Zi Chen

Broadband vibration isolation, particularly at low frequencies, remains a longstanding challenge across a range of engineering applications from high-precision fabrication systems to seismic protection of civil structures. In this study, we present a viscoelastic kagome lattice, a type of topological mechanical metamaterial, that integrates topologically protected edge modes with engineered material damping to achieve broadband attenuation that extends down to frequencies approaching zero. We first demonstrate that the elastic kagome lattice supports robust edge-localized modes below the bulk acoustic bands, enabling effective low-frequency isolation. By incorporating viscoelastic behavior modeled through a Standard Linear Solid (SLS) framework, we show that damping strongly attenuates the high-frequency bulk modes while preserving the topological edge modes. We introduce a three-stage band evolution theory that captures how viscoelastic parameters influence the transition and attenuation behavior of these modes, providing a systematic approach to optimize damping characteristics for broadband vibration isolation. This work establishes a design framework for viscoelastic mechanical metamaterials that combines topological robustness with tailored dissipation, offering new capabilities for advanced vibration control systems.

Tea polyphenols (TPs), potent antioxidants found in tea, offer cellular protection and health benefits. Dimethyl sulfoxide (DMSO), a widely used organic solvent in medicine, remains controversial due to its potential embryonic toxicity. This study explored the effects of TPs from oolong and black tea, DMSO exposure, and their combined treatment on embryonic development using a fruit fly model. TPs from oolong tea (rich in catechin and EGCG) and black tea (mainly catechin) promoted embryonic development, enhanced larval vitality, and improved oxidative stress resistance in adults. Catechin intervention mirrored the effects of TPs from oolong and black tea, while the effect of EGCG was sex‐dependent. DMSO showed dose‐dependent toxicity, with 1% concentrations disrupting organ development and preventing emergence. Notably, EGCG and oolong tea TPs supported normal organ formation. Furthermore, catechin and tea TPs alleviated 0.5% DMSO‐induced damage, boosting larval vitality, adult locomotion, and body weight in males, while reducing oxidative stress.

The intricate interplay between actomyosin contractility and extracellular matrix (ECM) strain stiffening is pivotal in cancer invasion. Despite the admitted impact of such feedback, current models are inadequate in predicting the largely overlapping ranges of cell shapes and their corresponding motility levels at intermediate ranges of collagen density. To address this gap, we introduce a free energy-based, trizonal model for cell shape transition under ECM stiffening, which delineates two distinct and one overlapping motility zones entitled with their implications for cancer progression: a low-motility zone with minimal invasiveness, a high-motility zone indicative of significantly invasive cells, and a mesoregion which harbors cells at crossroads of both states. This model integrates critical factors influencing the bidirectional interaction between the cell and ECM, thereby offering a deeper grasp of cancer cell behavior. Our findings reveal that the combined effects of ECM strain stiffening and cellular contractility are key drivers of cell population heterogeneity and invasiveness. This model goes beyond existing paradigms by accurately determining the optimal cell elongation at matrix-driven steady-state equilibrium, factoring in collagen density, contractility density, stress polarization, membrane-cortical tension, and integrin dynamics through the lens of total free energy minimization. The model’s predictive capability is further validated against measured cell shapes from histological sections. Altogether, this research not only bridges a crucial knowledge gap, but also provides a robust computational framework for predicting and replicating cell shape transitions observed in human functional tissue assays, thereby enhancing our ability to understand and potentially combat cancer invasion.

