To systematically evaluate the rate and risk factors for unplanned readmission in patients with ischemic stroke (IS), providing an evidence-based foundation for developing targeted prevention strategies. We systematically searched PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, Weipu Data and SinoMed databases for studies on the rate and risk factors of unplanned readmission in IS patients from their inception to July 30, 2025. Two researchers independently conducted literature screening, quality assessment, and data extraction. Meta-analysis was performed. A total of 44 studies involving 1,274,267 patients were included. The pooled rate of 30-day readmission was 14.2% (95% CI 11-18%), increasing to 13.9% at 90 days and 30.3% at 12 months, with substantial heterogeneity across studies (I 2 > 90%). Readmission rates were lower in North America (11.7%) and higher in Asian settings (17.2%). Atrial fibrillation (OR 1.34), heart failure (OR 1.59), diabetes (OR 1.29), and prior stroke (OR 1.50) were associated with increased likelihood of 30-day readmission. Longer hospital stay (OR 1.03 per unit increase) and greater stroke severity (NIHSS OR 1.13) were also associated with higher readmission risk. Infection (25.1%), recurrent stroke (21.8%), and cardiac events (13.7%) were the most consistently reported causes. This meta-analysis clarifies and updates the rate and core risk factors for unplanned readmission in ischemic stroke patients. It provides an evidence-based foundation for systematically identifying high-risk patients, developing risk assessment tools, and implementing targeted interventions, holding significant value for guiding clinical practice. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251157352, identifier CRD420251157352.
This study aimed to investigate the effects of skill level and tempo on coordination variability during consecutive ballet jumps (i.e., temps levé sauté) using continuous relative phase analysis. Eight skilled and eight less-skilled dancers performed the temps levé sauté jumps in first position (a fundamental foot position in ballet, one of the five basic positions in which the heels are together and the toes point outward) at three different tempos: 80 bpm, 100 bpm, and 120 bpm. Hip-knee and knee-ankle coordination was evaluated across three movement sub-phases: propulsion, flight, and landing. Phase deviations were used to quantify inter-joint variability, with larger deviation values indicating greater variability in the relationship between the two joints. The results showed that, during the landing phase, a significant interaction effect between skill level and tempo was observed in hip-knee coordination. Skilled dancers exhibited significantly lower variability in hip-knee coordination during the landing phase. Additionally, both groups showed increased variability at the slowest tempo (i.e., 80 bpm) when compared to the other tempos during the propulsion and landing phases. In the flight phase, however, coordination variability increased with faster tempo. These findings highlight the importance of tailored training strategies based on skill level to enhance ballet jump performance, with more emphasis on developing phase-specific coordination control and adaptability across various tempo conditions.
To provide evidence for selecting and developing reliable clinical assessment tools for hypoglycemia in diabetic kidney disease patients during haemodialysis. Review. Systematic searches were performed in 9 Chinese and English databases to collect literature regarding the development of hypoglycemia risk prediction models in haemodialysis patients with diabetic kidney disease. Two reviewers independently performed literature screening, data extraction, risk-of-bias assessment, and applicability evaluation. The Prediction Model Risk of Bias Assessment Tool was used to assess the risk of bias and applicability of the included studies. Meta-analysis was conducted using R software. CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, EMbase, Web of Science, and CINAHL. The search period covered from the establishment date of each database to December 2025. Six studies, comprising six prediction models, were included. Two studies performed internal validation, and three conducted external validation. All models reported the area under the curve, ranging from 0.813 to 0.866, and calibration measures. Four studies were rated as having a high risk of bias, while all six demonstrated good overall applicability. The meta-analysis showed that the pooled AUC value of the six studies was 0.846 (95% CI: 0.823-0.867). Research on hypoglycemia risk prediction models in haemodialysis patients with diabetic kidney disease remains in the developmental stage. Although the included prediction models exhibited satisfactory apparent discriminatory ability and clinical applicability, most of the original studies suffered from a high risk of bias and lacked adequate validation. The true predictive performance and clinical application value of these models remain to be further verified. Accordingly, routine and unconditional clinical application is not recommended at this stage. Future studies should include more high-quality, multicenter external validation and develop models with high generalizability, favourable clinical applicability, and robust predictive performance to facilitate early identification of hypoglycemia risk in this population. This study systematically evaluated the hypoglycemia risk prediction models for diabetic kidney disease patients during haemodialysis, and the research on hypoglycemia risk prediction models for maintenance haemodialysis patients during dialysis is still in the development stage. This study provides a reference for clinical medical staff to select or develop hypoglycemia risk prediction and assessment tools for diabetic kidney disease patients during haemodialysis. This study was conducted in accordance with the relevant guidelines of the EQUATOR Network and followed the TRIPOD-SRMA Checklist. No patient or public contribution. PROSPERO: CRD420251243352.
