Low-dose decitabine-intensified modified conditioning regimen alleviates aGVHD in AML/MDS patients treated with allogeneic hematopoietic stem cell transplantation.

Background: The widespread adoption of Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) has significantly improved the survival rates of patients with hematological malignancies. However, Graft-Versus-Host Disease (GVHD) remains a formidable complication, threatening patient prognosis. Recent research has indicated that decitabine (DAC), known for its hypomethylating properties may also exhibit immune-regulatory capabilities and a potential for reducing GVHD incidence and enhancing survival. Methods: We retrospectively reviewed data from AML/MDS patients who underwent Allo-HSCT at our center from January 2010 to January 2023. From a total of 251 patients with complete data, we employed propensity score matching (PSM) to create 100 matched pairs (200 patients) for comprehensive trial analysis. Patients receiving low-dose DAC-containing regimen were matched with those who did not receive DAC. Results: Patients in the DAC group exhibited a significantly lower incidence of grade II-IV acute GVHD (aGVHD) compared to non-DAC group (21% vs. 38%, P=0.013). Univariable and multivariable logistic regression analysis demonstrated DAC intervention as a protective factor against grade II-IV aGVHD (P=0.017, OR=0.47, 95% CI 0.23-0.81; P=0.018, OR=0.46, 95% CI 0.24-0.87). Multivariate competing risk regression further supported administration of decitabine as a protective factor against grade II-IV aGVHD (P=0.038, SHR=0.53, 95%CI 0.29-0.97). There was no significant difference between both groups concerning chronic GVHD, infection, disease relapse, overall survival, disease-free survival and GVHD free, relapse free survival. In MRD negative or intermediate risk subgroup, the grade II-IV aGVHD ameliorating effect of DAC was confirmed as well. Conclusion: Low-dose DAC-intensified modified conditioning regimen could improve prognosis in AML/MDS Patients treated with allogeneic hematopoietic stem cell transplantation.

High-Dose immunoglobulin Intervention as an effective and simple strategy for donor specific Anti-HLA antibody desensitization in haploidentical transplant.

Donor-specific anti-HLA antibody (DSA) is a significant obstacle to successful haploidentical hematopoietic stem cell transplantation (haplo-HSCT) and is associated with poor engraftment rates. DSA strongly positive patients with a mean fluorescence intensity (MFI) over 5000 have a primary poor graft function (PGF) rate of over 60%. Currently, there is no consensus on the desensitization of DSA, and existing strategies are complex and have limited effectiveness. To address this issue, we conducted a retrospective study on 19 patients with strongly positive DSA (MFI over 5000) who underwent haplo-HSCT and were treated with intravenous immunoglobulin (IVIg)-based therapy. We also included 38 baseline-matched patients with DSA-negative as controls. Our findings revealed that the cumulative incidence of engraftment, PGF, graft-versus-host disease (GVHD), virus infection, overall survival (OS), disease-free survival (DFS), relapse, and non-relapse mortality (NRM) in the DSA strongly positive group after desensitization were comparable to those in the DSA negative group (P > 0.05). Our multivariable analysis showed that disease remission was a protective factor against PGF (P = 0.005, OR = 0.019, 95% CI 0.001-0.312). Subgroup analysis revealed that the desensitization efficacy was equal regardless of DSA type against HLA-I or II, and MFI value over 5000 or not. In conclusion, we propose a simple and effective DSA desensitization strategy based on immunoglobulin to ensure successful engraftment and improve patient prognosis.

Tough and fatigue-resistant polymer networks by crack tip softening.

