Designing Multimodal Informative Sensing with an Exosome-Mediated Signal Coupling Transduction Strategy Based on a Single-Stimulus Multiresponse Recognition Interface

Given that exosomes released from cancer cells carry various tumor-specific proteins on their surface, they have emerged as a source of biomarkers for cancer diagnosis. However, developing accurate and reliable assays to detect exosomes in the early stages of disease with low abundance and complex systems remains challenging. Here, the prepared PDIG film has the ability to sense multiple signals from a single stimulus, in which the presence of cobalt(II) chloride and deep eutectic solvents (DES) endows PDIG with thermochromic and thermosensitive properties. Concretely, the PDIG served as the recognition interface in series with a bipolar electrode (BPE) that exhibits a highly sensitive color and conductivity response to temperature stimuli triggered by the light-harvesting probe TiO2@CNOs introduced via proximity hybridization assay triggering a rolling circle amplification strategy, resulting in the output of colorimetric, photoacoustic, and electrochemiluminescent signals for the detection of colorectal cancer exosomes. This work is expected to provide a new direction for exploring the multisignal amplification strategy of BPE, broaden the application of BPE in biological analysis, and provide new insights for developing highly information-sensing elements to ensure the multimodal coupling for cancer-specific exosome detection

Modular and Noncontact Wireless Detection Platform for Ovarian Cancer Markers: Electrochemiluminescent and Photoacoustic Dual-Signal Output Based on Multiresponse Carbon Nano-Onions

An electrochemiluminescent (ECL)–photoacoustic (PA) dual-signal output biosensor based on the modular optimization and wireless nature of a bipolar electrode (BPE) was constructed. To further simplify the detection process, the BPE structure was designed as three separate units: anode ECL collection, cathode catalytic amplification, and intermediate functional sensing units. Specifically, the anode unit was placed with Eosin Yellow, a cheap and effective ECL reagent, and the cathode unit was a laser-induced polyoxometalate–graphene electrode, which was helpful to enhance the anode ECL signal. The intermediate functional sensing unit consisted of a temperature-sensitive conductive film. Further, using a carbon nano-onion nanocomposite with excellent absorption performance in the near-infrared region as a signal tag not only leads to changes in the electrical conductivity of the film through heat transfer and thus affects the ECL signal but also produces a strong PA response. With this design, PA and ECL signals can be output simultaneously. This work not only realizes multiple modularization processes in the design of sensors but also implements the diversification of signal output modes, which will enrich the joint research field of ECL detection technology and other new detection methods

Image2_RNA 5-Methylcytosine Regulators Contribute to Metabolism Heterogeneity and Predict Prognosis in Ovarian Cancer.JPEG

5-Methylcytosine (m5C) is an abundant and highly conserved modification in RNAs. The dysregulation of RNA m5C methylation has been reported in cancers, but the regulatory network in ovarian cancer of RNA m5C methylation-related genes and its implication in metabolic regulation remain largely unexplored. In this study, RNA-sequencing data and clinical information of 374 ovarian cancer patients were downloaded from The Cancer Genome Atlas database, and a total of 14 RNA m5C regulators were included. Through unsupervised consensus clustering, two clusters with different m5C modification patterns were identified with distinct survivals. According to enrichment analyses, glycosaminoglycan and collagen metabolism–related pathways were specifically activated in cluster 1, whereas fatty acid metabolism–related pathways were enriched in cluster 2, which had better overall survival (OS). Besides the metabolism heterogeneity, the higher sensitivity to platinum and paclitaxel in cluster 2 can further explain the improved OS. Ultimately, a least absolute shrinkage and selection operator prediction model formed by ALYREF, NOP2, and TET2 toward OS was constructed. In conclusion, distinct m5C modification pattern exhibited metabolism heterogeneity, different chemotherapy sensitivity, and consequently survival difference, providing evidence for risk stratification.</p

Image1_RNA 5-Methylcytosine Regulators Contribute to Metabolism Heterogeneity and Predict Prognosis in Ovarian Cancer.JPEG

5-Methylcytosine (m5C) is an abundant and highly conserved modification in RNAs. The dysregulation of RNA m5C methylation has been reported in cancers, but the regulatory network in ovarian cancer of RNA m5C methylation-related genes and its implication in metabolic regulation remain largely unexplored. In this study, RNA-sequencing data and clinical information of 374 ovarian cancer patients were downloaded from The Cancer Genome Atlas database, and a total of 14 RNA m5C regulators were included. Through unsupervised consensus clustering, two clusters with different m5C modification patterns were identified with distinct survivals. According to enrichment analyses, glycosaminoglycan and collagen metabolism–related pathways were specifically activated in cluster 1, whereas fatty acid metabolism–related pathways were enriched in cluster 2, which had better overall survival (OS). Besides the metabolism heterogeneity, the higher sensitivity to platinum and paclitaxel in cluster 2 can further explain the improved OS. Ultimately, a least absolute shrinkage and selection operator prediction model formed by ALYREF, NOP2, and TET2 toward OS was constructed. In conclusion, distinct m5C modification pattern exhibited metabolism heterogeneity, different chemotherapy sensitivity, and consequently survival difference, providing evidence for risk stratification.</p

