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Pedestrian injury risks in car-to-pedestrian collisions are strongly influenced by anthropometric characteristics, yet existing human body models rarely represent small-stature Chinese female pedestrians. This study presents the Tianjin University of Science and Technology Injury Bionic Model (TUST IBMs F05-P), developed to represent a 5th percentile Chinese female pedestrian. Detailed anatomical structures were reconstructed directly from medical imaging data without geometric scaling, preserving subject-specific anatomical geometry, and the model was meshed predominantly with hexahedral elements. A representative walking posture was defined, and the model was evaluated through a certification procedure conducted according to the Euro NCAP CP540 pedestrian human body model certification protocol. Simulation results showed that key biomechanical indicators, including Head Impact Time (HIT), contact forces, and kinematic trajectories, predominantly fell within the response corridors specified in CP540. Quantitative assessment using the CORA (CORrelation and Analysis) method defined in ISO/TS 18571:2024 yielded an overall score of 0.84, indicating a high level of correlation with the CP540 reference corridors. The certification results indicate that the TUST IBMs F05-P produces stable and reproducible responses under the tested impact conditions. By providing an anatomically realistic representation of a small-stature Chinese female pedestrian, this model addresses the lack of population-specific pedestrian models and offers a validated basis for pedestrian injury analysis and vehicle front-end safety evaluation.

Current McDonald criteria for multiple sclerosis (MS) rely on complex statistical metaphors-dissemination in space and time-that are prone to clinical misapplication. This manuscript proposes a clinician-centred approach that simplifies diagnosis by focusing on four fundamental immunobiological pillars: confirming the condition is a chronic, inflammatory, demyelinating disease of the CNS. By reclassifying existing markers-such as the central vein sign, paramagnetic rim lesions, and neurofilaments-into these intuitive categories, the model provides clinicians greater flexibility to triangulate evidence based on available data. Crucially, this framework introduces Immunobiological MS (IBMS) (formerly Radiologically Isolated Syndrome) and Non-active CDMS as distinct diagnostic entities. These categories acknowledge the disease's biological diversity and accommodate variable treatment decisions.

Juvenile North Pacific albacore tuna (Thunnus alalunga) undertake annual long distance migrations between offshore waters and the California Current Large Marine Ecosystem (CCLME), yet the drivers of the timing of these movements remain unclear. Highly migratory marine predators like albacore often use environmental cues to track seasonal resources and optimize foraging. Mixed layer depth (MLD), defined as the well-mixed surface layer of the ocean, has previously been associated with important albacore physiological and behavioral patterns. Using electronic tagging data and an individual-based model (IBM) we show MLD has a pivotal role in influencing albacore migration timing and depth preferences. Albacore actively expand their vertical habitat in correspondence with wintertime MLD deepening and appear to utilize a 30m MLD threshold to initiate preemptive movements to reach seasonally and spatially explicit foraging resources. Model simulations using MLD-based rules and an ocean sea surface temperature (SST) constraint successfully capture the seasonality of movements and distribution of albacore. Climate projections suggest that by 2070–2099, SST warming will shift albacore distributions poleward and MLD shoaling will prolong their coastal residence, potentially increasing albacore concentrations in the Northern CCLME. These findings highlight the relevance of subsurface ocean conditions to the movement of highly migratory species and demonstrate the utility of IBMs in the study of complex migratory behaviors. The online version contains supplementary material available at 10.1038/s41598-026-46968-y.

