Identification of molecular markers for predicting the severity of heart failure after AMI: An Olink precision proteomic study.

BACKGROUND: Acute myocardial infarction (AMI) still has a high incidence of varying degrees of heart failure (HF). The aim of this study is to identify new molecular markers for predicting the severity of HF after AMI. METHODS: We analyzed demographic indicators, past medical history, clinical indicators, major adverse cardiac events (MACEs) and molecular markers in patients with different Killip classifications after AMI. Olink proteomics was used to explore new molecular markers for predicting different severity of HF after AMI. RESULTS: Neutrophil count was the independent risk factors for in-hospital MACEs. Nineteen differentially expressed proteins (DEPs) increased significantly with increasing Killip classification. Five DEPs were also found to have an AUC (95 % CI) value greater than 0.8: GDF-15, NT-pro BNP, TNF-R2, TNF-R1 and TFF3. CONCLUSIONS: Neutrophil count, GDF-15, TNF-R2, TNF-R1 and TFF3 were closely related to the Killip classification of HF after AMI, which suggests that the inflammatory response plays an important role in the severity of HF after AMI and that regulating inflammation might become a new target for controlling HF.

Glutamine supplementation alleviated aortic atherosclerosis in mice model and in vitro.

This study aimed to clarify the role of glutamine in atherosclerosis and its participating mechanism. Forty C57BL/6J mice were divided into wild control (wild Con), ApoE- /- control (ApoE- /- Con), glutamine + ApoE- /- control (Glut + ApoE- /- Con), ApoE- /- high fat diet (ApoE- /- HFD), and glutamine + ApoE- /- HFD (Glut + ApoE- /- HFD) groups. The degree of atherosclerosis, western blotting, and multiomics were detected at 18 weeks. An in vitro study was also performed. Glutamine treatment significantly decreased the degree of aortic atherosclerosis (p = 0.03). O-GlcNAcylation (O-GlcNAc), IL-1ß, IL-1α, and pyruvate kinase M2 (PKM2) in the ApoE- /- HFD group were significantly higher than those in the ApoE- /- Con group (p < 0.05). These differences were attenuated by glutamine treatment (p < 0.05), and aggravated by O-GlcNA transferase (OGT) overexpression in the in vitro study (p < 0.05). Multiomics showed that the ApoE- /- HFD group had higher levels of oxidative stress regulatory molecules (guanine deaminase [GUAD], xanthine dehydrogenase [XDH]), proinflammatory regulatory molecules (myristic acid and myristoleic acid), and stress granules regulatory molecules (caprin-1 and deoxyribose-phosphate aldolase [DERA]) (p < 0.05). These differences were attenuated by glutamine treatment (p < 0.05). We conclude that glutamine supplementation might alleviate atherosclerosis through downregulation of O-GlcNAc, glycolysis, oxidative stress, and proinflammatory pathway.

Calixarene-based cryoprotectants for ice recrystallization inhibition and cell cryopreservation.

The development of new cryoprotectants for cryopreservation of cells has attracted considerable interest. Herein, five calixarene-based CPAs (SC4A, S-S-C4A, S-SO2-C4A, SBAC4A, and CAC4A) were developed, and their IRI activity, DIS property and cryoprotective effect were studied. SBAC4A with a sulphobetaine zwitterion and SC4A with sulfo group modification possessed better cryoprotective effects than the other calixarene-based CPAs, especially for SBAC4A with the enhanced cell viabilities of 16.16 ± 1.78%, 12.60 ± 1.15% and 14.90 ± 1.66% against MCF-7, hucMSCs and A549 cells, respectively. This result provides a supramolecular principle for developing novel CPAs with consideration of the factors of hydrogen bonding, the macromolecular crowding principle and the three-dimensional (3D) structure.

An ecological assessment of the potential pandemic threat of Dengue Virus in Zhejiang province of China.

