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Concussions are common in stick-handling sports, including lacrosse or hockey, where high-speed play combines player contact with equipment- and projectile-related impacts. In a cohort of lacrosse and hockey athletes who sustained a sport-related concussion (SRC), this study compared: 1) injury mechanisms, 2) initial symptom burden, and 3) recovery timelines between the sports. In this retrospective cohort study of patients (12-23 years) with SRC from lacrosse or hockey, injury mechanism was categorized as player-to-surface, player-to-player, player-to-stick, or player-to-ball/puck. Outcomes included initial Post-Concussion Symptom Scale (PCSS) score and time to return-to-learn (RTL), symptom resolution (SR), and return-to-play (RTP). Nonparametric tests compared groups, and multivariable linear regression evaluated associations between sport and injury mechanism with outcomes, adjusting for age, sex, and prior concussions. Of 80 athletes (median age = 16.6), 37 played lacrosse (60% male) and 43 played hockey (86% male). Injury mechanism differed by sport (p = 0.03): lacrosse had more player-to-surface (35.1% vs. 27.9%), player-to-stick (24.3% vs. 11.6%), and player-to-ball/puck (21.6% vs 9.3%) injuries and less player-to-player (18.9% vs. 48.8%) injuries than hockey. Initial PCSS scores were higher after stick-related injuries (median = 47.5) than other mechanisms (surface = 26.0, player = 20.0, ball/puck = 31.0; p = 0.02), though mechanism was not a significant predictor in multivariable regression. Time to RTL, SR, and RTP did not differ by sport, injury mechanism, or competition setting. Symptom severity and recovery timelines were similar between sports and setting. Stick and ball/puck impacts were associated with greater initial symptom burden and longer RTL, which may warrant closer early monitoring and enhanced school accommodations.

Neonatal sepsis is a leading cause of morbidity and mortality in neonates. The underdeveloped neonatal immune system, particularly innate immune cells such as monocytes, plays a critical role in susceptibility to infection. Monocyte-mediated regulation of iron metabolism, a key component of "nutritional immunity," is known to influence sepsis outcomes in adults. In this study, we investigated differences in iron sensing, iron-regulated gene expression, and intracellular iron content between neonatal and adult monocytes. Monocytes were isolated from human umbilical cord blood and adult peripheral blood and stimulated in vitro with lipopolysaccharide (LPS), ferric nitrilotriacetate (FeNTA), or the iron chelator deferoxamine (DFO). Transferrin receptor 1 (TfR1) and differentiation markers were analyzed by flow cytometry, intracellular iron content by atomic absorption spectrometry, and metabolic and inflammatory responses via lactate and cytokine measurements. Neonatal monocytes exhibited lower basal TfR1 expression with a trend toward higher intracellular iron. LPS induced TfR1 upregulation exclusively in adult monocytes, while neonatal cells maintained consistently low expression. Although FeNTA increased intracellular iron in both groups, neonatal monocytes accumulated iron less efficiently. These findings indicate fundamental developmental differences in monocyte iron handling and immunometabolic adaptation, which may underlie the distinct immune profile observed in neonatal sepsis. Neonatal sepsis is a leading cause of morbidity and mortality in neonates. Particularly innate immune cells such as monocytes, play a critical role in susceptibility to infection. Monocyte-mediated regulation of iron metabolism, a key component of "nutritional immunity," is known to influence sepsis outcomes in adults. Our findings indicate fundamental developmental differences in monocyte iron handling and immunometabolic adaptation, which may play a role in both the distinct immune profile observed in neonatal sepsis and, consecutively, sepsis outcome. These findings imply that host-directed iron modulation could be a viable strategy to counteract immunoparalysis in neonatal sepsis without compromising cellular activation.

