Parenting links to parent-child interbrain synchrony: a real-time fNIRS hyperscanning study.

Parent-child interaction is crucial for children's cognitive and affective development. While bio-synchrony models propose that parenting influences interbrain synchrony during interpersonal interaction, the brain-to-brain mechanisms underlying real-time parent-child interactions remain largely understudied. Using functional near-infrared spectroscopy, we investigated interbrain synchrony in 88 parent-child dyads (Mage children = 8.07, 42.0% girls) during a collaborative task (the Etch-a-Sketch, a joint drawing task). Our findings revealed increased interbrain synchrony in the dorsolateral prefrontal cortex and temporo-parietal areas during interactive, collaborative sessions compared to non-interactive, resting sessions. Linear regression analysis demonstrated that interbrain synchrony in the left temporoparietal junction was associated with enhanced dyadic collaboration, shared positive affect, parental autonomy support, and parental emotional warmth. These associations remained significant after controlling for demographic variables including child age, child gender, and parent gender. Additionally, differences between fathers and mothers were observed. These results highlight the significant association between brain-to-brain synchrony in parent-child dyads, the quality of the parent-child relationship, and supportive parenting behaviors. Interbrain synchrony may serve as a neurobiological marker of real-time parent-child interaction, potentially underscoring the pivotal role of supportive parenting in shaping these interbrain synchrony mechanisms.

Self-Cascade Nanozyme Reactor as a Cuproptosis Inducer Synergistic Inhibition of Cellular Respiration Boosting Radioimmunotherapy.

Intrinsic or acquired radioresistance remained an important challenge in the successful management of cancer. Herein, a novel "smart" multifunctional copper-based nanocomposite (RCL@Pd@CuZ) to improve radiotherapy (RT) sensitivity is designed and developed. In this nanoplatform, DSPE-PEG-RGD modified on the liposome surface enhanced tumor targeting and permeability; capsaicin inserted into the phospholipid bilayer improved the hypoxic conditions in the tumor microenvironment (TME) by inhibiting mitochondrial respiration; a Cu MOF porous cube encapsulated in liposome generated highly active hydroxyl radicals (OH·), consumed GSH and promoted cuproptosis by releasing Cu2+; the ultrasmall palladium (Pd) nanozyme within the cubes exhibited peroxidase activity, catalyzing toxic OH· generation and releasing oxygen from hydrogen peroxide; and lastly, Pd, as an element with a relatively high atomic number (Z) enhanced the photoelectric and Compton effects of X-rays. Therefore, RCL@Pd@CuZ enhance RT sensitivity by ameliorating hypoxia, promoting cuproptosis, depleting GSH, amplifying oxidative stress, and enhancing X-ray absorption  , consequently potently magnifying immunogenic cell death (ICD). In a mouse model , RCL@Pd@CuZ combined with RT yielded >90% inhibition compared with that obtained by RT alone in addition to a greater quantity of DC maturation and CD8+ T cell infiltration. This nanoplatform offered a promising remedial modality to facilitate cuproptosis-related cancer radioimmunotherapy.

Screening and evaluation of antioxidants for retinal pigment epithelial cell protection: L-ergothioneine as a novel therapeutic candidate through NRF2 activation.

The continual exposure of retinal tissues to oxidative stress leads to discernible anatomical and physiological alterations. Specifically, the onslaught of oxidative damage escalates the irreversible death of retinal pigmented epithelium (RPE) cells, pinpointed as the fundamental pathological event in dry age-related macular degeneration (AMD). There is a conspicuous lack of effective therapeutic strategies to counteract this degenerative process. This study screened a library of antioxidants for their ability to protect RPE cells against oxidative stress and identified L-ergothioneine (EGT) as a potent cytoprotective agent. L-ergothioneine provided efficient protection against oxidative stress-damaged RPE and maintained cell redox homeostasis and normal physiological functions. It maintained the normal structure of the retina in mice under oxidative stress conditions. Transcriptomic analysis revealed that EGT counteracted major gene expression changes induced by oxidative stress. It upregulated antioxidant gene expression and inhibited NRF2 translocation. The inhibition of NRF2 abolished EGT's protective effects, suggesting that NRF2 activation contributes to its mechanism of action. In conclusion, we identified EGT as a safe and effective small-molecule compound that is expected to be a novel antioxidative agent for treating AMD.

Changes in emotion regulation strategies during the pandemic: prospective pathways to adolescent depressive symptoms.