Importance: Patients with chronic myeloid leukemia (CML) or Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL) resistant or intolerant to BCR-ABL1 tyrosine kinase inhibitors (TKIs) have limited treatment options. Olverembatinib, which is approved in China, has only been tested in Chinese patients.Objective: To assess the pharmacokinetics, safety, efficacy, and recommended dose of olverembatinib in patients with CML or Philadelphia chromosome–positive ALL resistant or intolerant to at least 2 TKIs.Design, Setting, and Participants: This multicenter phase 1b randomized clinical trial was conducted from January 28, 2020, to January 2, 2024, with a median (range) follow-up of 48 (0-166) weeks. Patients with CML or Philadelphia chromosome–positive ALL were enrolled. This bridging study was performed in part to confirm that there are no racial differences in the pharmacokinetic profile of olverembatinib.Interventions: Patients were randomly assigned to 30, 40, or 50 mg of olverembatinib orally every other day in 28-day cycles.Main Outcomes and Measures: Pharmacokinetic profile of olverembatinib.Results: Of 80 included patients, 46 (58%) were male, and the median (range) age was 54.0 (21-80) years. The pharmacokinetic profile of olverembatinib was compatible with alternate-day dosing and similar to that in Chinese patients. Based on investigators’ assessments, 60 patients (75%) experienced at least 1 treatment-related adverse event; 32 (40%) experienced grade 3 or higher treatment-related adverse events; and 12 (15%) experienced treatment-related serious adverse events, none of which were fatal. Frequently reported (10% or more) treatment-emergent adverse events included elevated blood creatine phosphokinase (all grades, 31 [39%]; grade 3 or higher, 10 [13%]) and thrombocytopenia (all grades, 23 [29%]; grade 3 or higher, 14 [18%]). Among evaluable patients with chronic-phase CML, complete cytogenetic response (CCyR) occurred in 31 of 51 patients (61%; 95% CI, 46.1-74.2), and major molecular response (MMR) occurred in 25 of 59 patients (42%; 95% CI, 29.6-55.9). Cytogenetic and molecular responses were similar in patients with or without T315I variants. A total of 15 of 26 patients with prior ponatinib treatment (58%; 95% CI, 36.9-76.6) achieved CCyR, and 11 of 30 (37%; 95% CI, 19.9-56.1) achieved MMR. A total of 4 of 8 patients with asciminib resistance (50%; 95% CI, 15.7-84.3) had CCyR, and 4 of 12 (33%; 95% CI, 9.9-65.1) had MMR. The recommended phase 3 dose of olverembatinib is 30 mg every other day in patients without T315I variants.Conclusions and Relevance: In this trial, olverembatinib had a favorable pharmacokinetic profile, was generally well tolerated, and showed strong antileukemic activity in patients with heavily pretreated chronic-phase CML with or without T315I variants, including prior ponatinib and/or asciminib failure. Olverembatinib may provide a viable new treatment option for patients after failure of 2 or more TKIs.Trial Registration: ClinicalTrials.gov Identifier: NCT04260022

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a rare autosomal recessive disorder affecting fatty acid β-oxidation, primarily caused by mutations in the ACADVL gene. This condition can manifest in neonates with severe symptoms, including hypoglycemia, cardiomyopathy, and sudden cardiac arrest, often leading to high mortality rates if not diagnosed early

Arterial thrombosis is a leading cause of death and disability worldwide with no effective bioassay for clinical prediction. As a symbolic feature of arterial thrombosis, severe stenosis in the blood vessel creates a high-shear, high-gradient flow environment that facilitates platelet aggregation towards vessel occlusion. Here, we present a thrombus profiling assay that monitors the multi-dimensional attributes of thrombi forming in such biomechanical conditions. Using this assay, we demonstrate that different receptor–ligand interactions contribute distinctively to the composition and activation status of the thrombus. Our investigation into hypertensive and older individuals reveals intensified biomechanical thrombogenesis and multi-dimensional thrombus profile abnormalities, endorsing the diagnostic potential of the assay. Furthermore, we identify the hyperactivity of GPIbα-integrin α_IIbβ₃ mechanosensing axis as a molecular mechanism that contributes to hypertension-associated arterial thrombosis. By studying drug-disease interactions and inter-individual variability, our work reveals a need for personalized anti-thrombotic drug selection that accommodates each patient’s pathological profile.

Trans-activating transcriptional activator (TAT), a cell-penetrating peptide, has been extensively used for facilitating cellular uptake and nuclear targeting of drug delivery systems. However, the positively charged TAT peptide usually strongly interacts with serum components and undergoes substantial phagocytosis by the reticuloendothelial system, causing a short blood circulation in vivo. In this work, an acid-active tumor targeting nanoplatform DA-TAT-PECL was developed to effectively inhibit the nonspecific interactions of TAT in the bloodstream. 2,3-dimethylmaleic anhydride (DA) was first used to convert the TAT amines to carboxylic acid, the resulting DA-TAT was further conjugated to get DA-TAT-PECL. After self-assembly into polymeric micelles, they were capable of circulating in the physiological condition for a long time and promoting cell penetration upon accumulation at the tumor site and de-shielding the DA group. Moreover, camptothecin (CPT) was used as the anticancer drug and modified into a dimer (CPT)2-ss-Mal, in which two CPT molecules were connected by a reduction-labile maleimide thioether bond. The FRET signal between CPT and maleimide thioether bond was monitored to visualize the drug release process and effective targeted delivery of antitumor drugs was demonstrated. This pH/reduction dual-responsive micelle system provides a new platform for high fidelity cancer therapy.

Schematic illustration of the preparation of PNS hydrogels and their biomedical applications.