Langerhans cells (LCs) play a crucial role in sensing and processing stimuli from the skin and the external environment. They are implicated in various skin disorders, acting either as pro-inflammatory agents or as regulatory elements. However, the exact function of LCs in the pathogenesis of psoriasis remains unclear. Psoriasis is characterized by a significant Th17/Treg immune imbalance. To elucidate the independent effect of Treg dysfunction on psoriatic inflammation, we established a Treg-inhibited psoriasis group using the Foxp3 inhibitor CMD178, in conjunction with LC depletion models to investigate the LC-Th17/Treg regulatory axis METHODS: Psoriasis models were established through the topical application of IMQ. Female C57BL/6N mice were divided into three groups: control, IMQ-induced psoriasis, and Treg-depleted psoriasis. Langerhans cells (LCs) were depleted using diphtheria toxin in Langerin-DTR mice, while Tregs were inhibited by CMD178. Inflammation was assessed through measurements of ear thickness, histopathology, apoptosis, and cytokine production. Additionally, RT-qPCR was utilized to detect the expression of S100A7, S100A8, and MMP2. Flow cytometry was employed to analyze the functional status of lymphocytes and T cell phenotypes. IMQ-induced psoriasis-like lesions exhibit activated LCs, an increase in Th17 cells, a decrease in Tregs, elevated levels of IL-17A and IL-22, and reduced levels of TGF-β and PD-L1. Depletion of LCs alleviated the lesions and restored the Th17/Treg balance, whereas depletion of Tregs exacerbated the inflammation. LCs play a central regulatory role in the psoriatic skin environment by influencing the Th17/Treg.

Gadiformes is one of the major taxa in the subarctic seas of the northeast Pacific Ocean, a region with significant high-latitude fishery production. However, little is known about Gadiformes species within these waters. Distribution and abundance fluctuations of Gadiformes are closely linked to shifts in the marine environment, and play a crucial role in maintaining ecosystem structural stability of high-latitude regions. This study examined the community composition and spatiotemporal distribution of Gadiformes in four major subarctic regions within the northeast Pacific (Aleutian Islands, Bering Sea shelf, eastern Bering Sea, and Gulf of Alaska) using bottom trawl survey data from the Alaska Fisheries Science Center (AFSC). Gadiformes diversity was assessed using ecological approaches such as diversity indices and cluster analysis, and the relationship between catch-per-unit-effort (CPUE) of the three dominant species and depth, sea surface temperature, and bottom temperature was examined using a generalized additive model (GAM). A comparative analysis was carried out for the cold years (2010/2011) and warm years (2015/2016) to investigate the influence of bottom water temperature on the dominant species. The results indicated that 13 species of Gadiformes from 4 families and 9 genera were present in these subarctic regions, with the dominant species being Gadus chalcogrammus, G. macrocephalus and Albatrossia pectoralis. Additionally, the distribution and abundance of these dominant species showed clear spatial patchiness, with G. chalcogrammus and G. macrocephalus mainly occurring on the eastern Bering Sea shelf, whereas A. pectoralis was primarily distributed in deeper waters. In addition, A. pectoralis exhibited totally higher abundance than the other two species. The GAM results indicated that bottom water temperature was the most influential variable, followed by depth and spatial location, with nonlinear relationships observed between CPUE and environmental factors. Comparing cold and warm years, the abnormal warming of seawater during the warm years expanded the suitable habitat area for G. chalcogrammus and G. macrocephalus, with increasing abundance, whereas habitat distribution and abundance of A. pectoralis exhibited almost no change. This study provides further understanding of Gadiformes distribution and species response to environmental change in the subarctic seas of the northeast Pacific.

The integration of artificial intelligence (AI) tools like DeepSeek into scientific research offers new opportunities for efficiency and innovation. However, attitudes and adoption among medical students remain underexplored. This study aims to investigate medical students' attitudes, usage patterns, and interest in learning with DeepSeek. A cross-sectional online survey was conducted among medical students from various academic levels and fields. The questionnaire assessed demographics, attitudes, usage frequency and purposes, and learning interests. Data were analyzed using descriptive statistics and independent sample t-tests. Among 589 respondents, most were familiar with DeepSeek (86.08%), and 70.29% used it. A majority held positive attitudes toward DeepSeek, agreeing that it is useful for academic success (77.91%), makes research easier (78.37%), and will play an important future role (74.51%). However, concerns included reliability (61.34%), overreliance (48.51%), and privacy risks (51.88%). Usage varied: 28.23% used DeepSeek frequently, while 29.76% had never used it. Common uses included problem-solving (406 users) and literature search (256 users). Over 80% expressed interest in learning to use DeepSeek more effectively. No significant differences in attitudes were found across demographic groups. Medical students view DeepSeek as a promising tool for academic and research support but have significant concerns regarding reliability and ethical use. There is strong interest in structured learning opportunities. Integrating AI literacy into medical education and providing targeted training are recommended to promote responsible and effective use.

