Active arterial mechanics, governed by vascular smooth muscle contraction, are critical to physiological regulation, cardiovascular disease progression, and clinical diagnosis. Although various in vivo methods have been developed to assess arterial stiffness, most cannot distinguish the contribution of smooth muscle tone; therefore, quantitative characterization of arterial activity remains challenging. In this study, we developed a pressure-area analysis framework integrating ultrasound imaging, blood pressure measurement, neural network-based segmentation of arterial cross-sectional area, and biomechanical model-driven inversion to infer active mechanical properties. A total of 233 volunteers (aged 18-65 year) were recruited to acquire cross-sectional ultrasound videos of the right common carotid artery for training the neural network. The segmentation results demonstrate good spatial and temporal performance of the neural network. We further recruited 10 additional volunteers (aged 25 ± 3year) to perform a 1min step test, followed by pressure-area measurements over a 30min recovery period. Using the proposed approach, we quantified post-exercise changes in carotid arterial active mechanics relative to baseline (i.e., the resting state). Results showed that active mechanics remained elevated for approximately 15min compared to baseline (p < 0.05), whereas systolic pressure differed significantly only within the first approximately 5min post-exercise (p < 0.001). These results indicate a dissociation between blood pressure and smooth muscle recovery, which may offer new insight into vascular smooth muscle regulation during physiological stress.

Electrostimulation can be an interesting and effective alternative or additional option to conventional treatments for facial paralysis, helping to prevent atrophy of the facial muscles following denervation caused by various factors. The success of electrostimulation depends on correctly selecting the stimulation parameters applied. Our study aims to evaluate whether needle electrodes (mimicking implantable electrodes) can selectively activate the zygomaticus muscle (ZYG) in patients with facial paralysis. Ten patients were recruited. Two monopolar needle electrodes, placed under ultrasound guidance, were used to deliver bipolar electrostimulation to the affected ZYG. The stimulation was conducted under general anaesthesia in three patients and under local anaesthesia in four patients. Three patients underwent stimulation in both settings. Selectivity of stimulation was assessed by visually detecting movement of the respective mouth corner, in the absence of contractions or co-contractions of other facial muscles or discomfort. A selective Zygomaticus response was observed in all patients with pulse widths between 0.5 and 5 ms and amplitudes between 1.5 and 2.5 mA when awake, and between 1.5 and 9 mA when under general anaesthesia. No adverse events or unspecific responses from other facial muscles were observed. The duration of facial paralysis did not significantly affect parameter selection. In conclusion, our initial results suggest that stimulation parameters compatible with implantable devices can elicit a specific response from the target muscle. Ultrasound-guided electrode placement ensures the safety of the procedure. If implanted into the ZYG, a fully implantable electrostimulation device should be able to increase muscle tone and trigger a contraction, enabling a bionic smile.

Indications, Trends, and Outcomes of Nerve Blocks for Spasticity Management: A Systematic Review.

Introduction: Coronavirus Disease 2019 (COVID-19) infection has been difficult to control despite advancements in medical science. Many short and long-term complications following COVID-19 infection are still being observed. The hypoxaemia episodes occurring in the first trimester of pregnant women and their potential role in causing congenital malformations in newborns remain unclear. Limited information is available regarding the effects of Severe Acute Respiratory Syndrome Coronavirus 2 (COVID-19) during the first trimester of pregnancy and its association with the risk of developing Major Congenital Malformations (MCMs). Aim: To compare the development of congenital malformations in pregnant women who tested SARS-CoV-2 positive and those who tested negative during the first trimester of pregnancy. Materials and Methods: A prospective cohort study was conducted in a small town in the Hooghly district of West Bengal between January 2021 and December 2021. Two nursing homes were selected for sample collection, with approximately 100 patients per centre. The study included 100 pregnant women in their first trimester who tested SARS-CoV-2 positive and another 100 pregnant women in their first trimester who tested negative. An unpaired t-test was performed to analyse the association between the development of MCMs in both groups. Results: The mean maternal age was comparable between the COVID-19-exposed group (24.6 years) and the nonexposed group (25.2 years). The proportions of primigravida and multigravida women were also similar in both groups (62% vs. 64% primigravida, respectively). The odds ratio for MCMs in the COVID-19-exposed group was 0.49, indicating a lower likelihood compared to the non-exposed group. The average Appearance (skin color), Pulse (heart rate), Grimace (reflex irritability/response), Activity (muscle tone), and Respiration (breathing effort) (APGAR) scores at 1 and 5 minutes were slightly higher in the exposed group (7.01 and 7.45) than in the non-exposed group (6.8 and 7.28), though the differences were not statistically significant (p=0.28 and p=0.50, respectively). Conclusion: The present study concludes that there is no evidence of increased risk of MCMs associated with firsttrimester maternal SARS-CoV-2 infection. Overall, the findings do not support any major teratogenic effects resulting from maternal COVID-19 infection in early pregnancy.

