Thermo-growing ion clusters enabled healing strengthening and tough adhesion for highly reliable skin electronics.

Self-healing and self-adhesion capacities are essential for many modern applications such as skin-interfaced electronics for improving longevity and reliability. However, the self-healing efficiency and adhesive toughness of most synthetic polymers are limited to their original network, making reliability under dynamic deformation still challenging. Herein, inspired by the growth of living organisms, a highly stretchable supramolecular elastomer based on thermo-responsive ion clusters and a dynamic polysulfide backbone was developed. Attributed to the synergic growth of ion clusters and dynamic exchange of disulfide bonds, the elastomer exhibited unique healing strengthening (healing efficiency >200%) and thermo-enhanced tough adhesion (interfacial toughness >500 J m-2) performances. To prove its practical application in highly reliable skin electronics, we further composited the elastomer with a zwitterion to prepare a highly conductive ionic elastomer and applied it in wearable strain sensing and long-term electrophysiological detection. This work provides a new avenue to realize high reliability in skin interfaced electronics.

Intergenerational caregiving on mental health of middle-aged and older adults in China: empirical insights.

Introduction: The impact of intergenerational caregiving on the mental health of providers remains a controversial topic, especially in countries like China where it is prevalent. Given the country's aging population and recent liberalization of the two-child policy, understanding the effects of intergenerational caregiving on the mental health of middle-aged and older adult(s) individuals is crucial. This study aimed to explore the impact of intergenerational caregiving on mental health among middle-aged and older adult(s) individuals. Methods: We analyzed data from the China Health and Aging Tracking Survey (CHARLS) 2013, consisting of 6602 participants finally. Personal information, family structure, financial support, health status, and physical measurements were selected for analysis. Correlation and regression analyses were used for relationships among variables controlling for potential confounding variables. Mental health status was evaluated using the depression self-rating scale. Results: There is a significant positive effect of intergenerational care on the mental health of middle-aged and older adult(s) people. Additionally, we re-profiled intergenerational care variables by considering the number and length of intergenerational caregivers, and found that the effects remained significant. Furthermore, the effects of intergenerational care vary across subgroups based on gender, age, nature of usual residence, marital status, and physical health status. Finally, we identified two mechanisms through which intergenerational caregiving positively affects mental health: intergenerational financial support and intergenerational spiritual support. Discussion: These findings have important implications for policymakers, healthcare professionals, and family members in promoting the mental health of middle-aged and older adult(s) individuals in China.

Selection and truncation of aptamers as fluorescence sensing platforms for selective and sensitive detection of nitrofurazone.

Nitrofurazone (NFZ) is an antibiotic banned in many countries, as its residue seriously harms the human body. Herein, anti-NFZ aptamers were selected and identified based on the magnetic bead SELEX technique using a ssDNA library with a full length of 90 nucleotides (nt). Five full sequence candidate aptamers (NFZ8, NFZ24, NFZ28, NFZ34, and NFZ70) were obtained by secondary structure analysis. We optimized the entire sequence to obtain a truncated aptamer, a 16 nt sequence (NFZ8-1:5'-GTTCTATTGAAAAAAC-3') that showed the highest affinity for NFZ (Kd = 76.11 nM). The binding site of NFZ and aptamer NFZ8-1 was found to be "GAA" by molecular docking. In addition, utilizing the most special truncated aptamer NFZ8-1 as the identification probe, a graphene oxide fluorescent aptasensor is an innovative for the detection of NFZ residue that showed a wide linear reach from 1.25 to 160 ng/mL and a low limit of detection of 1.13 ng/mL. In the actual water environment sample detection, the recovery rate ranged from 95.21 to 113.66%, and the coefficient of variation ranged from 3.53 to 11.24%. These results demonstrate that the NFZ-truncated aptamer applied to the aptasensor provides a novel methodology for recognizing NFZ residues.

High-Sensitive FAM Labeled Aptasensor Based on Fe3O4/Au/g-C3N4 for the Detection of Sulfamethazine in Food Matrix.

