Corneal stromal structure replicating humanized hydrogel patch for sutureless repair of deep anterior-corneal defect.

A critical shortage of donor corneas exists worldwide. Hydrogel patches with a biological architecture and functions that simulate those of native corneas have garnered considerable attention. This study introduces a stromal structure replicating corneal patch (SRCP) composed of a decellularized cornea-templated nanotubular skeleton, recombinant human collagen, and methacrylated gelatin, exhibiting a similar ultrastructure and transmittance (above 80 %) to natural cornea. The SRCP is superior to the conventional recombinant human collagen patch in terms of biomechanical properties and resistance to enzymatic degradation. Additionally, SRCP promotes corneal epithelial and stromal cell migration while preventing the trans-differentiation of stromal cells into myofibroblasts. When applied to an ocular surface (37 °C), SRCP releases methacrylated gelatin, which robustly binds SRCP to the corneal stroma after activation by 405 nm light. Compared to gelatin-based photocurable hydrogel, the SRCP better supports the restoration of normal corneal curvature and withstands deformation under an elevated intraocular pressure (100 mmHg). In an in vivo deep anterior-corneal defect model, SRCP facilitated epithelial healing and vision recovery within 2 weeks, maintained graft structural stability, and inhibited stromal scarring at 4 weeks post-operation. The ideal performance of the SRCP makes it a promising humanized corneal equivalent for sutureless clinical applications.

CoNglyPred: Accurate Prediction of N-Linked Glycosylation Sites Using ESM-2 and Structural Features With Graph Network and Co-Attention.

N-Linked glycosylation is crucial for various biological processes such as protein folding, immune response, and cellular transport. Traditional experimental methods for determining N-linked glycosylation sites entail substantial time and labor investment, which has led to the development of computational approaches as a more efficient alternative. However, due to the limited availability of 3D structural data, existing prediction methods often struggle to fully utilize structural information and fall short in integrating sequence and structural information effectively. Motivated by the progress of protein pretrained language models (pLMs) and the breakthrough in protein structure prediction, we introduced a high-accuracy model called CoNglyPred. Having compared various pLMs, we opt for the large-scale pLM ESM-2 to extract sequence embeddings, thus mitigating certain limitations associated with manual feature extraction. Meanwhile, our approach employs a graph transformer network to process the 3D protein structures predicted by AlphaFold2. The final graph output and ESM-2 embedding are intricately integrated through a co-attention mechanism. Among a series of comprehensive experiments on the independent test dataset, CoNglyPred outperforms state-of-the-art models and demonstrates exceptional performance in case study. In addition, we are the first to report the uncertainty of N-linked glycosylation predictors using expected calibration error and expected uncertainty calibration error.

Nucleon Electric Polarizabilities and Nucleon-Pion Scattering at the Physical Pion Mass.

We present a lattice QCD calculation of the nucleon electric polarizabilities at the physical pion mass. Our findings reveal the substantial contributions of the Nπ states to these polarizabilities. Without considering these contributions, the lattice results fall significantly below the experimental values, consistent with previous lattice studies. This observation has motivated us to compute both the parity-negative Nπ scattering up to a nucleon momentum of ∼0.5 GeV in the center-of-mass frame and corresponding Nγ^{*}→Nπ matrix elements using lattice QCD. Our results confirm that incorporating dynamic Nπ contributions is crucial for a reliable determination of the polarizabilities from lattice QCD. This methodology lays the groundwork for future lattice QCD investigations into various other polarizabilities.

Pomegranate Peel-Derived Hard Carbons as Anode Materials for Sodium-Ion Batteries.

Exploring high-performance carbon anodes that are low-cost and easily accessible is the key to the commercialization of sodium-ion batteries. Producing carbon materials from bio by-products is an intriguing strategy for sodium-ion battery anode manufacture and for high-value utilization of biomass. Herein, a novel hard carbon (PPHC) was prepared via a facile pyrolysis process followed by acid treatment using biowaste pomegranate peel as the precursor. The morphology and structure of the PPHC were influenced by the carbonization temperature, as evidenced by physicochemical characterization. The PPHC pyrolyzed at 1100 °C showed expanded interlayer spacing and appropriate oxygen group content. When used as a sodium ion battery anode, the PPHC-1100 demonstrated a reversible capacity of up to 330 mAh g-1, maintaining 174 mAh g-1 at an increased current rate of 1 C. After 200 cycles at 0.5 C, the capacity delivered by PPHC-1100 was 175 mAh g-1. The electrochemical behavior of PPHC electrodes was investigated, revealing that the PPHC-1100 possessed increased capacitive-controlled energy storage and improved ion transport properties, which explained its excellent electrochemical performance. This work underscores the feasibility of high-performance sodium-ion battery anodes derived from biowaste and provides insights into the sodium storage process in biomass-derived hard carbon.

