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Abstract The circadian clock coordinates the daily rhythmicity of biological processes, and its dysregulation is associated with various human diseases. Despite the direct targeting of rhythmic genes by many prevalent and World Health Organization (WHO) essential drugs, traditional approaches can't satisfy the need of explore multi‐timepoint drug administration strategies across a wide range of drugs. Here, droplet‐engineered primary liver organoids (DPLOs) are generated with rhythmic characteristics in 4 days, and developed Chronotoxici‐plate as an in vitro high‐throughput automated rhythmic tool for chronotherapy assessment within 7 days. Cryptochrome 1 (Cry1) is identified as a rhythmic marker in DPLOs, providing insights for rapid assessment of organoid rhythmicity. Using oxaliplatin as a representative drug, time‐dependent variations are demonstrated in toxicity on the Chronotoxici‐plate, highlighting the importance of considering time‐dependent effects. Additionally, the role of chronobiology is underscored in primary organoid modeling. This study may provide tools for both precision chronotherapy and chronotoxicity in drug development by optimizing administration timing.

As one of the most widely used personal protective equipment (PPE), body armors play an important role in protecting the human body from the high-velocity impact of bullets or projectiles. The body torso and critical organs of the wear may suffer severe behind-armor blunt trauma (BABT) even though the impactor is stopped by the body armor. A type of novel composite material through incorporating shear stiffening gel (STG) into ethylene-vinyl acetate (EVA) foam is developed and used as buffer layers to reduce BABT. In this paper, the protective performance of body armors composed of fabric bulletproof layers and a buffer layer made of foam material is investigated both experimentally and numerically. The effectiveness of STG-modified EVA in damage relief is verified by ballistic tests. In parallel with the experimental study, numerical simulations are conducted by LS-DYNA® to investigate the dynamic response of each component and capture the key mechanical parameters, which are hardly obtained from field tests. To fully describe the material behavior under the transient impact, the selected constitutive models take the failure and strain rate effect into consideration. A good agreement between the experimental observations and numerical results is achieved to prove the validity of the modelling method. The tests and simulations show that the impact-induced deformation on the human body is significantly reduced by using STG-modified EVA as the buffering material. The improvement of protective performance is attributed to better dynamic properties and more outstanding energy absorption capability of the composite foam.

Abstract Hyperuricemia, caused by an imbalance between the rates of production and excretion of uric acid (UA), may greatly increase the mortality rates in patients with cardiovascular and cerebrovascular diseases. Herein, for fast‐acting and long‐lasting hyperuricemia treatment, armored red blood cell (RBC) biohybrids, integrated RBCs with proximal, cascaded‐enzymes of urate oxidase (UOX) and catalase (CAT) encapsulated within ZIF‐8 framework‐based nanoparticles, have been fabricated based on a super‐assembly approach. Each component is crucial for hyperuricemia treatment: 1) RBCs significantly increase the circulation time of nanoparticles; 2) ZIF‐8 nanoparticles‐based superstructure greatly enhances RBCs resistance against external stressors while preserving native RBC properties (such as oxygen carrying capability); 3) the ZIF‐8 scaffold protects the encapsulated enzymes from enzymatic degradation; 4) no physical barrier exists for urate diffusion, and thus allow fast degradation of UA in blood and neutralizes the toxic by‐product H2O2. In vivo results demonstrate that the biohybrids can effectively normalize the UA level of an acute hyperuricemia mouse model within 2 h and possess a longer elimination half‐life (49.7 ± 4.9 h). They anticipate that their simple and general method that combines functional nanomaterials with living cell carriers will be a starting point for the development of innovative drug delivery systems.

Heart rate arrhythmia is an important manifestation of common clinical cardiovascular diseases, posing a serious threat to human life and health. Due to its suddenness, insidiousness and rapid changes, it often causes patients to miss the best treatment time. Therefore, real-time monitoring of heart rate changes is particularly important to monitor and prevent the onset of such diseases. Nonetheless, heart rate information in telemedicine systems is often presented in plaintext, rendering it vulnerable to interception or tampering, and posing a substantial threat to users’ privacy. To address this issue, we propose a privacy-preserving remote heart rate abnormality monitoring system, which utilizes a privacy comparison protocol. By implementing a two-server model, the privacy comparison protocol ensures privacy not only during the comparison process but also in the resulting outcomes. During the monitoring process, the monitor is only able to obtain the final number of abnormalities of the patient’s heart rate and cannot obtain information about the patient’s original heart rate. This allows for a more rational and effective use of medical experts, so that patients can enjoy a high level and quality of service from medical experts without having to leave home. Finally, a detailed security analysis demonstrates that our scheme can effectively protect the privacy and security of patient medical data and hospital health indicators. And our experimental results show that our scheme is computationally efficient and the scheme is effective and feasible.

In order to study the deformation and failure characteristics of rocks under different cyclic loading and unloading paths, three stress path tests were conducted, and acoustic emission (AE) monitoring was conducted simultaneously. The mechanical characteristics and AE characteristics under different stress paths were analyzed, and the influences of the different stress paths on the energy dissipation and deformation damage were investigated. The law of energy evolution considering viscoelasticity under different stress paths was obtained. The concept of ultimate damage energy and its calculation method was proposed. The results show that the “hardening effect” of sandstone and granite under the constant lower limit (CLLCL) is the most significant in maximizing the mechanical property. The CLLCL imparts a stronger elastic property to rocks than the variable lower limit (VLLCL) does, while the VLLCL causes more damage to rocks than the CLLCL. A significant linear relationship between the proportion of damage energy and the proportion of elastic energy was discovered. Based on this linear relationship, the ultimate damage energy can be calculated for sandstone and granite. The evolution of the damage variable based on damage energy was compatible with the real damage condition, which validates the ultimate damage energy calculation method. The research results lay a theoretical foundation for the design and construction of geotechnical engineering.