In this study, we developed a fluorescent aptasensor based on Fe3O4/Au/g-C3N4 and a FAM-labeled aptamer (FAM-SMZ1S) against sulfamethazine (SMZ) for the specific and sensitive detection of SMZ in food matrix. The FAM-SMZ1S was adsorbed by the Fe3O4/Au/g-C3N4 via π-π stacking and electrostatic adsorption, serving as a basis for the ultrasensitive detection of SMZ. Molecular dynamics was used to explain the reasons why SMZ1S and SMZ were combined. This aptasensor presented sensitive recognition performance, with a limit of detection of 0.16 ng/mL and a linear range of 1-100 ng/mL. The recovery rate ranged from 91.6% to 106.8%, and the coefficient of variation (CV) ranged from 2.8% to 13.4%. In addition, we tested the aptasensor for the monitoring of SMZ in various matrix samples, and the results were well-correlated (R2 ≥ 0.9153) with those obtained for HPLC detection. According to these results, the aptasensor was sensitive and accurate, representing a potentially useful tool for the detection of SMZ in food matrix.

Preparation of Monoclonal Antibody and Development of Indirect Competitive Enzyme-Linked Immunosorbent Assay and Fluorescence-Linked Immunosorbent Assay for Detecting 3-Amino-5-methylmorpholino-2-oxazolidinone (AMOZ) in Edible Animal Tissue.

To monitor the illegal used of furaltadone, a highly sensitive indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and fluorescence-linked immunosorbent assay (FLISA) based on a monoclonal antibody (mAb) were developed for the detection of 3-amino-5-methylmorpholino-2-oxazolidinone (AMOZ), the major metabolite of furaltadone in animal tissues. The highly specific mAb, which was very sensitive to a nitrophenyl derivative of AMOZ (2-NP-AMOZ) with IC50 values of 0.11 and 0.09 ng/mL for ic-ELISA and FLISA, respectively, was selected for the development of immunoassays. For both the ic-ELISA and FLISA for AMOZ-spiked experiments, acceptable recovery rates of 81.1-105.3% and coefficients of variation of 4.7-9.8% were obtained. In addition, results from both ic-ELISA and FLISA methods for spiked samples' data showed excellent correlation coefficients ranging from 0.9652 to 0.9927. Meanwhile, the proposed ic-ELISA and FLISA for thirty spiked samples were confirmed by standard LC-MS/MS with high correlation coefficients of 0.9911 and 0.9921, respectively. These results suggest that the developed ic-ELISA and FLISA are valid and cost-effective tools for high-throughput monitoring methods for AMOZ residues in animal tissues.

Glucocappasalin Induces G2/M-Phase Arrest, Apoptosis, and Autophagy Pathways by Targeting CDK1 and PLK1 in Cervical Carcinoma Cells.

Glucocappasalin (GCP), a natural product derived from the seeds of Descurainia sophia (L.) Webb. ex Prantl, exhibits potential antitumor activity in HeLa cervical carcinoma cells. In this study, we investigated the anti-cervical cancer property of GCP through the induction of cell cycle arrest, apoptosis, and autophagy in vitro and in vivo, and elucidated the underlying molecular mechanisms. We demonstrated that treatment with GCP inhibited the growth of HeLa, Siha, and Ca Ski cell lines in a dose-dependent manner, with HeLa cells displaying particular sensitivity to the GCP treatment. Subsequently, the expression of cyclin-dependent kinase 1 (CDK1) and polo like kinase 1 (PLK1) were evaluated in HeLa cells using the CDK1 kinase assay kit, the fluorescence polarization assay, real-time quantitative PCR, and western blotting. Our results demonstrate that GCP could be employed to attenuate the expression of CDK1 and PLK1 in a dose- and time-dependent manner. The complementary results obtained by flow cytometry and western blotting allowed us to postulate that GCP may exhibit its antitumor effects by inducing G2/M cell cycle arrest. Moreover, HeLa cells treated with GCP exhibited a loss in mitochondrial membrane potential, together with the activation of caspases 3 and 9, and poly ADP-ribose polymerase (PARP). Additionally, we found that GCP could increase the formation of acidic vesicular organelles (AVOs), as well as the levels of Beclin1, LC3-II, p62, and Atg5 proteins in HeLa cells. Further studies indicated that GCP triggered autophagy via the suppression of the PI3K/AKT/mTOR signaling pathways. The autophagy inhibitor 3-methyladenine (3-MA) was used to determine whether autophagy affects the apoptosis induced by GCP. Interestingly, the inhibition of autophagy attenuated apoptosis. In vivo anti-tumor experiments indicated that GCP (60 mg/kg, i.p.) markedly reduced the growth of HeLa xenografts in nude mice without apparent toxicity. Taken together, we demonstrate that GCP induces cell cycle G2/M-phase arrest, apoptosis, and autophagy by acting on the PI3K/AKT/mTOR signaling pathways in cervical carcinoma cells. Thus, GCP may represent a promising agent in the eradication of cervical cancer.

