uses linPVSED  uses comPVSED , so compAlthough the safety features discussed in the reviewed literature focused largely on compliant actuation, other complementary avenues for ensuring user safety, such as software-based velocity and force limits, could be implemented as well. Given the importance of safety for at-home rehabilitation devices, future literature should describe all potential safety features in the design, whether in hardware or software.Control algorithms for rehabilitation robots have three objectives: maintaining safe operation (stability), providing sensory feedback (haptic sensation), and providing therapeutic intervention (assistance/resistance). A wide variety of controllers have been designed to address each of these objectives. Detailed reviews of control algorithms that can be applied to upper limb rehabilitation have been published , 103.The design of a rehabilitation robot determines the types of controllers that can be applied to its operation. For example, some control methods –108 requControl algorithms that incorporate therapeutic intervention through assistance or resistance forces can require additional sensors to ensure patients remain engaged in the therapy . EMG canThese control algorithms not only determine the forms of assistance available, but also have important implications for safety. Atashzar et al.  have noteWrist [Ten of the devices presented in Table eWrist , 83 inclhow a patient performs a task is crucial to determining if they are overly reliant on compensation as well as how their recovery is progressing. Compensation involves the patient moving body parts over which they have more control, such as their trunk or shoulders, to compensate for body parts over which they have less control, such as their elbow or wrist [Only three of the 38 devices were designed to detect compensatory behaviours, such as leaning forward excessively, during therapy activities. Data on trunk orientation in addition to arm joint positions are important for therapists assessing the performance of a patient using these devices. Understanding or wrist . Compensor wrist , but theor wrist , inertiaor wrist , 90, or or wrist , 118.Identifying compensation behaviour from sensor data is a complex task: therapists can identify it visually by the motion of the patient’s whole body as they perform a set of tasks , but theLinking the design of these devices to therapeutic practice can guide designers on what sensory data must be collected. While traditional therapy measures are difficult to translate to robotic systems, novel measures of impairment  have beeArmAssist and hCAAR) consulted patients specifically. This indicates that many of the devices that are presented as rehabilitation robots have limited connection to specific user needs. Tying the design directly to user needs can improve the efficiency of the designs presented.Of the 38 devices included in this review, 17 took an entirely anatomical approach to their design, meaning that their design focused exclusively on anthropometric data. Four devices considered some basic user needs, such as space requirements and difficulty donning and doffing the device. Only six devices included user consultations prior to the design, of which only two  System [GT System to involve the patient’s distal as well as their proximal anatomy in therapy. The Smart Glove is an entirely unactuated flexible glove-like structure that measures hand motion through accelerometers and individual finger position through the deflection of its flexible structure [ArmAssist [ArmAssist’s design includes a detailed analysis of stakeholder needs justifying the approach taken [Being unactuated allows a device to achieve a large number of degrees of freedom at the expense of being less suitable for patients with severe impairment. The ) System  is unacttructure . The ArmrmAssist , 95 is armAssist  includesch taken . The quech taken , 121.Another issue related to the target users is the ability of a device to adapt to a user’s changing needs over time. Increasing challenge and a variety of exercises have been identified as key factors in maintaining user perseverance in at-home technology-supported therapy . The desATD explains the design of its passive springs to allow gravity compensation [While a force range of 10–30 N seems to be the consensus for unimanual reaching tasks, the reasons for this force range were not well explained in the literature. The ensation , but othhCAAR [HomeRehabMaster [SCRIPT [ArmAssist [Only a few of the devices approached the issue of motivation and engagement: the hCAAR , 48, HomabMaster , SCRIPT  [SCRIPT , and ArmrmAssist  each desrmAssist : attentiCost is a complex metric to consider for the design of at-home rehabilitation robots. Cost is difficult to estimate for an experimental device: the costs presented in the reviewed publications only reflect hardware costs which could be eclipsed by the labour costs in a commercial setting. As a concrete example, the device designed by Lu et al. had a retail price of approximately 10,000 USD, compared to the original project material cost of approximately 3000 USD .Affordability, the cost relative to a person’s ability to pay, should be considered in designs rather than cost alone. The target users for these devices are often dependent on insurance or government assistance to purchase such a device. It is therefore helpful for researchers and developers to compare their designs to locally available support programs, and to include that information as part of their design. Retailers of future rehabilitation robots may be able to lease devices to users, thereby reducing the up-front cost, however this approach still places the cost on the stroke survivors’ ability to pay.ArmeoSenso) or cameras (such as in HomeRehabMaster) can provide arm and body pose information to supplement the capabilities of actuated endpoint devices, while body-mounted cameras could potentially give joint-based devices hand position measurement capability [Given the gaps identified in the previous subsections, there is a need for devices allowing more complex motions related to real-world activities, but the limitations of the home-based setting make this difficult. One approach is to combine unactuated and actuated designs to allow more complex tasks while keeping the cost low. Different combinations of actuated and unactuated DOF could help patients with different needs and impairments. Proximal joint-based sensing through IMUs (such as in the pability . To deteThe user needs, both in terms of the specific physical impairments they experience and the tasks they wish to practise, should be central to the design of any device. However, stroke survivors’ recovery trajectory varies, therefore following a ‘one-size-fits-all’ approach is challenging. Devices that can change as the user’s ability changes will have broader applicability and be more attractive. By having the user only learn one device over the course of their recovery, less time is spent training them on the use of different devices. Modular designs that can be easily reconfigured as the patient progresses could meet a more diverse set of user needs.Furthermore, as researchers develop new designs they should endeavour to relate their work directly to the needs of the relevant stakeholders. As previously discussed, it is difficult to analyse the performance of the different devices presented in the literature because many of those devices are not designed for any specific rehabilitation therapy. Instead, it seems that they are designed to target specific anatomy and future rehabilitative therapies must be designed to fit the hardware. While this approach is reasonable, it may lead to reduced efficiency as the effectiveness of a given design can only be evaluated after an appropriate therapy has been designed for it. By taking the opposite approach, and basing designs on task-based therapies, or functional assessments, that are already known to be effective, researchers can evaluate the effectiveness of their designs earlier in the development process.Beyond considering the needs of users, the needs of the latest control algorithms need to be considered in the design depending on its application. As mentioned in the Control subsection of the Discussion, devices used for telerehabilitation, where the therapist and the patient can physically interact remotely through a robotic system, require additional sensors and accurate actuation to maintain patient–robot and robot–therapist interaction stability and safety. Such devices also require the means to establish a reliable network connection to allow the exchange of video, audio, force, and position data. In other words, devices primarily intended for independent therapy practice will differ from devices intended for remote-controlled therapy systems. Therefore, researchers should articulate the specific intended application of a given design beyond it being a home-based rehabilitation robot.The limitations of the review are as follows. The review was conducted in English, and only three databases were searched. The filtering of results was conducted by a single author. The search terms may not have covered all possible combinations or terminology for home-based rehabilitation robots. However, given these limitations we are confident that even if some devices were not discovered in the search, the categories and properties identified would not change.Interest in the area of home-based rehabilitation mechatronics has increased in the past 12 years, driven by the maturation of in-clinic rehabilitation mechatronic technology and a growing need to improve therapy access in patients’ homes without increasing the cost. Existing devices largely focus on reaching motions and have an insufficient sensory capability to evaluate critical aspects of task performance, such as detecting compensation. Very few of the publications reviewed described a stakeholder consultation process prior to or during the design. Even fewer mentioned consulting stroke survivors specifically. Clearly linking the design features to identified user needs is important to both ensure that those needs are met and to allow the effectiveness of the designs to to be evaluated. Future designs should more clearly link to the therapy tasks they are capable of, the impairments for which they assist, their measurement capabilities, and their cost, relative to the specific needs of patients and therapists. Future designs should also explore a mix of actuated and unactuated degrees of freedom to increase the capabilities of devices without greatly increasing the cost.Additional file 1. Mechatronic devices for home-based upper limb rehabilitation therapy.