Research shows completing a placement year is associated with improved academic and employment outcomes. For Biomedical science courses, pathology placements allow completion of the Institute of Biomedical Science (IBMS) registration training portfolio and obtaining Health and Care Professions Council (HCPC) registration post-graduation. This study sought to identify the barriers biomedical science students across the West Midlands region of England face when completing a placement year, to identify strategies which promote inclusivity to overcome these barriers. Level 5 and Level 6 students from Aston, Coventry, Keele and Wolverhampton universities were invited to complete a questionnaire which included a mixture of Likert scale and free-text responses. A range of questions assessed student perceptions on the importance of placement opportunities, as well as identifying factors which were important when pursuing a placement year. Likert scale data was analysed quantitatively, and a Mann Whitney U or Kruskal Wallis test were used to infer significance, whereas free text responses were analysed using thematic analysis. A total of 107 students completed the questionnaire. Students who declared a disability were less likely to undertake an unpaid placement compared to their peers (p = 0.013). Of those students who declared caring responsibilities, 33.3% chose not to apply for a placement year compared to 18.2% of those who did not have caring responsibilities (p = 0.020). Participants reported that funding was important when deciding whether to pursue a placement (88.8%). Thematic analysis revealed several recurring themes deterring student placement applications, including financial support and placement availability within their geographical area. Students valued the importance of professional recognition following the placement and the development of technical and transferable skills. Many of the barriers are fuelled by financial constraints which deter students from applying to placement positions. Despite the need to increase the Biomedical Scientist workforce, the strategies to increase training opportunities are not well established. Equity in placement funding from centralised sources is key to ensuring Biomedical Scientists can excel in their professional careers. Through availability of funding, marginalised populations will have the same opportunities as their peers therefore producing more employable graduates to meet pathology workforce demands.

Nuclear speckles are nuclear bodies enriched with RNA-processing proteins. Highly transcribed genes and their nascent pre-mRNAs are organized around nuclear speckles, facilitating co-transcriptional RNA processing. However, the mechanisms underlying this spatial organization remain unclear. Here, we identified a class of Alu repeat-containing RNAs that are highly enriched in nuclear speckles. These RNAs interact with actively transcribed genes through their Alu elements, partially via R-loop formation. They also engage with nuclear speckle proteins, promoting their coalescence, phase separation, and assembly into nuclear speckles, thereby contributing to the spatial organization of actively transcribed genes around these structures. Depletion of these RNAs reduces speckle size, displaces active genes, and impairs RNA processing. Moreover, this mechanism is critical for high expression of many erythroid differentiation genes during erythropoiesis. Our findings highlight an important role of Alu repeat-containing RNAs in nuclear speckles assembly and their function in mediating spatial co-transcriptional RNA processing.

The lack of rapid, reproducible carotid-specific atherosclerosis models in wild-type mice limits translational studies of plaque biology and therapies. This protocol describes a non-genomically edited, time-efficient method to induce reproducible carotid atherosclerosis in C57BL/6 mice by combining adeno-associated virus (AAV)-mediated PCSK9 overexpression, an atherogenic high-fat diet, and left partial carotid ligation (PCL). The objective is to provide a standardized workflow that reproduces key pathophysiological features of human carotid disease-hyperlipidemia plus disturbed flow-without requiring genetically modified animals. Methods include PCSK9-AAV dosing and administration, perioperative preparation, step-by-step surgical ligation of the left carotid, postoperative care, dietary regimen, tissue collection, and histological assessment including Oil Red O and Verhoeff-Van Gieson staining. The results indicate elevated circulating cholesterol and low-density lipoprotein levels compared with reference values. Pronounced atherosclerotic plaques develop at the left ligated carotid artery, with significantly increased lipid accumulation and significant arterial intima-media thickening relative to the right non-ligated control artery. This standardized protocol improves reproducibility and accessibility for investigators studying carotid plaque formation, progression, intervention strategies, and facilitates cross-laboratory comparisons of experimental therapies.