An Ultrasensitive Label-Free Fluorescent Aptasensor Platform for Detection of Sulfamethazine.

PURPOSE: Sulfamethazine (SMZ) exposed in the environment can enter the human body through the food chain and pose a serious threat to human health. Therefore, it is important to develop a rapid and sensitive method for detecting SMZ in environmental samples. In order to fastly and quantitatively detect SMZ in environmental samples, we developed a label-free fluorescent aptasensor based on specific aptamer (SMZ1S) and fluorescence resonance energy transfer (FRET) between gold nanoparticles (AuNPs) and rhodamine B (RhoB). METHODS: In the absence of SMZ, SMZ1S was adsorbed on the surface of AuNPs, which led to dispersion of the AuNPs in high concentration saline solution, thus effectively quenching the fluorescence of RhoB. With the increase of the SMZ concentration, the specific binding of SMZ1S and SMZ led to the aggregation of AuNPs in the presence of NaCl, which reduced the quenching of RhoB fluorescence and increased the fluorescence intensity. The sensitivity and linearity curve of the label-free fluorescent aptasensor were determined with different concentrations of sulfamethazine standard solutions. The specificity of this fluorescent aptasensor was determined by replacing sulfamethazine with different antibiotics. In addition, the actual water and soil samples were spiked and recovered. RESULTS: Under optimized conditions, the proposed fluorescent aptasensor demonstrated a good linear detection of SMZ in binding buffer from 1.25 ng mL-1 to 40 ng mL-1 and the limit of detection was 0.82 ng mL-1. The spiked recoveries for SMZ were 94.4% to 108.8% with a relative standard deviation of 1.8-10.3% in water and soil samples, respectively. CONCLUSION: The label-free fluorescent aptasensor investigated in the current study is a promising tool to detect and quantify SMZ in water and soil samples.

Selection and truncation of aptamers for ultrasensitive detection of sulfamethazine using a fluorescent biosensor based on graphene oxide.

We developed a fluorescent aptamer/graphene oxide (GO)-based biosensor to detect sulfamethazine (SMZ) residues in animal-derived foods. The SMZ-bound aptamers were identified and screened with an improved GO-SELEX technique using non-immobilizing ssDNA library. After seven rounds of selection, six SMZ aptamers were sequenced and analyzed for secondary structure, and their affinity and specificity were assessed by binding assays. The truncated aptamer (SMZ1S: 5'-CGTTAGACG-3') with a unique stem-loop structure showed the highest affinity (Kd = 24.6 nM) to SMZ and was used to develop a GO-based fluorescent aptasensor. The binding mechanism between SMZ1S and SMZ was further analyzed by molecular docking. Under optimal conditions, the fluorescent aptasensor showed low detection limits (0.35 ng/mL) and a wide dynamic linear range (from 2 to 100 ng/mL). The aptasensor was also validated against real samples spiked with SMZ, which showed a fluorescence recovery from 93.9 to 108.8% and a coefficient of variation of < 12.7%. Taken together, these results suggest that this novel aptasensor can be used to sensitively, selectively, and accurately detect SMZ residues in foods. Schematic illustration of fluorescent aptasensor based on aptamer/graphene oxide complex detection of of SMZ.

Bioinformatics Analysis of Key Candidate Genes and Pathways in Ulcerative Colitis.