Gliomas are heterogeneous primary central nervous system (CNS) tumors with diverse molecular subtypes and variable prognosis. A paradigm shift in histopathology is underway as samples are digitized into whole-slide images (WSIs). Deep learning (DL) shows great potential for glioma diagnosis, subtyping, grading, and prognosis. This review summarizes recent advances in WSI-based DL models, covering data preprocessing, model architectures, and translational performance. Model evolution has progressed from CNNs (e.g., ResNet, capturing local features via convolution) to Transformers (e.g., Vision transformer, modeling global dependencies via self‑attention), hybrid architectures, and large language model (LLM). Typical pipelines include quality control, stain normalization, patch extraction, feature integration, and prediction. Public datasets such as TCGA and CPTAC serve as key resources. On various datasets (public and institutional), a glioma‑specific model ResNet‑50 achieved AUC 0.983 for subtype classification; a Vision Transformer model reached AUC 0.960 for molecular typing; a hybrid model, ROAM, attained AUC 0.990; and the pan‑cancer hybrid model called CHIEF achieved AUC 0.9397 for diagnosis. Attention heatmaps and Shapley Additive exPlanations (SHAP) provide interpretability by linking model outputs to histologic regions. Novel multimodal fusion integrates genomic, proteomic, radiologic, and clinical data to enhance prediction and uncover biological relevance. Future research may focus on enhancing model generalizability and predictive accuracy via advanced architectures, developing lightweight models for resource-limited settings to facilitate clinical translation.
.
Self-affirmation interventions can protect individuals from perceived threats and enhance well-being. However, previous studies highlight the need to adapt these interventions to specific populations, particularly non-WEIRD ones, to achieve effective results. To our knowledge, this is the first study to use a mixed-methods participatory approach to develop self-affirmation techniques tailored to the threats Syrian forced migrants face during acculturation in European host societies. In the first qualitative study, 30 in-depth interviews explored threats encountered during acculturation, their negative effects and spontaneous self-affirmation mechanisms used to preserve well-being and self-image. A second experimental study assessed the effectiveness of tailored self-affirmation interventions. Three hundred and thirteen participants reported their acculturation orientations, read a threat-inducing text and were then assigned to one of three self-affirmation conditions (host-domain, heritage-domain or individual) or a control condition. We then measured hedonic well-being, self-esteem and a challenged sense of belonging. Contrast analysis showed that combined self-affirmation interventions enhanced hedonic well-being compared to control, particularly when aligned with individuals' acculturation orientations. Our studies contribute to the literature by developing culturally grounded interventions for a specific underrepresented population using mixed methods. Future research should test their effectiveness with similar forced migrant populations and continue adapting interventions to fit diverse cultural contexts and interindividual differences.