Due to their high spatial resolution, thin-section magnetic resonance (MR) images serve as ideal medical images for brain structure investigation and brain surgery navigation. However, compared with the clinically widely used thick-section MR images, thin-section MR images are less available due to the imaging cost. Thin-section MR images of infants are even scarcer but are quite valuable for the study of human brain development. Therefore, we propose a method for the reconstruction of thin-section MR images from thick-section images. A two-stage reconstruction framework based on generative adversarial networks (GANs) and a convolutional neural network (CNN) is proposed to reconstruct thin-section MR images from thick-section images in the axial and sagittal planes. A 3D-Y-Net-GAN is first proposed to fuse MR images from the axial and sagittal planes and to achieve the first-stage thin-section reconstruction. A 3D-DenseU-Net followed by a stack of enhanced residual blocks is then proposed to provide further detail recalibrations and structural corrections in the sagittal plane. In this method, a comprehensive loss function is also proposed to help the networks capture more structural details. The reconstruction performance of the proposed method is compared with bicubic interpolation, sparse representation, and 3D-SRU-Net. Cross-validation based on 35 cases and independent testing based on two datasets with totally 114 cases reveal that, compared with the other three methods, the proposed method provides an average 23.5% improvement in peak signal-to-noise ratio (PSNR), 90.5% improvement in structural similarity (SSIM), and 21.5% improvement in normalized mutual information (NMI). The quantitative evaluation and visual inspection demonstrate that our proposed method outperforms those methods by reconstructing more realistic results with better structural details.

Objective: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common form of autoimmune encephalitis in pediatric patients. In this study, we aimed to investigate the clinical features and long-term outcomes of pediatric patients with anti-NMDAR encephalitis in China.Methods: We conducted a retrospective study of children (age range: 0–18 years) with anti-NMDAR encephalitis treated at Children's Hospital of Fudan University between July 2015 and November 2018. Demographic characteristics, clinical features, treatment, and outcomes were reviewed.Results: Thirty-four patients with anti-NMDAR encephalitis were enrolled (age range: 5 months to 14 years; median age: 7 years; female: 18). The median follow- up duration was 20 months (range: 6–39 months). Eighteen (52.9%) patients initially presented with seizures and 10 (29.4%) with abnormal (psychiatric) behaviors or cognitive dysfunction. Thirty (88.2%) patients exhibited more than two symptoms during the disease course. No neoplasms were detected. Twelve (35.2%) patients had abnormal cerebrospinal fluid (CSF) findings, including leukocytosis, and increased protein concentration. Eighteen (52.9%) patients exhibited normal brain MRI findings. Electroencephalography revealed abnormal background activity in 27 (79.4%) patients, and epileptiform discharges in 16 (47.0%) patients prior to immunotherapy. All patients received first-line immunotherapy, with 30 (88.2%) and four (11.8%) patients achieving good (Modified Rankin Scale [mRS] score of 0–2) and poor outcomes (mRS score of 3–5), respectively. Initial mRS scores differed significantly between the good and poor outcome groups. Fourteen out of 18 patients (77.7%) with seizures accepted anti-epileptic drug (AED) administration, and seizure freedom was achieved in 12 out of 14 (85.7%) patients at the last follow-up. Ten of these 12 (83.3%) patients withdrew from AED treatment within 1 year.Conclusions: Most patients achieved seizure freedom, so long-term use of AEDs may not be necessary for pediatric patients with anti-NMDAR encephalitis. Among our patients, 83.3% were sensitive to first-line immunotherapy and achieved good outcomes. Higher mRS scores before immunotherapy predicted poor outcomes, highlighting the need for a comprehensive assessment of patients with anti-NMDAR encephalitis.

A new iridoid glycoside, named loganic acid ethyl ester (1), together with five known compounds: chlorogenic acid (2), caffeic acid (3), loganin (4), cantleyoside (5) and syringaresinol-4′,4′′-O-bis-β-D-glucoside (6) were isolated from the roots of Dipsacus asper. The structure of compound 1 was elucidated on the basis of detailed spectroscopic analyses. Lignan is isolated from Dipsacaceae species for the first time. Compounds 1, 4 and 5 had moderate neuroprotective effects against the Aβ25–35 induced cell death in PC12 cells.

A new iridoid glycoside, named loganic acid ethyl ester (1), together with five known compounds: chlorogenic acid (2), caffeic acid (3), loganin (4), cantleyoside (5) and syringaresinol-4',4''-O-bis-β-D-glucoside (6) were isolated from the roots of Dipsacus asper. The structure of compound 1 was elucidated on the basis of detailed spectroscopic analyses. Lignan is isolated from Dipsacaceae species for the first time. Compounds 1, 4 and 5 had moderate neuroprotective effects against the A#x03B2;25-35 induced cell death in PC12 cells. [ABSTRACT FROM AUTHOR]