Brachial plexus injury (BPI) is one of the most serious peripheral nerve injuries, resulting in severe and persistent impairments of the upper limb and disability in adults and children alike. With the relatively mature early diagnosis and surgical technique of brachial plexus injury, the demand for rehabilitation treatment after brachial plexus injury is gradually increasing. Rehabilitation intervention can be beneficial to some extent during all stages of recovery, including the spontaneous recovery period, the postoperative period, and the sequelae period. However, due to the complex composition of the brachial plexus, location of injury, and the different causes, the treatment varies. A clear rehabilitation process has not been developed yet. Rehabilitation therapy that has been widely studied focusing on exercise therapy, sensory training, neuroelectromagnetic stimulation, neurotrophic factors, acupuncture and massage therapy, etc., while interventions like hydrotherapy, phototherapy, and neural stem cell therapy are less studied. In addition, rehabilitation methods in some special condition and group often neglected, such as postoperative edema, pain, and neonates. The purpose of this article is to explore the potential contributions of various methods to brachial plexus injury rehabilitation and to provide a concise overview of the interventions that have been shown to be beneficial. The key contribution of this article is to form relatively clear rehabilitation processes based on different periods and populations, which provides an important reference for the treatment of brachial plexus injuries. Epidemiological studies conducted in both developing and developed countries have shown that brachial plexus injuries are very common in productive young men. Closed injury is the most common type of injury, caused primarily by strains, fractures, and compression injuries, medical injuries are also quite common . When a 2.Brachial plexus injuries  fall und3.The management of BPI depends on the type, location, and severity of the injury. It is usually determined by magnetic resonance imaging and/or computed tomography myelography. Surgeons now agree that the best time for surgery is 3–6 months after injury; traction injuries usually heal spontaneously within 3–6 months, and surgical exploration may cause secondary injury, so surgical intervention is recommended if nerve function has not recovered by the end of the spontaneous recovery period . Complet3.1.Axonal growth occurs at a pace of approximately 1 mm every day. The basic objectives of the spontaneous recovery period following brachial plexus injury are to ensure adequate muscle nutrition, preserve muscle function, and promote nerve regeneration until the nerve reaches the periphery because it takes a long time for nerves to reinnervate.3.1.1.Pain is present at all stages of brachial plexus injury, including acute neuromuscular injury pain, postoperative pain in the operative area, and chronic neuropathic pain, and it significantly reduces patients’ rehabilitation compliance, mental health, and quality of life. It should be addressed as soon as it is identified. A review by Tom et al. for the functional assessment of brachial plexus injury recommends the use of the Patient Reported Outcome Measure (PROM) preferably for those patients who can report pain autonomously, and the commonly used Visual Analog Scale (VAS) and Numeric Rating Scale (NRS) are also recommended . However3.1.2.Strong external fixation support of the damaged limb is necessary before commencing activities. When shoulder and elbow movements are compromised, shoulder straps and figure-eight bandages can be utilized to restrict the uncontrolled movement of paralyzed joints. When the wrist joint is affected, a splint can be utilized to maintain the wrist in an extended position for 10–20 degrees, assisting in the prevention of joint contracture and easing the patient’s pain . The advThere is a large amount of literature on motor re-education after brachial plexus injury. Typical therapies include passive range of motion, active-assisted range of motion, active range of motion, and strength, according to a systematic review based on proprioceptive neuromuscular facilitation (PNF) theory . This isIn comparison to simulative activities or pointless exercise, a systematic study revealed that involvement in purposeful activities for upper extremity motor therapy regularly leads to a greater quantity and quality of muscle building . Occupat3.1.3.Brachial plexus injury can cause sensory deficiencies in the upper extremities, including sensory anomalies and hypoesthesia. Standardized tests can evaluate sensory thresholds and functions in both children and adults including the two-point discrimination test, skin pressure thresholds, vibration perception, and assessments of pain and tactile sensations using needles and cotton . PatrickTraditional sensory re-education involves reestablishing impaired afferent sensory pathways through interactions with the environment to subsequently restore more discriminative senses. The European Consensus on Sensory Retraining in Peripheral Hand Neuropathy provides a systematic strategy to promote reeducation of tactile cognition by interacting with different textures, temperatures, forms, and objects . AlthougMirror visual feedback (MVF) is the process of superimposing the motion picture of the healthy hand on the location of the affected hand using a mirror that has been placed vertically on a table. This creates a motor-sensory connection between the hands . Such viCross-modal sensory replacement translates tactile information across several modalities using sensing technologies . Patient3.1.4.Once brachial plexus injury has been diagnosed, neurotrophic treatment will be used continually and regularly. B vitamins, mecobalamin , citicol3.1.5.Numerous studies have demonstrated the effectiveness of early modalities in reducing swelling, promoting edema absorption, relieving pain, and releasing adhesions. This therapy can be applied in a variety of settings, including ultrashort wave, infrared, and low-energy laser irradiation .Electrical nerve stimulation promotes nerve healing and regeneration and is a useful tool. Depending on the stimulation site, neural electrical stimulation can be classified as deep brain stimulation (DBS), transcutaneous neuromuscular electrical stimulation (NMES), spinal cord stimulation, and transcranial direct current stimulation (tDCS) . NeuromuIn addition, transcranial magnetic stimulation (TMS) is often used to collect motor-evoked potentials to assess neurological activity or to treat neuropathic pain as a complement to Noninvasive electrical brain stimulation . It is wThe benefit of neuro-electromagnetic stimulation in the treatment of neuropathic pain, which may be regularly utilized in pain management, should not be overlooked. However, further clinical investigations and systematic assessment research are required to better understand the suggested paradigms due to the diversity of stimulation paradigms resulting in varying effectiveness.3.1.6.Due to their capacity to stimulate the repair and regeneration of injured nerves, enhance local blood circulation in the treated area, and lessen postoperative pain, acupuncture and tui na are widely used in traditional Chinese medicine to treat brachial plexus nerve injury. Whereas using tui-na or acupuncture alone is preferable to using medication isolated, the combined rehabilitation impact of both with other treatment modalities is noticeably superior to using tui-na or acupuncture alone. Direct comparisons of various tui na massage or acupuncture point therapies are also scarce. Electroacupuncture was initially shown to be more successful than medication therapy alone in treating 54 individuals with peripheral nerve damage in 1995 . A furth3.1.7.Emotional and social factors may influence rehabilitation after brachial plexus injury, particularly in a productive young male population. Their high expectations of efficacy lead to an inability to accept the possibility of permanent disability and the long recovery time required for neurological recovery, making them prone to psychological disengagement, denial, and venting behaviors in the later stages of treatment, and highly cooperative in the earlier stages. As a consequence, it is essential to regularly monitor patients’ adherence to treatment during the later phases of recovery, prevent dangerous behaviors, and promptly offer psychosocial assistance such as psychotherapy, psychiatric medication, and family support. For the time being, there is no systematic psychological rehabilitation strategy for brachial plexus injury, and few studies on psychological rehabilitation have been conducted. Studies on psychological aspects in brachial plexus injury patients have demonstrated that these individuals typically employ adaptive coping strategies and self-distraction in the early phases of their recovery to deal with negative psychology . Therefo3.2.Before starting a structured rehabilitation program after surgery, the muscles and nerves must have had enough time to recover. Controlling pain and edema