High performance liquid chromatography (HPLC) remains a core separation and analytical technique in modern analytical chemistry. Boasting prominent advantages including high quantitative accuracy, rapid analysis speed, strong selectivity, and high sensitivity, it has deeply permeated key fields such as biochemistry, pharmaceutical R&D, food testing, environmental monitoring, and materials science, delivering crucial support for the accurate qualitative and quantitative analysis of target components in complex systems. However, with the increasing complexity of analytical samples in scientific research and industrial production, marked by enhanced matrix interference, an expanded polarity range of target compounds, and widespread coexistence of multiple components, the limitations of traditional single-mode chromatography (e.g., reversed-phase liquid chromatography (RPLC), hydrophilic interaction chromatography (HILIC), ion-exchange chromatography (IEC)) have become increasingly pronounced. Specifically, RPLC exhibits insufficient retention and separation capabilities for highly polar compounds, HILIC struggles to handle hydrophobic substances effectively, and IEC is only applicable to the separation of ionic components. None of these single-mode techniques can meet the demand for efficient and comprehensive separation of complex samples. To address this technical bottleneck, mixed-mode chromatography (MMC) has emerged as a viable solution. Its core innovation lies in integrating two or more separation mechanisms into a single chromatographic column. Through the synergistic effects of functionalized stationary phases, MMC enables efficient separation and accurate analysis of complex systems, thereby significantly expanding the application scope of HPLC. This paper briefly elaborates on the separation mechanisms of four mainstream mixed modes, namely RPLC/IEC, RPLC/HILIC, HILIC/IEC, and RPLC/HILIC/IEC. It also summarizes in detail the key chemical reaction types for stationary phase preparation (e.g., click chemistry reactions and free radical polymerization reactions), typical packing structures, as well as the characteristics and preparation strategies of novel functional materials such as porous organic cages (POCs), metal-organic frameworks (MOFs), covalent organic frameworks (COFs), carbon quantum dots (CQDs), microporous organic networks (MONs), and ionic liquids (ILs). Based on the latest research findings from 2020 to 2024, this paper systematically reviews the application cases of the aforementioned four mixed-mode stationary phases in practical scenarios such as traditional Chinese medicine component analysis, environmental pollutant detection, food quality control, and pharmaceutical research and development. It also conducts an in-depth analysis of the technical advantages of these four mixed modes, as well as the limitations of some stationary phases, including insufficient stability under extreme pH conditions, complex preparation processes, and high costs for large-scale production. Finally, this paper outlines the core challenges currently confronting mixed-mode stationary phases, including cumbersome synthesis steps, easy degradation and inactivation of functional groups, and difficulties in mobile phase optimization. It further points out that future development trends should focus on simplifying preparation processes, developing environmentally friendly and smart responsive materials, and enhancing the feasibility of large-scale production. The aim is to provide theoretical reference and technical support for the design and development of novel high-efficiency stationary phases, and facilitate greater breakthroughs in mixed-mode chromatography technology in the field of complex sample separation.
Seizures are symptoms of epilepsy but spontaneous seizure recurrence can also be considered a biomarker of disease progression. The temporary imbalance between excitatory and inhibitory drive that culminates in a hyperexcitable, hypersynchronous state clinically observed as seizure, initiates an insidious cascade of neurochemical, structural, genetic, epigenetic, and neuroinflammatory processes that increases seizure frequency, duration, and severity. As seizure activity increases, the hyperexcitable and hypersynchronous states entrain neuronal networks, leading to a further reduction in seizure threshold and further increases in seizure frequency, duration, and severity over time. The pathological circuitry generated and sustained by epileptic events not only drive hyperexcitable states within the seizure circuit but also can affect wider network connections. These effects lead to altered network physiology, which is associated with neuropsychiatric comorbidities, such as cognitive decline and psychiatric disorders, and can impact the operation of other organ systems. Here, we review the current understanding of how seizures can hijack normal brain function and set off a cascade of pathobiological events that support continued seizure activity and epilepsy progression. Understanding the neurobiology of seizure progression is fundamental to building comprehensive treatment strategies and developing new pharmacotherapies that aim to retrain seizure circuitry, with the goal of reducing overall seizure burden, improving quality of life, and limiting disease progression.
Here, we review the history, advancements, and broad utility of the NTR/prodrug system, and suggest future strategies for developing versatile ablation models. As a chemogenetic tool, the nitroreductase (NTR)/prodrug system enables precise spatiotemporal control over cell ablation. The technology leverages bacterial NTR enzymes (e.g. nfsB) to convert inert prodrugs into cytotoxic agents, thereby allowing researchers to induce targeted cell death. Although the NTR/prodrug approach was first implemented in transgenic mice, it was subsequently adapted to zebrafish, where it has been extensively optimized and applied. Consequently, zebrafish remain the primary focus of this review. Nevertheless, the utility of the NTR/prodrug system has expanded to other important model organisms, including Drosophila, Nematostella, Xenopus, medaka, and rats, enabling detailed studies of tissue damage and regeneration. This review highlights how the NTR system has been deployed to model a spectrum of human diseases, including Parkinson's disease, retinal degeneration, demyelinating disorders, and kidney disease. These models provide valuable platforms to study pathogenesis in vivo. Furthermore, the precise and controllable nature of NTR ablation makes it an ideal tool for high-throughput chemical and genetic screens aimed at discovering pro-regenerative and protective compounds. The development of NTR2.0, an enzyme variant with over 100-fold greater activity, along with more potent prodrugs such as ronidazole (RNZ), has dramatically broadened experimental possibilities. These improvements permit chronic ablation and long-term disease modeling at well-tolerated drug concentrations. Here, we present some key considerations, including transgenic design for optimal cell-type specificity, calibrating expression levels for desired ablation kinetics, and suitable controls to allow interpretation. These best practices will allow the researcher to develop a precise, reproducible, and versatile platform for either modeling human disease or dissecting regenerative mechanisms.