Free-radical triggered formation of dioxins from 2-chlorophenol pyrolysis investigated by synchrotron radiation photoionization mass spectrometry.

Polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and polychlorinated naphthalenes (PCNs) are a category of highly toxic and environmentally persistent pollutants released particularly via thermal processes of chlorine-containing materials. However, the detailed reaction mechanism, especially the evolution of related radicals remains elusive for decades. Herein we have for the first time characterized the radicals and intermediates during pyrolysis of 2-chlorophenol resulting in PCDD/Fs and PCNs, using a flow tube reactor coupled with in-situ synchrotron radiation photoionization mass spectrometry (SR-PIMS). Transient species including 2-chlorophenoxy (C6H4ClO•), phenoxy (C6H5O•), chloro-cyclopentadienyl (•C5H4Cl), chloro-cyclopentadiene (C5H5Cl), fulvenone ketene (C6H4O) and o-benzyne (o-C6H4), were identified via m/z and photoionization efficiency profile. Potential energy surfaces of the early-stage mechanism and the associated rate constants and branching ratios were elucidated. Successively, the formation mechanisms of PCDD/Fs and PCNs from these transient intermediates at high temperatures were proposed which have experimentally validated and refined the previous mechanism. The results suggested that the combination of 2-chlorophenoxy radicals with another 2-chlorophenoxy, phenoxy, phenyl, or o-benzyne leads to the formation of PCDD/Fs, while PCNs are generated from the self-coupling of chloro-cyclopentadienyl.

LAMTOR1 ablation impedes cGAS degradation caused by chemotherapy and promotes antitumor immunity.

Chemotherapy resistance remains a significant obstacle that limits the long-term efficacy of cancer therapy, necessitating further investigations into the underlying mechanisms. Here, we find that DNA fragments induced by chemotherapeutic agents trigger the degradation of cGAS, a potent double-strand DNA (dsDNA) sensor, by lysosomes. Mechanically, the lysosome-localized protein LAMTOR1 is up-regulated, and the interaction between LAMTOR1 and cGAS is enhanced upon exposure to DNA fragments, boosting the accumulation and digestion of cGAS in lysosomes through the receptor protein p62. LAMTOR1 deficiency increases cGAS abundance and promotes activation of the cGAS-STING pathway, leading to subsequent production of type I interferons induced by cytosolic DNA stimulation. Loss of LAMTOR1 synergizes with immunotherapy and chemotherapy to inhibit tumor growth and prolong the survival time of tumor-bearing mice by promoting the infiltration of effective T lymphocytes. Thus, our study reveals a regulation of cGAS abundance and provides a potential strategy to overcome chemotherapy resistance by targeting LAMTOR1.

PocketDTA: an advanced multimodal architecture for enhanced prediction of drug-target affinity from 3D structural data of target binding pockets.

MOTIVATION: Accurately predicting the drug-target binding affinity (DTA) is crucial to drug discovery and repurposing. Although deep learning has been widely used in this field, it still faces challenges with insufficient generalization performance, inadequate use of 3D information, and poor interpretability. RESULTS: To alleviate these problems, we developed the PocketDTA model. This model enhances the generalization performance by pre-trained models ESM-2 and GraphMVP. It ingeniously handles the first 3 (top-3) target binding pockets and drug 3D information through customized GVP-GNN Layers and GraphMVP-Decoder. In addition, it uses a bilinear attention network to enhance interpretability. Comparative analysis with state-of-the-art (SOTA) methods on the optimized Davis and KIBA datasets reveals that the PocketDTA model exhibits significant performance advantages. Further, ablation studies confirm the effectiveness of the model components, whereas cold-start experiments illustrate its robust generalization capabilities. In particular, the PocketDTA model has shown significant advantages in identifying key drug functional groups and amino acid residues via molecular docking and literature validation, highlighting its strong potential for interpretability. AVAILABILITY AND IMPLEMENTATION: Code and data are available at: https://github.com/zhaolongNCU/PocketDTA.

