Mitosis entry is tightly regulated by a complex network of mechanisms involving epigenetic modifications, signaling pathways, transcriptional control, and structural changes. Although substantial progress has been made in understanding these processes individually, the mechanisms integrating chromatin dynamics with mitotic regulators are still not fully understood. Here, we identify a functional antagonism between the deacetylase SIRT2 and the acetyltransferase MOF in the G2-M transition and mitotic progression. This interplay, which involves MOF deacetylation by SIRT2, regulates key histone marks, including H4K16ac (histone 4 lysine-16 acetylation) deacetylation and H4K20me1 (histone 4 lysine-20 monomethylation) deposition, condensin II loading, and the stability of the key mitotic regulator PLK1, and contributes to the FOXM1-mediated transcriptional control of mitosis. Our findings reveal a previously unrecognized layer of regulation in G2-M progression with possible impact in cancer, highlighting the intricate cross-talk between chromatin dynamics and mitotic control and providing important insights into chromosomal stability.
Pediatric glioblastoma (pGBM) is an aggressive central nervous system (CNS) tumor whose pathological progression is significantly influenced by exosomal signaling. This study integrated and analyzed transcriptomic datasets (GSE50161, GSE35493) from the Gene Expression Omnibus (GEO), focusing on the intersection between exosome-related genes (ERGs) and disease-associated differentially expressed genes (DEGs). Key biomarkers, FGF9, TGFBR1, and PLCB4, were identified using a machine learning model. The results demonstrated that TGFBR1 expression was up-regulated in the tumor microenvironment, whereas FGF9 and PLCB4 were down-regulated. These genes were closely associated with the γ/α (IFN-γ/α) signaling pathway and E2F target activation. Immune profiling revealed that low expression of FGF9 and PLCB4 correlated with a reduction in central memory CD4+T cells, while high TGFBR1 expression was associated with an increase in memory B cells. Further regulatory network analysis uncovered potential epigenetic regulatory mechanisms. In silico drug screening and molecular docking suggested that the histone deacetylase inhibitor Trichostatin A may hold therapeutic potential. This study provides novel biomarkers and insights for the diagnosis and targeted therapy of pGBM.
Stigma impacts outcomes across stigmatizing conditions, including substance use disorders (SUDs). Recent policy changes give patients rapid access to clinical notes in the electronic health record (EHR), which may include stigmatizing language. The objective of this study was to assess the perspectives of women with history of pregnancy and SUDs on typical language used in clinical notes. Women with a history of pregnancy and SUD were recruited through an online crowd-sourcing platform. Respondents viewed examples of clinical language and answered survey questions about perceived stigma. An inductive approach was used to analyze open-text responses, and themes were developed. Three hundred seventy survey respondents wrote a response to at least one open-text question. Thematic analysis yielded 4 major themes: (1) anticipation of future stigma facilitated by EHR documentation can affect patients' care decisions for themselves and their babies; (2) documented SUD history could have short- and long-term effects on patients' experience of stigma and discrimination, especially in labor and delivery; (3) phrases using "denies" and quotes within quotation marks could be perceived as stigmatizing and decrease trust in providers; (4) nonstigmatizing language and acknowledgement of recovery in notes can facilitate positive experiences for patients, but patients want more acknowledgement of recovery and positive language. Electronic health record documentation can modulate stigma experiences for women during and after pregnancy through stigmatizing language in clinical notes and facilitating discrimination, decreasing trust in providers and negatively impacting health outcomes. Raising providers' awareness of nonstigmatizing and positive language or implementing technology to prompt nonstigmatizing terminology could contribute to positive experiences among women with a history of pregnancy and SUD.
Approved in 1997, vagus nerve stimulation (VNS) is now a mainstay treatment of refractory epilepsy. While the safety and efficacy of this treatment modality are well established, the authors investigated the patient- and disease-related factors that impact efficacy. The authors conducted a retrospective analysis of 356 patients who underwent VNS therapy at their center from 2000 to 2023. Data collected included age at implantation, age of first seizure, seizure type and etiology, seizure frequency and number of antiseizure medications before and after VNS, presurgical workup, and second surgery after VNS implantation. Responders were classified as those with at least 50% improvement in seizure frequency. Primary outcome was ≥ 50% reduction in seizure frequency. Age at implantation and sex had no significant effect on seizure frequency. Patients with low seizure frequency had a significantly better response than patients with other seizure frequencies. Patients with a baseline seizure frequency of 1-2/year (OR -3.14, 95% CI -5.371 to -0.909) had significantly better outcomes than the other groups, and patients with baseline seizure frequency of 1-2/month also had a significant outcome (OR -1.803, 95% CI -2.875 to -0.730). The authors' study showed no significant difference in VNS outcomes based on known etiology and imaging findings. Patients with 1-2 seizures/year also had a significant decrease in antiseizure medication burden after surgery (p = 0.026). This study showed that patients with refractory epilepsy who experience low baseline seizure frequency (< 1-2/month and < 1-2/year) received the most benefit from VNS. All patients with refractory seizures should be considered for VNS therapy but should undergo careful case selection to manage expectations and maximize seizure outcomes and medication burden.