Stroke remains a leading cause of mortality and long-term disability globally, with profound consequences for both survivors and their families. In Ghana, where formal post-stroke rehabilitation and long-term care services are limited, family caregivers play a central role in supporting stroke survivors. However, there is limited qualitative evidence on how caregivers understand stroke and experience caregiving within their sociocultural context, creating a gap in knowledge needed to inform context-specific interventions. This qualitative study explored the experiences of family caregivers of stroke survivors attending Suntreso Government Hospital in Ghana. Fifteen caregivers were purposively selected. Data were collected through in-depth, semi-structured interviews and analyzed using thematic analysis. Caregivers demonstrated partial awareness of stroke risk factors, particularly hypertension and diabetes; however, stroke onset was often perceived as sudden and unexpected, reflecting gaps between knowledge and functional preparedness. Caregiving involved intensive support with activities of daily living, including feeding, bathing, mobility assistance, and medication management, which substantially disrupted caregivers' social, economic, and occupational lives. Many caregivers reduced or discontinued work, resulting in significant financial strain. In addition, some caregivers reported stigma linked to sociocultural beliefs attributing stroke to spiritual causes or curses. Despite these challenges, caregivers relied on coping strategies such as religious faith, hope for patient recovery, and a strong sense of familial obligation. Family caregivers of stroke survivors in Ghana experience multidimensional burdens shaped by intensive care demands, economic constraints, stigma, and limited formal support systems. The findings highlight the need for integrated interventions that extend beyond patient-focused care to include caregiver training, psychosocial support, financial protection mechanisms, and community-based rehabilitation services. Strengthening these systems is essential for improving both caregiver well-being and stroke recovery outcomes in resource-limited settings.

Prevention and control strategies play an essential role in reducing new infections of infectious diseases, while uniform and instantaneous responses to disease outbreaks are assumed in traditional epidemic models. To model the adaptive public health policies that account for hysteresis effects and heterogeneous control measures, we proposed an SIQR epidemic model with multiple two-threshold structures to describe the prevalence-dependent real-time control strategies. The formulated model incorporated the Preisach operator which effectively characterizes time-varying control strategies that depend on the historical evolution of a disease. We established the global stability of this steady-state set through an innovative analytical approach by constructing a series of Lyapunov functions corresponding to different branches of the hysteresis operator. Specifically, our results indicate that: (i) heterogeneity facilitates the convergence of system trajectories to a point within the continuum of steady-state, and (ii) greater heterogeneity leads to higher peaks of infected individuals during the evolution of an epidemic and more severe disease prevalence in the long term. Our findings reveal that the hysteresis phenomenon in control events may lead to existence of a continuum of endemic equilibria, significantly altering the effectiveness of disease suppression strategies. These results provide a theoretical foundation for designing adaptive control policies, emphasizing the importance of incorporating past intervention effects in epidemic modeling.

To describe the design process, through participatory diagnosis and community validation, of a municipal digital well-being strategy with a preventive approach focused on families with children under 16 years of age. A community-based participatory action research study with a longitudinal design (November 2023-November 2025) was conducted in El Prat de Llobregat, framed within the Local Plan for Childhood and Adolescence. It was structured into three phases: 1) participatory diagnosis through a questionnaire administered to 1583 guardians and four focus groups; 2) collaborative desing inolving plenary sessions and age- stratified working groups; and 3) community, institutional, and political validation. The theory of change and qualitative-quantitative methodological triangulation were applied. The diagnosis identified five thematic categories: parental overwhelm, normative inconsistency, impact on free play and physical activity, demand for practical age-adapted tools, and the tension between protection and autonomy in adolescence. The collaborative design culminated in an action plan comprising four strategic lines. Community validation demonstrated an acceptance rate exceeding 85%, with unanimous institutional and political support. The materials are publicly available (www.elprat.cat/benestardigital). A process that incorporated participatory diagnosis, intersectoral leadership, community validation, application of the Theory of Change, and the production of accessible materials enabled the design of a municipal strategy for the digital well-being of families with children under 16 that was widely accepted and theoretically reproducible. The impact evaluation of the strategy, scheduled for 2026-2027, is expected to provide evidence on the effectiveness of the interventions in real-world implementation contexts.