in the acute postoperative period is the main therapy objective . PostopeAdditionally, there is general agreement to start early passive mobility of the proximal and distal joints of the trauma and to locally immobilize the nerve anastomosis site in the acute postoperative phase. The purpose is to safeguard the surgical site, promote nerve gliding, and eventually reduce pain and encourage functional recovery. The best period for postoperative fixation is not universally agreed upon; however, it is crucial to hold off until the nerve anastomosis site is tension-free, particularly after repairing a nerve with significant local tension. Based on randomized controlled research of comprehensive postoperative therapy in patients with brachial plexus injuries, the passive motion of the joint within an unrestricted range of motion is advised and needs to be combined flexibly depending on the type of surgery. In conclusion, it is critical to consider the functional recovery of the primary injury site as well as the remaining neuromuscular functional compensation after a surgical transfer, such as after a phrenic nerve transfer to the anterior branch of the superior brachial plexus, which requires both flexions of the elbow joint and deep inspiration . Numerou3.3.Even with complete rehabilitation and satisfactory neurological recovery, associated complications, including pain, muscle atrophy, restricted joint mobility, and subsequent abnormalities, are still possible . Conside4.Clinical rehabilitation and research on brachial plexus injuries in children have been widely conducted, particularly in children aged 1–12 years. However, the rehabilitation treatment of neonatal brachial plexus injury (NBPI) confronts challenges such as poor patient compliance, difficult efficacy assessment, and high family participation, resulting in slow advancement and becoming an insurmountable barrier for brachial plexus injury. It’s the fact that some demographics indicate a gradually declining frequency of brachial plexus injury following a neonatal birth injury, because of fewer forceps used . First, For neonates with a clear diagnosis, early referral to an integrated multidisciplinary management model is advised by several systematic reviews of NBPP rehabilitation. The fundamental rehabilitation strategies advised are parallel to those for adults, which include treatments such as passive/active motor exercises, smooth joint motor, sensory stimulation, electrical stimulation, and botulinum toxin injections . To serv5.The functional recovery of brachial plexus injury is a worldwide challenge. This study compiled the various rehabilitation modalities for clinicians, arranged them into rehabilitation protocols from the time a brachial plexus patient was seen until clinical remission  and enabCurrently, a significant proportion of patients with brachial plexus injury are young adults and newborns, and these patients usually have an expectation of immediate recovery. However, brachial plexus injury typically requires a lengthy recovery period due to the complexity of the injury and the slow recovery tempo. During long-term rehabilitation, the degree of neurological recovery , psychological status, and complications of the affected limb vary widely, requiring the clinician to develop an individualized rehabilitation program, which requires a great deal of experience. Therefore, patients may be in various stages of rehabilitation at the time of consultation, and there is no clinical consensus on how to manage patients in each stage in an integrated manner, making it easy to overlook the various aspects of rehabilitation principles that require attention at various stages of disease development. We will do some sorting later to fill in the gaps in this section.The efficacy of comprehensive rehabilitation therapy is well established. For patients with brachial plexus who do not need emergency surgery and proceed to the spontaneous recovery stage of rehabilitation. Local external fixation support, motor and sensory re-education, and neurotrophic therapy are common alternatives. When specific treatment requirements are met, physical factor therapy, traditional Chinese medicine treatment, psychosocial support, and other supplementary treatment methods can be applied. For patients undergoing postoperative acute rehabilitation postemergency surgery, passive movement of the afflicted limb and nerve removal site, with suggested mobility within the unrestricted joint range, can be used to reduce pain and edema. For further rehabilitation, conservative therapy options available throughout the spontaneous recovery period may be selected. It is impossible to totally eliminate complications, and when they do arise, the patient moves into the sequelae phase of rehabilitation. These complications include muscular atrophy, joint stiffness, chronic neuropathic pain, etc. To accomplish functional compensation and improve the patient’s quality of life, an end-stage rehabilitation approach might be adopted, mostly employing vigorous replacement therapy. Neurotrophic therapy, pain and swelling control, and psychosocial support can all be consistently employed at different phases because pain and psychiatric illnesses might flare up at various periods. Complete recovery from brachial plexus injury is exceptional, but when clinical remission—that is, increased performance and quality of life—is attained, the patient feels sufficiently better to jump their treatment protocol and return to home rehabilitation. This page also provides an overview of the fundamental principles of rehabilitation for generally slow-progressing neonatal brachial plexus injuries, which can help to hasten the development of treatment approaches to this specific demographic problem.Artificial intelligence and rehabilitation techniques have been developed in the last 3 years. An electroencephalography (EEG)-based human-machine interface combined with contralateral C7 transfer surgery can treat brachial plexus injury, but further research is required to understand how it promotes cortical remodeling . VirtualThe literature review deserves some essential conclusions and insights to be presented. The lack of sufficient case studies, inadequate follow-up time, the lack of a recognized control group, and the propensity to employ comprehensive rehabilitation as an intervention to improve treatment results are more or fewer defects of the literature on brachial plexus injury treatment methods. Therefore, techniques like stem cell therapy that remain at the level of animal trials are not included in the clinical approach presented in this work. Our work excludes the mention of efficient treatment methods in case reports involving a small number of patients but keeps useful comments. This takes into account treatment approaches that have all been shown in numerous case reports to be successful. Randomized controlled studies reporting effective rehabilitation treatment modalities and clinical studies with a long-term follow-up process were considered first. The rehabilitation protocols described in this article are experimental and can be supplemented with additional clinical treatment modalities that show benefits. Unfortunately, due to a lack of quantitative assessment methods, this article only develops a comprehensive treatment protocol rather than offering a suitable rehabilitation therapy approach for individuals with varying injury severity and locations. The determination of the optimal treatment approach for a specific patient is still left to the discretion of qualified medical staff and therapists. In summary, it is strongly advised that future research focus on the efficiency of potential comprehensive rehabilitation programs in the management of BPI.6.The efficacy of comprehensive rehabilitation therapy is well established. Physical therapy, traditional Chinese medicine treatment, psychosocial support, and other supplementary treatment methods can be applied when someone undergoes a brachial plexus injury, in addition, artificial intelligence and rehabilitation techniques are popular in these years which need further research. All the rehabilitation protocols we described are experimental and they show benefits as supplemented with additional clinical treatment modalities. In summary, we strongly advised that future research focus on the efficiency of potential comprehensive rehabilitation programs in the management of BPI, which will facilitate the return of patients, physical activity levels.HL: visualization and methodology. JC: writing—review and editing, conceptualization. JW: writing—original draft, visualization. TZ: supervision. ZC: authors may have contributed in multiple roles. