Entropy-Driven Design of Highly Impact-Stiffening Supramolecular Polymer Networks with Salt-Bridge Hydrogen Bonds.

Impact-stiffening materials that undergo a strain rate-induced soft-to-rigid transition hold great promise as soft armors in the protection of the human body and equipment. However, current impact-stiffening materials, such as polyborosiloxanes and shear-thickening fluids, often exhibit a limited impact-stiffening response. Herein, we propose a design strategy for fabricating highly impact-stiffening supramolecular polymer networks by leveraging high-entropy-penalty physical interactions. We synthesized a fully biobased supramolecular polymer comprising poly(α-thioctic acid) and arginine clusters, whose chain dynamics are governed by highly specific guanidinium-carboxylate salt-bridge hydrogen bonds. The resulting material exhibits an exceptional impact-stiffening response of ∼2100 times, transitioning from a soft dissipating state (21 kPa, 0.1 Hz) to a highly stiffened glassy state (45.3 MPa, 100 Hz) with increasing strain rates. Moreover, the material's high energy-dissipating and hot-melting properties bring excellent damping performance and easy hybridization with other scaffolds. This entropy-driven approach paves the way for the development of next-generation soft, sustainable, and impact-resistant materials.

Improved Multistage In-Motion Attitude Determination Alignment Method for Strapdown Inertial Navigation System.

This paper derives an improved multistage in-motion attitude determination alignment (IMADA) for strapdown inertial navigation system, which integrates the traditional IMADA and the designed dual velocity-modeling IMADA, as well as the multiple repeated alignment process, to address the principled model errors and the calculation errors of traditional V b -aided IMADA. With the proposed algorithm, not only the designed drawbacks of traditional V b -based IMADA can be solved, but also the degradation phenomenon of high-level alignment for multistage IMADA would be largely less. Moreover, the degradation of the alignment accuracy with the vehicle velocity is also removed. Finally, the 30 groups of car-mounted experiments and the Monte Carlo simulation experiments with the navigation-grade SINS are carried out to demonstrate the validity of the proposed algorithm. The results show that the number of the heading degradation of the second-level alignment is reduced to 10 as compared the traditional number 20. Moreover, the alignment accuracy of heading is improved by 23%. Even with the different speeds of 20 m/s, 60 m/s, 80 m/s, the heading alignment accuracies are 1.3063°, 1.3102°, 1.3564° and are still almost the same.

Physical interaction and assembly of Bacillus subtilis spore coat proteins CotE and CotZ studied by atomic force microscopy.

The spore of Bacillus subtilis, a dormant type of cell, is surrounded by a complex multilayered protein structure known as the coat. It is composed of over 70 proteins and essential for the spore to withstand extreme environmental conditions and allow germination under favorable conditions. However, understanding how the properties of the coat arise from the interactions among all these proteins is an important challenge. Moreover, many specific protein-protein interactions among the coat proteins are crucial for coat assembly. In this study, atomic force microscopy (AFM) based single molecule force spectroscopy (SMFS) was applied to investigate the interaction as a dynamic process between two morphogenetic coat proteins, CotE and CotZ. The unbinding force and kinetic parameters characterizing the interaction between CotE and CotZ were obtained. It is found that there is a strong affinity between CotE and CotZ. Furthermore, the assembly behaviors of CotE and CotZ, individually or in combination, were studied by AFM at solid-liquid interfaces. Our results revealed that CotE-CotZ assembly is dependent on their molar ratios and the interaction between CotE and CotZ involves in the CotE-CotZ assembly.

Study of the interactions between the key spore coat morphogenetic proteins CotE and SpoVID.

The capability of Bacillus subtilis spores to withstand extreme environmental conditions is thought to be conferred especially by their outermost proteinaceous protective layer, called the spore coat. Of the over 70 proteins that form the spore coat, only a small subset of them affect its morphogenesis, they are referred to as morphogenetic proteins. In this study we investigated the interaction between two spore coat morphogenetic proteins SpoVID and CotE. SpoVID is involved in the process of spore surface encirclement by individual coat proteins, these include CotE, which controls the assembly of the outer coat layer. Both proteins were proposed to be recruited to a common protein scaffold, but their direct association has not been previously shown. Here we studied the interactions between CotE and SpoVID in vitro for the first time by using molecule recognition force spectroscopy, which allows the detection of piconewton forces between conjugated biological pairs and also facilitates the investigation of dynamic processes. The most probable CotE-CotE unbinding force was 49.4±0.1pN at a loading rate of 3.16×10³ pN/s while that of SpoVID-CotE was 26.5±0.6pN at a loading rate of 7.8×10² pN/s. We further analyzed the interactions with the bacterial two hybrid system and pull-down experiments, which also indicate that SpoVID interacts directly with CotE. In combination with the previously identified direct contacts among SpoIVA, SpoVID and SafA, our data imply that the physical association of key morphogenetic proteins forms a basic skeleton where other coat proteins could be attached.