When multi-group selection meets mystery of cooperation in structured public goods games.

Cooperation is the cornerstone of social stability and human development. In order to promote mutual cooperation among individuals, some researchers analyzed the important factors influencing individual behavior from the perspective of group selection, while others revealed the evolutionary mechanism of cooperative behavior in groups from the perspective of network reciprocity. However, group selection and network reciprocity actually work together and simultaneously drive individuals to cooperate with each other. Analyzing each mechanism in isolation provides an incomplete understanding of the interaction process. Inspired by this, we integrate the coupled effects of both group selection and network reciprocity on the behavior of individuals. We develop a structured public goods game model to study the evolution of individual cooperative behavior in multiple groups, where each individual can interact not only with intra-group individuals but also with inter-group individuals. Based on the fixed probabilities of multi-group selection, including intra-group and inter-group selection, we derive a general condition that promotes cooperation among individuals. Besides, we discuss the effects of the number of neighbors in a group, group size, and group size on the selection of cooperative behavior. Finally, we systematically compare our model with the well-mixed case, and the results show that a structured population enhances cooperation. Increasing the number of populations boosts the fixation probability of cooperation. To the best of our knowledge, this paper is the first to study the cooperative evolutionary dynamics of multi-group selection in structured populations through public goods games.

Covering corneal stromal lenticule for macular hole in pathological myopia.

AIM: To evaluate the clinical effect of a new surgery technique (covering corneal stromal lenticule, CSL) for macular hole (MH) in pathological myopia. METHODS: This was a prospective non-randomized series case study. Fourteen eyes of 14 patients whose axial length were more than 29 mm and suffered from MH and macular hole retinal detachment (MHRD) were included in this study. All cases were treated with 25-gauge pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling, covering CSL and C3F8 gas tamponade. These cases were followed for 6mo, and the best-corrected visual acuity (BCVA), healing status of MH, the reattached rate of retinal detachment (RD), and reoperation rate were analyzed. RESULTS: All cases were successfully performed the surgery and the postoperative follow-up was completed. After surgery, MHs were healed in all 14 eyes (100%, 14/14) after assessed by optical coherence tomography. The reattachment of retina was achieved in all 6 eyes (100%, 6/6) with MHRD. BCVA was improved in 12 eyes (85.71%, 12/14), and had no significant change in 2 eyes (14.29%, 2/14). The overall mean BCVA was improved from 1.80±0.77 to 0.82±0.46 logMAR (F=10.46, P<0.01). No serious complications occurred in all cases. CONCLUSION: The new surgery technique (covering CSL) has high reattached rate of RD and high healing rate of MH in pathological myopia in the preliminary study. And it can effectively improve the visual function of patients. This new technique offers meaningful new ideas for treating refractory MH in pathological myopia.

NUCLEAR FACTOR-Y-POLYCOMB REPRESSIVE COMPLEX2 dynamically orchestrates starch and seed storage protein biosynthesis in wheat.

The endosperm in cereal grains is instrumental in determining grain yield and seed quality, as it controls starch and seed storage protein (SSP) production. In this study, we identified a specific nuclear factor-Y (NF-Y) trimeric complex in wheat (Triticum aestivum L.), consisting of TaNF-YA3-D, TaNF-YB7-B, and TaNF-YC6-B, and exhibiting robust expression within the endosperm during grain filling. Knockdown of either TaNF-YA3 or TaNF-YC6 led to reduced starch but increased gluten protein levels. TaNF-Y indirectly boosted starch biosynthesis genes by repressing TaNAC019, a repressor of cytosolic small ADP-glucose pyrophosphorylase 1a (TacAGPS1a), sucrose synthase 2 (TaSuS2), and other genes involved in starch biosynthesis. Conversely, TaNF-Y directly inhibited the expression of Gliadin-γ-700 (TaGli-γ-700) and low molecular weight-400 (TaLMW-400). Furthermore, TaNF-Y components interacted with SWINGER (TaSWN), the histone methyltransferase subunit of Polycomb repressive complex 2 (PRC2), to repress TaNAC019, TaGli-γ-700, and TaLMW-400 expression through trimethylation of histone H3 at lysine 27 (H3K27me3) modification. Notably, weak mutation of FERTILIZATION INDEPENDENT ENDOSPERM (TaFIE), a core PRC2 subunit, reduced starch but elevated gliadin and LMW-GS contents. Intriguingly, sequence variation within the TaNF-YB7-B coding region was linked to differences in starch and SSP content. Distinct TaNF-YB7-B haplotypes affect its interaction with TaSWN-B, influencing the repression of targets like TaNAC019 and TaGli-γ-700. Our findings illuminate the intricate molecular mechanisms governing TaNF-Y-PRC2-mediated epigenetic regulation for wheat endosperm development. Manipulating the TaNF-Y complex holds potential for optimizing grain yield and enhancing grain quality.