BACKGROUND: Emotion regulation (ER) is considered central in adolescent psychopathology, and ER strategies may change during challenging times, such as a global pandemic. Despite this, there remains a limited understanding of individual differences in ER mechanisms and their associations with psychopathology. This study examined whether and how cognitive reappraisal, expressive suppression, and self-compassion changed over COVID-19 and how these changes uniquely predicted adolescents' depressive symptoms. METHODS: A total of 2,411 adolescents (58.6% females; Mage = 18.51, SD = 0.80) completed the Emotional Regulation Questionnaire, the Self-compassion Scale, and the Symptom Checklist-90 before COVID-19 (in 2019) and during COVID-19 (in 2020). The predictive associations between each ER strategy and depressive symptoms were tested with latent change score models. RESULTS: Adolescents' use of expressive suppression and self-compassion strategies both increased during COVID-19. More increases in expressive suppression predicted more depressive symptoms, whereas more increases in self-compassion predicted fewer depressive symptoms. Although, on average, cognitive reappraisal did not change, it did show significant variations within the sample - increases (vs. decreases) in cognitive appraisal predicted fewer depressive symptoms. CONCLUSIONS: The study indicates how adolescents' ER strategies changed during the unprecedented global pandemic. It underscores protective roles of increased cognitive reappraisal and self-compassion, as well as the adverse consequence of heightened expressive suppression on adolescents' depressive symptoms. Findings offer insights for targeted interventions aimed at addressing specific ER strategies.

A context-dependent perspective to understand the relation between parent-child physiological synchrony and child socioemotional adjustment.

Physiological synchrony is an important biological process during which parent-child interaction plays a significant role in shaping child socioemotional adjustment. The present study held a context-dependent perspective to examine the conditional association between parent-child physiological synchrony and child socioemotional adjustment (i.e., relationship quality with parents and child emotion regulation) under different (i.e., from highly unsupportive to highly supportive) emotional contexts. One hundred and fifty school-age Chinese children (Mage = 8.64 years, 63 girls) and their primary caregivers participated in this study. After attaching electrocardiogram (ECG) electrodes, parent-child dyads were instructed to complete a 4-minute conflict discussion task. Parent-child physiological synchrony was calculated based on the within-dyad association between parents' and children's respiratory sinus arrhythmia (RSA) levels across eight 30-second epochs. Parental emotional support, child relationship quality with parents, and child emotion regulation during the discussion task were coded by trained research assistants. Supporting our hypotheses, parental emotional support moderated the relations of parent-child RSA synchrony with both child relationship quality with parents and child emotion regulation. Furthermore, the Johnson-Neyman technique of moderation indicated that the associations between parent and child RSA synchrony and child socioemotional adjustment indicators shifted from negative to positive as the parental emotional support became increasingly high. Our findings suggest that parent-child physiological synchrony may not be inherently adaptive or maladaptive, highlighting the importance of understanding the function of parent-child physiological synchrony under specific contexts. RESEARCH HIGHLIGHTS: Physiological synchrony may not be inherently adaptive or maladaptive, and the meanings of parent-child physiological synchrony might be contingent on contextual factors. Parental emotional support moderated the relations between parent-child respiratory sinus arrhythmia (RSA) synchrony and child socioemotional adjustment indicators (i.e., child relationship quality with parents and child emotion regulation). More positive/less negative parent-child RSA synchrony was associated with better child socioemotional adjustment under a supportive emotional context, whereas with poorer child socioemotional adjustment under an unsupportive emotional context. These findings highlight the significance of considering the emotional context in physiological synchrony studies.

Parental autonomy support and psychological control and children's biobehavioral functioning: Historical cohort differences in urban China.

This study examined parental autonomy support and psychological control and their relations with child biobehavioral functioning. Participants included 238 Chinese parent-child dyads (Mage-child = 8.38 years, 42.0% girls) in two cohorts (2013 and 2021). Parents in the 2021 cohort displayed higher levels of autonomy support and psychological control during the parent-child interaction than in the 2013 cohort. Parental psychological control was positively associated with emotion regulation and negatively associated with externalizing problems in the 2013 cohort, but not in the 2021 cohort. Parental psychological control was also negatively associated with vagal suppression in the 2021 cohort, but not in the 2013 cohort. The result suggests that sociocultural contexts may shape the display of parental behaviors and their significance for child development.

Respiratory sinus arrhythmia (RSA) dynamics matter for children's emotion regulation: RSA inertia and instability within a stress task.