Anthocyanins are key flavonoid pigments responsible for the red, blue and purple colouration of many fruit crops and play important roles in determining fruit quality, nutritional value and stress tolerance. Beyond their contribution to visual appeal, anthocyanins function as potent antioxidants that protect plant cells against diverse abiotic stresses, including high light, temperature extremes and oxidative damage. The biosynthesis of anthocyanins occurs as an extension of the flavonoid biosynthetic pathway and is regulated by complex genetic and molecular networks that integrate developmental signals with environmental cues. Central to this regulation are transcriptional complexes composed of MYB, bHLH and WD40 proteins that coordinate the expression of structural genes in the anthocyanin biosynthetic pathway. In addition to transcriptional control, emerging evidences highlight the importance of epigenetic regulation, post translational modification of regulatory proteins and cellular mechanisms governing anthocyanin transport and vacuolar sequestration. Environmental factors such as light, temperature, nutrient availability and cellular pH further influence anthocyanin biosynthesis and stability, particularly under conditions of climate variability. This review synthesizes current advances in understanding the molecular and environmental regulation of anthocyanin biosynthesis in fruit crops and presents a multi-layered regulatory framework while discussing the emerging approaches, including multi-omics and genome editing. However, a major challenge remains in the adoption of genome editing techniques in fruit crops, where genetic complexity including polyploidy and allele redundancy limits precise trait improvement, highlighting the need for more efficient molecular breeding strategies to improve pigment stability and climate resilience in fruit production systems.

Emotional difficulties are common among individuals with Eating Disorders (EDs). Following Panksepp's theoretical model, which conceptualises primary emotional systems as the evolutionary foundation of personality, this study aimed to identify distinct profiles of primary emotional systems within a clinical eating disorder (ED) sample. It further examined differences in sociodemographic, clinical, and psychopathological characteristics across profiles, as well as associations between clinical features and profile membership. In this cross-sectional study, data were obtained from the Regional Centre for ED registry at the University Hospital of Verona. Measures included the Affective Neuroscience Personality scales, the Eating Disorder Examination, the Symptom CheckList-90-Revised, the Life Stressor Checklist-Revised, and the Impact of Event Scale-Revised. A Latent Profile Analysis was conducted, followed by inferential analyses. Among 122 patients, three profiles emerged: (1) high FEAR and SADNESS, and low SEEKING and PLAY; (2) low negative primary emotional systems and CARE; (3) high positive primary emotional systems and high SADNESS and ANGER. Profiles differed by age, sex, illness duration, trauma burden, depressive-anxiety symptoms, and ED severity. Findings revealed emotional heterogeneity among ED patients, underscoring the importance of considering individual emotional differences in treatment planning. Study limitations and directions for future research are discussed.

Prostate cancer is known to have a cold tumor microenvironment (TME) that promotes immune evasion through different cellular pathways. Aggressive disease progression is often linked to Regulatory T cells (Tregs) which play an important role in immunosuppression. While immunotherapy aims to use the immune system to fight tumor cells, its efficacy is frequently hindered by Tregs, which prevent effector T cells from reaching and fighting tumor cells. This review evaluates the impact of different immunotherapeutic interventions, alone or in combination, on Treg frequency and function within the prostate TME. Following PRISMA guidelines, a systematic search of major databases identified studies investigating immunotherapeutic effects on Tregs in prostate cancer. Studies were included if they evaluated monotherapies or combination strategies, as defined by inclusion criteria. 31 studies met the inclusion criteria. Qualitative analysis revealed that monotherapies, including immune checkpoint inhibitors and vaccines, produced inconsistent effects on Treg populations, which in many cases did not significantly decrease their levels or suppressive function. Notable exceptions included targeted recruitment inhibitors such as anti-CCR4 and specific viral-mediated therapies. In contrast, combination therapies proved to be more effective in reshaping the TME. When immunotherapy and other treatment such as androgen deprivation therapy, immunogenic chemotherapy, and targeted molecular inhibition are combined, enhanced anti-tumor immunity is observed. Successful modulation of the prostate TME requires shifting from monotherapy toward combination strategies that overcome Treg-mediated immunosuppression. Effector-to-Treg ratios and functional markers, rather than Treg frequency alone, may better predict outcomes, as CD8⁺ infiltration does not always reflect restored cytotoxicity. These findings highlight the dual potential of Tregs as therapeutic targets and biomarkers in prostate cancer.

