Advancing Open Science

Regulation of mRNA 3′ poly(A) tail length plays a central role in post-transcriptional gene regulation by controlling mRNA stability and translational efficiency. Although cytoplasmic polyadenylation has been extensively studied in oocytes and neurons, the mechanisms that mediate post-transcriptional poly(A) tail extension in somatic cells remain incompletely understood. Here, we identify Ataxin-2L as a factor that promotes post-transcriptional poly(A) tail extension and translational activation. Using MS2 tethering assays, we found that recruitment of Ataxin-2L to a reporter mRNA increased mRNA abundance, protein output, and translation efficiency. Northern blot analysis showed that Ataxin-2L promoted poly(A) tail extension even when deadenylation was inhibited by catalytically inactive Caf1 and Pan2 mutants. A transcriptional turn-on assay further demonstrated an increase in poly(A) tail length after transcriptional induction, supporting a role for Ataxin-2L in post-transcriptional polyadenylation. Efficient poly(A) tail extension required the PAM2-mediated interaction with PABPC1 and was reduced by deletion of amino acids 671–842. Ataxin-2L also associated with the cytoplasmic poly(A) polymerase PAPD4/TENT2, and this association remained detectable after deletion of amino acids 671–842. In addition, depletion of Ataxin-2L shortened the poly(A) tail of endogenous NUFIP2 and CUX1 mRNAs. Together, these findings establish Ataxin-2L as a mediator of cytoplasmic poly(A) tail extension and support a broader role for RNA-binding proteins in post-transcriptional polyadenylation in somatic cells.

Background/Objectives: Topical therapies, primarily imiquimod (IMQ) and 5-fluorouracil (5-FU), have emerged as valuable treatment options in non-melanoma skin cancers (NMSC) due to their facile administration and minimal systemic reactions, especially for patients who are poor surgical candidates. This systematic review evaluates the clinical and histologic clearance rates, recurrence rates as well as the utility of non-invasive imaging modalities in the diagnosis and monitoring of basal cell carcinomas (BCC) and cutaneous squamous cell carcinoma (SCC). Methods: The systematic search was conducted in PubMed, Web of Science and Scopus to identify studies assessing the efficacy of topical therapies in BCC and SCC by clinical examination, histopathologic analysis or non-invasive imaging techniques. Articles in which at least ten lesions were evaluated were included. Risk of bias was assessed using validated tools adapted to study design. A network meta-analysis was performed on trials which provided at least one within-trial comparison. Results: Seventy-eight papers encompassing 5066 BCC and 1081 SCC were included in our analysis. The network meta-analysis was constructed from 14 trials, comprising 1633 lesions, 17 treatment nodes, 57 direct treatment comparisons and 12 designs. Favorable clearance rates were reported not only in superficial BCC (sBCC) and Bowen’s disease (BD), but also in nodular BCC (nBCC) and invasive SCC (invSCC), suggesting that these therapies may be an effective approach in selected patients with aggressive tumors. Relapse rates remain higher than after surgical excision, highlighting the need for patient follow-up. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) improved the detection of recurrent and relapsed tumors in comparison to clinical and dermoscopic examination alone and correlated significantly with histopathological findings, proving that these modalities can contribute significantly to diagnosis and monitoring. Conclusions: Our systematic review demonstrates the efficacy of topical therapies, especially IMQ and 5-FU, in selected cases of sBCC and BD. Results should, however, be interpreted with caution, given the small number of studies included in the network and the heterogeneity of treatment regimens.