The present study employed two key dynamic indicators (i.e., inertia and instability) to the psychophysiological research of child emotion regulation (ER) and examined whether respiratory sinus arrhythmia (RSA) dynamics were associated with child ER during a stress task. Eighty-nine Chinese school-age children (Mage = 8.77 years, SD = 1.80 years; 46.1% girls) and their primary caregivers participated in the study. After controlling for RSA static reactivity, multiple regression analyses indicated that lower RSA inertia was related to fewer in-task negative emotions rated by children and their caregivers, and higher RSA instability was associated with better child trait ER. This study introduces physiological indicators of the dynamic aspects of parasympathetic activity to the study of child ER.

The survival prediction of advanced colorectal cancer received neoadjuvant therapy-a study of SEER database.

PURPOSE: The aim of study was to screen factors associated with the overall survival of colorectal cancer patients with lymph nodes metastasis who received neoadjuvant therapy and construct a nomogram model. METHODS: All enrolled subjects of the SEER database were randomly assigned to the training and testing group in a ratio of 3:2. The patients of Tangdu Hospital were seemed as validation group. Univariate cox regression analysis, lasso regression and random forest survival were used to screen variables related to the survival of advanced CRC patients received neoadjuvant therapy in the training group. Area under curves were adopted to evaluate the 1,3,5-year prediction value of the optimal model in three cohorts. Calibration curves were drawn to observe the prediction accuracy of the nomogram model. Decision curve analysis was used to assess the potential clinical value of the nomogram model. RESULTS: A total of 1833 subjects were enrolled in this study. After random allocation, 1055 cases of the SEER database served as the training group, 704 cases as the testing group and 74 patients from our center as the external validation group. Variables were screened by univariate cox regression used to construct a nomogram survival prediction model, including M, age, chemotherapy, CEA, perineural invasion, tumor size, LODDS, liver metastasis and radiation. The AUCs of the model for predicting 1-year OS in the training group, testing and validation group were 0.765 (0.703,0.827), 0.772 (0.697,0.847) and 0.742 (0.601,0.883), predicting 3-year OS were 0.761 (0.725,0.780), 0.742 (0.699,0.785), 0.733 (0.560,0.905) and 5-year OS were 0.742 (0.711,0.773), 0.746 (0.709,0.783), 0.838 (0.670,0.980), respectively. The calibration curves showed the difference between prediction probability of the model and the actual survival was not significant in three cohorts and the decision curve analysis revealed the practice clinical application value. And the prediction value of model was better for young CRC than older CRC patients. CONCLUSION: A nomogram model including LODDS for the prognosis of advanced CRC received neoadjuvant therapy was constructed and verified based on the SEER database and single center practice. The accuracy and potential clinical application value of the model performed well, and the model had better predictive value for EOCRC than LOCRC.

RSA instability in mothers of preschoolers and adolescents is related to observations of supportive parenting behaviors.

Respiratory sinus arrhythmia (RSA; a measure of respiratory modulation of vagal control of heart rate) is a dynamic process. For mothers, RSA functioning has been associated with depressive symptoms and coincides with supportive parenting. However, research has largely focused on RSA suppression (i.e., difference score from rest to stress task). The present study examined depressive symptoms and supportive parenting with RSA instability-a dynamic measure of the magnitude of RSA change across a task. In two samples of mothers (N = 210), one with preschoolers (Study 1: n = 108, Mage = 30.68 years, SD = 6.06, 47.0% Black, 43.0% White) and one with adolescents (Study 2: n = 102, Mage = 35.51, SD = 6.51, 75.2% Black), RSA instability was calculated during an interaction task. In both studies, instrumental supportive parenting behaviors were negatively related to RSA instability. Findings provide preliminary support for RSA instability as an indicator of physiological dysregulation for mothers.

Peer Stress Spills Over to Family Stress in the Context of Emotion Regulation Difficulties: A Daily Diary Study with Chinese Adolescents.

Conflict in peer and family relationships becomes more common in the adolescent period when compared to previous developmental periods. These typical developmental challenges can be exacerbated in the context of poor emotion regulation skills. Using daily diary data, the current study examined the stress spillover effects of peer and family stress on one another, as well as the moderating role of emotion regulation challenges (i.e., emotional inhibition, dysregulation). A sample of 310 Chinese adolescents (Mage = 13.02 years, SD = 0.76 years, 50.7% boys) completed an initial measure of emotion regulation difficulties, then reported on peer and family stress for 10 consecutive weekdays. Results indicated that there was an overall same-day peer stress spillover effect in which adolescents' peer stress on a given day was negatively associated with later conflictual interactions with their parents. Further, the relation between peer stress and same- and next-day family stress was exacerbated in the context of high levels of emotional inhibition. Family stress did not significantly relate to next-day peer stress, nor was this association moderated by difficulties with emotion regulation. These results highlight the temporal sequence of daily peer-to-family stress spillover. Though emotional inhibition may be culturally adaptive for maintaining interpersonal harmony, it can be maladaptive in managing stress for Chinese adolescents.