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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Hipposideros larvatus, plays an ecological role in controlling insect populations. Studying its reproductive patterns, specifically testicular morphology, is essential for its conservation, especially in areas where it is at risk. This study focused on examining the testes morphology and the expression of two proteins, AR and AMH, in male H. larvatus bats from various parts of Thailand and during different sampling periods. Results indicated seasonal breeding patterns with significant differences in testes morphometric data, AR and AMH expression depending on the location and sampling period. Notably, bats from Dong Phayayen and Chiang Dao showed higher testicular activity in June, as evidenced by greater AR protein expression. By contrast, decreased AR expression was associated with lower testicular morphometric data and increased AMH expression. This suggests that AR is linked to active testicular functions, while AMH indicates a less active or regressive phase in H. larvatus bat in Thailand.The intermediate roundleaf bat, hipposideros larvatus (intermediate roundleaf bat) is one of the insectivorous bats which has an agro-ecological role as a controller of the insect population. The reproductive patterns of H. larvatus are intricately linked to its ecological role and survival. An understanding of the testicular morphology can contribute to conservation for this species particularly in areas where its populations might be declining or under threat. However, these bats may also be associated with zoonotic diseases which can have significant public health implications. The aims of the study were to examine the morphological data as well as the expression of the androgen receptor (AR) and anti-Müllerian hormone (AMH) in the male reproductive organs of H. larvatus from different areas of Thailand and at different sampling periods. Their testes were processed for histological investigation and immunohistochemistry for AR and AMH. The results showed differences among the various sampling areas and different sampling periods, which suggested seasonal breeding characteristics. The higher testicular morphometric data were observed in H. larvatus from the Dong Phayayen (DY) and Chiang Dao (CD) areas during June, while the size of seminiferous tubules decreased thereafter. High AR immunostaining was noticed when the testicular morphometric data were higher in DY bats during June. On the other hand, low AR was observed in bats during August and September, which was concomitant with the decreases in seminiferous tubule size and germinal epithelial height. The results suggest a potential correlation between AR immunostaining and the active phase of testicular functions in H. larvatus during June which may imply the involvement of AR with the enhancement of testicular activity. Conversely, the low expression of AR may contribute to the upregulation of AMH in the testes and may indicate lower testicular activity in H. larvatus in Thailand.The  Myotis nigricans demonstrated that only Sertoli cells and spermatogonia could be observed in the testis during the regressive period [Macrotus waterhousii bats during late September and the testes are involuted by early December [Hipposideros larvatus has not yet been performed.The reproductive system of bat species is complex and most exhibit the characteristics of seasonal breeders . The bate period . The bree period . On the December . RegardiDecember . As veryH. larvatus stands as one member, holding the designation of a species of least concern with the Red List of Threatened Species [The family Hipposideridae refers to insectivorous bats composed of 90 species. Among these,  Species . RoundleArtibius lituratus testis demonstrated that AR localisation is restricted mainly to the nuclei of somatic cells rather than in the germ cells [H. larvatus bat.The testis is the main target for androgens, acting via androgen receptors (ARs) in specific cells of the seminiferous tubule. Androgen plays an important role in testicular development, especially in the maturation of Sertoli cells, since the number of these cells has a crucial role in supporting the number of developing germ cells . An earlrm cells . In contrm cells . Despiterm cells . Furtherrm cells . The higrm cells . Studiesrm cells ,13; neveThe anti-Müllerian hormone (AMH) in the testes of mammals is known to act negatively in testicular steroidogenesis and Leydig cell differentiation. AMH is a member of the transforming growth factor-beta superfamily that contributes to the development of seminiferous tubules. The level of AMH is comparatively high in the prepubertal period in most mammals and decreases at puberty with the onset of spermatogenesis . TherefoH. larvatus, using samples obtained from different areas of Thailand and at different sampling periods. The study included the expression of AR and AMH in the testis in addition to testicular morphometric data in order to investigate the relationship between these proteins and the reproductive function in male H. larvatus.In the present study, we aimed to examine the morphological data of the male reproductive organs, mainly the testis of H. larvatus bats, sourced from various areas across Thailand, spanning the period from June to September. The acquisition of samples was conducted under approved protocol in accordance with the standard observational procedure outlined “The survey for bat population and Rabies virus investigation”. This initiative falls under the purview of the Wildlife Research Division, Wildlife Conservation Office, Department of National Parks, Thailand (project year 2019–2021). In order to optimize the utilization of animal resources, the left testicular specimens underwent subsequent investigation to study their histomorphology. The specimens were collected from (1) Dong-Phayayen, Khao-Yai wildlife research station, Nakhon Ratchasima province, north-eastern , (2) Id cave, Chiang-Dao district, Chiang Mai province, northern , in June; (3) Nangkwak cave , Kamphaengphet province, central, in July, (4) Khaoruenai , (5) Khaothamlad temple , Chachoengsao province, eastern, in August, and (6) Prathun cave , Lansak district, Uthaithani province, lower northern, in September. The details of sample collection including the distance from Bangkok, the centre of Thailand, and the mean temperature of each sampling point are shown in The testes were procured from Immediately after necropsy, the reproductive organs were dissected for anatomical study. Thereafter, the organs were fixed in 4% formaldehyde, slightly cut and processed histologically. All slides were stained with Haematoxylin and Eosin. In addition, the tissues were cut 4 mm thick and processed further for immunohistochemistry.®, Vector Laboratories Inc., Burlingame, CA, USA). In order to visualise the bound enzyme, chromogen 3′,3′-diaminobenzidine  was applied in the final steps. All slides were counterstained with Haematoxylin, mounted in glycerine/gelatine, scanned by digital slide scanner and analysed by image analysis software .Immunohistochemistry was performed to study the localisation of AR and AMH as previously described by the earlier studies in other species ,19. Brie2 random area of testicular tissue.Both morphological and immunohistochemical slides were studied using a digital slide scanner . Briefly, whole-slide digitalisation was applied to each sample section to visualise the whole picture. After slide scanning, testicular morphometrics were evaluated with Caseviewer. One hundred sections of seminiferous tubules were chosen randomly and measured. The seminiferous tubule diameter and the height of the germinal epithelium were measured, and their means were calculated. For the interstitial area, the investigation was performed by evaluating the interstitial area per 0.9 mmFor immunohistochemical staining, the expressions of AR and AMH protein in the testicular tissues of all samples were investigated by CellQuant and reported as a H-score. The immunohistochemical staining of each protein was categorised into different positive staining levels  and negative staining was set as default value for all evaluations. The positive staining intensity levels were determined based on multiple stained slides to ensure accurate measurement of all positive levels. Once the calibration was finalized, the settings were saved to a file which was then applied to all subsequent slide evaluations. Specific calibration levels were established for each protein under investigation, including AMH and AR. In the final step, the expressions of AR and AMH in the digital sections reported as a H-score were calculated from the formula :H-score All statistical analyses were carried out using the R programming language (version 4.1.2). The morphometric data and H-score were presented as mean ± standard error of the mean (SEM). The Shapiro–Wilk test was used to confirm that the data were distributed normally. The statistical model was used to evaluate fixed effect (location and season), and the Wilcoxon rank-sum test with Bonferroni correction or ANOVA followed by the Tukey–Kramer test were used to assess the differences in the evaluations in nonparametric and parametric data, respectively.H. larvatus testes from different locations and different sampling periods are shown in H. larvatus during June. On the other hand, the interstitial area was relatively high in groups with a low testicular diameter and germinal epithelial height.In this present study, all the examined bat carcasses were adults, with an average body weight of 22.77 ± 