BACKGROUND AND AIM: Dengue fever, transmitted by Aedes mosquitoes, is a significant public health concern in tropical and subtropical regions. With the end of the COVID-19 pandemic and the reopening of the borders, dengue fever remains a threat to mainland China, Zhejiang province of China is facing a huge risk of importing the dengue virus. This study aims to analyze and predict the current and future potential risk regions for Aedes vectors distribution and dengue prevalence in Zhejiang province of China. METHOD: We collected occurrence records of DENV and DENV vectors globally from 2010 to 2022, along with historical and future climate data and human population density data. In order to predict the probability of DENV distribution in Zhejiang province of China under future conditions, the ecological niche of Ae. aegypti and Ae. albopictus was first performed with historical climate data based on MaxEnt. Then, predicted results along with a set of bioclimatic variables, elevation and human population density were included in MaxEnt model to analyze the risk region of DENV in Zhejiang province. Finally, the established model was utilized to predict the spatial pattern of DENV risk in the current and future scenarios in Zhejiang province of China. RESULTS: Our findings indicated that approximately 89.2% (90,805.6 KM2) of Zhejiang province of China is under risk, within about 8.0% (8,144 KM2) classified as high risk area for DENV prevalence. Ae. albopictus were identified as the primary factor influencing the distribution of DENV. Future predictions suggest that sustainable and "green" development pathways may increase the risk of DENV prevalence in Zhejiang province of China. Conversely, Fossil-fueled development pathways may reduce the risk due to the unsuitable environment for vectors. CONCLUSIONS: The implications of this research highlight the need for effective vector control measures, community engagement, health education, and environmental initiatives to mitigate the potential spread of dengue fever in high-risk regions of Zhejiang province of China.

Experimental study on FBG sensing technology-based stress monitoring at the corners of reinforced soil retaining walls.

As a unique type of flexible slope fill-retaining structure, reinforced soil-retaining walls have the advantages of convenient construction, broad application conditions, good seismic performance, and high economic benefits. In general, reinforced soil-retaining walls appear at corners due to the restriction in topographic conditions during engineering construction. However, their special structures and stress conditions are usually ignored, thus triggering panel bulging, cracking, and collapse. In this study, an experimental method based on fiber Bragg grating (FBG) sensing technology was proposed for a physical model of reinforced soil-retaining walls. Then, a uniformly distributed load experiment was performed on this model by combining the measurement advantages of intelligent wire-type soil pressure sensors and the flexible characteristics of geotechnical reinforcement materials. The deformation development of this reinforced soil-retaining wall was monitored. Results revealed that before and after the loading of the reinforced soil-retaining wall, the deformation was mainly concentrated above the retaining wall, and the deformation scale at the corners was larger than that in the bilateral linear parts. After loading, the largest force deformation area on the retaining wall was transferred from the corners to the load area. The maximum strain was right beneath the load above the retaining wall, and the peak value at the other layers gradually approached the retaining wall. The experimental results prove that FBG sensing technology is feasible and effective for the whole-process monitoring of reinforced soil-retaining walls and is thus worthy of popularization and application.

A hypoxia-responsive supramolecular formulation for imaging-guided photothermal therapy.

Photothermal agents (PTAs) based on organic small-molecule dyes emerge as promising theranostic strategy in imaging and photothermal therapy (PTT). However, hydrophobicity, photodegradation, and low signal-to-noise ratio impede their transformation from bench to bedside. In this study, a novel supramolecular PTT formulation by a stimuli-responsive macrocyclic host is prepared to overcome these obstacles of organic small-molecule PTAs. Methods: Sulfonated azocalix[4]arene (SAC4A) was synthesized as a hypoxia-responsive macrocyclic host. Taking IR780 as an example, the supramolecular nanoformulation IR780@SAC4A was constructed by grinding method, and its solubility, photostability, and photothermal conversion were evaluated. The hypoxia tumor-selective imaging and supramolecular PTT of IR780@SAC4A were further evaluated in vitro and in vivo. Results: IR780@SAC4A is capable of enhancing the solubility, photostability, and photothermal conversion of IR780 significantly, which achieve this supramolecular formulation with good imaging-guided PTT efficacy in vitro and in vivo. Conclusions: This study demonstrates that the supramolecular PTT strategy is a promising cancer theranostic method. Moreover, this supramolecular approach is applicative to construct kinds of supramolecular PTAs, opening a general avenue for extending smart PTT formulations.