Pulmonary fibrosis is characterized by progressive deposition of fibrotic scar tissue within the lung parenchyma, leading to severely impaired gas exchange. It underlies a spectrum of chronic interstitial lung diseases, notably idiopathic pulmonary fibrosis, a condition associated with an exceedingly poor prognosis. Given the lack of effective therapies, robust mouse models are critical for elucidating underlying pathological mechanisms and evaluating novel antifibrotic interventions. Bleomycin-induced pulmonary fibrosis remains the most extensively utilized experimental model. Common routes of administration in mice include intravenous and intraperitoneal injections, invasive open-tracheal instillation, and noninvasive tracheal dripping. However, invasive surgical methods often cause secondary tissue injury, potentially compromising model reproducibility and stability. Conversely, noninvasive tracheal dripping usually results in uneven bleomycin distribution across lung lobes and poses a risk of asphyxiation, thus reducing reproducibility and increasing technical challenges. To address these limitations, a refined aerosol-based intratracheal delivery method is developed that is operationally simpler, minimally invasive, highly reproducible, and ethically superior by significantly reducing animal distress. Using a small-animal laryngoscope to visualize the rima glottidis directly, a specialized aerosolizing needle is inserted into the trachea, markedly narrower than the mouse tracheal diameter. Bleomycin solution is delivered under precisely controlled pressure, generating a fine aerosol. This ensures uniform and efficient distribution of the agent throughout the lung parenchyma. Moreover, one can selectively target the left or right lung by directing the needle into the appropriate bronchus. This optimized model's dose-response relationship is extensively characterized by systematically monitoring changes in lung function, histopathological manifestations, and lung hydroxyproline content. This refined experimental protocol is anticipated to facilitate laboratory standardization, ultimately accelerating the development and preclinical validation of novel antifibrotic therapeutics.

Hepatic sarcomatoid carcinoma (HSC) is a rare and highly aggressive liver malignancy with an extremely poor prognosis. The lack of well-validated cellular models has severely limited mechanistic and translational research on this disease. In this study, we established and comprehensively characterized a novel HSC cell line, designated PUMC-LICA3. This cell line was derived from surgically resected tumor tissue of a 58-year-old male patient and has been continuously cultured for more than 40 passages, with a population doubling time of 51.77 h and an epithelial-like morphology. Long-read sequencing identified HBV DNA integration at chromosome 17p11.2 without detectable covalently closed circular DNA (cccDNA) or viral antigen expression, indicating a non-replicative viral status. PUMC-LICA3 exhibited 100% tumorigenicity in NOD/SCID mice. Xenograft tumors displayed immunohistochemical features consistent with sarcomatoid carcinoma, characterized by the co-expression of epithelial markers (CK and CK19) and the mesenchymal marker vimentin. E-cadherin expression was patchy, with partial loss in subsets of tumor cells, whereas N-cadherin was diffusely expressed. Notably, PUMC-LICA3 exhibited a high epithelial-mesenchymal transition (EMT) score and, among 22 hepatocellular carcinoma (HCC), clustered most closely with JHH-6 and SNU-387. Drug sensitivity assays showed that the cell line was sensitive to cisplatin, doxorubicin and sorafenib, but resistant to 5‑fluorouracil. Whole-exome sequencing (WES) analysis revealed that the cell line largely preserved the genetic characteristics of its parental tumor throughout long-term culture. In conclusion, the newly established PUMC-LICA3 cell line represents a reliable and valuable experimental model for investigating the biological characteristics and therapeutic strategies of hepatic sarcomatoid carcinoma.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. COPD is characterized by progressive airflow restriction and wide-spectrum heterogeneity across clinical manifestations, treatment responses, and underlying mechanisms. While recent omics approaches have advanced our understanding of COPD, in-depth multi-omics characterization remains scarce, leaving a critical gap in knowledge for the understudied population. We conducted deep multi-omics profiling on a unique Chinese population from a region with high COPD prevalence, high-altitude residence, and widespread exposure to biomass fuels (74.8%). We recruited 159 COPD patients from 5 medical centers and integrated their radiomics, metabolomics, microbiomics, and genomics data, identifying three distinct molecular subtypes: "stable state" (SS), "restrained state" (RS), and "crumbly state" (CS). The SS subtype is marked by the least acute exacerbation and mildest airflow limitation with potential eosinophilic inflammation. The RS subtype is characterized by extensive pulmonary structural damage, greatest airflow limitation, but mild clinical symptoms. The CS subtype is typified by disturbed microbial interaction, high triethanolamine, coal dust exposure, and nicotine dependence. This study provides a comprehensive multi-omics profile of COPD in a previously understudied population and reveals three molecular subtypes that enhance the understanding of COPD heterogeneity.

