SERS Multiplex Profiling of Melanoma Circulating Tumor Cells for Predicting the Response to Immune Checkpoint Blockade Therapy.

Immune checkpoint blockade (ICB) therapy has achieved remarkable success in many cancers including melanoma. However, ICB therapy benefits only a small proportion of patients and produces severe side effects for some patients. Thus, there is an urgent need to identify patients who are more likely to respond to ICB therapy to improve outcomes and minimize side effects. To predict ICB therapy responses, we design a surface-enhanced Raman scattering (SERS) assay for multiplex profiling of circulating tumor cells (CTCs) under basal and interferon-γ (IFN-γ) stimulation. Through simultaneous ensemble and single-cell measurements of CTCs, the SERS assay can reveal tumor heterogeneity and offer a comprehensive CTC phenotype for decision-making. Anisotropic gold-silver alloy nanoboxes are utilized as SERS plasmonic substrates for improved signal readouts of CTC surface biomarkers. By generating a unique CTC signature with four surface biomarkers, the developed assay enables the differentiation of CTCs from three different patient-derived melanoma cell lines. Significantly, in a cohort of 14 melanoma patients who received programmed cell death-1 blockade therapy, the changes of CTC signature induced by IFN-γ stimulation to CTCs show the potential to predict responders. We expect that the SERS assay can help select patients for receiving ICB therapy in other cancers.

Amplification-Free SARS-CoV-2 Detection Using Nanoyeast-scFv and Ultrasensitive Plasmonic Nanobox-Integrated Nanomixing Microassay.

The implementation of accurate and sensitive molecular detection for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is paramount to effectively control the ongoing coronavirus disease 2019 (COVID-19) pandemic. In this regard, we herein propose the specific and highly sensitive SARS-CoV-2 detection based on nanoyeast single-chain-variable fragment (scFv) and ultrasensitive plasmonic nanobox-integrated nanomixing microassay. Importantly, this designed platform showcases the utility of nanoyeast-scFvs as specific capture reagents targeting the receptor-binding domain (RBD) of the virus and as monoclonal antibody alternatives suitable for cost-effective mass production and frequent testing. By capitalizing on single-particle active nanoboxes as plasmonic nanostructures for surface-enhanced Raman scattering (SERS), the microassay utilizes highly sensitive Raman signals to indicate virus infection. The developed microassay further integrated nanomixing for accelerating molecular collisions. Through the synergistic working of nanoyeast-scFv, plasmonic nanoboxes, and nanomixing, the highly specific and sensitive SARS-CoV-2 detection is achieved as low as 17 virus/µL without any molecular amplification. We successfully demonstrate SARS-CoV-2 detection in saliva samples of simulated patients at clinically relevant viral loads, suggesting the possibility of this platform for accurate and noninvasive patient screening.

Study on the Preparation of Ionic Liquid Doped Chitosan/Cellulose-Based Electroactive Composites.

Electro-actuated polymer (EAP) can change its shape or volume under the action of an external electric field and shows similar behavioral characteristics with those of biological muscles, and so it has good application prospects in aerospace, bionic robots, and other fields. The properties of cellulose-based electroactive materials are similar to ionic EAP materials, although they have higher Young's modulus and lower energy consumption. However, cellulose-based electroactive materials have a more obvious deficiency-their actuation performance is often more significantly affected by ambient humidity due to the hygroscopicity caused by the strong hydrophilic structure of cellulose itself. Compared with cellulose, chitosan has good film-forming and water retention properties, and its compatibility with cellulose is very excellent. In this study, a chitosan/cellulose composite film doped with ionic liquid, 1-ethyl-3-methylimidazolium acetate ([EMIM]Ac), was prepared by co-dissolution and regeneration process using [EMIM]Ac as the solvent. After that, a conductive polymer, poly(3,4-ethylenedioxythiophene)/poly (styrene sulfonate) (PEDOT: PSS), was deposited on the surface of the resulted composite, and then a kind of cellulose-based electroactive composites were obtained. The results showed that the end bending deformation amplitude of the resulted material was increased by 2.3 times higher than that of the pure cellulose film under the same conditions, and the maximum deformation amplitude reached 7.3 mm. The tensile strength of the chitosan/cellulose composite film was 53.68% higher than that of the cellulose film, and the Young's modulus was increased by 72.52%. Furthermore, in comparison with the pure cellulose film, the water retention of the composite film increased and the water absorption rate decreased obviously, which meant that the resistance of the material to changes in environmental humidity was greatly improved.