Optical and Acoustic Synergetic Sensing Platform Enabled by a Pyrene-Based Conjugated Polymer Self-Circulating Amplified System for Lung Cancer Detection

A stable and reusable electrochemiluminescent (ECL) signal amplification strategy was proposed through a pyrene-based conjugated polymer (Py-CP) triggered self-circulating enhancement system. Specifically, the delocalized conjugated π-electrons of Py-CPs made it an excellent coreactant to arouse the initial ECL signal improvement of Ru(phen)32+, but the subsequent signal reduction was attributed to the consumption of Py-CPs, in which this stage was called the signal sensitization evoking phase (SSEP). Then, the maximum use of ECL luminescence of Ru(phen)32+ produced in the SSEP was made to irradiate the photosensitizer Py-CPs for in situ producing numerous ·OH, and a stronger and more stable ECL response stage defined as the signal sensitization stabilize phase was reached. Encouragingly, the incorporation of Nb2C MXene quantum dots with an exceptional physicochemical property not only foreshortens the SSEP for quickly acquiring a stable ECL signal but also introduces the photoacoustic (PA) transduce mechanism for achieving dual-signal outputting. Ultimately, the portable and miniaturized ECL-PA synergetic sensing platform based on the closed-bipolar electrode realized sensitive let-7a detection in a wide linear range from 10–9 to 10–2 nM with a low detection limit of 3.3 × 10–10 nM and also demonstrated good selectivity, excellent stability, and high reliability. The successful application of an innovative signal transduction mechanism and dexterous coupling modality will provide new insights for advancing the development of flexible analytical devices

Image3_RNA 5-Methylcytosine Regulators Contribute to Metabolism Heterogeneity and Predict Prognosis in Ovarian Cancer.JPEG

5-Methylcytosine (m5C) is an abundant and highly conserved modification in RNAs. The dysregulation of RNA m5C methylation has been reported in cancers, but the regulatory network in ovarian cancer of RNA m5C methylation-related genes and its implication in metabolic regulation remain largely unexplored. In this study, RNA-sequencing data and clinical information of 374 ovarian cancer patients were downloaded from The Cancer Genome Atlas database, and a total of 14 RNA m5C regulators were included. Through unsupervised consensus clustering, two clusters with different m5C modification patterns were identified with distinct survivals. According to enrichment analyses, glycosaminoglycan and collagen metabolism–related pathways were specifically activated in cluster 1, whereas fatty acid metabolism–related pathways were enriched in cluster 2, which had better overall survival (OS). Besides the metabolism heterogeneity, the higher sensitivity to platinum and paclitaxel in cluster 2 can further explain the improved OS. Ultimately, a least absolute shrinkage and selection operator prediction model formed by ALYREF, NOP2, and TET2 toward OS was constructed. In conclusion, distinct m5C modification pattern exhibited metabolism heterogeneity, different chemotherapy sensitivity, and consequently survival difference, providing evidence for risk stratification.</p

Data_Sheet_1_Peptide Tat(48–60) YVEEL protects against necrotizing enterocolitis through inhibition of toll-like receptor 4-mediated signaling in a phosphatidylinositol 3-kinase/AKT dependent manner.pdf

Necrotizing enterocolitis (NEC) is a catastrophic disease largely occurring in preterm infants, and toll-like receptor 4 (TLR4) has been implicated in its pathogenesis. The current therapeutic strategies for NEC are, however, far from optimal. In the present study, a whey-derived antioxidative peptide conjugated with a cell-penetrating TAT [Tat (48–60) YVEEL] was prepared to endow it with enhanced cell uptake capability and bioavailability. The protective effect of Tat (48–60) YVEEL on experimental NEC was evaluated both in vitro and in vivo. Inhibition of TLR4-mediated signaling by Tat (48–60) YVEEL was assessed in FHC and IEC-6 enterocytes, neonatal rat model of NEC, and the mechanism underlying this effect was determined. Tat (48–60) YVEEL significantly inhibited TLR4-mediated expression of pro-inflammatory cytokines, p65 nuclear translocation and restored the impaired enterocyte migration in cultured enterocytes. In addition, Tat (48–60) YVEEL administration strikingly increased the survival rate, and reduced the severity of NEC in rats through inhibition of TLR4-mediated signaling. These protective effects of Tat (48–60) YVEEL occurred in a PI3K/AKT dependent manner, as administration of PI3K activator Ys49 abrogated its protective effects. Combined with liposomes, Tat (48–60) YVEEL demonstrated longer retention in the intestines that better for potential clinical applications. These data demonstrate that Tat (48–60) YVEEL protects against NEC through inhibition of TLR4-mediated signaling in a PI3K/AKT dependent manner, and offer a potential therapeutic approach to this disease.</p