Diabetes is highly prevalent among care home residents and is associated with increased clinical complexity due to multimorbidity, frailty, and cognitive impairment. Care home staff play a central role in diabetes management; however, there is limited theoretical understanding of how diabetes care is organised and delivered in long-term care settings. This study aimed to explore care home staff experiences of supporting residents living with diabetes and to develop an empirically grounded explanation of the processes shaping diabetes care in care homes. A qualitative study informed by Glaserian grounded theory was conducted. Semi-structured interviews were undertaken with 20 care home staff across 17 care homes in Northern Ireland, including registered nurses, care assistants, home managers, and catering staff. Data collection and analysis proceeded concurrently using constant comparative methods and theoretical sampling. Analysis focused on identifying key processes influencing how diabetes care was prioritised, enacted, and sustained in everyday practice. Three interrelated categories were identified: Prioritisation, Risk, and Labour. Diabetes education was inconsistently prioritised relative to mandatory training and was unevenly distributed across staff roles. Diabetes-related risk was primarily conceptualised in terms of avoiding acute events, particularly hypoglycaemia, with less attention to longer-term complications or interactions with multimorbidity. Substantial informal and relational labour was undertaken by staff to support residents' quality of life, negotiate dietary practices, and coordinate care. These categories were integrated through a core category of Misalignment, describing the disconnect between the complexity of diabetes care needs and the organisation of education, roles, and support within care home systems. Diabetes care in care homes is sustained through adaptation, informal labour, and pragmatic risk management within systems that are not fully aligned to the demands of long-term diabetes care. Addressing this misalignment is essential to strengthening staff capability and informing the development of contextually appropriate educational and service-level interventions for care home settings. Not applicable.

Diabetic retinopathy (DR), a leading cause of vision loss in working-age adults, is increasingly recognized as a combination of neurodegenerative and microvascular disease of the retina. Its pathological mechanism is complex, involving the regulation of multiple processes such as abnormal neovascularization, nerve damage, oxidative stress, and chronic inflammation. As a key molecular mechanism for regulating protein function, post-translational modifications (PTMs) can dynamically modulate the activity and function of core cells (including retinal endothelial cells, Müller cells, and pericytes) and related signaling molecules including various forms (e.g., phosphorylation, glycosylation, acetylation, methylation, ubiquitination, and SUMOylation), thereby deeply participating in the pathological progression of DR. In addition, PTMs play a crucial role in the regulating signaling pathways, including PI3K/Akt, MAPK, AMPK, NF-κB and JAK/STAT, in the development of DR. Moreover, increasing evidence demonstrates that targeting PTMs with small molecules, either as inhibitors or activators, can reverse protein misfolding and preserve neuroretinal integrity to halt the progression of DR. This review systematically summarizes the variation characteristics of different types of PTMs in DR, analyzes the involvement of PTMs on signaling cascade and cellular processes, reviews the association between ageing and PTMs, and sorts out the research progress of PTMs as potential diagnostic biomarkers and neuroprotective therapeutic targets for DR. It aims to offer a theoretical foundation for in-depth understanding of DR pathogenesis and the development of novel prevention and treatment strategies.

A substantial recent literature has investigated readers' failure to detect transposed words in otherwise grammatical sentences. This phenomenon may reflect a process of rational inference, whereby a reader's prior over word strings overrides the bottom-up perceptual evidence. In three experiments, we tested the prediction emerging from the rational inference framework that failure to detect a transposition should be most common when the prior probability of the untransposed string is high. We found that the frequency of the trigram consisting of the two transposed words and the preceding word predicts failure to notice the transposition: Readers are more likely to miss a transposition of the final two words of a high-frequency trigram such as close the gate than a lower-frequency trigram such as close the pool. We also found a weaker role for the conditional probability of the transposed words based on the entire preceding sentence context. The results support a role for rational inference in 'correcting' errors, and also contribute further evidence that multi-word units play an important role in language processing.