Multiplexed SERS Detection of Soluble Cancer Protein Biomarkers with Gold-Silver Alloy Nanoboxes and Nanoyeast Single-Chain Variable Fragments.

Highly sensitive, multiplexed detection of soluble cancer protein biomarkers can facilitate early cancer screening as well as enable real-time monitoring of patients' sensitivity and resistance to therapy. Current technologies for detection of soluble cancer protein biomarkers, e.g., enzyme-linked immunosorbent assay, however, suffer from limited sensitivity, as well as the requirement of expensive monoclonal antibodies, which undergo the quality variability. Herein, we propose a sensitive, cheap, and robust surface-enhanced Raman scattering technology to detect a panel of soluble cancer protein biomarkers, including soluble programmed death 1 (sPD-1), soluble programmed death-ligand 1 (sPD-L1) and soluble epithermal growth factor receptor (sEGFR), which are related to disease progression and treatment efficacy. In this assay, gold-silver alloy nanoboxes that have strong Raman signal enhancement capability were used as plasmonic nanostructures to facilitate highly sensitive detection. In addition, nanoyeast single-chain variable fragments were utilized as mAb alternatives to allow specific and stable protein capture performance. We successfully detected sPD-1, sPD-L1, and sEGFR with a limit of detection of 6.17 pg/mL, 0.68 pg/mL, and 69.86 pg/mL, respectively. We further tested the detection of these three soluble cancer protein biomarkers in human serum and achieved recovery rates between 82.99% and 101.67%. We believe our novel platform that achieves sensitive, multiplexed, and specific detection of soluble cancer protein biomarkers could greatly benefit cancer treatment and improve patient outcome.

Chinese parents' intention to vaccinate their 0-5-year-old children with the EV-71 vaccine against hand, foot, and mouth disease and willingness-to-pay.

Background: This study aimed to determine the intention and willingness-to-pay (WTP) of Chinese parents/guardians to vaccinate their children with the EV-71 vaccine. Knowledge levels about hand, foot, and mouth disease (HFMD) and the EV-71 vaccine were also investigated. Methods: A cross-sectional, self-administered online survey was conducted between November 2022 and March 2023. A stratified multi-stage random sampling method was used to recruit parents/guardians of children aged 0-5 years in southeastern China. Results: A total of 3,626 complete responses were received. The mean knowledge score of HFMD was 9.99 (±4.23) out of a total of 14 points. The majority of the participants reported a somewhat willing intent (58.8%), followed by an extremely willing intent (28.9%). Participants who did not consider the EV-71 vaccine expensive (OR = 2.94, 95%CI 2.45-3.53) perceived that the EV-71 vaccine is effective (OR = 2.73, 95%CI 1.52-4.90), and a high knowledge level of HFMD (OR = 1.90, 95%CI 1.57-2.29) had the highest significant odds of having an extremely willing intent to vaccinate their children with the EV-71 vaccine. The median (interquartile range [IQR]) of WTP for the EV-71 vaccine was CNY¥200/USD$28 (IQR CNY¥100-400/USD$14-56). The highest marginal WTP for the vaccine was mainly influenced by the perceived high cost of the vaccine. Those participants who did not consider the EV-71 vaccine expensive had more than 10 times higher odds of vaccinating their children (OR = 10.86, 95%CI 8.49-13.88). Perceived susceptibility, perceived benefits, and perceived barriers were also significant influencing factors in the highest marginal WTP. Conclusion: The findings demonstrate the importance of improving health promotion and reducing the barriers to EV-71 vaccination. Therefore, it is important to improve health promotion and reduce the barriers to EV-71 vaccination.

Bioengineered Neutrophils for Smart Response in Brain Infection Management.