2.21 g and an average forearm length of 63.91 ± 1.60 mm. The testicular morphometric data of H. larvatus from the URN and KTL areas. The lowest H-score of AMH immunostaining in the H. larvatus testis was found in the groups from the CD and DY areas (p < 0.01) in the testes of H. larvatus.Immunolocalization of AR and AMH is shown as a H-score, which was calculated from both the intensity and proportion of the positive staining . PositivDY areas . When coDY areas . In addiH. larvatus collected from different locations in Thailand and at different periods. It was widely accepted that Hipposideridae bats are seasonal breeders which was confirmed by our results, which showed a diversity in testicular morphometric data at different periods of the year. During June, the greatest seminiferous tubule diameter and germinal epithelial height were observed, indicating more active testes compared to the other periods of the year. Furthermore, it may imply the most suitable breeding time of the year for H. larvatus in Thailand. The morphometric data on H. larvatus testis is in accordance with those of other bat species, which demonstrate the breeding season when the temperature is warm [Myotis nigricans in Brazil, two peaks of spermatogenesis were observed, during September and January, with regression periods in November and June [H. caffer from Nigeria, spermatogenesis began in March and May, although the seminiferous tubules showed no spermatozoa or enlargement [H. cyclops in Uganda was found during December [H. larvatus in Thailand, an earlier study showed that the highest mating activity was found during July and August in the Uthaithani province, but there were no morphometric data of the male gonad in that study [The present study reported morphometric data on the testes of  is warm . On the and June . These oargement , while tDecember . This inat study .H. larvatus indicated an active reproductive period during June; consequently, the testes started to enter a period of regression during July, which was completed in August and September, as shown by the decreases in testicular size and germinal epithelial height. From the example from AR knockout mice, the absence of ARs in Sertoli and Leydig cells has a negative effect on spermatogenesis. Furthermore, a lack of AR in smooth muscle and peritubular myoid cells can cause a decrease in sperm output, although spermatogenesis was maintained [H. larvatus during June may indicate a more active testicular function that was mediated through the expression of AR in the testes compared to other locations and sampling periods. Regarding active and regressive testes, our findings were similar to those of the earlier study on Myotis nigricans [Molossus molossus bats from Brazil [Artibeus literatus bats increased during the non-reproductive phase [H. larvatus may be under other regulatory mechanisms in addition to regulation from circulatory and testicular androgen.From the results of AR immunostaining, the present study showed the highest AR H-score in the DY during June, which is concomitant with the greatest seminiferous tubule diameter and germinal epithelial height. The diameter of the seminiferous tubule in intained . Howeverigricans  and Molom Brazil , where am Brazil . In contve phase . The expve phase ; therefoAMH is a member of the Transforming Growth Factor-β family that is expressed in the testis of both foetal and adult mammals ,28. The H. larvatus, as evidenced by discernible variations in testicular morphometric data and the expression levels of AR and AMH within different regions and sampling periods. Specifically, the higher testicular morphometric data observed in bats from the DY and CD areas during June might reflect optimal environmental and nutritional conditions favouring reproductive activity in these regions at that period. Nonetheless, it is essential to recognize a limitation in our study, especially sample collection. The bat carcasses were obtained from the survey study project, and consequently, the feasibility of obtaining a uniformly balanced distribution of samples across various locations and time points might have been limited. Moreover, aside from the geographical impacts on bat testes morphology, the expression of AR and AMH in bat testes is also influenced by other factors such as age and reproductive status. In our current findings, even though all sampled bats were adults, the expression levels of AR and AMH varied across different sampling periods. This variation might indicate that the reproductive state of the bats, whether they are in an active reproductive phase or a regressive one, plays a role in the expression of these proteins.According to the results from the present study, it may suggest that geography and timing appear to be significant factors influencing the reproductive physiology of H. larvatus during August and September, in contrast to a low AMH during June and July. These studies, together with our results, suggest that AMH may play a role in the testicular cycle in seasonal breeding animals, including bats. Regarding pathological conditions, a negative correlation between AMH expression and gonadal weight and sperm motility has been observed in mice treated with cytotoxic drugs. The increase in testicular AMH expression can cause an elevation of apoptosis and a reduction in cell proliferation . RegardiH. larvartus. This may suggest the reproductive period of this species to be when the expression of AR was high while AMH immunostaining was low. On the other hand, the regression period in the testis was demonstrated by the high AMH H-score and low negative AR H-score. In addition, some seasonally breeding bat species demonstrated two peaks of active and regressive testis throughout the year. For that reason, additional investigations at different periods of the year should be considered in further studies.The study of AR and AMH in the testis revealed that the downregulation of AMH in Sertoli cells was mediated through AR . The decH. larvatus. The variation in morphometric data and the expression of AR and AMH in the testis across different habitats and at different times of the year indicated the presence of seasonal breeding characteristics in this species. The higher testicular morphometric data, higher AR and lower AMH expression in bats during June may suggest an active reproductive period, while the lower testicular morphometric data, lower AR and higher AMH expression during August and September may suggest a testicular regression period in H. larvatus bats in Thailand.In conclusion, this study demonstrated, for the first time, the association between morphometric data, AR and AMH expression in the testis of


Secondary diabetes mellitus (DM) in secretory pheochromocytomas and paragangliomas (PPGLs) is encountered in up to 50% of cases, with its presentation ranging from mild, insulin resistant forms to profound insulin deficiency states, such as diabetic ketoacidosis and hyperglycemic hyperosmolar state. PPGLs represent hypermetabolic states, in which adrenaline and noradrenaline induce insulin resistance in target tissues characterized by aerobic glycolysis, excessive lipolysis, altered adipokine expression, subclinical inflammation, as well as enhanced gluconeogenesis and glucogenolysis. These effects are mediated both directly, upon adrenergic receptor stimulation, and indirectly, via increased glucagon secretion. Impaired insulin secretion is the principal pathogenetic mechanism of secondary DM in this setting; yet, this is relevant for tumors with adrenergic phenotype, arising from direct inhibitory actions in beta pancreatic cells and incretin effect impairment. In contrast, insulin secretion might be enhanced in tumors with noradrenergic phenotype. This dimorphic effect might correspond to two distinct glycemic phenotypes, with predominant insulin resistance and insulin deficiency respectively. Secondary DM improves substantially post-surgery, with up to 80% remission rate. The fact that surgical treatment of PPGLs restores insulin sensitivity and secretion at greater extent compared to alpha and beta blockade, implies the existence of further, non-adrenergic mechanisms, possibly involving other hormonal co-secretion by these tumors. DM management in PPGLs is scarcely studied. The efficacy and safety of newer anti-diabetic medications, such as glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors (SGLT2is), as well as potential disease-modifying roles of metformin and SGLT2is warrant further investigation in future studies. PPGL5 , as well1), alpha 2 (α2), beta 1 (β1), beta 2 (β2) and beta 3 (β3) adrenergic receptors (ARs), as well as on dopamine receptors type 1 and 2 [Normally, catecholamines mediate the fight or flight response, i.e. the physiological reaction to harmful event, attack, or threat to survival, upon acting on their receptors, alpha 1  or rarely corticotropin releasing hormone (CRH), somatostatin (SS), vasoactive intestinal peptide (VIP), parathyroid hormone (PTH), parathyroid hormone-related peptide (PTH-rP), enkephalins, endorphins, insulin-like growth factor 2 (IGF-2), chromogranin A (CgA), calcitonin (CT), CT-related peptide, atrionatriuretic