Background: Depression, anxiety,, and PTSD are leading global causes of disability. Standard interventions utilize slow mechanisms of action, high attrition, and significant accessibility barriers. While intravenous (IV) and intranasal ketamine are rapid-acting alternatives, high cost and intensive logistical requirements limit adoption. Sublingual (SL) at-home ketamine addresses some gaps but is constrained by low bioavailability and variable absorption. Subcutaneous (SC) administration offers high bioavailability and precise dosing, potentially bridging the gap between in-clinic effectiveness and at-home accessibility. Objective: This retrospective observational study evaluated the safety, feasibility, and clinical outcomes of a telehealth, at-home SC ketamine protocol using a convenience sample of de-identified health records collected via Mindbloom's telehealth platform across 38 states. Methods: A sample of N=3,870 patients with moderate-to-severe symptoms of depression (PHQ-9 ≥ 10), anxiety (GAD-7 ≥ 10), or PTSD (PCL-5 ≥ 33) participated in a structured program involving clinical assessment, mandatory peer monitoring, and remote physiological screening. Injection kits and blood pressure monitors were mailed home. Dosing followed a subanesthetic protocol starting at 0.5 mg/kg with clinician-guided titration. Primary outcomes were measured at baseline and after weeks 2, 4, and 6 using the PHQ-9, GAD-7, and PCL-5 via online survey. Linear mixed-effects models with cubic splines analyzed symptom trajectories and accounted for time-varying assessments. Statistical significance was defined as alpha = .05; effect sizes were reported. Sensitivity analyses utilized multiple imputation and LOCF. Results: Patients (mean age 44.7 years; 52.4% female) demonstrated high adherence, with 0.5% switching from SC to SL administration. After 6 sessions (approximately 44 days), adjusted marginal means showed significant declines: PHQ-9 scores dropped from 14.64 (13.99-15.29) to 6.30 (5.90-6.70), GAD-7 from 13.06 (12.45-13.67) to 6.09 (5.72-6.47), and PCL-5 from 46.7 (43.30-50.10) to 27.5 (25.40-29.70) with large effect sizes ($d_z$) ranging from 1.35 to 1.58. Minimal Clinically Important Difference (MCID) was achieved by 81.8% of MDD, 80% of GAD, and 84.6% of PTSD patients ($p < .001$ for all). Adverse events were low (2.8%-3.2%), with no serious complications related to SC administration. Conclusions: This study is the first large-scale evaluation of at-home SC ketamine. Results suggest at-home SC ketamine is a safe, feasible intervention associated with high rates of symptom reduction in depression, anxiety, and PTSD. It differs from existing literature by utilizing a high-bioavailability (93%) SC route in a remote setting, whereas patients typically receive infusions of this potency in-clinic. Patients achieved clinical outcomes comparable to or exceeding traditional and intranasal therapies, potentially closing the access gap for treatment-resistant populations and supporting the expansion of supervised telehealth models in mental health care.
Biodiversity in Southeast Asia is currently facing a significant decline, with primate species particularly impacted due to deforestation, poaching, global warming, and various other challenges. All 20 recognized gibbon species are considered at risk of extinction due to rapidly decreasing population sizes. The northern white-cheeked gibbon (Nomascus leucogenys) is among six gibbon species belonging to the genus Nomascus documented in Vietnam. This gibbon has been recorded in several protected areas, but significant populations persist only in a few locations, potentially including Vu Quang National Park (52.733 km2). In our study, we utilized the auditory point count method to collect data in the field and applied a distance sampling method to estimate the abundance of northern white-cheeked gibbons in Vu Quang National Park. A total of 27 gibbon groups were documented during our field survey. The estimated gibbon group density was approximately 0.48 groups/km², leading us to estimate the gibbon population size in Vu Quang National Park at about 155 groups. Vu Quang National Park therefore has the largest documented population of northern white-cheeked gibbons in Vietnam, highlighting the urgent need for prioritizing the conservation of this species.