In recent years, Coxsackievirus A6 (CV-A6) has gradually replaced Enterovirus 71 (EV-71) and Coxsackievirus A16 (CV-A16) as the main pathogen causing hand foot mouth disease (HFMD) in China. This article reports a fatal case of HFMD caused by CV-A6, leading to fulminant cerebral edema and cardiopulmonary arrest. A 6-year-old boy was admitted with a chief complaint of "fever for 1 day, two episodes of seizures". On admission, the patient exhibited unresponsiveness, no spontaneous breathing, bilateral fixed and dilated pupils, complete muscle weakness, and loss of muscle tone. The brain computed tomography (CT) revealed diffuse decrease in brain parenchymal density. On the 3rd day of admission, the patient presented with a red rash on the hands, feet, knees, buttocks, and perianal area, and a nasopharyngeal swab was positive for CV-A6. Considering the symptoms, physical examination, laboratory tests, and imaging results, the diagnosis of "severe HFMD, fulminant cerebral edema" is considered. On the 16th day of admission, the patient was diagnosed with brain death, and on the 57th day, the patient died. CV-A6 infection can lead to severe neurological complications, characterized by fulminant cerebral edema, which can result in fatal consequences.

Background: Botulinum toxin injections are widely used in the orofacial region for cosmetic and therapeutic purposes. Recently, interest has grown in combining Botulinum toxin A injection with facial exercises to enhance or sustain aesthetic and functional outcomes. Objective: To examine the efficacy of Botulinum toxin injections with facial exercise on orofacial disorders. Methods: A comprehensive electronic literature search was conducted across databases. Studies were screened for eligibility, and reviewers independently assessed quality and bias. Results: An electronic search of databases up until Feb 2026 revealed 164,916 Articles. Seven studies met the inclusion criteria, including four RCTs and three prospective clinical studies conducted in a hospital-based setting. Different Botulinum toxins have been used in these studies. Two studies used Onabotulinumtoxin A, two used botulinum toxin (Dysport), and two RCTs used botulinum A toxin (Botox). Additionally, the presented studies performed various myofunctional therapy. Conclusion: The current evidence suggests that facial exercise following Botulinum toxin A injections may enhance treatment outcomes in the orofacial area by sustaining muscle tone and prolonging aesthetic benefits. Further research with larger sample sizes and standardized protocols must establish the effectiveness and best practices of this combined approach.