While much progress has been made in reducing the incidence of HIV-1 infection in sub-Saharan Africa in recent years, bringing the epidemic to an end will require identification of the demographic groups that continue to contribute to transmission. Pathogen phylogenetics and individual-based mathematical models (IBMs) of transmission are approaches that enable researchers to explore such questions. Here, we used both methods to characterise the ages and sexes of the individuals involved in heterosexual transmission in the context of the HPTN 071 (PopART) trial in Zambia. The two methods produced largely concordant results, strengthening confidence in both. A principal finding was that when the age gap in transmission (the difference of ages between the two individuals) was stratified by recipient age, the largest differences were for the youngest female recipients and the smallest for the youngest males. For women under 21 this stood at a male 9.87 years older (95% CI: 8.02 - 11.59) in the phylogenetics, compared to 6.93 (95% HDI: 6.56 - 7.32) in the IBM. As the age of female recipients increased, this gap decreased towards parity. Conversely, the under-21 male recipients saw the smallest gaps with the female older by 0.14 years (95% CI: -2.95 - 3.23) in the phylogenetics and 1.38 years (95% HDI: 0.98 - 1.68) in the IBM. As the age of male recipients decreased, this gap steadily increased. The consequence of this pattern is that transmission to new age cohorts first entering into sexual activity is driven predominantly by male-to-female transmission. We also showed that targeting interventions at younger adults captures most of the benefit of population-wide approaches. We used the IBM to simulate the PopART universal testing and treatment intervention into the future, showing that effective treatment of under-35-year-olds would account for 94.3% (95% HDI: 65.8% - 126.6%) of the reduction in incidence by 2039 that would be achieved by treating the entire population, while effective treatment of under-35 men accounts for 60% (95% HDI: 23.2% - 92.1%). Finally, we simulated a one-year cessation of ART treatment for the whole population, which resulted in an immediate increase in both incidence and the average age at transmission of both sources and recipients. The magnitude of this was 4.6 years (95% HDI: 2.17 - 6.24) for female recipients, 5.3 (95% HDI: 2.74 - 7.09) for male recipients, 5.24 (95% HDI: 2.78 - 6.97) for female sources, and 6.04 (95% HDI: 2.92 - 8.09) for male sources. These changes would be slow to reverse even after ART was restored. These findings indicate that substantial reductions in HIV incidence can be achieved through intensified testing and treatment of individuals aged under 35, and in particular young men, a group that drives the infection of younger women and for whom engagement with care remains disproportionately low.

In this work, we introduce a new qubit mapping strategy for the Variational Quantum Eigensolver (VQE) applied to nuclear shell model calculations, where each Slater Determinant (SD) is mapped to a qubit, rather than assigning qubits to individual single-particle states. While this approach may increase the total number of qubits required in some cases, it enables the construction of simpler quantum circuits that are more compatible with current noisy intermediate-scale quantum (NISQ) devices. We apply this method to seven nuclei: Four lithium isotopes [Formula: see text]Li from the p-shell, [Formula: see text]F from the sd-shell, and two heavier nuclei ([Formula: see text]Po, and [Formula: see text]Pb). We run circuits representing their ground states on a noisy simulator (IBM's FakeFez backend) and quantum hardware ([Formula: see text]). For heavier nuclei, we demonstrate the feasibility of simulating [Formula: see text]Po and [Formula: see text]Pb as 22- and 29-qubit systems, respectively. Additionally, we employ Zero-Noise Extrapolation (ZNE) via two-qubit gate folding to mitigate errors in both simulated and hardware-executed results. Post-mitigation, the best results show less than 4 % deviation from shell model binding energy predictions across all nuclei studied. This SD-based qubit mapping proves particularly effective for lighter nuclei and two-nucleon systems, offering a promising route for near-term quantum simulations in nuclear physics.