Transient gene expression in mesophyll protoplasts is a valuable approach for investigating gene function, plant physiological processes, and molecular mechanisms. Rubber dandelion (Taraxacum kok-saghyz, TKS) is an ideal model for studying rubber biosynthesis and serves as a promising source of natural rubber and inulin. However, developing efficient protoplast-based systems for TKS remains challenging. In this study, we established a robust method for isolating mesophyll protoplasts from TKS by optimizing enzymatic conditions for cell wall digestion. We subjected the protoplasts to PEG/calcium-mediated transfection and evaluated promoter activities, expressed and detected target proteins, confirmed the subcellular localization of the target proteins, and examined transcription factor-DNA interactions under physiological conditions. We also developed a rapid assessment strategy for genome-editing tools in TKS protoplasts using multiple reporter systems. We evaluated these optimized tools in a tissue-culture-free hairy root transformation system, establishing a dual-platform toolkit for functional genomics in TKS. This work provides an efficient approach for TKS protoplast preparation, facilitating studies of gene function and advancing biotechnological research in this rubber-producing crop.
In 1989, Oregon passed SB 27, overhauling Medicaid by insuring all impoverished residents while explicitly rationing covered treatments. Rather than excluding some of the poor, the state established the Oregon Health Services Commission (OHSC), an eleven-person citizen body tasked with developing a prioritized list of 1,600 condition-treatment pairings based on cost-effectiveness and public values. This effort became central to debates over who should determine the availability of health services in public insurance programs. We analyzed a new data source - meeting minutes and internal documents from 1990-1991 - using reflexive thematic analysis in ATLAS.ti. Themes centered on commissioners' emotional experiences, technical challenges, and the role of subjective decision-making, situated within broader discussions of judgement in participatory governance and cost-effectiveness analysis. The Commission faced profound technical obstacles, namely limited data, methodological uncertainty, and growing frustration under public pressure. As technical approaches faltered, commissioners increasingly relied on collective judgment to complete the list. The common narrative that the OHSC abandoned technical rigor overlooks the reality that health policy decisions always embed subjective judgements. Its innovation was affording those judgements to citizens rather than experts or politicians. Reliance on subjectivity reflected the nature of cost-effectiveness analyses and participatory governance, not failure.