Synthesis, characterization and anticancer, antibacterial activities of pentacyclic triterpenoid glycoside derivatives.

As a kind of glycoside, pentacyclic triterpenoid saponins have good biological activities, such as anticancer, antibacterial, antiviral and hypoglycemic effects [1]. In this paper, twenty-four pentacyclic triterpenoid derivatives, including twelve monosaccharide derivatives, were designed and synthesized. The anticancer effect and antibacterial activities of all compounds were evaluated. It is noteworthy that compound UA-2b has the strongest inhibitory effect on the growth of A549, Hela and HepG2 cancer cells (IC50 = 5.37 ± 0.22 µM, 5.82 ± 0.25 µM and 5.47 ± 0.06 µM, respectively). Compounds OA-2b, OA-6a, OA-6b, UA-2b and UA-6a have the best activity against Escherichia coli 1924 (MIC = 16 µg/ml).

Presence of triple positive driver mutations in JAK2, CALR and MPL in primary myelofibrosis: a case report and literature review.

BACKGROUND: Primary myelofibrosis (PMF) is the most advanced subtype among the classic Philadelphia chromosomenegative myeloproliferative neoplasms (MPNs). A majority of patients carry one of three mutually-exclusive somatic driver mutations: JAK2 (60-65%), CALR (20-25%), or MPL (5%). Co-occurrence of these mutations is rarely reported. Here we report a case with a triple positive combination of JAK2, CALR and MPL driver mutations. CASE PRESENTATION: A 69-year-old male was admitted to hospital for acute exacerbation of chronic obstructive pulmonary disease (COPD) and was found to have splenomegaly and leukocytosis. Nextgeneration revealed JAK2, CALR, MPL mutations, and additional variants in SF3B1, SRSF2, and STAG2. The patient was diagnosed with PMF and treated with ruxolitinib and COPD therapy. Due to nausea, the ruxolitinib dose was reduced. After therapy, spleen volume decreased and hematologic responses were poor. Another genetic mutation of ASXL1 was later found. After adjusting the medication and adding antiemetics, the patient's condition improved. CONCLUSIONS: The rare coexistence of JAK2, CALR, and MPL mutations challenges the assumption of their mutual exclusivity. Further study of these mutations is essential for developing better treatment strategies.

Personalized Prediction of Long-Term Renal Function Prognosis Following Nephrectomy Using Interpretable Machine Learning Algorithms: Case-Control Study.

BACKGROUND: Acute kidney injury (AKI) is a common adverse outcome following nephrectomy. The progression from AKI to acute kidney disease (AKD) and subsequently to chronic kidney disease (CKD) remains a concern; yet, the predictive mechanisms for these transitions are not fully understood. Interpretable machine learning (ML) models offer insights into how clinical features influence long-term renal function outcomes after nephrectomy, providing a more precise framework for identifying patients at risk and supporting improved clinical decision-making processes. OBJECTIVE: This study aimed to (1) evaluate postnephrectomy rates of AKI, AKD, and CKD, analyzing long-term renal outcomes along different trajectories; (2) interpret AKD and CKD models using Shapley Additive Explanations values and Local Interpretable Model-Agnostic Explanations algorithm; and (3) develop a web-based tool for estimating AKD or CKD risk after nephrectomy. METHODS: We conducted a retrospective cohort study involving patients who underwent nephrectomy between July 2012 and June 2019. Patient data were randomly split into training, validation, and test sets, maintaining a ratio of 76.5:8.5:15. Eight ML algorithms were used to construct predictive models for postoperative AKD and CKD. The performance of the best-performing models was assessed using various metrics. We used various Shapley Additive Explanations plots and Local Interpretable Model-Agnostic Explanations bar plots to interpret the model and generated directed acyclic graphs to explore the potential causal relationships between features. Additionally, we developed a web-based prediction tool using the top 10 features for AKD prediction and the top 5 features for CKD prediction. RESULTS: The study cohort comprised 1559 patients. Incidence rates for AKI, AKD, and CKD were 21.7% (n=330), 15.3% (n=238), and 10.6% (n=165), respectively. Among the evaluated ML models, the Light Gradient-Boosting Machine (LightGBM) model demonstrated superior performance, with an area under the receiver operating characteristic curve of 0.97 for AKD prediction and 0.96 for CKD prediction. Performance metrics and plots highlighted the model's competence in discrimination, calibration, and clinical applicability. Operative duration, hemoglobin, blood loss, urine protein, and hematocrit were identified as the top 5 features associated with predicted AKD. Baseline estimated glomerular filtration rate, pathology, trajectories of renal function, age, and total bilirubin were the top 5 features associated with predicted CKD. Additionally, we developed a web application using the LightGBM model to estimate AKD and CKD risks. CONCLUSIONS: An interpretable ML model effectively elucidated its decision-making process in identifying patients at risk of AKD and CKD following nephrectomy by enumerating critical features. The web-based calculator, found on the LightGBM model, can assist in formulating more personalized and evidence-based clinical strategies.