Molecular recognition force spectroscopy study of the dynamic interaction between aptamer GBI-10 and extracellular matrix protein tenascin-C on human glioblastoma cell.

Molecular recognition force spectroscopy (MR-FS) was applied to investigate the dynamic interaction between aptamer GBI-10 and tenascin-C (TN-C) on human glioblastoma cell surface at single-molecule level. The unbinding force between aptamer GBI-10 and TN-C was 39 pN at the loading rate of 0.3 nN sec⁻¹. A series of kinetic parameters concerning interaction process such as the unbinding force f(u) , the association rate constant k(on) , dissociation rate constant at zero force k(off) , and dissociation constant K(D) for aptamer GBI-10/TN-C complexes were acquired. In addition, the interaction of aptamer GBI-10 with TN-C depended on the presence of Mg²âº. This work demonstrates that MR-FS can be used as an attractive tool for exploring the interaction forces and dynamic process of aptamer and ligand at the single-molecule level. As a future perspective, MR-FS may be used as a potential diagnostic and therapeutic tool by combining with other techniques.

Non-equilibrium-Growing Aesthetic Ionic Skin for Fingertip-Like Strain-Undisturbed Tactile Sensation and Texture Recognition.

Humans use periodically ridged fingertips to precisely perceive the characteristics of objects via ion-based fast- and slow-adaptive mechanotransduction. However, designing artificial ionic skins with fingertip-like tactile capabilities remains challenging because of the contradiction between structural compliance and pressure sensing accuracy (e.g., anti-interference from stretch and texture recognition). Inspired by the formation and modulus-contrast hierarchical structure of fingertips, an aesthetic ionic skin grown from a non-equilibrium Liesegang patterning process is introduced. This ionic skin with periodic stiff ridges embedded in a soft hydrogel matrix enables strain-undisturbed triboelectric dynamic pressure sensing as well as vibrotactile texture recognition. By coupling with another piezoresistive ionogel, an artificial tactile sensory system is further fabricated as a soft robotic skin to mimic the simultaneous fast- and slow-adaptive multimodal sensations of fingers in grasping actions. This approach may inspire the future design of high-performance ionic tactile sensors for intelligent applications in soft robotics and prosthetics.

Multi-omics analysis of pyroptosis regulation patterns and characterization of tumor microenvironment in patients with hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver, and pyroptosis has been identified as a novel cellular program that plays a role in numerous diseases including cancer. However, the functional role of pyroptosis in HCC remains unclear. The purpose of this study is to explore the relationship between the two found hub genes and provide targets for clinical treatment. Methods: The Cancer Genome Atlas (TCGA) database was used to collect the gene data and clinically-related information of patients with HCC. After the differentially expressed genes (DEGs) were identified, they were intersected with the genes related to pyroptosis, and a risk prediction model was established to predict the overall survival (OS). Subsequently, drug sensitivity analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) was used to analyze the biological characteristics of the DEGs. Different immune cell infiltration and related pathways were analyzed, and hub genes were identified by protein-protein interaction (PPI). Finally, the expression of hub genes was verified by real-time quantitative PCR (qRT-PCR) and immunohistochemistry. Results: We conducted a comprehensive bioinformatics analysis to investigate the molecular mechanisms of pyroptosis in hepatocellular carcinoma (HCC). A total of 8,958 differentially expressed genes were identified, and 37 differentially expressed genes were associated with pyroptosis through intersection. Moreover, we developed an OS model with excellent predictive ability and discovered the differences in biological function, drug sensitivity, and immune microenvironment between high-risk and low-risk groups. Through enrichment analysis, we found that the differentially expressed genes are related to various biological processes. Then, 10 hub genes were identified from protein-protein interaction networks. Finally, midkine (MDK) was screened from the 10 hub genes and further verified by PCR and immunohistochemistry, which revealed its high expression in HCC. Conclusion: We have developed a reliable and consistent predictive model based on the identification of potential hub genes, which can be used to accurately forecast the prognosis of patients, thus providing direction for further clinical research and treatment.

Facile fabrication of SERS arrays through galvanic replacement of silver onto electrochemically deposited copper micropatterns.