Deep Cavitand Calixarene-Solubilized Fullerene as a Potential Photodynamic Agent.

Fullerene has attracted much attention in biomedical research due to its unique physical and chemical properties. However, the hydrophobic nature of fullerene is limited to deploy in the body, given that the biofluids are mainly water. In this study, a water-soluble supramolecular nanoformulation based on a deep cavitand calixarene (SAC4A) and fullerene is developed to overcome the hydrophobicity of fullerene and is used as a potential photodynamic agent. SAC4A solubilizes fullerene very well with a simple grinding method. The significantly increased water solubility of fullerene enables efficient activation of reactive oxygen species. The host-guest strategy to solubilize fullerene can not only provide a new method to achieve water solubility but also expand the biomedical applications of fullerene.

Calixarene-Embedded Nanoparticles for Interference-Free Gene-Drug Combination Cancer Therapy.

Combination therapy based on molecular drugs and therapeutic genes provides an effective strategy for malignant tumor treatment. However, effective gene and drug combinations for cancer treatment are limited by the widespread antagonism between therapeutic genes and molecular drugs. Herein, a calixarene-embedded nanoparticle (CENP) is developed to co-deliver molecular drugs and therapeutic genes without compromising their biological functions, thereby achieving interference-free gene-drug combination cancer therapy. CENP is composed of a cationic polyplex core and an acid-responsive polymer shell, allowing CENP loading and delivering therapeutic genes with improved circulation stability and enhanced tumor accumulation. Moreover, the introduction of carboxylated azocalix[4]arene, which is a hypoxia-responsive calixarene derivatives, in the polyplex core endows CENP with the capability to load molecular drugs through the host-guest complexation as well as inhibit the interference between the drugs and genes by encapsulating the drugs into its cavity. By loading doxorubicin and a plasmid DNA-based CRISPR interference system that targets miR-21, CENP exhibits the significantly enhanced anti-tumor effects in mice. Considering the wide variety of calixarene derivatives, CENP can be adapted to deliver almost any combination of drugs and genes, providing the potential as a universal platform for the development of interference-free gene-drug combination cancer therapy.

A General Hypoxia-Responsive Molecular Container for Tumor-Targeted Therapy.

Enhanced drug delivery can improve the therapeutic efficacy of drugs and help overcome side effects. However, many reported drug-delivery systems are too complex and irreproducible for practical use. In this work, the design of a hypoxia-responsive molecular container based on calixarene, called CAC4A, which presents a significant advance in practical, hypoxia-targeted drug-delivery, is reported. CAC4A enables a wide variety of clinical drugs to be quantitatively loaded to improve their solubility and stability, as well as enable the administration of reduced doses. Furthermore, as a result of its azo functional groups, which are sensitive to reduction within a hypoxic environment, it is possible to achieve tumor-targeted drug-release with reduced side effects. CAC4A fulfils all essential requirements for a drug-delivery system in addition to multiple advantages, including facile preparation, well-defined molecular weight, and structure, and universal applicability. Such features collectively enable supramolecular prodrugs to be formulated simply and reproducibly, with potential for bench-to-bedside translation. Moreover, CAC4A is amenable to other therapy modalities and can be facilely decorated with functional groups and hybridized with nanomaterials, providing ample possibilities for its role in future drug-delivery systems.

Enzyme-responsive supramolecular polymers by complexation of bis(p-sulfonatocalixarenes) with suberyl dicholine-based pseudorotaxane.

A linear supramolecular ternary polymer was fabricated by iteratively threading cyclodextrin with suberyl dicholine and end-capping with bis-calixarenes, showing desired cholinesterase response.