Data quality in face-to-face interviews may be affected by sociodemographic characteristics of interviewers and respondents (age, education, and gender) as well as their (dis)similarity. Similarity in these characteristics may foster rapport, potentially enhancing cooperation and improving data quality. This study examined the associations between interviewer and respondent sociodemographics, their similarity, and data quality, and whether rapport mediates these relationships in a sample of respondents with and without a depressive or anxiety disorder. Baseline data from the Netherlands Study of Depression and Anxiety were analyzed. Data quality was measured using item nonresponse and socially desirable responses to sensitive questions; rapport was assessed via post-interview evaluations from both parties. Multilevel regression and mediation analyses were conducted. Rapport was lower among older respondents but higher with older interviewers. More dissimilarity in age was negatively associated with rapport sum score and dissimilarity in education was negatively associated with rapport scores from interviewers. Furthermore, older respondents had higher item nonresponse and, along with male respondents and those with higher education, gave more socially desirable responses. Rapport partially mediated the effect of respondent age on data quality. Additionally, having a depressive or anxiety disorder was negatively associated with rapport. Experiencing a depression was also linked to more item nonresponse, in contrast, having a depressive disorder or anxiety leads to less socially desirable responses. These findings highlight the importance of interviewer training in rapport-building, particularly with older respondents and respondents who suffer from a psychiatric disorder, to enhance data quality.
This study aimed to examine the symptom burden reported by survivors treated in survivorship clinics by describing the severity of symptoms and symptom interference with life activities, comparing symptom severity by sex, and identifying predictors of the three most prevalent moderate to severe symptoms. This secondary data analysis examined patient-reported symptom burden data using the MD Anderson Symptom Inventory collected for clinical purposes from January to December 2023. Sex differences in symptom burden were compared using t-tests. Multivariate logistic regressions identified predictors of the three most prevalent moderate to severe symptoms. Among 2550 survivors (mean age 61.9 ± 12.1 years; 69.9% female, 36.4% breast cancer), the average time in survivorship care was 4.04 ± 4.00 years. Over 75% of survivors reported experiencing ≥ 1 symptom, and 45% reported ≥ 1 moderate-severe symptom. The three most prevalent moderate to severe symptoms were fatigue (25%), sleep disturbance (24%), and problems remembering (15%). Compared with males, females reported significantly more symptoms (p < 0.05) and more moderate to severe symptoms (p < 0.01). Female survivors and those under the age of 65 were more likely to report moderate to severe fatigue, sleep disturbance, and problems remembering (all p < 0.01). The high prevalence of persistent symptoms among cancer survivors in this sample supports the need for routine symptom assessments in survivorship care. Age and sex are important considerations in tailoring supportive interventions. As the population of cancer survivors grows, understanding symptom burden across diagnoses is critical to inform effective supportive care strategies.
The primary goal of this systematic review was to identify risk factors linked to mental health outcomes and related conditions, categorized across academic, biological, financial (academic/institutional funding), lifestyle, comorbidities, psychological, and social domains. The secondary goal was to estimate the prevalence of these mental health and related conditions. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review analyzed observational studies reporting risk factors associated with mental health outcomes and related conditions. Multiple factors associated with mental health outcomes and related conditions were identified, with the highest number of reports in the following domains: academic (37.0%; 47 factors) and psychological (19.7%; 25 factors), followed by social (13.4%; 17 factors), comorbidities (12.6%; 16 factors), biological (8.6%; 11 factors), lifestyle (6.3%; 8 factors), and financial (2.4%; 3 factors). Regarding prevalence estimates, perceived stress ranged from 18.6% to 88.0%; anxiety symptoms, from 18.8% to 75.0%; depressive symptoms, from 10.1% to 89.1%; suicide-related outcomes, from 1.8% to 9.9%; and problems with eating behavior, from 5.8% to 29.9%. The results of this systematic review demonstrate several risk factors associated with mental health outcomes and related conditions, suggesting that multiple aspects influence the mental health of graduate students. These findings, combined with the high prevalence estimates observed, justify the development of university policies to promote mental health in graduate education.