Scatter me: A fast and cost-effective approach for the fabrication of surface-enhanced Raman scattering (SERS) arrays is developed. The method applied combines microcontact printing, electrodeposition, and galvanic replacement without the need for expensive instruments and intricate processing. The as-prepared arrays show excellent SERS activity and high reproducibility for Rhodamine 6G.

Diagnostic accuracy of contrast-enhanced ultrasound for microvascular invasion of hepatocellular carcinoma: A protocol for systematic review and meta-analysis.

BACKGROUND: Microvascular invasion is an independent risk factor for the recurrence of hepatocellular carcinoma (HCC). Early detection and timely treatment can reduce the recurrence and prolong the overall survival of HCC. Contrast-enhanced ultrasound (CEUS) has been validated for their predictive potential of microvascular invasion in HCC patients, although the conclusion remains controversial. Therefore, a meta-analysis is necessary to be conducted to validate the diagnostic value of CEUS for microvascular invasion in HCC, thus supporting guideline development and clinical practice. METHODS: Relevant studies reporting the potential diagnostic value of CEUS for microvascular invasion in HCC patients published before February 2022 will be searched in the PubMed, EMBASE, Cochrane Library, and Web of Science. Data will be extracted by 2 researchers independently. The risk of bias will be assessed by the Quality Assessment of Diagnostic Accuracy Studies-2. All of the above statistical analysis will be carried out with Stata 14.0. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will comprehensively evaluate the diagnostic accuracy of CEUS for microvascular invasion in HCC patients, thus providing high-quality evidence to support clinical practice and guideline development.

The functions of N6-methyladenosine (m6A) RNA modifications in colorectal cancer.

Colorectal cancers (CRC), which includes colon cancer (CC) and rectal cancer (RC), are some of the most common malignant tumors that are prone to distant metastasis. Its high incidence rate and high mortality rate have attracted much attention. In recent years, epigenetics has attracted increasing attention and has been the focus of many research studies. N6-methyladenosine(m6A) RNA modifications can modify eukaryotic mRNA to impact metabolism. The changes in the m6A regulatory genes are related to the occurrence and development of CRC and play an important role in the pathogenesis of CRC. The effect of m6A RNA modification is regulated by its related regulatory factors ("writer", "eraser", "reader"). In this review, we comprehensively analyzed the effect of m6A methylation on CRC and the relationship between the expression of related regulatory factors and the development and occurrence of CRC. Then, we summarized the roles of m6A and its regulatory factors in CRC and its potential clinical value, which provides a basis for further research on the mechanism of m6A methylation in CRC.

Ano1 is a Prognostic Biomarker That is Correlated with Immune Infiltration in Colorectal Cancer.

BACKGROUND: Anoctamin 1 (ANO1) has been observed to be overexpressed in gastrointestinal and pulmonary epithelial cells, as well as in a number of cancers. Although Ano1 is involved in the prognosis of colorectal cancer (CRC), its mechanism of action in metastatic CRC has not been fully elucidated. METHODS: The expression of Ano1 was assessed in samples obtained from The Cancer Genome Atlas (TCGA) database. Then, we used Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene set enrichment analysis (GSEA), Gene set variation analysis (GSVA), and Weighted Correlation Network Analysis (WGCNA) to determine the functions of Ano1. Additionally, random survival forest, Cox multivariate analysis, Kaplan Meier analysis, and ROC were used to determine the predictive value of Ano1 on clinical outcomes in CRC patients. Finally, HE staining, immunohistochemical (IHC) analysis and qRT-PCR were used to explore the expression of the Ano1 gene in CRC tissue. RESULTS: The expression level of Ano1 in CRC was significantly elevated, and the prognosis was poor. The modules with a higher proportion of upregulated genes tended to be positively correlated with Ano1-high. KNG1, GNG4, F2, POSTN, THBS2, SPP1 and FGA were identified as hub proteins of the PPI network. The heatmap showed that the expression level of the Ano1-high group was significantly negatively correlated with immune infiltrate. The overexpression of the Ano1 gene in CRC tissue samples was also confirmed by HE staining, immunohistochemical (IHC) analysis and qRT-PCR. CONCLUSION: High expression of Ano1 is closely related to a poor prognosis in patients with colorectal cancer. Ano1 may participate in the metastasis and progression, as well as the immune regulation of CRC. In summary, Ano1 can act as a potential prognostic biomarker and a novel target for CRC therapy.

Molecular recognition force spectroscopy of a specific lectin-carbohydrate interaction at single-molecule level.