This study aimed to assess long-term memory outcomes in patients with temporal lobe epilepsy (TLE) who underwent anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH), compared to nonoperated TLE over a 10-year follow-up period. A total of 48 participants were studied: 10 ATL, 26 SAH, and 12 patients with nonoperated mesial temporal lobe epilepsy (MTLE). Verbal memory was assessed using the S&#xf6;zel Bellek S&#xfc;re&#xe7;leri Testi (SBST-a test of verbal memory processes), and nonverbal memory was evaluated with the Wechsler memory scale-visual reproduction (WMS) (Turkish adaptation). Given the small and unbalanced groups, linear mixed-effects models (LMMs) were used as the primary inferential analyses to test group &#xd7; time interactions. Statistically reliable individual changes were identified using the reliable change index (RCI). Neuropsychological outcomes were analyzed longitudinally over a 10-year follow-up period. A significant group &#xd7; time interaction was observed for verbal total learning (p&#x2009;=&#x2009;0.001). The nonoperated TLE group showed a significant decline over time, whereas both surgical groups differed significantly from it. The ATL group demonstrated significant improvement. For delayed verbal recall, a significant main effect of group was observed; however, the group &#xd7; time interaction was not statistically significant. Visual immediate recall showed a significant group &#xd7; time interaction (p&#x2009;=&#x2009;0.004), with a significant interaction effect in the ATL group. Visual delayed recall demonstrated a significant group &#xd7; time interaction (p&#x2009;<&#x2009;0.001), with significant interaction effects in both surgical groups. Seizure freedom was achieved in 90% of ATL and 80% of SAH cases; however, seizure outcome was not significantly associated with memory outcomes. Reliable change index analyses indicated lateralization-dependent patterns of change. ATL, particularly left-sided ATL, was associated with statistically significant long-term improvements in verbal memory and significant longitudinal changes in visual memory. SAH demonstrated significant longitudinal effects in selected memory domains. In contrast, nonoperated TLE patients showed significant cognitive decline over time. These findings highlight differential long-term cognitive trajectories across treatment approaches and the role of lateralization in memory outcomes following epilepsy surgery. We examined memory changes over 10&#x2009;years in people with temporal lobe epilepsy who underwent different surgical treatments or received medical management alone. Patients who underwent anterior temporal lobectomy (ATL), particularly on the left side, showed improvement in certain memory measures over time. Those who had selective amygdalohippocampectomy (SAH) demonstrated more domain-specific cognitive changes despite good seizure control. In contrast, patients who did not undergo surgery experienced a decline in verbal learning. These findings suggest that surgical approach and brain lateralization play important roles in long-term memory outcomes.

Therapist actions, qualities and strategies are a potentially modifiable factor influencing outcome in psychological therapies for eating disorders. This study aims to hear the perspectives of those with lived experience, to identify therapist actions and behaviours which were helpful or unhelpful in change and recovery, and to construct a theory of the processes by which these therapist actions might impact on recovery. Eighteen participants who had undergone various psychological therapies for EDs took part in semi-structured interviews. They described helpful and unhelpful therapist behaviours, their emotional and cognitive impacts, and how these influenced recovery. Using a constructivist grounded theory approach, data were analysed through initial and focused coding, comparative methods, theoretical sampling, and memo-writing to develop a theoretical model. Participants described two interacting major categories of therapist actions, strategies and qualities: therapist 'style and stance' along with 'tasks of therapy'. These were described as having some direct pathways of influence on 'change processes and recovery', but also acted through three core categories of interacting intervening processes: 'the person seen heard and cared for', 'trust and openness to therapy' and 'turning towards change'. These processes are the core of the model, acting to catalyse (or block) change. Elements of therapist style and the tasks of therapy influence recovery both directly and through key intervening processes: feeling seen, heard and cared for; developing trust and openness to therapy; and turning towards change. The constructed model and categories are considered in light of psychotherapy theory. The identified aspects of therapist style and tasks are relevant to clinicians and can inform the co-production of guidance for future use in training and delivery of ED therapies. Therapists play an important role in helping people recover from eating disorders, but we still know relatively little about which therapist behaviours are most helpful, and how they support change. This study explored these questions by listening to the experiences of people who had received psychological therapy for an eating disorder. Eighteen adults took part in in-depth interviews about what their therapists did that helped or hindered their recovery, how this made them feel and think, and how it influenced their willingness and ability to change. We analysed these interviews to develop a model explaining how therapist actions may affect recovery. Participants described two main aspects of therapy that mattered: the therapist&#x2019;s style and personal approach (such as warmth, respect, and collaboration) and the tasks of therapy (what the therapist focused on). These influenced recovery both directly and by shaping three key experiences: feeling seen, heard and cared for; developing trust and openness to therapy; and turning towards change. These findings highlight therapist behaviours that may help create the conditions needed for recovery and can inform future training and delivery of eating disorder therapies.