peptide (ANP), and neuropeptide Y (NPY); these molecules may also affect glucose metabolism –21. MoreDespite the high prevalence of glucose metabolism disorders in PPGLs, the interaction between catecholamines and glucose metabolism is not entirely understood. According to a recent clinical study in non-diabetic patients, adrenaline is shown to mainly inhibit insulin secretion, while noradrenaline appears to principally impair insulin sensitivity in parallel with stimulating insulin secretion . In thisAuthors collected, analyzed and qualitatively resynthesized information regarding secondary diabetes mellitus in pheochromocytomas and paragangliomas. The impact of adrenaline and noradrenaline on glucose metabolism at molecular level, as well as evidence from preclinical and clinical studies was explored. English language literature was searched in PubMed until June 2023 using combinations of relevant terms.Catecholamine excess is a hypermetabolic state, characterized by enhanced energy expenditure and insulin resistance . The for1 and β2- AR stimulation of glucagon secretion from alpha pancreatic cells [2-AR activity of each compound [Insulin resistance is mediated both directly, via AR stimulation of target tissues, and indirectly, via αic cells . Adrenalic cells . The cenic cells , 28. Thicompound . Howevercompound .In a recent cross-sectional study of a general Japanese population, a significant correlation between urine normetanephrine level and homeostatic model assessment of insulin resistance (HOMA-IR) is found, suggesting that catecholamines might affect glucose homeostasis even at levels in the upper end of the normal range .1-AR and β2-AR, the 2 principal types of ARs expressed in skeletal muscle. Both adrenaline and noradrenaline activate these receptors, with the former bearing a higher affinity for β2-AR and the latter for α1-AR [As per their teleological purpose, catecholamines adapt glucose metabolism in order to meet the increased energy requirements of skeletal muscle during ‘’fight or flight” response. Thus, glucose uptake is expected to be increased upon activation of αor α1-AR .2-AR may preferentially activate different signaling pathways [Upon β-AR stimulation , glucose transporter 4 (GLUT-4) is translocated to the plasma membrane, as shown in vitro, ex vivo, and in vivo –32. Howepathways . The thipathways , 34.1-AR effects, data from transgenic mice models with constitutively active mutant (CAM) and knockout (KO) forms of α1A-AR and α1B-AR, demonstrate that α1-AR stimulation leads to increased glucose uptake ex vivo, accompanied by increased glucose tolerance in vivo [Regarding α in vivo .1-AR and β2-AR stimulation. In addition, increased glucose uptake due to α1-AR is expected in PPGLs with noradrenergic phenotype. However, given that both ARs desensitize after prolonged exposure to catecholamines [Considering that adrenaline-secreting PPGLs are frequently accompanied by impaired insulin secretion (see Insulin secretion section), glucose uptake would be increased due to αolamines , 37, theolamines .Patients with noradrenergic phenotype are shown to preferentially use carbohydrates as energy substrates . In both1 -AR and β3-AR. Adrenaline and noradrenaline have the same affinity for β3-AR, while noradrenaline has higher affinity for α1 -AR.In order to serve ‘’fight or flight” response, catecholamines are expected to increase lipolysis in adipose tissue in order to generate energy substrates in the form of FFAs, and to simultaneously inhibit glucose uptake, so that glucose is spared for skeletal muscle and vital organs. Patients with adrenergic phenotype are shown to preferentially use lipids as energy substrates . Adipose3-AR is not desensitized, thus the above effects are sustained during chronic catecholamine exposure [3-AR agonists were studied as potential anti-diabetic agents in the past [In response to β-AR stimulation (isoproterenol), there is enhanced lipolysis and impaired glucose uptake, as shown in vitro –43. Inteexposure . Puttingthe past . On the 1-AR stimulation is demonstrated to increase glucose uptake in adipose tissue ex vivo, in transgenic mice that express a CAM form of the receptor (α1A-AR and α1B-AR isoforms), as well as in vivo, in humans treated with phenylephrine [1 -AR stimulates lipolysis, which, interestingly, occurs in parallel with increased leptin secretion, further amplifying the above lipolytic effect via adenosine monophosphate-activated protein kinase (AMPK) signaling [1-AR is desensitized after prolonged exposure to catecholamines [Similar to skeletal muscle, αlephrine , 45. In ignaling . Albeit,olamines , the aboS-protein-PKA-dependent pathway in dose-dependent manner, with significant effect starting at low doses [Furthermore, catecholamines have been speculated to alter adiponectin expression, with inconsistent findings amongst studies. In two studies, patients with pheochromocytoma have lower adiponectin level in comparison to normal-weight hypertensive patients and age, sex and body mass index (BMI) – matched healthy controls , 47. Of ow doses . In contow doses . In addiow doses .Moreover, resistin, an insulin-antagonizing adipokine, is shown to be higher in patients with pheochromocytoma and DM than in non-diabetic ones, with its level being decreased post-surgery .Finally, secretory PPGLs lead to subclinical inflammation, as shown by increased c-reactive protein (CRP) level  and tumo3-AR stimulation by noradrenaline or due to other ‘’browning factors” secreted from PPGLs or is related to succinate dehydrogenase (SDH) mutations. Interestingly, these patients have higher mortality rate in comparison to age, gender, and BMI-matched PPGLs controls; the explanation of this phenomenon is not clear and might involve increased sympathetic tone, increased host stress, cachexia and wasting [Finally, few PPGLs have been shown to bear active brown adipose tissue (BAT) in 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (18F-FDG PET/CT), which occurs due to β wasting . To the In order to serve ‘’fight or flight” response, catecholamines are expected to increase glucose output from liver, so that glucose supply to skeletal muscle is amplified. The release of glycolysis-derived lactate and alanine from skeletal muscle , as well as from lipolysis-derived FFAs provides liver with substrates and is well-orchestrated with enzymatic up-regulation of gluconeogenesis and glycogenolysis.1-AR  and β2-AR at equal proportions [The hyperglycemic effects of catecholamines have been recognized from early hepatic vein catheterization studies in humans , 53. Durportions , 55. Botportions .1- and β2-ARs enhances EGP. The first study, during which adrenaline is administrated at pharmacological doses, reveals a sustained-over time β-AR stimulatory effect in EGP in the absence of α-AR effect [2-AR stimulation, there is increased expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6P). Interestingly, the same study shows that β2-AR stimulation is accompanied by glycogen levels depletion, suggesting that glucogenolysis could be, in part, a direct adrenergic effect [To characterize the direct effects of AR stimulation, the conditions of insulin and glucagon need to be controlled and this can be achieved by somatostatin administration. Under these circumstances, two human studies establish that direct stimulation of αR effect . In contR effect . Ex vivoc effect .1- and β2- ARs in alpha pancreatic cells and involves increase of intracellular calcium (Ca2+)i and subsequent exocytocis of glucagon granules [2- AR stimulation by adrenaline, cAMP signaling activates protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC2), which, in turn, activate two-pore channel 2 (Tpcn2) and liberate nicotinic acid adenine dinucleotide phosphate (NAADP) respectively. This results into Ca2+ release from intracellular lysosomal stores, which then triggers further Ca2+ release from endoplasmic reticulum (ER) [1-AR stimulation increases (Ca2+)i is not clear; it could involve α1-AR-induced activation of phospholipase C (PLC), crosstalk with β2-AR, or both [Regarding their indirect effects, both catecholamines, especially adrenaline, are well-known stimuli for glucagon secretion , 23, 58.granules . Upon β2lum (ER) . The exa or both .However, given that both aforementioned ARs are desensitized after prolonged exposure to catecholamines , 37, theImpaired insulin secretion is the principal cause of hyperglycemia in secretory PPGLs and has been recognized from early case series of patients with pheochromocytomas , 58. The2-AR, for which adrenaline has a greater affinity than noradrenaline [2A-AR, the most abundant subtype in pancreatic islets, is key to the process [2-AR agonists, mice exhibit hypoinsulinemia and glucose intolerance. Both effects are exacerbated in transgenic mice with α2A-AR overexpression and abolished or eliminated in transgenic α2A-AR KO mice or upon α2 -AR antagonist administration [The inhibitory effect of catecholamines on insulin secretion is mediated via αrenaline , 66. In  process . In respstration , 69.2-AR-induced inhibition of GSIS is well-established, the impact in basal insulin secretion is less clear, with rodent data ranging