Background: Magnesium is a key intracellular cation influencing bronchial smooth muscle tone and mediator release, yet its relationship with acute severe asthma remains inadequately characterized. Objective: To evaluate serum magnesium levels and determine their association with acute severe asthma severity by comparing biochemical and demographic parameters between asthmatic and non-asthmatic individuals. Methods: This hospital-based cross-sectional analytical study was conducted over two years in a tertiary care medical department. A total of 152 participants were enrolled, including 76 patients with acute severe asthma (Group I) and 76 age- and sex-matched non-asthmatic controls (Group II). Clinical assessment, sociodemographic profiling, and serum magnesium estimation were performed. Data were analyzed using SPSS version 22. Results: The mean age was 39.88 ± 10.83 years in asthmatics and 36.38 ± 12.34 years in controls (p = 0.087). Male predominance was observed in both groups (52.6% vs 55.3%; p = 0.742). Hypomagnesemia prevalence was significantly higher among asthmatics (35.5%) compared with controls (17.1%) (χ² = 6.12; p = 0.013). Mean serum magnesium was significantly lower in Group I (1.90 ± 0.28 mg/dL) than Group II (2.01 ± 0.19 mg/dL; p = 0.004). Asthmatics with hypomagnesemia demonstrated higher respiratory rate (28.4 ± 4.1 vs 24.6 ± 3.8/min; p = 0.001) and increased need for bronchodilator therapy (p &lt; 0.05). No significant association was observed with socioeconomic status or residence (p &gt; 0.05). Conclusion: Hypomagnesemia was significantly associated with acute severe asthma and greater clinical severity, supporting routine serum magnesium assessment as a potential adjunct marker in acute asthma management.

The purpose of the study is to investigate the characteristics of peripheral hemodynamics in children with spastic diplegia who engage in cyclic sports. Research methods and organization. Three groups of children were examined: children not attending additional extracurricular physical fitness and wellness activities, children engaged in track and field, and children participating in swimming. All children were diagnosed with 'Cerebral Palsy: Spastic Diplegia (G80.1),' classified as level I according to the GMFCS. Assessments included rheovasography indices for the 'thigh-calf' and 'shoulder-forearm' recordings, muscle tone using the Ashworth scale, muscle strength, and joint range of motion using six-point scales. Research results and conclusions. In children with spastic diplegia, peripheral hemodynamics of the upper and lower limbs are characterized by increased vascular resistance and impaired microcirculation. A comparison of different types of cyclic motor activity using rheovasography indicators revealed statistically significant differences, indicating adaptation of peripheral hemodynamics in the working muscle groups. Children engaged in track and field exhibit more effective microcirculation and more pronounced venous outflow compared to children practicing swimming.

Traditional hypertonia diagnosis relies on the Modified Ashworth Scale (MAS), which is subjective and dependent on doctors' experience. Although previous studies have explored the use of force sensors and surface electromyography (sEMG), finding a reliable and valid detection method remains a challenge. This study aims to develop a simple yet effective platform that integrates biomechanical and sEMG data for upper-limb muscle tone assessment, providing a more objective and quantitative evaluation approach. A detection platform was developed to collect biomechanical and sEMG data from 59 subjects, including 49 patients (MAS Ⅰ = 21, MAS Ⅰ + = 16, MAS Ⅱ = 12) and 10 healthy individuals, at different movement speeds (15°/s, 20°/s, and 25°/s). The acquired data underwent feature extraction, including signal processing and statistical analysis. Dimensionality reduction was applied to optimize the extracted features, and these features were then integrated into a classification algorithm for further analysis. The extracted features effectively distinguished patients from healthy individuals, with statistically significant differences (p < 0.01). Furthermore, the strong correlation between the extracted features and MAS scores (p < 0.01) confirmed the reliability of the proposed method. Finally, the classification algorithm demonstrated high consistency with clinical evaluations, validating its potential for clinical application in muscle tone assessment. This study introduces an objective and quantitative method for assessing muscle tone, shifting away from the traditional subjective MAS evaluation. By enhancing diagnostic accuracy, the proposed approach provides a more reliable basis for hypertonia diagnosis and treatment. The findings hold significant promise for optimizing clinical decision-making, ultimately improving patient management and therapeutic strategies.