A preliminary study of renal function for renal artery stenosis using multiparametric magnetic resonance imaging.

OBJECTIVE: To comprehensively evaluate the renal structure and function of patients with renal artery stenosis (RAS) using multiparametric magnetic resonance imaging (MRI), and analyze the correlation between magnetic resonance (MR) parameters and renal function. MATERIALS AND METHODS: Renal multiparametric MRI was conducted on 62 patients with RAS utilizing a Philips Ingenia CX 3.0 T MRI system. The scanning protocols encompassed arterial spin labeling, phase contrast MRI, diffusion weighted imaging, T1 mapping, and blood oxygen level-dependent MRI. All patients underwent radionuclide renal dynamic imaging to calculate the glomerular filtration rate (GFR) for assessing renal function. RESULTS: Most MR parameters were correlated with GFR: renal parenchymal volume (R = 0.603), whole kidney renal blood flow (RBF) (R = 0.192), renal cortical RBF (R = 0.294), renal artery mean velocity (R = 0.593), stroke volume (R = 0.599), mean flux (R = 0.629), renal cortical apparent diffusion coefficient (ADC) (R = 0.466), medullary ADC (R = 0.332), cortical T1 value (R = - 0.206), corticomedullary T1 difference (R = 0.204), cortical T2* value (R = 0.448), and medullary T2* value (R = 0.272). The best prediction model for GFR using multiparametric MRI was obtained, including renal PV, whole kidney RBF, cortical RBF, mean velocity, mean flux, and CMD T1. CONCLUSION: Multiparametric MRI is a novel noninvasive examination method that can effectively and comprehensively assess the renal structure and function of RAS.

Ocean wave energy harvesting with high energy density and self-powered monitoring system.

Constructing a ocean Internet of Things requires an essential ocean environment monitoring system. However, the widely distributed existing ocean monitoring sensors make it impractical to provide power and transmit monitored information through cables. Therefore, ocean environment monitoring systems particularly need a continuous power supply and wireless transmission capability for monitoring information. Consequently, a high-strength, environmentally multi-compatible, floatable metamaterial energy harvesting device has been designed through integrated dynamic matching optimization of materials, structures, and signal transmission. The self-powered monitoring system breaks through the limitations of cables and batteries in the ultra-low-frequency wave environment (1 to 2 Hz), enabling real-time monitoring of various ocean parameters and wirelessly transmitting the data to the cloud for post-processing. Compared with solar and wind energy in the ocean environment, the energy harvesting device based on the defective state characteristics of metamaterials achieves a high-energy density (99 W/m3). For the first time, a stable power supply for the monitoring system has been realized in various weather conditions (24 h).

Formononetin Alleviates Ischemic Acute Kidney Injury by Regulating Macrophage Polarization through KLF6/STAT3 Pathway.