Quality control of traditional Chinese medicine (TCM) has always been a key and challenging issue in the field of its modernization research. This has posed a high demand for advanced separation materials due to the complex compositions. Covalent organic framework materials (COFs) are a new class of porous crystalline materials composed of multidentate organic units connected by covalent bonds. They have demonstrated significant application value in areas such as catalysis and chromatographic analysis. This study focused on developing a novel core-shell-type chromatographic stationary phase using 2,4,6-tris(4-aminophenyl)-1,3,5-triazine (TAPT) and 1,4-benzenedicarboxaldehyde (TA) as building units. The TAPT-TA-COF@SiO2 core-shell composite materials were successfully prepared on the surface of silica microspheres using a multi-step polymerization strategy, in which the SiO2 cores were fabricated using the polymerization-induced colloidal aggregation (PICA) method. The imine-linked TAPT-TA-COF@SiO2 core-shell stationary phase was subjected to comprehensive physicochemical characterization and chromatographic evaluation experiments. The analytical techniques employed included scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectroscopy analysis (EDS), nitrogen adsorption-desorption isotherms, Fourier transform infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD). The systematic characterization results clearly indicate that the prepared stationary phase exhibits excellent monodispersity, and the COF layer is uniformly coated on the surface of the SiO₂ core. TEM characterization demonstrated that the thickness of the COF materials on the surface of SiO2 is approximately 110 nm. Furthermore, FT-IR spectra were collected and the results demonstrated that the characteristic stretching vibrations at 3 209, 2 927, and 1 515 cm-1, attributed to N-H, C-H, and C=N stretching, confirm the condensation reaction between TAPT and TA. In the XRD pattern, the peaks observed at 16.6°, 18.9°, 25.2° and 27.5° were attributed to the COF material and were consistent with previous reports, thereby confirming the successful synthesis of this derivative. The N2 adsorption-desorption isotherm analysis confirmed that the material possesses a typical mesoporous structure. Its specific surface area and pore size distribution are similar to those of the original porous SiO₂ microspheres, subsequently providing a structural basis for efficient chromatographic mass transfer kinetics. In addition, the chromatographic performance was investigated. And it was confirmed that the stationary phase was effectively used for the separation of representative neutral polar or non-polar compounds such as benzenes, alkylbenzenes, phthalate esters, formamides, and aniline mixtures. These compounds are separated due to hydrophobic interactions, π-π interactions, and the unique mesoporous structure in the reversed-phase chromatography mode. ACN-water (30∶80 or 40∶60, volume ratio) was selected as the mobile phase at a flow rate of 1 mL/min. The results of the methodological validation indicate that the intra-batch relative standard deviations (RSDs) of one TAPT-TA-COF@SiO₂ packed chromatographic column were less than 1.6%, demonstrating excellent preparation reproducibility. Furthermore, this stationary phase was applied to the quality control of traditional Chinese medicine. Specifically, it was used to determine the content of astragaloside Ⅳ in Astragalus according to pharmacopoeial records. The measured result met the pharmacopoeia standard of ≥0.08%. This research work not only provides new opportunities for advancing fundamental and applied research on novel COF stationary phases, but also helps to further promote in-depth research on the application of COF materials at the intersection of separation science and pharmaceutical sciences.
Gastric cancer (GC), which primarily originates from gastric mucosal epithelium, is driven by factors such as Helicobacter pylori infection, genetic susceptibility and lifestyle. GC poses a serious threat to patient survival and quality of life. Metabolic reprogramming, a hallmark of tumorigenesis and progression, enables cancer cells to continuously adapt their energy metabolism to support proliferation, invasion, metastasis and drug resistance. Circular RNAs (circRNAs) are a class of non‑coding RNAs characterized by a covalently closed circular structure, which confers high stability. They are differentially expressed in tumor cells and facilitate tumor proliferation and metastasis through multiple mechanisms such as microRNA sponging, protein binding, short peptide translation and N6‑methyladenosine modification. Furthermore, circRNAs contribute to tumor metabolic remodeling, meeting the energy demands of tumor cells by regulating key enzymes and transporters involved in metabolic pathways, thereby modulating the synthesis or degradation of metabolites. The present review summarizes the mechanisms by which circRNAs mediate different metabolic modes during the initiation and progression of GC as well as discusses their potential as biomarkers for GC. By systematically elucidating the intricate interactions between circRNAs and metabolic reprogramming in GC, the present study aims to provide a theoretical foundation for the development of innovative therapeutic strategies against GC.
This study introduces a novel interface engineering strategy for high-performance cellulose/poly (vinyl alcohol) (PVA) aerogels derived from coir fiber waste. To address structural fragility, postsynthesis reinforcement was achieved through conformal liquid epoxy-acrylate infiltration. Quantitative Barrett-Joyner-Halenda (BJH) analysis confirmed the existence of a pore-wall thickening mechanism that preserved the internal mesoporous network (radius: 1.9-2.6 nm) without interstitial blockage. The functionalized scaffold demonstrated significant thermal stabilization, with the maximum degradation temperature (Tmax) shifting from 283°C to 307°C, coupled with superior mechanical resilience and a bulk density of 0.051 g/cm3. Methylene blue (MB) adsorption tests achieved 97.3% removal at pH 10, accurately modeled by pseudo-second-order kinetics and the Freundlich isotherm (R2 = 0.980, RMSE = 1.507, and Χ2 = 0.884), indicating spontaneous and endothermic multilayer physisorption. Furthermore, regeneration studies established 70% capacity retention over three cycles while maintaining full macroscopic integrity. These findings indicate that strategic resin infiltration provides a robust and sustainable pathway for the development of durable adsorbents for industrial wastewater remediation.