from no effect to tonic suppression. Insulin content is no different in pancreatic islets of transgenic mice with either α2A-AR overexpression or α2A-AR KO, indicating that insulin synthesis is not affected [While the αaffected , 69.2A-AR-mediated suppression of GSIS is complex. From early studies in vitro, α2-agonists , have been demonstrated to decrease (Ca2+)i concentration, via either α2 -AR agonist-induced membrane repolarisation or inhibition of voltage-dependent calcium channels (VDCCs) though pertussis toxin-sensitive G-protein [2+)i level restores insulin release at a minor extent, suggesting that decreased Ca2+ influx is not the major operating mechanism [+ channels (KATP). Adrenaline is demonstrated to inhibit the glucose-induced and incretin-potentiated cAMP production. In addition, it inhibits the activity of transient receptor potential melastatin 2 (TRPM2) channel, a type of NSCCs, in cAMP-dependent manner. In turn, this leads to prolonged lag time and decreased beta cell membrane excitability, and therefore to attenuated insulin secretion. Adrenaline inhibits TRPM2 current exclusively by α2Α-AR in the presence of tolbutamide, a sulfonylurea keeping KATP closed, indicating that the induced effect occurs downstream KATP [The underlying mechanism of α-protein , 71. Howechanism . Recent eam KATP .2-AR activity upregulation seems to participate in pathogenesis of ‘’wild-type” glucose intolerance. Naturally-occurring single-nucleotide polymorphisms of α2 -AR overexpression decrease insulin secretion  and increase the risk of type 2 diabetes mellitus (T2DM) in human and rat, via impaired granule docking at the plasma membrane and beta cell exocytosis, at stage distal to elevation of (Ca2+)i [2 -AR agonists inhibit and α2 -AR antagonists enhance insulin secretion [Beyond the clinical setting of secretory PPGLs, α (Ca2+)i . As a geecretion , with thecretion , 75. Howecretion .2-AR activation, β-AR activation stimulates insulin secretion via inducing adenylate cyclase (AC) activity, increases insulin content and reduces beta cell apoptosis [Contrary to the inhibitory effect of αpoptosis , 77.2Α-AR stimulation and stimulatory upon α1-AR and β1-AR stimulation [2Α-AR and noradrenaline’s preferential affinity for α1-AR and β1-AR, a dimorphism of effect in terms of GLP-1 and insulin secretion between adrenaline- and noradrenaline-secreting PPGLs is plausible. In line with this notion, a recent prospective study in patients with pheochromocytomas with adrenergic phenotype, demonstrates impaired first phase of insulin secretion and GLP-1 secretion [Apart from their direct effects in pancreatic beta cells, catecholamines affect glucagon-like peptide 1 (GLP-1) expression via their ARs in distal gut. However, their effect depends on AR type, being inhibitory upon αmulation , 79. Conecretion .Similar to insulin sensitivity outcomes, surgical removal of PPGLs restores insulin secretion more effectively than α-blockade , 63, sugBeing consistent with its pathogenesis, secondary DM in PPGLs is more strongly associated with parameters of impaired insulin secretion than of increased insulin resistance . FurtherK(M) electrical current in pheochromocytoma cell lines; the subsequent perturbance of membrane excitability in these cells might have functional implications [Few studies have addressed the management of secondary DM in PPGLs. According to a retrospective study of 204 patients with PPGLs and secondary DM, 40% of patients are controlled on diet, 27% of patients receive metformin as monotherapy or in combination with other oral anti-diabetic medications (sulfonylureas or dipeptidyl peptidase 4 inhibitors) and 33% of patients are insulin-treated ; Regardiications . Howeverications . Similarications  and primications .There are no studies assessing the glycemic efficacy of alpha- and beta-adrenergic blockade in patients with secondary DM due to PPGLs. In few studies investigating its impact in non-diabetic patients with PPGLs, both insulin sensitivity  and insuPost-operatively, DM is shown to markedly improve, with complete resolution being observed at 57–79% of cases in cohort studies  and up tDisorders of glucose homeostasis in secretory PPGLs are common, being encountered in almost half of the reported cases; therefore, the co-existence of unexpected, according to age and BMI, hypertension and DM should alert the clinicians to the possibility of such tumors. The aim of this review was to characterize the pathogenesis, presentation, prognosis, and management of secondary DM in this clinical setting.2α-AR mediated inhibition of insulin and GLP-1 secretion  than in tumors of the other 2 clusters, in order to understand if anaerobic glycolysis in these PPGLs is limited to the tumor cells or expanded to encompass insulin-sensitive tissues, such as muscle and adipose tissue. Furthermore, exploring the genetic basis and role of insulin expression by tumor cells and BAT in glucose metabolism could shed light to other pathogenetic aspects of secondary DM in this setting.Secondary DM in PPGLs remits at a high percentage post-surgery; on the other hand, alpha and beta blockade, as well as metyrosine, improve glucose metabolism at a lesser extent; this possibly reflects either that PPGLs affect glucose metabolism through multiple hormonal co-secretion or that the dosage used for blood pressure control is not adequate for glycemic control. The persistence of DM post-operatively reflects either co-existence of other pathogenetic factors, such as increased age or BMI, or persistence of underlying disease. Regarding the latter, the possible disease-modifying effects of metformin and SGLT2is deserve further investigation in preclinical and clinical studies, as their use could be relevant in cases of persistent DM due to metastatic or recurrent disease.In conclusion, our perspective towards secondary DM in PPGLs should include the existence of 2 distinct glycemic phenotypes. Their biochemical, genetic and cardiovascular classification, alongside with pathophysiology-targeted management, seems to be the only way towards personalized management of secondary DM in PPGLs.Publication License


R2 = 0.94), and RSBC (R2 = 0.97)] of process optimization model suggesting that this model was significant, where pH and adsorbent dose expressively stimulus removal efficiency including 99.88, and 99.89% for PETWBC, and RSBC at pH (2). Furthermore, the machine learning approaches (ANN and BB-RSM) revealed a good association between the tested and projected value. Pseudo-second-order was the well-suited kinetics, where Freundlich isotherm could explain better equilibrium adsorption data. Thermodynamic study shows AR 27 adsorption is favourable, endothermic, and spontaneous. Environmental friendliness properties are confirmed by desorption studies and satisfactory results also attain from real wastewater experiments. Finally, this study indicates that PETWBC and RSBC could be potential candidates for the adsorption of AR 27 from wastewater.This study focuses on the probable use of PET waste black carbon (PETWBC) and rice straw black carbon (RSBC) as an adsorbent for Acid Red 27 (AR 27) adsorption. The prepared adsorbent is characterized by FE-SEM and FT-IR. Batch adsorption experiments were conducted with the influencing of different operational conditions namely time of contact (1–180 min), AR 27 concentration (5–70 mg/L), adsorbent dose (0.5–20 g/L), pH (2–10), and temperature (25–60°C). High coefficient value [PETWBC ( Organic dyes are extensively used as colouring agents in many industries including textiles, leather, paint, cosmetics, rubber, paper, ceramics, varnishes, pulp mills, ink, plastics, pharmaceuticals, and tanneries . Globall85-95%). Lab-grade de-ionised water was used for the whole study.In the entire experiment, using every chemical and reagent was laboratory-grade, purchased from Sigma-Aldrich (Germany), namely Acid Red 27  until getting moisture free, and cool at ambient conditions. After that, PETWBC and RSBC were produced by burning in an electric furnace at 600°C for 100 min and 500°C for 15 min retention time, respectively. Then carbonize products were crushed and preferred size portions (0.5 to 1.0 mm) were collected through a conventional sieve. Finally, store it in a sealed glass bottle for next experimental uses. Synthesize graphene was characterized using FT-IR, and SEM. The surface morphology of prepared graphene was investigated with FE-SEM, Zeiss Sigma 300, Carl Zeiss, Germany, at 10 kV voltages. Before analysis, the graphene powder was coated with gold for better imaging and to escape the addition of native electrical charges. The surface chemistry was investigated by FTIR , where the recorded spectra range varied from 400–4,000 cm3, then successive dilution approaches were used to prepare the preferred working solution from the stock solution. Adsorption of AR 27 onto PETWBC and RSBC was carried out in a batch mode at 200 rpm using the following operational conditions: pH (2–10), time of contact (1–180 min), temperature (25–60 0C), graphene dose (0.5–20 g/L), and AR 27 concentration (5–70 mg/L). For pH adjustment, 0.1 N acid (HNO3) and base (NaOH) solution was used. After