Recent research has indicated that formononetin demonstrates a potent anti-inflammatory effect in various diseases. However, its impact on sterile inflammation kidney injury, specifically acute kidney injury (AKI), remains unclear. In this study, we utilized an ischemia/reperfusion-induced AKI (IRI-AKI) mouse model and bone marrow-derived macrophages (BMDMs) to investigate the effects of formononetin on sterile inflammation of AKI and to explore the underlying mechanism. The administration of formononetin significantly preserved kidney function from injury, as evidenced by lower serum creatinine and blood urea nitrogen levels compared to IRI-AKI mice without treatment. This was further confirmed by less pathological changes in renal tubules and low expression of tubular injury markers such as KIM-1 and NGAL in the formononetin-treated IRI-AKI group. Furthermore, formononetin effectively suppressed the expression of pro-inflammatory cytokines (MCP-1, TNF-α, and IL-1ß) and macrophage infiltration into the kidneys of AKI mice. In vitro studies showed that formononetin led to less macrophage polarization towards a pro-inflammatory phenotype in BMDMs stimulated by LPS and IFN-[Formula: see text]. The mechanism involved the KLF6 and p-STAT3 pathway, as overexpression of KLF6 restored pro-inflammatory cytokine levels and pro-inflammatory polarization. Our findings demonstrate that formononetin can significantly improve renal function and reduce inflammation in IRI-AKI, which may be attributed to the inhibition of KLF6/STAT3-mediated macrophage pro-inflammatory polarization. This discovery presents a new promising therapeutic option for the treatment of IRI-AKI.

Protein phosphatase 2A regulates blood cell proliferation and differentiation in Drosophila larval lymph glands.

Protein phosphatase 2A (PP2A), one of the most abundant protein phosphatases, has divergent functions in multiple types of cells. Its inactivation has been closely associated with leukemia diseases. However, the physiological function of PP2A for hematopoiesis has been poorly understood in organisms. Drosophila hematopoiesis parallels the vertebrate counterpart in developmental and functional features but involves a much simpler hematopoietic system. Here, utilizing the Drosophila major larval hematopoietic organ lymph gland, we studied the function of PP2A for hematopoiesis in vivo. By knocking down the expression of Pp2A-29B that encodes the scaffold subunit of the PP2A holoenzyme complex, we found that PP2A silencing in the differentiating hemocytes resulted in their excessive proliferation. Furthermore, this PP2A inhibition downregulated the expression of Smoothened (Smo), a crucial component in the Hedgehog pathway, and smo overexpression was able to rescue the phenotypes of PP2A depletion, indicating that Smo functions as a downstream effector of PP2A to restrict the hemocyte proliferation. PDGF/VEGF-receptor (Pvr) overexpression also restored the Smo expression and lymph gland morphology of PP2A silencing, suggesting a PP2A-Pvr-Smo axis to regulate lymph gland growth and hemocyte proliferation. Moreover, inhibiting PP2A activity in the blood progenitor cells promoted their differentiation, but which was independent with Smo. Together, our data suggested that PP2A plays a dual role in the Drosophila lymph gland by preserving the progenitor population and restraining the hemocyte proliferation, to properly regulate the hematopoietic process.

Human umbilical cord-derived mesenchymal stromal cells for the treatment of steroid refractory grades III-IV acute graft-versus-host disease with long-term follow-up.

Introduction: Mesenchymal stromal cells (MSCs) have been extensively studied as a potential treatment for steroid refractory acute graft-versus-host disease (aGVHD). However, the majority of clinical trials have focused on bone marrow-derived MSCs. Methods: In this study, we report the outcomes of 86 patients with grade III-IV (82.6% grade IV) steroid refractory aGVHD who were treated with human umbilical cord-derived mesenchymal stromal cells (UC-MSCs). The patient cohort included 17 children and 69 adults. All patients received intravenous infusions of UC-MSCs at a dose of 1 × 106 cells per kg body weight, with a median of 4 infusions (ranging from 1 to 16). Results: The median time between the onset of aGVHD and the first infusion of UC-MSCs was 7 days (ranging from 3 to 88 days). At day 28, the overall response (OR) rate was 52.3%. Specifically, 24 patients (27.9%) achieved complete remission, while 21 (24.4%) exhibited partial remission. The estimated survival probability at 100 days was 43.7%. Following a median follow-up of 108 months (ranging from 61 to 159 months), the survival rate was approximately 11.6% (10/86). Patients who developed acute lower GI tract and liver GVHD exhibited poorer OR rates at day 28 compared to those with only acute lower GI tract GVHD (22.2% vs. 58.8%; p= 0.049). No patient experienced serious adverse events. Discussion: These finding suggest that UC-MSCs are safe and effective in both children and adults with steroid refractory aGVHD. UC-MSCs could be considered as a feasible treatment option for this challenging conditon. (NCT01754454).