Currently, in vitro models of microvascular biology rely on self-assembly of vascular cells in compatible gels. However, the stochastic nature of this process results in large variations in lumen sizes, perfusion continuity, and shear stresses, making systematic and reproducible analysis challenging. Here, we report a new technology to generate artificial capillaries on a chip with custom control over lumen sizes and architectures using a combination of femtosecond laser cavitation and collagen casting within multi-chambered microfluidic chips. The design allows seeding of endothelial cells within capillary-sized microchannels and seeding of stromal cells within top-open silos, with independent control over seeding sequence and media compositions. Results show that endothelialized microchannels, coined as artificial capillaries, exhibit excellent barrier function with reproducible control over lumen sizes (ϕ=8-40µm) and their architectures (straight, curvatures, tapered, branched). The physical flow parameters measured across the lumen (namely, flow shear) and at the channel outlets (flow velocities) have been validated against high-fidelity numerical assessments from the Large Eddy Simulation scheme within the digitized versions of microchannels. The experiment-computation compatibility enabled us to predict changes in regional velocity and wall shear stresses within artificial capillaries for various capillary architectures. We also show that in situ editing of artificial capillaries in the form of adding new branches or adding occlusions is possible. Lastly, we developed a co-culture model that enables the study of stromal cells with artificial capillaries using conventional imaging methods. We envision that acellular chips with two seeding ports can be readily shipped worldwide and could potentially be adopted as a new technology to study microvascular biology in a reproducible manner.
Insect-Inspired Flapping-wing Micro Aerial Vehicles (FWMAVs) have attracted significant attention due to their unique advantages in agility, manoeuvrability, low noise, and adaptability to cluttered environments. Over the past two decades, research in this field has progressed from early conceptual demonstrations to more advanced platforms capable of hovering, rapid manoeuvres and limited autonomous flight. This review summarizes the historical development of FWMAVs, highlights key unsteady aerodynamic mechanisms such as the leading-edge vortex, wake capture, clap-and-fling, rotational lift and added-mass effects, and analyses their roles in enabling lift enhancement under low Reynolds number conditions. Actuation approaches including motor-driven, piezoelectric, electromagnetic and emerging soft-material-based systems are examined, together with structural innovations in wing configurations such as two-wing, four-wing, X-wing, and multi-wing architectures. Control strategies for tailless vehicles, including wing-kinematics modulation, attitude feedback control and onboard sensing, are systematically reviewed. Despite significant progress, current FWMAVs still face major challenges in energy efficiency, endurance, lack of adaptability to different environments, environmental robustness and material limitations. Future development will require integration across disciplines such as smart materials, high-efficiency power systems, micro-fabrication and advanced control algorithms to achieve truly autonomous, robust, and long-range bio-inspired flight.
The mass production of electronic and optoelectronic devices and even their research and development phase have relied so far to a large extent on optical lithography, implemented via application of pre-fabricated templates (masks), required to selectively expose parts of the substrate to deposition or removal of functional materials. Even a simple device structure may require numerous masks, in order to form the necessary 3D architecture of interconnected semiconductor, dielectric, and metal segments. At the stage of development of many devices and applications, it is necessary to test many different architectures and parameters of each of the components. A viable alternative to the traditional mask-based lithography, at least for µm or sub-µm components and devices, is a direct optical patterning of the substrates, functional layers, protective coatings or electrodes. There are two different ways of implementation of direct optical lithography, referred to as maskless optical lithography and direct laser writing, respectively. A variety of materials and their role in devices or applications have been addressed by these techniques. In particular, the local removal of material, or its recrystallisation, or changing its composition, reduction or oxidation, etc., result in changes of optical, electrical or mechanical properties of the treated material at the µm or sub-µm scale. In the present review we summarize the recent advances and current limitations of these approaches when applied to semiconductor and dielectric materials, including their nanostructures, such as 2D materials and quantum dots.