Ulcerative colitis (UC) is chronic, idiopathic disease that affects the colon and the rectum and the underlying pathogenesis of UC remains to be known. The clinical drugs are mainly work based on anti-inflammation and immune system. However, most of them are expensive and have severe side effects. Therefore, identification of novel targets and exploring new drugs are urgently needed. In this study, several bioinformatics approaches were used to discover key genes and further in order to explore the pathogenesis of UC. Two microarray datasets, GSE38713 and GSE9452 were selected from NCBI-Gene Expression Omnibus database. Differentially expression genes (DEGs) were identified by using LIMMA Package of R. Then, we filtered clustered candidate genes into Gene Ontology (GO) and pathway enrichment analysis with the Database for Annotation, Visualization and Integrated Discovery (DAVID), KEGG pathway based on functions and signaling pathways with significant enrichment analysis. The protein-protein interaction (PPI) network was constructed by the Search Tool for the Retrieval of Interacting Genes/ Proteins (STRING) analysis, and visualized by Cytoscape and further analyzed by Molecular Complex Detection. Lastly, 353 up-regulated and 145 down-regulated genes were than recognized. After consulting a number of references and network degree analysis, four hub genes, namely FCGR2A, C3, INPP5A, and ACAA1 were identified, and these genes were mainly enriched in complement and coagulation cascades, mineral absorption, and Peroxisome Proliferator-Activated Receptor (PPAR) signaling pathways. In conclusion, this study would provide new clues for the pathogenesis and identification of drug targets of UC in the near future.

Systems biology approaches based discovery of a small molecule inhibitor targeting both c-Met/PARP-1 and inducing cell death in breast cancer.

Breast cancer is the second most common types of cancer worldwide. Molecular strategies have developed rapidly; however, novel treatments strategies with high efficacy and lower toxicity are still urgently demanded. Notably, biological networks estimated from microarray data and functional activity network analysis could be utilized to identify and validate potential targets. In this study, two microarray data (GSE13477, GSE31192) were firstly selected, and analyzed by multi-functional activity network analysis to generate the core protein-protein-interaction (PPI) network. Several potential targets were subsequently identified and c-Met and poly (ADP-ribose) polymerase-1 (PARP-1) were manually chosen as the key targets in breast cancer. Furthermore, virtual screening and molecular dynamics (MD) simulations were utilized to recognize novel c-Met/PARP-1 inhibitors in Specs products database. Three small molecules, namely, ZINC19909930, ZINC20032678 and ZINC13562414 were selected. Additionally, these compounds were synthesized, and two breast cancer cell lines, MDA-MB-231 and MCF-7 cells were used to validate our bioinformatic findings in vitro. MTT assay and Hoechst staining showed that ZINC20032678 significantly induced breast cancer cell death, which was mediated through apoptosis by flow cytometry. Furthermore, ZINC20032678 was shown to target the active sites of the both targets and recruitment of downstream apoptotic signaling pathways, eventually inducing breast cancer cell apoptosis. Collectively, our findings not only offer systems biology approaches based drug target identification, but also provide the new clues for developing novel inhibitors for future breast cancer research.

Hydrophobized SN38 to redox-hypersensitive nanorods for cancer therapy.

The clinical application of SN38 (7-ethyl-10-hydroxy-camptothecin) is severely restricted by its extremely low water solubility. Nanoaggregates formed by amphiphilic SN38 prodrugs have been widely used for the delivery of SN38. In this study, we used a hydrophobized SN38 prodrug, rather than a typical SN38 amphiphile, to construct rod-shaped nanoaggregates for efficient SN38 delivery. The hydrophobized SN38 was synthesized by conjugating SN38 with oleic acid using disulfanyl-ethyl carbonate as the linker. Interestingly, the resulting prodrug self-assembled into nanorods with high drug loading capacity (45%) and colloidal stability. Moreover, these nanorods displayed an impressively high redox-sensitivity to release 100% SN38 within 1 h in 10 mM DTT, versus 1% in phosphate buffer (pH 7.4). The efficient drug release resulted in an uncompromised in vitro cytotoxicity, which was comparable to free SN38 and nearly 93-fold more potent than CPT-11. Most importantly, these novel prodrug nanoaggregates exhibited potent antitumor activity in the CT26 colorectal cancer xenograft. The nanoaggregates of such redox-hypersensitive hydrophobized SN38 represent an effective alternative strategy for developing novel SN38 nanomedicines.