DataSheet_1_Immune Dysfunction Mediated by the ceRNA Regulatory Network in Human Placenta Tissue of Intrahepatic Cholestasis Pregnancy.zip

Pregnancy-related intrahepatic cholestasis (ICP) is a serious complication with adverse perinatal outcomes of preterm labor, fetal distress, or stillbirth. As a result, it is important to investigate and identify the potential critical pathogenic mechanisms of ICP. First, we collected the placental tissues from the ICP with placental weight and fetal birth weight loss for the whole transcriptome sequencing. Then we analyzed the differentially expressed (DE) circRNAs (DEcircRNAs) by SRPBM, DElncRNAs by FRKM, DEmiRNAs by TPM, and DEmRNAs by TPM and RSEM. Based on differential expression of term pregnancy placental tissues from pregnancies impacted by ICP (n=7) as compared to gestational aged matched control tissues (n=5), the circ/lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) regulatory networks were constructed. The ceRNA regulatory networks covered 3,714 events, including 21 DEmiRNAs, 36 DEcircRNAs, 146 DElncRNAs, and 169 DEmRNAs. According to the functional analysis, ICP complications were linked to the immune system, signal transduction, endocrine system, cell growth and death, and transport and catabolism. Further evidence suggested that the expression of immune-related genes KLRD1, BRAF, and NFATC4 might have a potential ceRNA mechanism by individual lncRNA sponging miR372-3p, miR-371a-3p, miR-7851-3p, and miR-449a to control downstream the level of TNF-α, IFN-γ, and IL-10, thereby regulating the pathophysiology of ICP. Furthermore, our results were validated by the qRT-PCR, western blotting and ELISA assays. In conclusion, this study is the first to evaluate placental ceRNA networks in pregnancies affected by ICP, showing alterations in immune regulatory networks which may impact fetal and placental growth. Overall our these data suggest that the ceRNA regulatory network may refine biomarker predictions for developing novel therapeutic approaches in ICP.</p

Biotransformation of 5-en-3β-ol steroids by <i>Mucor circinelloides lusitanicus</i>

<p>In this work, we report the mode of biotransformation of 5-en-3β-ol steroids using <i>Mucor circinelloides lusitanicus</i> for the first time. Here, we selected seven 5-en-3β-ol steroids as substrates. The main characteristic of the fungus was to introduce a 7α-hydroxyl group into substrates <b>1</b>--<b>5</b>. With substrate <b>2</b>, 3β, 7α, 11α-trihydroxypregna-5-en-20-one (<b>2b</b>) was obtained as the final product in good yield (46.4%). All the metabolites were determined by infrared spectra, high-resolution mass spectrometry, proton nuclear magnetic resonance, and carbon-13 nuclear magnetic resonance.</p

Poly(vinyl alcohol)-Based Nanofibers with Improved Thermal Conductivity and Efficient Photothermal Response for Wearable Thermal Management

The development and research of flexible and smart textiles have garnered significant attention in recent times. The incorporation of phase change materials into stimulus-responsive nanofibers has the potential to react to external stimuli and provide a comfortable microclimate for the human body. This approach holds promise for achieving instant energy conversion and storage and temperature regulation in smart clothing. However, the production of efficient and flexible intelligent thermoregulated nanofibers remains a challenge. In this study, we successfully prepared intelligent thermoregulated nanofibers with an adjustable temperature, efficient thermal storage capacity, and excellent thermal conductivity using the emulsion electrostatic spinning method. By incorporating lauric acid as the phase change material and optimizing its addition ratio in the spinning emulsion, we obtained nanofibers with a uniform diameter and eliminated the issue of material leakage. This resulted in outstanding phase change behavior and thermal storage capacity of the nanofibers, with an enthalpy value reaching 103.13 J/g, equivalent to 72% of pure lauric acid. Furthermore, the incorporation of carbon nanotubes and zinc oxide particles into the fibers provided UV resistance and a high thermal conductivity of 0.665 W·m–1·K–1. The use of a poly(vinyl alcohol) matrix ensured the flexibility of the nanofibers, with an elongation at break of approximately 25%, meeting international standards (10∼30%). Additionally, the pollution-free polydimethylsiloxane coating not only protected the internal structure of the nanofibers but also imparted superior hydrophobicity and self-cleaning properties. Consequently, these intelligent thermoregulated nanofibers, with their comprehensive performance, offer an option for the development and application of wearable systems and protective fabrics