Extreme weather events (EWEs) are increasing in both intensity and frequency globally. For long-lived, slow-reproducing marine predators, repeated or sequential EWE-driven breeding failures can have population-level consequences. We quantified effects of EWEs on reproductive output and identified temporal windows of vulnerability during breeding in three sentinel species across 14 colonies with varying population trajectories in Tasmania, Australia. Using long-term breeding datasets and daily weather records, we found that Australian fur seals (Arctocephalus pusillus doriferus), short-tailed shearwaters (Ardenna tenuirostris), and shy albatross (Thalassarche cauta) exhibited species- and colony-specific vulnerabilities. Storm surges reduced pup production in a low-lying fur seal colony, extreme rainfall lowered shearwater breeding success, and albatross productivity declined with exposure to extreme heat, rainfall, and wave events. These results highlight the importance of identifying critical extreme weather thresholds and periods of vulnerability to inform ecological forecasting. Proactive, climate-informed management strategies tailored to specific colonies are needed to enhance the resilience of vulnerable populations under accelerating climate change.
The inflorescence meristem (IM) of flowering plants is a stem cell niche that is the source of aboveground organs such as stems and flowers. Although transcriptional profiling has elucidated some cell types within this tissue, the transcriptional dynamics of differentiation from stem cells into the diverse cell types in these organs remain unknown. We used single-nucleus RNA sequencing to characterize the transcriptional landscape of the IM, linking shoot stem cells to early differentiation cell types. Although our analysis of previously known domains uncovered the role of GH3 gene family members in meristematic activity and phyllotaxis, we also identified unknown transcriptional patterns, including early cortex patterning within developing primordia. Trajectory inference analysis revealed the dynamics of the S-G2-M cell cycle phases, as well as gene expression programs driving differentiation toward specialized cell types such as early primordia, cortex, cambium, xylem, and phloem. Collectively, our findings advance the understanding of the cell fate transcriptional dynamics shaping shoot organ development.
Sepsis is a life-threatening condition and its management should be a hospital priority. The European Sepsis Care Survey (ESCS) investigated the implementation of guideline recommendations and the availability of infrastructure for sepsis care across Europe. Our objective was to provide a country‑level baseline assessment of sepsis care in hospitals and to identify deficiencies in sepsis recognition and management. Data from 55 hospitals located in Poland were analyzed regarding sepsis definitions, screening, management, infrastructure, and quality improvement programs (QIPs) in emergency departments (EDs), wards, and intensive care units (ICUs). Sepsis-3 criteria were applied in 44% of hospitals. Sepsis screening and standardized management were used in 27% and 38.2% of EDs, 21% and 30.8% of wards, and 62% and 86.7% of ICUs, respectively. QIPs were present in 37% of hospitals, yet regular sepsis training across departments was reported by only 6.6%. In hospitals with QIPs, key indicators of sepsis care were monitored more frequently, including sepsis cases (76.5% versus 41.4%), mortality (70.6% versus 20.7%), time-to-antibiotics (29.4% versus 0%), bundle compliance (35.3% versus 0%), and also antibiotic stewardship (100% versus 58.6%) (all p < 0.05). Computed tomography (CT) or magnetic resonance imaging (MRI) was available 24 h a day in 94.2% of hospitals. Surgical source control was available 24 h a day in 92.7% of hospitals. Source control by interventional radiology was available in 34.5% of hospitals. Point-of-care lactate testing was available in 80% of emergency departments. Hospital guidelines for antimicrobial therapy in patients with sepsis were present in 65.5% of hospitals. Our study provides a country‑level baseline assessment of sepsis care in hospitals. Overall, adherence to established guidelines for sepsis recognition and management remains low and demands urgent improvement. Hospitals that implemented quality improvement programs demonstrated significantly higher compliance with these guidelines. Strengthening institutional support, establishing structured sepsis programs, and adopting systematic quality improvement approaches are essential to advancing sepsis care. ClinicalTrials.gov identifier, NCT05059808.