Three-dimensional (3D) bioprinting enables the fabrication of complex tissue constructs with integrated vascular architectures, offering promising applications in transplantation. It is commonly assumed that dense, pre-formed microvascular networks are required to ensure survival and function of bioprinted organs immediately after implantation.
This in vivo study aimed to evaluate the feasibility of bioprinting and transplanting a vascularized pancreatic tissue construct featuring a single perfusable vessel in a porcine model, with a focus on maintaining stable perfusion and supporting post-transplantation microvascular development.
The study included 14 pigs, in which a 3D-bioprinted construct was transplanted and connected to the iliac artery or abdominal aorta. Two vascular connection strategies were evaluated: the Decell group (n = 5), using decellularized and recellularized external vessels for anastomosis, and the Bionic group (n = 9), using a vascular prosthesis. Immediate perfusion was achieved in all transplanted constructs. Three animals from the Bionic group completed a 4 week follow-up period. Computed tomography imaging and histopathological analyses demonstrated sustained perfusion of the constructs and progressive development of microvascular structures within the bioprinted tissue over time.
These findings demonstrate the feasibility of fabricating and transplanting a perfusable, mechanically stable, bioprinted pancreatic tissue construct capable of supporting in vivo vascular remodeling without a pre-fabricated dense capillary network. This work provides a preclinical proof-of-feasibility for simplified vascular design strategies in bioprinted tissue constructs and supports their further development toward translational applications.
Young adults (18-29 years old) often report difficulties coping during suicide crises. However, the responses that young adults employ to manage suicidal ideation (SI) are underexplored. This study developed a new measure to quantify how young adults with a history of suicidal thoughts and behaviors (STBs) respond to their SI, and conducted an initial evaluation of the measure's psychometric properties. Using inductive and deductive approaches, we developed a preliminary item set (n = 79) for the Response to Suicide Ideation Inventory (RSII). Thereafter, 491 participants (Mage = 22.0, SDage = 3.3, 18-29 years old), completed the RSII, as well as questionnaires assessing the RSII's content validity, general coping, emotion dysregulation, history of STBs, reasons for living, and future expectations of engaging in STBs. Results from an exploratory factor analysis indicated that a 43-item, seven-factor solution was an appropriate fit to the data. The RSII and its subscales showed acceptable reliability, as well as preliminary content validity. The RSII's subscales also demonstrated medium-sized positive correlations with measures of general coping, and weak associations with emotion dysregulation, suicide resilience, and expectations of future STBs. Our results point to some important directions for refining the RSII. Exploring the range and types of responses young adults engage in to manage their SI may improve our understanding of, and ability to predict, fluctuations in SI severity.
Alkaloids represent a class of naturally-occurring nitrogen-containing compounds widely distributed across diverse plant species. Owing to their well-documented potential to induce adverse effects on human health, certain alkaloids are explicitly prohibited from being used in cosmetic formulations. The escalating global popularity of essential oil-based cosmetics, which commonly incorporate complex botanical extracts, presents a potential avenue for the inadvertent introduction of these prohibited substances. Consequently, the development of robust, sensitive, and efficient analytical methods for their monitoring is of utmost significance for consumer safety and regulatory compliance. This study devises a reliable, high-throughput approach for the simultaneous determination of 13 prohibited alkaloids in essential oil-based cosmetics. It integrates optimized QuEChERS sample preparation with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The sample preparation procedure was meticulously designed to maximize efficiency and minimize analyte loss. Chromatographic separation was accomplished on a Waters ACQUITY UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) maintained at a constant temperature of 30 ℃. The mobile phase was composed of (A) acetonitrile and (B) 0.1% (volume fraction) formic acid aqueous solution. A gradient elution program was implemented at a stable flow rate of 0.3 mL/min according to the following profile: an initial 5, a linear increase to 15 (0-2 min), a rapid rise to 70 (2-4.5 min), followed by an immediate reversion to the initial 5 (4.5-5.5 min), which was maintained for re-equilibration until 7.0 