a certain time, samples were taken, and, filtered for AR 27 concentration analysis using a UV-visible spectrophotometer  at 520 nm wavelength. A duplicate test was conducted to gating accurate results. The total AR 27 adsorption rate and removal efficiency was estimated using Eqs The required quantity of dye powder is dissolved in distilled water for preparing 1000 ppm stock solution and kept the stock solutions pH was less than 2.0 using HNOWhere,o = initial AR 27 concentration (mg/L)Ce = equilibrium AR 27 concentrations (mg/L),Ce = amount of AR 27 adsorbed (mg/g)qV = volume of liquid solution (L)s = graphene mass (g).mAdsorption isotherm studies were carried out into 250 mL dye solutions of varied dye concentrations (5 to 70 mg/L), at pH 2, where 10 g/L adsorbent dose (PETWBC and RSBC) was added and stirred the solution at 200 rpm with ambient temperature for 150 min. While kinetics experiments were run in 300 mL dye solution at a fixed concentration (20 mg/L) and kept the other condition constant, then samples were taken out after following time intervals 1, 5, 7, 10, 15, 20, 30, 60, 90, 120, 150, and 180 min, filtered, and analyzed. This study applied Langmuir and Freundlich for equilibrium data modelling while pseudo-first-order and pseudo-second-order were used for kinetic modelling, detailed presented in S1 Table in 2) tests, and root means square errors (RMSE) error analysis test  from the kinetic models, qcal is the calculated adsorption data (mg/g) from models, and n represents the number of data sets.Error analysis is applied for every used model to assess the level of error as compared with obtained and experimental results. In this study, residual sum square (RSS) chi-square Thermodynamics is a vital parameter for adsorption study, where temperature variation is needed for conducting this study. In this study, Gibbs free energy change (ΔG), enthalpy (ΔH) and entropy (ΔS) are calculated by applying the following Eqs 1 = pH, X2 = AR 27 concentration, and X3 = graphene dose and three levels are stated as upper (1), central (0), and lower (-1), detailed presented in Box- Behnken designing (BBD) approach is an appropriate statistical tool widely used for process optimization, where the least number of experiments were applied to explore the probable association between the experimental parameters and their influences on the adsorbate adsorption . This ste (Cd), qe (Pb), qe (Cu), qe (Zn), β0 = Constant, βi = linear coefficient. βij = interface coefficients, βii = quadratic coefficients, and Ai and Aj = process variables.Where Z is the projected response (dye adsorption (%); qf) vs pHi, where 2.99 and 4.7 were discovered as the pHpzc value for PETWBC, and RSBC respectively. According to the pHpzc concept, the graphene shows a positive attitude at solution pH< pHpzc value, conversely a negative attitude expresses at solution pH > pHpzc value. FTIR analysis represents the surface chemistry of graphene (before and after adsorption), where diverse functional groups influence the linkage between adsorbate and adsorbent, obtained results presented in S1a Fig in The pHpzc is a crucial component that delivers a clear concept regarding adsorbent surface charging and its relations with the target component. −1 matching the in-plane C = C vibration indicates the graphite properties, that is inborn properties of sp2 graphitic ingredients [−1  an experiment was conducted where other factors are kept constant . Pollutant elimination from wastewater is suggestively influenced by adsorbent dosage . To asse(R2) and lower error values  and RMSE) of the model, and the applied model parameters are represented in 2 and lower RSS, χ2, and RMSE values for AR 27 adsorption as compared with pseudo-first-order kinetic, additionally, the calculated  value from the pseudo-second-order kinetic model also corresponds to the experimental value , indicating that pseudo-second-order was best fitted kinetic model for adsorption data.Adsorption kinetics is needed to design an effluent treatment plant unit, where adsorbate could be removed pollutants at a certain rate. In the present study, two commonly uses kinetics models such as Lagergren’s pseudo-first-order, and Ho’s pseudo-second-order applied for AR 27 adsorption onto PETWBC and RSBC. The model accuracy depends on the high correlation coefficient The experimental data were also evaluated by intraparticle (IP) diffusion to determine the diffusion mechanisms. The two-stage of the IP plot did not pass through the origin , represeR2 = 0.964, RSBC: R2 = 0.959), lower error , and chi-square value  and  as compare Langmuir isotherm   , showingRL values of graphene were between 0 and 1, representing that AR 27 adsorption onto adsorbent was appropriate under the studied experimental conditions. Conversely, the value of adsorption intensity (n) was higher than 1 and higher KF, demonstrating that the adsorption process was promising for AR 27 adsorption from aqueous solutions using PETWBC AND RSBC (T < 8 KJ), and (E < 8 KJ/mol)  , respectR2 values of 0.956, and 0.943 for PETWBC, and RSBC, respectively. 0 demonstrate that AR 27 adsorption processes are thermodynamically spontaneous and useful [The thermodynamic study represents the role of temperature for adsorption, the nature of the linkage between adsorbate and adsorbent, direction and mechanism of reaction with changing the experimental temperature . These sd useful .0. Lower ∆H0 value (< 40 kJ/mol) recommends that physisorption is the main mechanism for AR 27 adsorption [0 also suggests that physical alterations happen on the adsorbent during dye uptake through the ion exchange process. Sackey et al. [The endothermic type of adsorption is confirmed by the positive result of ∆Hsorption , besidesy et al.  detect tFor process optimization, the three factors including pH, initial MHs concentration and the adsorbent dose were applied and the studied responses are presented in S2 Table in The statistical association between the nominated experimental factors and the response was explained by a quadratic model with corresponding coded factors and their best fitted using the following equations.2, and B2, respectively are significant model (p<0.05) terms for AR 27 adsorption using both adsorbents. Adsorbent dose and pH significantly influence AR 27 adsorption. Moreover, the R2 value of PETWBC = 0.94, and RSBC = 0.97 showed that 94, and 97% of the whole variability of the result was explained by this model. A good agreement was attained between experimental (R2) and projected (R2adj) results for AR 27 dye adsorption  is vital for assessing the significance level of the second-order model and the result of ANOVA for AR 27 adsorption, presented in S3 and S4 Tables in Artificial neural network modeling. ANNs are widely used for recording the non-linear relation between independent and dependent variables and are suitable to apply to any condition [ondition . This st2) did not represent the same outcome in the training phase. In the case of AR27 adsorption, all training, validation, and testing phase of tan-sigmoidal and topology was selected according to high R-value and its associated lower MSE value  experiments. The physicochemical characteristics of RWW were pH (8.3), TDS (482 mg/L), EC (988 μS/cm), and salinity (0.4 ppt). The initial concentration of AR 27 in RWW was 291.5 mg/L and after the treatment at pH 2, the concentration was found 89.67, and 62.17 mg/L, for PETWBC, and RSBC respectively at 520 nm absorbance. The removal rate of AR 27 was 69, and 78%, for PETWBC, and RSBC, respectively . This diThis process is applied to assess the possibility of further contamination when the treated adsorbent comes into the environment. The desorption rate of adsorbent significantly influences by the nature of bonding  between adsorbate and adsorbent . In thisThis present study explores the usability of PETWBC and RSBC as potential biosorbents for AR 27 removal from simulated wastewater under batch adsorption experiments. Study finding shows that synthesize adsorbent has high performance in removing AR 27 dye from wastewater. The elimination efficiency of AR 27 decreases with rising dye concentration  and pH  while enhancing with rising temperature  and adsorbent dose . The equilibrium contact time of AR 27 was 150 min, and the optimum pH was (2). BBD and ANN models are suitable for AR 27 adsorption modelling, where both models showed a good agreement between predicted and experimental results. Pseudo-second-order was the best-matching kinetic model for AR 27adsorption data. The equilibrium data was well explained by the Freundlich isotherm model. The monolayer maximum adsorption capacity of AR 27 was 4.108, and 4.840 mg/g for PETWBC and RSBC, respectively. Thermodynamic study shows the adsorption is endothermic, physical, and spontaneous for AR 27 removal. Cost-effectiveness, obtainability, and favourable study results make PETWBC and RSBC suitable and effective adsorbents for removing dyes and other environmental pollutants. Consequently, PETWBC and RSBC could be applied for effluent treatment, where a centralized wastewater treatment system is not accessible.S1 File(DOCX)Click here for additional data file.