Metal-associated free fatty acids (FFAs) on cardiometabolic diseases have rarely been studied. To investigate metallomics-FFAs relationship, and identify FFAs as potential mediators linking metals to cardiometabolic diseases. In a nationally representative survey, 18 metals (blood/serum/urine) and 30 serum FFAs were assessed. Weighted linear regression, least absolute shrinkage selection operator, quantile g-computation and receiver operating characteristic were used to analyze associations between metal exposure and FFAs, with mediation and bioinformatics analyses exploring underlying mechanisms. Blood selenium (Se), mercury (Hg), lead (Pb); serum copper (Cu), zinc (Zn); and urinary arsenic (As) were positively correlated with FFAs [effect range: 5.74% (95% CI: 2.71, 8.85) to 33.08% (95% CI: 28.73, 37.58)], whereas urinary tungsten, molybdenum, and cobalt showed negative associations [-6.17% (95% CI: -9.54, -2.68) to -9.68% (95% CI: -13.75, -5.42)]. Metal mixture was positively associated with most FFAs [15.66% (95% CI: 0.11, 33.62) to 60.35% (95% CI: 40.19, 83.42)]. Key contributors to FFAs disturbance include serum Cu/Zn, blood Hg/Pb, and urinary As. FFAs (primarily nervonic acid and docosapentaenoic acid) mediated the associations of blood metals (Pb, Hg, Se) and serum Zn with cardiometabolic markers (proportions: 6.98%-84.71%). Inflammatory pathways (e.g., IL-17, TNF) may link metal-induced FFA dysregulation to lipotoxicity and cardiometabolic risk. Our findings provide exploratory evidence connecting metallomics with FFAs and cardiometabolic diseases, suggesting FFAs as potential biomarkers for metal exposure and cardiometabolic diseases prevention.

Chronic social isolation stress (CSIS) disrupts redox homeostasis and promotes neuroinflammation, contributing to depressive-like behavior. Carvacrol (CV), a monoterpenoid phenol with antioxidants and anti-inflammatory properties, has been studied merely in stress-induced depression. Adult male NMRI mice underwent 6 weeks of CSIS and received CV (10 or 20 mg/kg, i.p.) or a positive control during the final 2 weeks. Depressive-like behavior was evaluated using open-field, splash, and forced-swim tests. Medial prefrontal cortex (mPFC) and hippocampal dentate gyrus tissues were assayed for catalase (CAT) and glutathione-S-transferase (GST) activities, reduced glutathione (GSH), and lipid peroxidation (LPO; TBARS), together with selected proinflammatory cytokines. Hematoxylin-eosin staining assessed cytoarchitecture, and molecular docking examined putative interactions of CV with the Nrf2/Keap1 complex and NF-κB. CSIS increased behavioral despair and reduced exploration and grooming, accompanied by decreased CAT, GST, and GSH, elevated TBARS, and higher inflammatory mediators, with neuronal alterations in mPFC and dentate gyrus. CV dose-dependently improved locomotor and grooming behavior, restored antioxidant defenses, reduced TBARS, and lowered inflammatory markers while preserving neuronal structure. Docking supported plausible binding (≈ -5.8 kcal/mol for Nrf2/Keap1; ≈ -5.1 kcal/mol for NF-κB), consistent with the observed molecular changes. These findings indicate that CV produces antidepressant-like effects in CSIS by reinforcing redox balance and attenuating neuroinflammation in stress-sensitive brain regions, supporting its therapeutic potential for stress-related mood disorder.