min. The injection volume was 5 µL. Detection and quantification were conducted using a triple quadrupole mass spectrometer equipped with an electrospray ionization (ESI) source operating in positive ion mode (ESI+). Data acquisition was carried out in the multiple reaction monitoring (MRM) mode to ensure superior specificity and sensitivity. For each of the 13 alkaloids, two specific ion transitions were monitored: one for quantitative analysis and the other for confirmatory identification. The method was rigorously validated in accordance with accepted analytical guidelines. All 13 target alkaloids displayed excellent linearity within a mass concentration range of 0.2 to 50 ng/mL, with correlation coefficients (R2) consistently exceeding 0.99. The limits of detection (LODs) and limits of quantification (LOQs), determined with acceptable accuracy and precision, ranged from 1 µg/kg to 4 µg/kg and 2 µg/kg to 10 µg/kg, respectively. Method accuracy and precision were assessed through recovery tests at three spiking levels, with six replicates at each level. The mean recoveries for all analytes ranged from 83.9% to 119.1%, with associated relative standard deviations (RSDs) all being ≤7.3%, validating the method's high reliability and repeatability. Systematic evaluation indicated that the matrix effects for the 13 analytes were negligible; hence, the solvent calibration curve was adopted for quantitative analysis. The practical applicability of the validated method was demonstrated through the analysis of 50 batches of commercially available essential oil-based cosmetics. This market survey encompassed 15 products specifically marketed for infants or children and 35 products intended for adult use. As a result, none of the 13 target prohibited alkaloids were detected in any of the tested samples above their respective LOQs. A particularly notable accomplishment of this work is the successful development of a sensitive and reliable quantification strategy for oleandrin, a potent cardiotoxic alkaloid for which standardized detection methods in complex cosmetic matrices such as essential oils have been conspicuously absent. In conclusion, this study successfully establishes a simple, rapid, sensitive, and robust QuEChERS-UPLC-MS/MS method. It is comprehensively validated and clearly well-suited for the routine screening, risk monitoring, and quality control of 13 prohibited alkaloids in a wide array of essential oil-based cosmetics. The method offers reliable technical support for regulatory bodies to enforce safety standards and for manufacturers to ensure the safety and compliance of their products, thereby effectively contributing to the protection of consumer health.
A supercritical fluid chromatography (SFC) method coupled with UV detection was developed for the separation of linagliptin and its S-enantiomer. The method was validated and successfully applied to detect the S-enantiomer in real pharmaceutical samples. The separation of the enantiomer was investigated using six different chromatographic columns, and different cosolvents were studied. Chromatographic conditions, including column temperature, backpressure, and flow rate, were optimized. The DAICEL CHIRALPAK AD-H column (250 mm×4.6 mm, 5 μm) was used for separation. Supercritical CO2 served as mobile phase A, and ethanol-isopropanol (1∶1, volume ratio) containing 0.25% diethanolamine and 0.25% trifluoroacetic acid was used as mobile phase B. Isocratic elution was carried out at a ratio of A∶B=73∶27 (volume ratio) with a flow rate of 1.5 mL/min. The column temperature was set at 40 ℃, back pressure at 15 MPa, injection volume at 6 μL, and detection wavelength at 220 nm. Under these conditions, linagliptin and its S-enantiomer were separated with a resolution of 3.1 and good peak shapes. Both linagliptin and its S-enantiomer exhibited good linearity in the concentration range of 2-90 μg/mL, with correlation coefficients of 0.999 7 and 0.999 9 (n=8), respectively. The limit of detection (LOD) for both was 0.8 μg/mL (S/N=3), and the limit of quantification (LOQ) for both was 2 μg/mL (S/N=10). The average recoveries of the S-enantiomer spiked at low, medium, and high concentrations in active pharmaceutical ingredients and tablets were 97.4% (RSD=1.1%, n=9) and 101.6% (RSD=1.2%, n=9), respectively. S-Enantiomer was not detected in three batches of active pharmaceutical ingredients or in three batches of tablets from two different manufacturers. This study represents the first application of SFC for the separation of linagliptin and its S-enantiomer. The method is environmentally friendly, sensitive, and highly efficient, offering good repeatability of peak area. It provides a solid foundation for the quality control of linagliptin and the inclusion of the SFC method in pharmaceutical quality standards, while also offering a useful approach for the rapid separation and impurity control of other chiral drugs.