Brain infections, frequently accompanied by significant inflammation, necessitate comprehensive therapeutic approaches targeting both infections and associated inflammation. A major impediment to such combined treatment is the blood-brain barrier (BBB), which significantly restricts therapeutic agents from achieving effective concentrations within the central nervous system. Here, a neutrophil-centric dual-responsive delivery system, coined "CellUs," is pioneered. This system is characterized by live neutrophils enveloping liposomes of dexamethasone, ceftriaxone, and oxygen-saturated perfluorocarbon (Lipo@D/C/P). CellUs is meticulously engineered to co-deliver antibiotics, anti-inflammatory agents, and oxygen, embodying a comprehensive strategy against brain infections. CellUs leverages the intrinsic abilities of neutrophils to navigate through BBB, accurately target infection sites, and synchronize the release of Lipo@D/C/P with local inflammatory signals. Notably, the incorporation of ultrasound-responsive perfluorocarbon within Lipo@D/C/P ensures the on-demand release of therapeutic agents at the afflicted regions. CellUs shows considerable promise in treating Staphylococcus aureus infections in mice with meningitis, particularly when combined with ultrasound treatments. It effectively penetrates BBB, significantly eliminates bacteria, reduces inflammation, and delivers oxygen to the affected brain tissue, resulting in a substantial improvement in survival rates. Consequently, CellUs harnesses the natural chemotactic properties of neutrophils and offers an innovative pathway to improve treatment effectiveness while minimizing adverse effects.

Durable cellulose paper by grafting thiol groups and controlling silver deposition for ultrahigh electromagnetic interference shielding.

Electromagnetic interference (EMI) shielding paper with durability and high effectiveness is of significant importance to long-term service for preventing EMI pollution. Herein, we report a practical method for preparing cellulose paper/Ag composite with outstanding durable and ultrahigh EMI shielding performance by electroless silver plating. The silver deposition process, the surface morphology, the silver content and conductivity of the composite can be controlled by varying the amount of N-acetyl-L-cysteine (NAC) grafted onto the cellulose fibers and ammonia amount for silver-ammonia complex formation. Moreover, the grafted NAC with thiol groups on cellulose can enhance the adhesion between silver and cellulose paper, meanwhile, NAC as the reducing agent can result in a more complete flower-shaped silver structure and reducing the reflection of electromagnetic waves in silver layer. The composite exhibited excellent conductivity, EMI shielding effectiveness (SE) up to 106 dB and outstanding durability. After 10,000 bending times and 60 abrasion cycles respectively, the electrical resistance of the composite only increased from 0.030 Ω/sq. to 0.041 Ω/sq. and 0.050 Ω/sq., and the EMI SE decreased to 102 dB and 105 dB.

Preparation of conductive cellulose fabrics with durable antibacterial properties and their application in wearable electrodes.

Electroless silver plating on fabrics can obtain conductive and antibacterial bifunctional materials which can be used as electrodes in wearable electronic products. However, these activities are deteriorated easily after washing because of the falling off of silver coating resulted from the weak adhesion. In order to improve the binding force between silver and cellulose fabrics, 3-mercaptopropytrimethoxysilane (MPTS) was applied to modify cellulose fabrics before silver electroless plating to develop the durable conductive fabrics with excellent antibacterial. The silver nanoparticles (Ag NPs) deposition process was observed via field emission scanning electron microscopy (FESEM), thermal properties were evaluated by thermogravimetric analysis (TGA). A dense and uniform silver layer was formed on the fabric. The initial electrical resistance of the conductive fabric was 0.04 Ω/sq and lowered than 2 Ω/sq after 200 washing cycles. The antibacterial efficiency of the fabric after 200 washing cycles remained 92.82%, compared to 100% with the fabric before washing. Moreover, the inhibition rate was determined by optical density of bacteria suspension at 260 nm and further substantiated by releasing of Ag+ from the fabric. The conductive fabrics were applied as wearable electrodes to capture electrocardiogram (ECG) signals of human in static states and running states.

Plasma-induced polymerization for enhancing paper hydrophobicity.

Hydrophobic modification of cellulose fibers was conducted via plasma-induced polymerization in an attempt to graft the hydrophobic polymer chains on paper surface, this increasing the hydrophobicity of paper. Two hydrophobic monomers, butyl acrylate (BA) and 2-ethylhexyl acrylate (2-EHA), were grafted on cellulose fibers, induced by atmospheric cold plasma. Various influencing factors associated with the plasma-induced grafting were investigated. Contact-angle measurement, Fourier Transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM) were used to ascertain the occurrence of the grafting and characterized the changes of the cellulose fiber after modification. The results showed that the hydrophobicity of the modified paper sheet was improved significantly after the plasma-induced grafting. The water contact angle on the paper surface reached up to 130°. The morphological differences between modified and unmodified samples were also revealed by SEM observation. The resulting paper is promising as a green-based packaging material.