There are high frequencies of worse clinical outcomes and major cardiovascular events (MACE) reported in women. We aimed to determine that comparable baseline presentation and contemporary percutaneous coronary intervention (PCI) techniques overcome the gender-based differences in MACE at 1 year follow-up study. This prospective cohort study enrolled 288 consecutive acute coronary syndrome patients (ACS) from September 2022 to March 2023 at Kuwait Teaching Hospital, Peshawar, Pakistan. All the enrolled patients were followed for 1 year and MACE were compared between males and females. Data was analyzed using SPSS version 26.0. There were no statistically significant differences observed between demographic factors including age, BMI, and waist (p value&#x2009;>&#x2009;0.05). Similarly, no significant differences were observed between biochemical parameters in male and females (p value&#x2009;>&#x2009;0.05). Men were more physically active (p value 0.001). Smoking and snuffing were significantly higher in male then in female (p values&#x2009;<&#x2009;0.001) while female had higher rate of diabetes mellitus (DM) and hypertension (HTN) with p values&#x2009;<&#x2009;0.001 and 0.03, respectively. Overall incidence of 1 year MACE was 22% in males while 21.7% in females (p value 1.00). The male gender had less cardiovascular events over time as compared to females. However, the differences were not statistically significant (p-value 0.96). When baseline presentations, PCI techniques, and post PCI medication are identical in patients with ACS, gender does not impact the MACE at 1 year post PCI.

Transmission-dynamic models are commonly used to study infectious disease epidemiology. Calibration involves identifying model parameter values that align model outputs with observed data or other evidence. Inaccurate calibration and inconsistent reporting produce inference errors and limit reproducibility, compromising confidence in the validity of modeled results. No standardized framework exists for reporting on calibration of infectious disease models, and an understanding of current calibration approaches is lacking. We developed the Purpose-Inputs-Process-Outputs (PIPO) framework for reporting calibration practices and applied it in a scoping review to assess calibration approaches and evaluate reporting comprehensiveness in transmission-dynamic models of tuberculosis, HIV and malaria published between January 1, 2018, and January 16, 2024. We searched relevant databases and websites to identify eligible publications, including peer-reviewed studies where these models were calibrated to empirical data or published estimates. We identified 411 eligible studies encompassing 419 models, with 74% (n&#x2009;=&#x2009;309) being compartmental models and 20% (n&#x2009;=&#x2009;81) individual-based models (IBMs). The predominant analytical purpose was to evaluate interventions (71% of models, n&#x2009;=&#x2009;298). Parameters were calibrated mainly because they were unknown or ambiguous (40%, n&#x2009;=&#x2009;168), or because determining their value was relevant to the scientific question beyond being necessary to run the model (20%, n&#x2009;=&#x2009;85). The choice of calibration method was significantly associated with model structure (p-value<0.001) and stochasticity (p-value&#x2009;=&#x2009;0.006), with approximate Bayesian computation more frequently used with IBMs and Markov-Chain Monte Carlo with compartmental models. Regarding reporting comprehensiveness, all PIPO framework items were reported in 4% (n&#x2009;=&#x2009;18) of models; 11-14 items in 66% (n&#x2009;=&#x2009;277), and 10 or fewer items in 28% (n&#x2009;=&#x2009;124). Implementation code was the least reported, available in only 20% (n&#x2009;=&#x2009;82) of models. Reporting on calibration is heterogeneous in recent infectious disease modeling literature. Our proposed framework for reporting of calibration approaches could support improved reproducibility and credibility of modeled analyses.