Mitochondrial dysfunction has been recognized as one of the three hallmark biological features of autism spectrum disorder. This study is intended to investigate the molecular mechanisms underlying prenatal psychological fear stress&#x2011;induced hippocampal mitochondrial damage in offspring. Bioinformatics analysis revealed that the calcium signaling pathway, particularly the phospholipase C beta 1(PLC&#x3b2;1)- inositol 1,4,5&#x2011;trisphosphate receptor (IP3R)- voltage&#x2011;dependent anion channel 1(VDAC1) pathway, may play a key role in prenatal stress&#x2011;induced hippocampal mitochondrial damage in offspring. To validate this, we examined pathway activation in the offspring hippocampus of prenatal fear stressed rats and in corticotropin-releasing hormone (CRH; also known as CRF in rodents) overexposed SH&#x2011;SY5Y cells, along with mitochondrial calcium levels in the cells. Prenatal fear stress induced depressive-like behavior and HPA axis activation in pregnant dams, and reduced survival and growth in offspring. Placental and neonatal brain CRF levels were elevated. At the early socialization stage (Postnatal day 21-30), model offspring showed normal basal but exaggerated stress-induced HPA responses. Their hippocampus exhibited expanded MAM coverage, reduced ER-mitochondria distance, and upregulated PLC&#x3b2;1, IP3R1, VDAC1 expression, along with increased GRP75&#x2011;VDAC1 co&#x2011;localization, confirming MAM remodeling at the molecular level. In vitro, CRH (20 &#xb5;M for 48&#xa0;h or 5-20 &#xb5;M for 96&#xa0;h) inhibited SH-SY5Y cell proliferation, upregulated CRH receptor 1(CRHR1), PLC&#x3b2;1, VDAC1, and increased mitochondrial calcium; these effects were reversed by the CRHR1 antagonist CP376395 or PLC&#x3b2;1 knockdown. Furthermore, the MCU inhibitor DS16570511 partially reversed CRH&#x2011;induced mitochondrial calcium elevation and proliferation inhibition, suggesting that mitochondrial calcium overload contributes to the proliferation inhibition. Collectively, these results suggest that prenatal fear stress may, via the CRF-CRFR1 axis, influence the PLC&#x3b2;1-IP3R-VDAC1 pathway, inducing MAM remodeling and mitochondrial calcium overload, thereby contributing to offspring hippocampal neuronal damage.

Phenazines are important nitrogen-containing heterocycles with diverse applications in the chemical and pharmaceutical industry. Alkoxylated phenazines, in particular, exhibit promising acaricidal and fungicidal properties. Currently, chemical synthesis is the main approach for alkoxylated phenazines and derivatives production. However, these processes are associated with harsh reaction conditions, accumulation of chemical waste (e.g., organic solvents, noble metal catalysts), and environmental concerns. In this study, we developed biocatalytic systems for the synthesis of alkoxylated phenazines by designing enzymatic systems and de novo biosynthetic pathways. The O-methyltransferase LaphzM from Lysobacter antibioticus OH13 was shown to catalyze the alkoxylation of phenazines using SAM analogs generated in situ by halide methyltransferases (HMTs) from Burkholderia xenovorans and Arabidopsis thaliana. Using these enzymatic systems, we successfully synthesized six alkoxylated phenazine derivatives, including three novel compounds. We further established de novo biosynthetic pathways for 1-ethoxyphenazine and 2-ethoxyphenazine in Pseudomonas chlororaphis via the direct sulfurylation pathway from S. cerevisiae. To improve production, we optimized whole-cell systems, achieving 486.3&#xa0;mg/L (54% yield) of 2-ethoxyphenazine, 218.1&#xa0;mg/L (22.8% yield) of 2-propoxyphenazine and 378.2&#xa0;mg/L (78.4% yield) of 1-ethoxyphenazine-N'10-oxide within 7&#xa0;h using microbially produced 2-hydroxyphenazine (for 2-ethoxyphenazine and 2-propoxyphenazine) or 1-hydroxyphenazine (for 1-ethoxyphenazine-N'10-oxide) as the substrate, along with ethyl iodide (EtI) or propyl iodide (PrI) accordingly. Overall, we successfully established biocatalytic platforms for alkoxylated phenazines through enzymatic catalysis and de novo biosynthetic pathways. Methyltransferases derived from diverse species, including LaphzM and HMTs, play key roles in the SAM-analog-mediated alkylation of phenazines. This study provides a promising alternative to conventional chemical synthesis, with significant potential for the manufacturing of alkoxylated phenazine derivatives.