Background: Mechanization in olive harvesting has improved productivity but introduced new ergonomic challenges, particularly related to vibration exposure and sustained overhead work. This study investigates the acute and short-term physiological effects of using an electric olive harvester through objective instrumental assessment. Methods: Ten healthy male volunteers performed a standardized 15-min simulated harvesting task using an electric olive harvester. Muscle tone, stiffness, and elasticity of bilateral deltoid, biceps, and triceps were assessed by myotonometry at baseline (T0), immediately post-task (T1), and after 2 h recovery (T2). Infrared thermography evaluated cervical, dorsal, and lumbar skin temperature at the same timepoints. Results: Significant, side-dependent alterations in myotonometric parameters were observed, with marked increases in tone and stiffness of dominant upper-limb muscles and asymmetric adaptations between limbs (p &lt; 0.001, large effect sizes). Infrared thermography revealed significant post-task reductions in skin temperature across spinal regions, with a partial return toward baseline within the 2 h observation window (p &lt; 0.01). These findings describe short-term, task-related thermoregulatory responses following sustained work. Conclusions: Even short-term use of electric olive harvesters induces measurable biomechanical and thermophysiological stress. The integrated use of myotonometry and infrared thermography provides a sensitive, field-adaptable framework for early ergonomic risk detection and prevention of work-related musculoskeletal disorders in agriculture.

Background: The objective of this study was to assess the tension of selected postural muscles during the jaw-sucking movement in four body positions (standing position, all-fours position, lying on front, lying on the side). Material and Methods: The research involved 30 young adults with an average age of 22.6 ± 0.72 years. Suprahyoid, trapezius, gluteus maximus, and gastrocnemius muscles were assessed in all study participants in the standing, kneeling, and belly lying positions (prone position). Measurements were taken twice for each position: once without jaw activity and once with jaw movements simulating sucking. Muscle function was determined by measuring muscle tension using surface electromyography (sEMG). Results: Engaging jaw movements in the prone position resulted in significantly increased tension in the gastrocnemius muscle. In the all-fours position, there was a notable rise in tension in both the gastrocnemius and gluteus maximus muscles. When standing, significantly higher tension was observed in the trapezius and gluteus maximus muscles. In contrast, the side-lying position exhibited no significant changes in muscle tension. Conclusions: The study's findings suggest that activating jaw function may affect the tone of the gastrocnemius muscle in both prone and quadrupedal positions. In contrast, there were no clear or statistically significant changes observed in the tone of trapezius muscles in either position, while, for the tension of the gluteus medius muscle, variability was shown only in the all-fours position.

Cerebral palsy (CP) is a non-progressive condition involving movement and muscle tone difficulties due to injury to the developing brain. Most cases arise around birth, but a smaller proportion (postneonatal CP) experience brain injuries between 29 days and 2 years of age. Causes of postneonatal CP are often modifiable and may be more prevalent in socio-economically deprived areas, yet few studies have investigated this issue. We addressed this gap using a population-wide CP register in Northern Ireland. We conducted a retrospective study linking births between 1981 and 2016 to area-level deprivation data. Bayesian regression models assessed associations between deprivation, postneonatal CP and related outcomes. Postneonatal CP declined steadily across the study period (IRR=0.89; 89% uncertainty interval (UI) 0.85 to 0.93), especially among individuals from the most deprived backgrounds. While the odds of infection-related postneonatal CP decreased overall, these did not decrease among CP individuals from deprived backgrounds, who also displayed higher odds of postneonatal CP due to head injuries (OR=2.72, 89% UI 1.09 to 5.30). Postneonatal CP was associated with higher odds of severe motor impairment (OR=1.47, 89% UI 1.07 to 2.00), intellectual delay (OR=2.54, 89% UI 1.83 to 3.55) and seizures (OR=2.55, 89% UI 1.84 to 3.56). Although prevalence has declined, socioeconomic inequalities remain in the causes and consequences of postneonatal CP. These findings highlight the need for targeted public health interventions and further research to address persistent disparities and prevent modifiable causes of CP.

Spinal Cord Injury (SCI) results from a traumatic event often caused by car and motorcycle accidents, gunshot and stab wounds, falls from heights, and even diving into shallow water. It corresponds to the interruption of the nerve, sensory, and motor tracts of the spinal cord in any structural portion, resulting in partial or total impairment of function. The objective of this study is to understand the nursing care provided to victims of spinal cord injury, to present the main complications of SCI, and to describe the epidemiology and pathophysiology of spinal cord injury. The methodology used was integrative literature review. The study was conducted between July and November 2025. Using the descriptors “Nurse, Spinal Cord Injury and Complications,” 10 studies with a time frame of 2020-2025 were selected from the SciELO, BVS, and PubMed databases. Due to the danger of spinal cord injury, the affected individual faces long periods of hospitalization and rehabilitation, during which various complications may emerge, such as deep vein thrombosis, neurogenic bladder, neurogenic bowel, pressure injuries, pneumonia, loss of muscle tone, and neurogenic shock. Therefore, the nurse in this context becomes fundamental in reducing or even preventing such complications, playing a relevant role in the care of individuals with spinal cord injury.