Cardiovascular-kidney-metabolic (CKM) syndrome links metabolic dysfunction, kidney injury, and cardiovascular disease; however, how real-world toxic exposures and social disadvantage accelerate CKM progression is not well defined. We followed a pollution-exposed rural cohort in Northeast China from 2016 to 2021 (n&#x202f;=&#x202f;472; 2360 person-visits). Urinary chromium (Cr), cadmium (Cd), manganese (Mn), and lead (Pb) were measured by inductively coupled plasma mass spectrometry, and CKM stage was assigned using the current American Heart Association framework. We modeled advanced CKM (stages 3-4) versus non-advanced CKM (0-2) using generalized linear mixed-effects models (LME) with participant-level random intercepts, and evaluated nonlinearity, mixture effects, and metal-metal interactions using random-intercept Bayesian kernel machine regression (BKMR). Higher urinary Cd [odds ratio (OR) 1.43, confidence interval (CI) 1.01-2.03], Pb (1.38, 1.05-1.80), and Mn (1.35, 1.02-1.80) were associated with advanced CKM, whereas Cr showed an inverse association (0.79, 0.60-0.97). The metal mixture as a whole increased advanced CKM risk and displayed nonlinear, interacting behavior (notably Cd- and Mn-driven effects and Cr&#xd7;Cd, Cr&#xd7;Mn, Pb&#xd7;Cd, Pb&#xd7;Mn interactions). Although single social determinants of health (education, income, employment, insurance) did not independently predict advanced CKM, cumulative disadvantage (&#x2265;2 adverse factors) amplified the Cd-CKM association (interaction OR 2.12, 1.00-4.54), indicating that inequity modifies biological susceptibility. Network and pathway analysis highlighted STAT3 as a central inflammatory-metabolic hub linking metal-responsive signaling to cardio-renal-metabolic injury, and molecular docking suggested direct coordination of Cd&#xb2;&#x207a;, Mn&#xb2;&#x207a;, and Pb&#xb2;&#x207a; to STAT3. Notably, this study leverages a longitudinal repeated-measures design and mixture modeling framework to assess combined metal exposures in relation to CKM progression, and integrates epidemiological inference with systems-level analyses to generate mechanistic hypotheses. These findings outline an exposure-inequity-inflammation axis and nominate mixture reduction and social protection as dual prevention targets.

RNA-binding proteins (RBPs) are crucial regulators of gene expression, and their dysfunctions have been implicated in various tumor types. Isocitrate dehydrogenase 1 (IDH1) is a prognostic marker in glioma and has recently been identified as an RBP. This study aimed to investigate the role of IDH1 in glioblastoma (GBM) progression and its regulatory impact on RNA biology. Bioinformatics analysis of The Cancer Genome Atlas (TCGA) data observed that IDH1 expression levels increase with glioma grade and correlate with poor patient survival. Functional assays confirmed that IDH1 acts as an oncogenic factor in GBM cells. Using enhanced crosslinking and immunoprecipitation (eCLIP) and RNA immunoprecipitation (RIP), we identified numerous IDH1-bound transcripts, including p62/SQSTM1 which was validated as a functional target. These findings indicate that IDH1 facilitates glioma progression by binding and suppression of p62.