To develop and externally validate an interpretable machine learning model for predicting 7-day stroke-associated pneumonia (SAP) using routine clinical data collected within 24 h of admission. This multicenter study utilized a development cohort from the Henan Stroke Cohort and an independent external validation cohort from three Zhengzhou hospitals. Adult patients with imaging-confirmed ischemic or hemorrhagic stroke were eligible. Patients with infection at admission or who developed SAP within 24 h of admission were excluded. We evaluated 26 candidate predictors obtained within 24 h of admission. Nine machine learning algorithms were trained following recursive feature elimination. Model performance was evaluated based on discrimination, calibration, and clinical utility. The optimal model was interpreted using SHapley Additive exPlanations (SHAP) and deployed as an online calculator. The development and external validation cohorts comprised 1201 and 645 patients, with 7-day SAP incidences of 20.6 % (n = 247) and 24.8 % (n = 160), respectively. Among the nine algorithms, stochastic gradient boosting (SGBT) demonstrated the most balanced overall performance. In internal validation, SGBT achieved an area under the receiver operating characteristic curve (AUC) of 0.947 in the training set and 0.905 in the test set. In external validation, the model yielded an AUC of 0.906, alongside an accuracy of 0.864, sensitivity of 0.712, specificity of 0.918, positive predictive value (PPV) of 0.756, negative predictive value (NPV) of 0.899, and F1-score of 0.733. The final model retained 10 predictors: stroke subtype, fibrinogen, D-dimer, C-reactive protein, uric acid, triglycerides, homocysteine, and clinical scores (ADL, GCS, NIHSS). SHAP analysis identified early neurological impairment and inflammatory burden as the primary contributors to SAP prediction. An interpretable SGBT model utilizing routine admission data accurately predicted 7-day SAP and remained robust during external validation. The accompanying online calculator facilitates individualized risk estimation to support early preventive decision-making in hospitalized patients with stroke.
Age-dependent physiology makes interpreting high-sensitivity cardiac troponin T (hsTnT) challenging in early childhood. Values below the analytical limit create left-censored data, complicating reference interval (RI) estimation. We combined two paediatric cohorts (CALIPER, n=277; LIFE Child, n=1,358; ages 0-10 years) to derive continuous, age-dependent hsTnT RIs. Empirical quantiles were estimated using a sliding-window approach and fitted with four-parameter logistic functions. To address the high proportion of values below the analytical limit of detection (LOD; 3 ng/L), the 2.5th percentile was inferred from the 65th and 97.5th percentiles assuming lognormal distribution. A closed-form zlog transformation was established to standardise hsTnT values. Pointwise 95 % bootstrap confidence bands (100,000 stratified resamples) were computed for both reference limits. HsTnT concentrations declined steeply during infancy and stabilised at low levels thereafter, with 46 % of samples below the analytical limit. The closed-form approach modelled reference limits according to the following logistic equation f x = 1 1 + e - a + b · x · maxv - minv + minv with parameters: a=-1.15 and 0.47, b=-4.13 and -6.64, minv=1.13 and 7.50 and maxv=124.13 and 210.3 for lower and upper limits, respectively. Bootstrap confidence bands were widest in the first six months of life and narrowed substantially thereafter. The zlog transformation effectively removed age dependency, with >95 % of values within the theoretical RI (-1.96 to +1.96). We present the first continuously modelled, closed-form RIs and corresponding zlog-transformation for paediatric hsTnT (ages 0-10 years). This framework enables direct LIS/EHR deployment without specialized software and facilitates age-independent interpretation and longitudinal monitoring in paediatric cardiology.
Wearable bio-based fibers are emerging as platforms for biomechanical sensing and physiological interaction. However, achieving high sensitivity to subtle mechanical cues while maintaining flexibility, self-powered output, and distributed perception remains challenging. Inspired by the helical twining mechanics of climbing plant stems, we design a mechano-adaptive auxetic electronic bio-based fiber as an embodied intelligence sensing unit. The dual-modulus helical confinement, achieved by wrapping rigid aramid fiber/polydimethylsiloxane helices around a flexible collagen aggregate/waterborne polyurethane core, enables programmable deformation and a stable negative Poisson's ratio (ν = -0.47). Nonlinear intercomponent coupling facilitates synergistic axial-radial dynamics, amplifying interfacial contact variation under strain. The optimized fiber exhibits ultrahigh sensitivity (strain factor: 11.75), strong electrical output (8.1 volts), and remarkable power density (8.48 milliwatts per square meter) with excellent cyclic stability. Integrated into fiber-sensing arrays, it decodes microstrain patterns linked to lower-limb function, offering a scalable strategy for self-powered, adaptive, and durable biomechanical monitoring.
This work presents the design, development, and initial proof of concept testing of a dosimetry device intended for FLASH radiotherapy. The system incorporates organic scintillating fibers coupled to a silicon photomultiplier (SiPM) and an FPGA-based readout, with fiber geometry optimized to minimize perturbations to a clinical proton beam, as confirmed through measurements at the Huntsman Cancer Institute (HCI). Tests using a portable X ray unit demonstrated a strong correlation between integrated charge and delivered dose (up to ∼35 mrem s-1) and showed that the detector can respond on nanosecond timescales, enabling the potential for rapid safety interlock triggering with minimal latency. Preliminary proton irradiations at HCI further indicated that the device can resolve individual beam pulses, a capability valuable for both FLASH research and conventional radiotherapy. These results highlight the need for continued refinement of the experimental setup, readout electronics, and detector performance to fully realize real time, in situ dose and pulse monitoring.