Lower extremity stability is closely related to sports injuries and muscle fatigue, with the calf complex playing a crucial role. This study aims to investigate the effects of manipulation using traditional Chinese medicine functional manipulation (TCMFM) and maintaining it through the application of kinesiology tape (KT). Forty-five participants were recruited and randomized to two groups using a crossover design. All research in this study was conducted at the same university. In this randomized crossover trial, participants received either TCMFM with KT (TCMFM-KT) or KT alone, separated by a washout period to minimize carryover effects. Eight positions on the lower limbs were measured using MyotonPRO® to assess soft tissue changes, and the feeling of discomfort was recorded using a visual analog scale. TCMFM facilitates the redistribution of mechanical load from the calf muscle to adjacent or synergistic muscle groups, thereby mitigating localized strain. The variation in muscle tone (∆F%), defined as the proportion of muscle tone at a given measurement point compared with the baseline value (day 1, before intervention), was higher in the TCMFM-KT than in the KT session at the lateral leg from day 1 to day 3. The ∆F% at the anterior leg on day 2 and at the medial leg on day 7 were lower in the TCMFM-KT session than in the KT session. The VAS score in the KT session was higher on day 2 and day 3 than on day 1, whereas no significant change was observed in the TCMFM-KT session. TCMFM has the potential to improve overall muscle activation and coordination in the lower limbs, reducing the impact of muscle fatigue. Functional manipulation, Kinesiology taping, Muscle fatigue, Traditional Chinese medicine.

Introduction The higher education years represent a critical period for social and emotional development, often marked by elevated stress and challenges to self-regulation that impact students' wellbeing and interpersonal functioning. These demands are particularly relevant for future childhood educators, whose professional effectiveness depends partly on their ability to model and support children's emotional development. Methods This mixed-methods, non-randomized study examined the effects of an 8 week psychomotor relaxation program on a small single-group sample of 20 first-year female university students in Education Sciences. Following a 4 week within-subject control phase, participants engaged in biweekly psychomotor relaxation sessions combining body awareness, muscle tone regulation, and breathing exercises. A single-arm repeated-measures design assessed changes in objective and subjective stress indicators, interoceptive awareness, affective states, and psychological wellbeing. Additionally, students' perceptions of the program's personal and professional impact were explored through open-ended questions and thematic analysis. Results Quantitative findings revealed selective improvements in emotional and bodily awareness, a reduction in confusion, and an enhanced sense of purpose in life. Qualitative data supported these results, with most students reporting regular use of learned strategies in daily life and recognizing the relevance of these skills for managing classroom stress and fostering children's emotional wellbeing in their future roles as childhood educators. Discussion These results reinforce the potential value of integrating body-oriented interventions, particularly those based on relaxation, into higher education curricula to support social and emotional development during this formative life stage.