Friend Emotional Support and Dynamics of Adolescent Socioemotional Problems.

Emotional support from friends is a crucial source of social support for adolescents, significantly influencing their psychological development. However, previous research has primarily focused on how this support correlates with general levels of socioemotional problems among adolescents, neglecting the significance of daily fluctuations in these problems. The aim of this study was to explore the relationship between friend emotional support and both the average and dynamic indicators of daily emotional and peer problems in adolescents. These dynamic indicators include within-domain dynamics-such as inertia, which reflects the temporal dependence of experiences, and volatility, which indicates within-person variance-and cross-domain dynamics, such as transactional effects, which measure the strength of concurrent or lagged associations between daily emotional and peer problems. Participants were 315 seventh-grade Chinese adolescents (Mage = 13.05 years, SD = 0.77 years; 48.3% girls). Adolescents reported on their friends' emotional support at baseline and then completed measures of daily emotion and peer problems over a 10-day period. Using dynamic structural equation models, the results revealed that higher levels of friend emotional support were associated with fewer daily socioemotional problems. This was evident both in terms of average levels and dynamic aspects, characterized by lower mean levels of daily emotional and peer problems, reduced inertia and volatility of these problems, and a weaker spillover effect from daily emotional issues to peer problems. These findings highlight the significant role of friend-emotional support in mitigating adolescents' daily socioemotional challenges.

Optimal Decoding Order and Power Allocation for Sum Throughput Maximization in Downlink NOMA Systems.

In this paper, we consider a downlink non-orthogonal multiple access (NOMA) system over Nakagami-m channels. The single-antenna base station serves two single-antenna NOMA users based on statistical channel state information (CSI). We derive the closed-form expression of the exact outage probability under a given decoding order, and we also deduce the asymptotic outage probability and diversity order in a high-SNR regime. Then, we analyze all the possible power allocation ranges and theoretically prove the optimal power allocation range under the corresponding decoding order. The demarcation points of the optimal power allocation ranges are affected by target data rates and total power, without an effect from the CSI. In particular, the values of the demarcation points are proportional to the total power. Furthermore, we formulate a joint decoding order and power allocation optimization problem to maximize the sum throughput, which is solved by efficiently searching in our obtained optimal power allocation ranges. Finally, Monte Carlo simulations are conducted to confirm the accuracy of our derived exact outage probability. Numerical results show the accuracy of our deduced demarcation points of the optimal power allocation ranges. And the optimal decoding order is not constant at different total transmit power levels.

NRG1 Regulates Proliferation, Migration and Differentiation of Human Limbal Epithelial Stem Cells.

Limbal epithelial stem/progenitor cells (LESCs) proliferate, migrate and differentiate into mature corneal epithelium cells (CECs) that cover the ocular surface. LESCs play a crucial role in the maintenance and regeneration of the corneal epithelium, and their dysfunction can lead to various corneal diseases. Neuregulin 1 (NRG1) is a member of the epidermal growth factor family that regulates the growth and differentiation of epithelial tissues. Here, we depicted the dynamic transcriptomic profiles during human CEC differentiation, identifying six gene co-expression modules that were specific to different differentiation stages. We found that the expression of NRG1 was high in human LESCs and decreased dramatically upon differentiation. Knockdown of NRG1 significantly inhibited LESC proliferation and upregulated the expression of the terminal differentiation marker genes KRT3, KRT12 and CLU. In addition, the scratch wound closure assay showed that knockdown of NRG1 attenuated wound closure of LESCs over 24 h. Together, we dissected the transcriptional regulatory dynamics during CEC differentiation and identified NRG1 as a key regulator that promoted LESC proliferation and migration and maintained the undifferentiated state.

Simultaneous Thermal Enhancement of Upconversion and Downshifting Luminescence by Negative Thermal Expansion in Nonhygroscopic ZrSc(WO4)2PO4:Yb/Er Phosphors.