Soft materials fail by crack propagation under external loads. While fracture toughness of a soft material can be enhanced by orders of magnitude, its fatigue threshold remains insusceptible. In this work, we demonstrate a crack tip softening (CTS) concept to simultaneously improve the toughness and threshold of a single polymeric network. Polyacrylamide hydrogels have been selected as a model material. The polymer network is cured by two kinds of crosslinkers: a normal crosslinker and a light-degradable crosslinker. We characterize the pristine sample and light-treated sample by shear modulus, fracture toughness, fatigue threshold, and fractocohesive length. Notably, we apply light at the crack tip of a sample so that the light-sensitive crosslinkers degrade, resulting in a CTS sample with a softer and elastic crack tip. The pristine sample has a fracture toughness of 748.3 ± 15.19 J/m2 and a fatigue threshold of 9.3 J/m2. By comparison, the CTS sample has a fracture toughness of 2,774.6 ± 127.14 J/m2 and a fatigue threshold of 33.8 J/m2. Both fracture toughness and fatigue threshold have been enhanced by about four times. We attribute this simultaneous enhancement to stress de-concentration and elastic shielding at the crack tip. Different from the "fiber/matrix composite" concept and the "crystallization at the crack tip" concept, the CTS concept in the present work provides another option to simultaneously enhance the toughness and threshold, which improves the reliability of soft devices during applications.

A novel hexamerin with an unexpected contribution to the prophenoloxidase activation system of the Chinese oak silkworm, Antheraea pernyi.

Hexamerin was originally identified as a storage protein but later confirmed to be involved in many physiological processes. In the present study, we cloned and characterized a novel hexamerin complementary DNA sequence from the Chinese oak silkworm, Antheraea pernyi (Ap-hexamerin), which shows high homology with reported insect methionine-rich hexamerins. The tissue distribution and time course of expression demonstrated that Ap-hexamerin was predominantly synthesized in the fat body and the expression level was significantly increased in response to the microbial challenge, suggesting the relevance of Ap-hexamerin to immune responses. In further immune functional studies, Ap-hexamerin was confirmed to take part in the upregulation of prophenoloxidase (PPO) activation in A. pernyi haemolymph triggered by pathogen-associated molecular patterns (PAMPs). Additional molecular interaction analysis revealed that Ap-hexamerin is capable of binding the PAMPs used in the phenoloxidase assay, suggesting hexamerin in A. pernyi may positively regulate haemolymph PPO activation, acting as a pattern recognition protein.

Fast Digital Patterning of Surface Topography toward Three-Dimensional Shape-Changing Structures.

Exiting strategies for 3D shape-changing structures are constrained by either the complicated fabrication process or the harsh demands of active materials. Facile preparation of 3D shape-changing structures with an extremely simple approach based on the elastomeric polymer still remains a challenging topic. Here, we report a fast digital patterning of surface topography of a single-layer elastomeric polymer toward 3D shape-changing structures. The surface topography features digitally engraved grooves by a laser engraver on a poly(dimethylsiloxane) (PDMS) sheet, which is surface oxidized by the UV-ozone treatment. The resulting engraved PDMS sheets exhibit programmable shape-changing behaviors to form various 3D structures under the action of organic solvent. Experimental and numerical studies reveal the fundamental aspects of surface topography-guided 3D shape-changing structures. Demonstrations of this concept in developing various complex 3D shape-changing structures illustrate the simplicity and effectiveness of our approach, thereby creating engineering opportunities in a wide range of applications such as actuators and soft robots.

Persistent luminescent metal-organic frameworks with long-lasting near infrared emission for tumor site activated imaging and drug delivery.

Luminescent porous materials have been widely used in biosensing, bioimaging and drug delivery by virtue of the special porous structure and luminescent property. The main obstacle for the application in biosensing and bioimaging is the background interference of external irradiation. Herein, we report a background interference-free persistent luminescent metal-organic framework (PLMOF) with persistent luminescent near infrared (NIR) luminescence for tumor site activated persistent luminescence imaging. The PLMOF (PLNPs@ZIF-8) was prepared by in-situ growth of MOF on the persistent luminescent nanoparticles (PLNPs) via a surface adsorption induced self-assembly method. The PLMOF possessed NIR persistent luminescence and renewable NIR luminescence and thus enabled deep-tissue and long-term imaging without external excitation. Specifically, the PLMOF showed acidic tumor site activated persistent luminescence for in vitro and in vivo tumor imaging, which was also help to reduce the background interference. The mechanism of acidic activation was attributed to the protonation of imidazole that induces disassembly of ZIF-8. In addition, the PLMOF presented a high anti-cancer drug loading capacity, acidity-responsive drug release behavior, and significant anti-tumor effect. All these results indicate that our PLMOF can serve as a promising theranostic platform for precision medicine.