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide. Intraocular pressure (IOP) is its only validated therapeutic target, yet some patients progress despite controlled IOP, sustaining interest in a vascular contribution. This narrative review summarizes the anatomy and autoregulation of the optic nerve head circulation, the evidence linking low ocular perfusion pressure, impaired autoregulation and endothelial dysfunction to POAG, and the imaging modalities used to assess ocular hemodynamics. Color Doppler imaging consistently shows reduced retrobulbar flow velocities, particularly end-diastolic, and increased resistive indices, whereas OCT angiography shows reduced peripapillary and macular vessel density correlated with structural and functional damage. However, most evidence is cross-sectional and associative, and cannot establish whether hypoperfusion causes or follows retinal ganglion cell loss. No hemodynamic biomarker has been validated for clinical decision-making, and evidence of prognostic value beyond conventional structural and functional assessment remains inconsistent. Laser Doppler holography, a contactless technique providing pulsatile retinal blood flow waveforms, is presented as an emerging tool whose glaucoma-specific evidence is currently limited to a pilot study of four eyes. Vascular biomarkers therefore remain research tools pending standardized acquisition, normative databases and longitudinal validation.

Delayed wound healing in diabetes mellitus represents a formidable clinical challenge, characterized by core pathological hallmarks including persistent inflammation, impaired angiogenesis, excessive oxidative stress, and heightened infectivity. Chitosan, a natural cationic polysaccharide, exhibits inherent advantages such as biocompatibility, hemostatic activity, and antibacterial properties; however, its poor solubility at neutral pH and insufficient mechanical performance have constrained its clinical utility. Chemical derivatization—encompassing carboxymethylation, quaternization, thiolation, phosphorylation, and arginine grafting—modulates chitosan’s solubility, charge, and functional groups in a derivative-specific manner, so that individual derivatives acquire distinct antibacterial, antioxidant, immunomodulatory, pro-angiogenic, or ECM-remodeling activities rather than a uniform set of functions. Derivative-based smart hydrogels, such as glucose/pH dual-responsive, immunomodulatory, pro-angiogenic, and antioxidant/antibacterial systems, are designed to target selected pathological features of the diabetic wound microenvironment rather than all features simultaneously. By exerting a cascading effect of “ glucose regulation–antibacterial action–repair promotion,” these hydrogels effectively disrupt the stagnation of wound healing. This review systematically summarizes the types of chitosan derivatives, their modification strategies, and recent advances in their application for diabetic wound healing. Additionally, it analyzes the challenges hindering clinical translation and outlines future research directions.

State-of-the-art vision–language models (VLMs) show emerging reasoning but demand prohibitive computation, limiting deployment in constrained environments. This research addresses this via a dual-phase framework: trace distillation for structured reasoning priors, reinforcement learning for policy alignment, and test-time scaling. On ScienceQA-IMG, it decouples visual context from textual reasoning via dense visual metadata from Gemini 3.7 Flash (long context) or Qwen2.5-VL-7B-Instruct (short context). Qwen-3-8B undergoes LoRA supervised fine-tuning on only 5214 verified teacher reasoning traces (40.97% of the full training set), achieving 95.14% accuracy. GRPO with custom rewards yields stable convergence (policy loss: 2.49 × 10⁻⁶; KL: 1.25 × 10⁻³). Distillation generalizes across model sizes (LFM2.5-2.6B, Qwen3-4B, Gemma4-12B, Qwen3-14B, Qwen3.5-9B) and visual context variations (Long/Short) with consistent gains. Further, we propose a three-phase test-time scaling pipeline: (1) Gaussian Calibration-Weighted Voting (five rollouts), (2) Continuous Uncertainty Error Detection to flag high-risk samples, and (3) Sequential Remediation with a dynamic logit-calibrated critic followed by targeted N = 15 CWV with dampened weighting. This elevates the long-context model (DRLTSL-Qwen3-8B-Stage3-Phase3) to 95.79% IMG accuracy (seven-seed mean: 95.66 ± 0.12%), surpassing the fine-tuned LLM-based methods compared in the ScienceQA IMG category (accuracies as reported on the test split), while using 59.03% fewer training examples than the full ScienceQA training split and 16.15% fewer than the ScienceQA-IMG training set, conditioned on teacher-correct supervision. The short-context model (DRLTSS-Qwen3-8B-Stage3-Phase3) achieves 92.51%. It shows that careful design and efficient distillation/scaling can achieve performance competitive with the best reported IMG results with reduced compute and data, enabling consumer-grade GPU deployment of the text-only reasoning model with 32 GB VRAM or more, given visual descriptions from an upstream extractor.