Psoriasis is a refractory immune-related disease. In recent years, it has been discovered that mesenchymal stem cells (MSCs) can be used as a new therapeutic approach for psoriasis, but their potential therapeutic mechanism remains unclear. This study aims to explore the role of MSCs in the treatment of psoriasis. We employed a mouse psoriasis model induced by imiquimod (IMQ) in vivo and a co-culture system of MSCs and HaCaT keratinocytes (KCs) cell line in vitro. These approaches allowed us to investigate the effect of MSCs on the levels of inflammatory factors and the activation of inflammasomes in both contexts. Mouse-targeted amino acid sequencing, transmission electron microscopy for in vitro observation, immunofluorescence for both in vivo and in vitro analyses, and siRNA transfection in vitro were employed in this study. Our results showed that MSCs significantly improved the skin lesion of mice with psoriasis, and reduced the levels of inflammatory factors and chemokines including IL-1&#x3b2;, IL-6, IL-8, TNF-&#x3b1;, MCP-1, CCL7, CCL20 and CCL27 in the mouse skin lesion areas and M5- induced psoriatic KCs models in vitro. Likewise, MSCs repaired the skin barrier by enhancing claudin-1 expression in vivo. In addition, MSCs increased KRT1 and decreased KRT6 levels in vivo and in vitro. Amino acid metabolism analysis showed that MSCs could improve the serine metabolism level in the mouse skins and upregulated the key enzyme phosphoserine phosphatase (PSPH) in serine metabolism. In vitro experiments demonstrated that knockdown of PSPH could reverse the therapeutic effects of MSCs on psoriasis. Furthermore, studies in vitro and in vivo revealed that MSCs can activate the PINK1-Parkin pathway. It was specifically manifested by elevated levels of PINK1, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, coupled with a reduction in P62 protein. Subsequently, the activation of PINK1-Parkin led to decreased expressions of IL-1&#x3b2;, IL-6, IL-8, TNF-&#x3b1;, CCL7, CCL20, CCL27, and MCP-1. In vitro and in vivo experiments indicated that MSCs can reduce the levels of IL-1&#x3b2;, IL-6, IL-8, TNF-&#x3b1;, CCL7, CCL20, CCL27, and MCP-1 by inhibiting the activation of NLRP3 inflammasomes. Meanwhile, PSPH knockdown in vitro can reverse the activating effects of MSCs on the PINK1-Parkin, as shown by decreased levels of PINK, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, concurrently with an elevation in P62.. The results of this study indicated that MSCs can alleviate IMQ-induced psoriasiform dermatitis in mice by upregulating serine metabolism. The key serine metabolism enzyme PSPH may enhance PINK1/Parkin-mediated mitochondrial autophagy in psoriatic HaCaT and inhibit NLRP3 inflammasome activation in HaCaT cells, thereby alleviating skin inflammatory responses and suppressing skin p roliferation in psoriatic mice.

Slope displacement forecasting is crucial for geotechnical early warning. Conventional deterministic models cannot adapt easily to real-time monitoring, and large deep-learning models demand extensive data and compute. We leverage IBM's Tiny Time Mixer (TTM), a compact, MLP-Mixer inspired time-series model with specialized temporal and channel mixing that scales linearly with sequence length. TTM was applied to daily aggregated data from six instrumented highway embankment slopes, including soil moisture, matric suction and temperature at 1.5-5&#xa0;m depths, plus rainfall. These inputs yielded 16-channel time series of roughly 950-998 points per slope, while the displacement target is available only at sparse measurement times, comprising approximately 36-38 inclinometer surveys per slope over ~&#x2009;2.75 years. A transfer-learning protocol was used; the model was sequentially fine-tuned on four slopes and evaluated zero-shot on two held-out slopes. On trained slopes, TTM forecasts proved highly accurate. For example, on the active Terry Road slope the fine-tuned model gave MAE&#x2009;&#x2248;&#x2009;0.394&#xa0;mm (R2=0.99), and on the I-220&#xa0;N Ramp MAE&#x2009;&#x2248;&#x2009;0.257&#xa0;mm (R2=0.97). Even on more stable slopes, absolute errors were sub-millimetric (e.g. MAE&#x2009;&#x2248;&#x2009;0.005-0.023&#xa0;mm, with R2=0.84 and 0.72). Crucially, in zero-shot tests the model maintained high accuracy on unseen sites: the Sowell Road slope forecast had MAE&#x2009;=&#x2009;0.132&#xa0;mm (R2=0.99) and McRaven Road MAE&#x2009;=&#x2009;0.203&#xa0;mm (R2=0.96). These results indicate that learned precipitation-displacement relationships transfer robustly across slopes. Overall, this study shows that lightweight, efficient time-series models like TTM can deliver accurate, real-time slope forecasts for early warning in resource-constrained geotechnical monitoring applications.