To assess the inter-rater and test-retest reliability of DIERS pedogait system for measuring gait parameters in patients with knee osteoarthritis (KOA), and to explore inter-limb differences in Achilles tendon (AT) properties, as well as the associations between the AT stiffness asymmetry index (AsyStiffness (AT)) and gait abnormalities, visual analog scale (VAS) scores, and Kellgren-Lawrence (K/L) grades. A total of 36 patients with KOA (19 unilateral, 17 bilateral) were enrolled. Two independent assessors used DIERS pedogait system to measure gait parameters, with retesting by the first assessor 1 week later. Inter-rater and test-retest reliability were quantified using intraclass correlation coefficients (ICC), while absolute reliability was assessed using standard error of measurement (SEM), minimum detectable change (MDC), and Bland-Altman analysis. Bilateral AT muscle tone and stiffness were evaluated using the MyotonPRO. Spearman correlation and multiple linear regression analyses were performed to explore the associations of AsyStiffness (AT) with both clinical variables and gait parameters. DIERS pedogait system exhibited excellent inter-rater (ICC: 0.900-0.987) and test-retest reliability (ICC: 0.927-0.988). Inter-rater SEM and MDC ranged from 0.07 to 44.26 and 0.20 to 122.68, respectively, while test-retest SEM and MDC ranged from 0.05 to 39.59 and 0.13 to 109.74. Bland-Altman analysis revealed no significant systematic bias. In addition, AT muscle tone and stiffness were significantly higher in the relatively severe leg (RSL) compared with the moderate leg (RML) (P < 0.05). AsyStiffness (AT) was positively correlated with stance phase symmetry index (ρ = 0.514, P = 0.001), stride time (ρ = 0.381, P = 0.022), VAS score (ρ = 0.373, P = 0.025), and K/L grade (ρ = 0.542, P = 0.001), and negatively correlated with gait speed (ρ = -0.374, P = 0.025). Multiple linear regression identified stance phase symmetry index (β' = 0.298, P = 0.043), K/L grade 2 (β' = 0.533, P = 0.017) and K/L grade 3 (β' = 0.778, P = 0.002) as independent factors associated with AsyStiffness (AT). DIERS pedogait system is a reliable and objective tool for assessing gait in KOA patients. AT stiffness asymmetry is associated with gait abnormalities, pain, and KOA severity. These findings suggest that early-mid interventions targeting gait abnormalities and mitigating Achilles tendon stiffness asymmetry may provide novel prophylactic and therapeutic strategies for KOA.

The viscoelastic properties of muscle tissue are important factors affecting muscle performance; they play a significant role in maintaining spinal stability, as well as muscle contraction and function. Changes in these properties can result in pain, restricted movement, or poor posture. However, there is limited information in the literature regarding the viscoelastic properties of the paraspinal muscles, such as tone and stiffness, in individuals with chronic low back pain, which is one of the most common musculoskeletal disorders. The main aim of our study was to investigate the effects of reformer Pilates exercises on muscle viscoelastic properties in individuals with chronic low back pain for 4 weeks. In addition, our secondary aim was to examine the effects of Pilates-based exercises on body anthropometric values, pain intensity, functionality and kinesiophobia levels, sleep, and quality of life in individuals with chronic low back pain and to compare these parameters with a healthy group without low back pain. The study was carried out in a private clinic center and involved a total of 52 participants: 24 healthy subjects (control group) and 28 subjects with chronic low back pain (CLBP group). Pilates-based exercises were applied 2 days a week for 8 sessions for a total of 4 weeks. Muscle viscoelastic properties, body anthropometric values, pain intensity, functional status, kinesiophobia, sleep quality, and quality of life of all cases were evaluated. Muscle viscoelastic values were measured with a portable myotonometer, MyotonPro. After 4 weeks of Pilates-based training, no significant improvements were observed in the parameters of muscle tone and stiffness in both groups (p > 0.05). It was found that pain intensity (p = 0.001), sleep quality (p = 0.004), quality of life (p = 0.019), and disability level (p = 0.003) improved after 4 weeks of Pilates-based training in subjects with chronic low back pain. In addition, there were significant differences in the parameters of the chest, waist, hip, and thigh circumferences after 4 weeks of Pilates-based training, except for the abdomen, in both groups (p < 0.05). A period of four weeks of Pilates exercises did not lead to significant changes in the muscle viscoelastic properties of the lumbar and abdominal muscles, although performing these exercises did result in regional thinning. The efficacy of Pilates exercises in reducing pain, disability, and kinesiophobia and in improving sleep and quality of life has been demonstrated in individuals suffering from chronic low back pain.