Piezo-driven microinjectors have been widely applied in the biomedical field as an effective tool for cell micromanipulation. To improve the survival rate and efficiency of injection, the puncture force and the position of the microinjector should be controlled accurately to reduce cell damage. However, due to the cellular viscoelasticity, piezoelectric hysteresis, and switching oscillation between force and position controllers, smooth switching control design has become a very challenging task. To this end, this paper proposes a new precise force-position switching control scheme with hysteresis and viscoelasticity compensation for a piezo-driven cell microinjection system. Specifically, in force control mode, a new adaptive backstepping integral terminal sliding mode impedance controller is designed without prior information about the external environment, enhancing the system robustness against cellular viscoelasticity. In position control mode, it is realized by an inversion-based PID controller, where an inverse fractional-order normalized Bouc-Wen model is adopted to compensate for the asymmetric and rate-dependent hysteresis nonlinearity. By combining two modes with a double-sigmoid-function switching criterion, a stable and smooth transition is finally guaranteed. Experimental results of zebrafish embryo injection show that both the designed force and position controllers enable to perform high trajectory tracking accuracy. Benefiting from the proposed switching control scheme, the switching oscillations for the two modes are mitigated by over 67.9% and 50.1%, respectively, compared with traditional methods, significantly reducing cell damage.

This study investigates the long-term wetting-induced deformation of an unsaturated expansive-soil embankment under seasonal rainfall and drying and evaluates the effects of pile reinforcement. A two-dimensional hydro-mechanical model incorporating the Barcelona Basic Model was implemented in FLAC2D and driven by 473 days of measured daily rainfall. Field vertical displacements at depths of 1.5 and 4.5 m were used to evaluate the untreated section. The model reproduced the main seasonal, cumulative, and time-lagged deformation characteristics, with correlation coefficients of 0.963 and 0.948 at the two monitoring depths. Rainfall infiltration occurred mainly through the exposed slope surface, causing concentrated wetting and settlement near the shoulder–slope transition zone. Within the continuous-strip cases, increasing pile modulus provided only limited additional benefit, whereas increasing pile length more effectively reduced deep settlement. The continuous-strip model predicted greater pavement settlement reduction than the structural-pile model under the adopted modeling assumptions. In the quicklime–cement composite pile-treated section, the equivalent swelling-pile case captured the observed contrast between shallow upward displacement and deeper settlement, suggesting a possible contribution of pile swelling. However, it underestimated shallow uplift and did not reproduce the measured deep-settlement history.

The development of efficient visible-light-responsive photocatalysts is essential for the sustainable remediation of water contaminated with persistent organic pollutants. In this work, BiAlO₃ perovskite was investigated as a pristine photocatalyst for the first time for the visible-light-driven degradation of Rhodamine B (RhB). The synthesized material exhibited a well-crystallized rhombohedral perovskite structure, while electron microscopy revealed irregularly aggregated particles composed of nanoscale structural features. Optical characterization revealed an optical band gap of approximately 2.7 eV, together with pronounced energy-dependent dielectric, conductivity, and charge-relaxation responses, indicating favorable light–matter and charge-dynamic characteristics. Under visible-light irradiation, BiAlO₃ achieved 87.54% RhB degradation within 90 min, compared with only 9.63% removal by direct photolysis, demonstrating its intrinsic photocatalytic activity. Scavenger experiments identified photogenerated holes and hydroxyl radicals as the main reactive species contributing to RhB degradation. The photocatalyst also retained approximately 75% degradation efficiency after six consecutive cycles, demonstrating good operational stability and reusability. The combination of a relatively narrow band gap, favorable optical and charge-dynamic characteristics, efficient visible-light photocatalytic activity, and satisfactory cycling stability highlights BiAlO₃ as a promising lead-free perovskite photocatalyst for organic pollutant remediation. More broadly, this work establishes the previously unexplored BiAlO₃/RhB photocatalytic system and provides new insight into the relationship between the intrinsic optical and charge-dynamic properties of BiAlO₃ and its photocatalytic performance.