To synthesize the evidence regarding the effectiveness of the participatory approach (PA) on return to work (RTW) of sick-listed workers compared to usual care and other interventions. A systematic review and meta-analysis were conducted according to the PRISMA guidelines, searching five databases for evidence from their inception until February 2025. Studies were eligible for inclusion if they included sick-listed workers, conducted a PA intervention at the workplace focused on RTW, and included a comparison group. Data on RTW, health, and economic outcomes were extracted, and the quality of the studies was appraised. Data on time until full and lasting RTW were pooled, and a meta-analysis was conducted, followed by an assessment of the certainty of the evidence. Eight randomized controlled trials reported across 14 papers were included. Half of the studies had a good quality score, whereas the remaining studies were considered of poor (n = 3) or fair (n = 1) quality. While no significant overall effect of the PA on time until full and lasting RTW was found, a statistically significant effect in favor of the PA was observed among sick-listed workers with low back pain (LBP) compared to control conditions. The evidence provides moderate certainty that the PA is effective in reducing time to full and lasting RTW for sick-listed workers with LBP compared to usual care. However, for workers sick-listed due to mental health conditions or mixed health complaints, the evidence does not support its effectiveness, and the certainty of this evidence is very low. More high-quality research and realist evaluations across different settings and populations are needed to strengthen the evidence on the PA as an RTW intervention and to explain its underlying working mechanisms.
Over one million hernia repairs are performed annually in the United States, with more than 20 million worldwide. Although randomized trials support watchful waiting in select cases, delayed repair can lead to strangulation, which is rare but life-threatening. This study examines race and sex-based differences in postoperative outcomes following nonemergent and emergent incarcerated hernia repair. Retrospective cohort study utilizing National Surgical Quality Improvement Program database (2013-2023). Adults undergoing incarcerated repair were identified using Current Procedural Terminology codes for nonemergent and emergent abdominal wall and inguinal hernias. Outcomes included 30-d complications, readmission, reoperation, and length of stay (LOS). Multivariable regression models assessed associations between race, sex, and postoperative outcomes, adjusting for demographic, clinical, and perioperative covariates. Analyses were stratified on subgroup analysis by operative urgency. Among 185,791 incarcerated hernia repairs, 159,351 were nonemergent, and 26,440 were emergent. In emergent repairs, race and sex were not associated with 30-d complications, readmissions, or reoperations, though Black and Asian patients experienced longer LOS. In nonemergent repairs, Black and female patients were associated with longer LOS. Female sex was also associated with higher complication rates (odds ratio: 1.145, 95% confidence interval: 1.091-1.201) and readmissions (odds ratio: 1.065, 95% confidence interval: 1.005-1.129). Race was not associated with 30-d complications, readmissions, or reoperations. Race and sex were not associated with major postoperative outcomes following emergent hernia repair, whereas female sex was associated with increased complications, readmissions, and LOS in nonemergent repair. These findings highlight differences in outcomes by operative urgency and sex.
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In recent years, research of matrine (MAT) and oxymatrine (OMT) has shifted from merely discovering pharmacological activities to exploring mechanisms, expanding new indications, and improving formulations. However, comparative analyses of their similarities and differences remain limited. Beyond their well-known functions in cancer treatment-such as regulating non-coding RNAs, preventing metastasis, and triggering apoptosis and ferroptosis-these compounds also show notable immunomodulatory effects, particularly in synergizing with immune checkpoint inhibitors to enhance tumor responsiveness. Furthermore, they show efficacy in inflammatory and autoimmune diseases (e.g., colitis, psoriasis, encephalomyelitis), neuroprotection, cardioprotection, and anti‑fibrosis. To overcome limitations such as hepatotoxicity and poor bioavailability, significant progress has been made in the structural modification of MAT and in the advanced formulation of OMT, thereby enhancing potency, selectivity, and targeted delivery. This review systematically consolidates recent advances in their multitarget mechanisms and expanding their therapeutic landscape. It also provides a unified mechanism overview and highlights the transformation strategy. These collective efforts will improve our understanding of MAT and OMT, offering a valuable reference for the further development of these natural products into modern therapeutics.