Thermal quenching (TQ) is still a critical challenge for lanthanide (Ln3+)-doped luminescent materials. Herein, we report the novel negative thermal expansion nonhygroscopic phosphor ZrSc(WO4)2PO4:Yb3+/Er3+. Upon excitation with a 980 nm laser, a simultaneous thermal enhancement is realized on upconversion (UC) and downshifting (DS) emissions from room temperature to 573 K. In situ temperature-dependent X-ray diffraction and photoluminescence dynamics are used to reveal the luminescence mechanism in detail. The coexistence of the high energy transfer efficiency and the promoted radiative transition probability can be responsible for the thermally enhanced luminescence. On the basis of the luminescence intensity ratio of thermally coupled energy levels 2H11/2 and 4S3/2 at different temperatures, the relative and absolute sensitivities of the targeted samples reach 1.10% K-1 and 1.21% K-1, respectively, and the low-temperature uncertainty is approximately 0.1-0.4 K on the whole temperature with a high repeatability (98%). Our findings highlight a general approach for designing a hygro-stable, thermostable, and highly efficient Ln3+-doped phosphor with UC and DS luminescence.

Developmental Sex Differences in Negative Emotion Decision-Making Dynamics: Computational Evidence and Amygdala-Prefrontal Pathways.

Sex differences in human emotion and related decision-making behaviors are recognized, which can be traced back early in development. However, our understanding of their underlying neurodevelopmental mechanisms remains elusive. Using developmental functional magnetic resonance imaging and computational approach, we investigated developmental sex differences in latent decision-making dynamics during negative emotion processing and related neurocognitive pathways in 243 school-aged children and 78 young adults. Behaviorally, girls exhibit higher response caution and more effective evidence accumulation, whereas boys show more impulsive response to negative facial expression stimuli. These effects parallel sex differences in emotion-related brain maturity linking to evidence accumulation, along with age-related decrease in emotional response in the basolateral amygdala and medial prefrontal cortex (MPFC) in girls and an increase in the centromedial amygdala (CMA) in boys. Moreover, girls exhibit age-related decreases in BLA-MPFC coupling linked to evidence accumulation, but boys exhibit increases in CMA-insula coupling associated with response caution. Our findings highlight the neurocomputational accounts for developmental sex differences in emotion and emotion-related behaviors and provide important implications into the neurodevelopmental mechanisms of sex differences in latent emotional decision-making dynamics. This informs the emergence of sex differences in typical and atypical neurodevelopment of children's emotion and related functions.

Patterns of childhood maltreatment influence sleep quality: The role of emotion regulation.

Childhood maltreatment exerts long-term consequences on sleep health, and different subtypes could constitute maltreatment patterns. However, how naturally occurring patterns of childhood maltreatment affect subsequent sleep quality and the underlying mechanisms remain relatively unclear, particularly in youths undergoing a transitional period and in the Chinese cultural context. In this study, we identified childhood maltreatment patterns and explored how these patterns predicted sleep problems through differential emotion regulation strategies. We tracked 1929 Chinese youths (M age = 18.49; 63.1% females) for one year. Three latent profiles were identified: low maltreatment exposure, high physical and emotional maltreatment, and high sexual abuse. Compared with "low maltreatment exposure," youths in "high physical and emotional maltreatment" used fewer cognitive reappraisal strategies, and those in "high sexual abuse" used more expressive suppression, and then leading to more sleep problems. This study reveals new insights into the patterns of childhood maltreatment in Chinese youths and implies that individuals exposed to sexual abuse or a combination of physical and emotional maltreatment experience sleep problems through the impairment of differential emotion regulation processes. It also highlights the necessity of setting differential targets on emotion regulation strategies for distinct groups of maltreatment and considering the co-occurrence of physical and emotional maltreatment.

Efficacy and safety of long-term use of a positive expiratory pressure device in chronic obstructive pulmonary disease patients, a randomized controlled trial.