Carbohydrates are involved in many essential biological recognition processes in physiological and pathological states. Thus, it is important to understand the mechanism of protein-carbohydrate interactions at molecular level. In the present study, molecular recognition force spectroscopy was applied to investigate the interactions between RCA120, a lectin from Ricinus communis, and galactose (Gal) and asialofetuin (ASF) at the single-molecule level. RCA120 coupled to the AFM tip could specifically recognize Gal and ASF, respectively. The unbinding forces of RCA120-Gal and RCA120-ASF increase linearly with the logarithm of loading rate. The results reveal that the binding capability of RCA120 toward Gal is weaker than that of ASF, implicating a multivalent effect in the RCA120-ASF interaction.

Multiple Weak H-Bonds Lead to Highly Sensitive, Stretchable, Self-Adhesive, and Self-Healing Ionic Sensors.

Herein, we demonstrate a ternary ionic hydrogel sensor consisting of tannic acid, sodium alginate, and covalent cross-linked polyacrylamide as skin-mountable and wearable sensors. Based on the multiple weak H-bonds and synergistic effects between the three components, the as-prepared hybrid hydrogel exhibits ultrastretchability with high elasticity, good self-healing, excellent conformability, and high self-adhesiveness to diverse substrates both in air and underwater. More importantly, the ternary hydrogel exhibits high strain sensitivity especially under subtle strains with a gauge factor of 2.0, which is close to the theoretical value of the ionic hydrogel sensors; an extremely large workable range of strain (0.05-2100%); and a low operating voltage 0.07 V. Consequently, the sensor demonstrates superior sensing performance for real-time monitoring of the large and subtle human motions, including limb motions, swallowing, smiling, and wrist pulse. Therefore, it is believed that the STP hydrogel has great potential applications in health monitoring, smart wearable devices, and soft robots.

The interactions of spore-coat morphogenetic proteins studied by single-molecule recognition force spectroscopy.

Bacillus subtilis can form a spore, which is a dormant type of cell, when its external environment becomes unsuitable for vegetative growth. The spore is surrounded by a multilayered proteinaceous shell called a spore coat, which plays a crucial role in dormancy and germination. Of the over 70 proteins that form the spore coat, only a small subset of them affect its morphogenesis; they are referred to as morphogenetic proteins. How these morphogenetic proteins interact, and furthermore, how they build the ordered, functional coat layers is not well understood. Elucidating the self-assembly mechanism of individual proteins into such a complex structure may contribute to its potential use in nano-biotechnology applications for preparing highly organized, robust, and resistant proteinaceous layers. Herein, direct, noncovalent, low-affinity interactions between the spore-coat morphogenetic proteins SpoIVA, SpoVID, and SafA were studied by using single-molecule recognition force spectroscopy in vitro for the first time. Based on the real-time examination of interactions between these three proteins, a series of dynamic kinetic data were obtained. It was also observed that the SafA-SpoVID interaction was stronger than that of SafA-SpoIVA.

Fractal self-assembly of single-stranded DNA on hydrophobic self-assembled monolayers.

The self-assembled structures possess superior stability, biocompatibility and mechanical strength, and their study can provide insight into the use of creating novel biomaterials. Atomic force microscopy (AFM) images of single-stranded DNA (ssDNA) nanostructures show that well-ordered organization, high homogeneity, and molecular dimensions fractal-shaped fibers formed on a gold substrate covered with self-assembled monolayers (SAMs) of 1-hexadecanethiol (HDT). The nanoscaled architectures of ssDNA on HDT/Au changed remarkably following the process of diffusion-limited cluster aggregation (DLA) over time. The ssDNA fibers prefer to form on hydrophobic SAMs instead of hydrophilic SAMs, and the ssDNA has to have complementary regions in their sequences. This method might not be used only for the construction of fractal patterns, but also for the design and fabrication of functional DNA-based, self-assembled materials that exhibit self-similarity at multiple length scales.

Single molecular recognition force spectroscopy study of a luteinizing hormone-releasing hormone analogue as a carcinoma target drug.

The luteinizing hormone-releasing hormone- Pseudomonas aeruginosa exotoxin 40 (LHRH-PE40), is a candidate target drug associated with elevated LHRH receptor (LHRH-R) expression in malignant tumor tissue. The capability of LHRH-PE40 to recognize LHRH-Rs on a living cell membrane was studied with single molecular recognition force spectroscopy (SMFS) based on atomic force microscopy (AFM). The recognition force of LHRH-PE40/LHRH-R was compared with that of LHRH/LHRH-R by dynamic force spectroscopy. Meanwhile, cell growth inhibition assay and fluorescence imaging were presented as complementary characterization. The results show that LHRH moiety keeps its capability to recognize LHRH-R specifically, which implies that recombinant protein LHRH-PE40 can be a promising target drug.