The accuracy and morbidity of prostate cancer radiotherapy are influenced by unpredictable variations in rectal filling and patient motion. We developed a soft robotic hydraulic endorectal actuator that aims to reduce rectal motion and retract the rectum to restore the anorectal angle, improve target accuracy, and reduce toxicity during prostate cancer radiotherapy. The ability of the endorectal actuator to stabilize the rectum and improve prostate radiotherapy outcomes has not yet been assessed. This study evaluates the actuator's performance in a simulated rectal phantom. We fabricated a rectal phantom using silicone and motor-controlled elastic ribbons to simulate muscle tone and control the phantom diameter. The rectal compliance of the phantom was validated using a barostat balloon and was deliberately set low to simulate a high resistance to distension to challenge the actuator's capabilities. We assessed the actuator's ability to (1) resist dynamic peristaltic forces and (2) reproduce the rectal position and anorectal angle from varying initial displacements. The anterior-posterior rectal diameter and anterior rectal wall (ARW) displacements were measured using video tracker software. The phantom demonstrated a rectal compliance of 4.19 ml/mmHg within the 40 ml-60 ml volume range, meeting the low-compliance target. During dynamic compression, the endorectal actuator reduced the change in the anterior-posterior diameter and ARW displacement from 25 mm and 15 mm, respectively, to less than 5 mm in both. The actuator reduced the increase in rectal volume from 132.3 cm3 (control) to 59.7 cm3 (actuator). When the phantom was translated anteriorly, the actuator reduced the anorectal angle deviation from +12° to +2° and anterior displacement of the ARW from 13 mm to 4 mm. Within this rectal phantom, the endorectal actuator reduced the variations in rectal motion. These findings suggest that the actuator may improve target accuracy and reduce radiation-induced toxicity in prostate radiotherapy, pending in vivo validation of the results.

Pulmonary arterial hypertension (PAH) is a serious disorder, in which increased vascular tone is one of the critical hallmarks. Since beta arrestins (bArrs) have been shown to regulate smooth muscle tone in the airways, we investigated the function of bArr1 in the pulmonary vasculature. Here, we report that bArr1 is essential for maintaining normal pulmonary arterial tone. Specifically, pulmonary arteries from bArr1-/- mice exhibited reduced NO-dependent vasorelaxation due to impaired soluble guanylyl cyclase (sGC) activity, which was restored by the heme-independent sGC activator BAY58-2667. We identified bArr1 as a binding partner of sGC and the sGC heme reductase cytochrome b5 reductase (Cyb5r3), indicating that bArr1 is vital for sensitizing sGC to NO. Finally, mice with either ubiquitous or smooth muscle-specific bArr1 deficiency developed pulmonary hypertension (PH). These findings highlight the important role of bArr1 in regulating pulmonary vascular tone and propose it as a potential therapeutic target for the treatment of PH.

Phenylaminojuglones were synthesized under solvent-free conditions via silica gel-mediated aza-Michael addition between juglone and substituted anilines, namely, aniline, 4-methoxyaniline, and 3,4,5-trimethoxyaniline. Among the synthesized derivatives, phenylaminojuglone (AJ-2) exhibited the most potent spasmolytic activity on rat ileal smooth muscle. Molecular docking studies revealed that AJ-2 exhibits potential binding affinities with multiple targets implicated in smooth muscle contraction, including muscarinic receptors, β-adrenergic receptors, nitric oxide synthase, guanylate cyclase, and the CaV1.2 calcium channel. Absorption, distribution, metabolism, excretion, and toxicity predictions indicated that AJ-2, AJ-8, and AJ-11 comply with Lipinski's rule of five and do not present major predicted toxicity liabilities, supporting their pharmacological viability. Functional assays demonstrated that AJ-2 significantly inhibited both pharmacomechanical (ACh-induced) and electromechanical (KCl-induced) contractions. Mechanistic studies suggested that its relaxant effects might be mediated by the activation of β-adrenergic receptors, the NO-sGC-cGMP signaling pathway, and the opening of KV and KCa channels. AJ-2 also inhibited extracellular Ca2+ influx, as shown by its interaction with verapamil and attenuation of CaCl2-induced contractions. These findings support AJ-2 as a promising multifunctional spasmolytic agent derived from green chemistry principles and highlight the pharmacological relevance of phenylaminojuglones as novel modulators of the intestinal smooth muscle tone.