BACKGROUND: Exercise intolerance is among the most common symptoms experienced by patients with chronic obstructive pulmonary disease (COPD), which is associated with lung dynamic hyperinflation (DH). There was evidence that positive expiratory pressure (PEP), which could be offered by less costly devices, could reduce DH. The purpose of this study was to evaluate the efficacy and safety of long-term domiciliary use of PEP device in subjects with COPD. METHODS: A randomized controlled trial was conducted and 25 Pre-COPD or mild-to-very severe subjects with COPD were randomized to intervention group (PEP device, PEP = 5 cmH2O, n = 13) and control group (Sham-PEP device, PEP = 0 cmH2O, n = 12). PEP device was a spring-loaded resistor face mask. Subjects were treated 4 h per day for a total of 2 months. Six-minute walk test (6MWT), pulmonary function, the Modified British Medical Research Council score, and partial pressure of end-tidal carbon dioxide were evaluated at baseline and after two months. RESULTS: The 6MWD (- 71.67 ± 8.70 m, P < 0.001), end-dyspnea (P = 0.002), and end-fatigue (P = 0.022) improved significantly in the intervention group when compared with the control group. All subjects in the intervention group reported that 4 h of daily use of the PEP device was well tolerated and accepted and there were no adverse events. CONCLUSION: Regular daily use of PEP device is safe and may improve exercise capacity in subjects with COPD or pre-COPD. PEP device could be used as an add-on to pulmonary rehabilitation programs due to its efficacy, safety, and low cost. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT04742114).

Stable metal anodes enabled by a labile organic molecule bonded to a reduced graphene oxide aerogel.

Metallic anodes (lithium, sodium, and zinc) are attractive for rechargeable battery technologies but are plagued by an unfavorable metal-electrolyte interface that leads to nonuniform metal deposition and an unstable solid-electrolyte interphase (SEI). Here we report the use of electrochemically labile molecules to regulate the electrochemical interface and guide even lithium deposition and a stable SEI. The molecule, benzenesulfonyl fluoride, was bonded to the surface of a reduced graphene oxide aerogel. During metal deposition, this labile molecule not only generates a metal-coordinating benzenesulfonate anion that guides homogeneous metal deposition but also contributes lithium fluoride to the SEI to improve Li surface passivation. Consequently, high-efficiency lithium deposition with a low nucleation overpotential was achieved at a high current density of 6.0 mA cm-2 A Li|LiCoO2 cell had a capacity retention of 85.3% after 400 cycles, and the cell also tolerated low-temperature (-10 °C) operation without additional capacity fading. This strategy was applied to sodium and zinc anodes as well.

Capilliposide B inhibits the migration of prostate cancer by inducing autophagy through the ROS/AMPK/mTOR pathway.

Capilliposide B (CPS-B), a novel oleanane triterpenoid saponin derived from Lysimachia capillipes Hemsl, is a potent anticancer agent. However, its anticancer mechanism remains elusive. In the present study, we demonstrated the potent anti-tumor activity and molecular mechanism of CPS-B both in vitro and in vivo. Proteomic analysis using isobaric tags for relative and absolute quantitation techniques suggested that CPS-B modulated autophagy in prostate cancer (PC). Moreover, Western blotting showed that both autophagy and epithelial-mesenchymal transition occurred place after CPS-B treatment in vivo, which was also proven in PC-3 cancer cells. We deduced that CPS-B inhibited migration by inducing autophagy. We examined the accumulation of reactive oxygen species (ROS) in cells, and in downstream pathways, LKB1 and AMPK were activated while mTOR was inhibited. Transwell experiment results showed that CPS-B inhibited the metastasis of PC-3 cells and that this effect was significantly attenuated after pretreatment with chloroquine, indicating that CPS-B inhibited metastasis via autophagy induction. Altogether, these data suggest that CPS-B is a potential therapeutic agent for cancer treatment that acts by inhibiting migration through the ROS/AMPK/mTOR signaling pathway.

Idelalisib inhibits experimental proliferative vitroretinopathy.

Proliferative vitreoretinopathy (PVR) is a fibrotic eye disease that develops after rhegmatogenous retinal detachment surgery and open-globe traumatic injury. Idelalisib is a specific inhibitor of phosphoinositide 3-kinase (PI3K) δ. While PI3Kδ is primarily expressed in leukocytes, its expression is also considerably high in retinal pigment epithelial (RPE) cells, which play a crucial part in the PVR pathogenesis. Herein we show that GeoMx Digital Spatial Profiling uncovered strong expression of fibronectin in RPE cells within epiretinal membranes from patients with PVR, and that idelalisib (10 µM) inhibited Akt activation, fibronectin expression and collagen gel contraction induced by transforming growth factor (TGF)-ß2 in human RPE cells. Furthermore, we discovered that idelalisib at a vitreal concentration of 10 µM, a non-toxic dose to the retina, prevented experimental PVR induced by intravitreally injected RPE cells in rabbits assessed by experienced ophthalmologists using an indirect ophthalmoscope plus a + 30 D fundus lens, electroretinography, optical coherence tomography and histological analysis. These data suggested idelalisib could be harnessed for preventing patients from PVR.