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An unsteady-state model for predicting mass-transfer coefficient kL of bubbles with mobile surface was developed for turbulent gas-liquid dispersions. This model was derived from an unsteady-state convection and diffusion equation through a characteristics method. Unlike the previous work, this model considered the contributions of the amount of fluid structures of different scales (i.e., eddies) existing in the turbulent flows, the frequency of eddies arriving at the surface, the deformation and oscillation of bubbles to mass transfer. This model was based on the framework of wide energy spectrum and can account for the role of eddies of different sizes in mass transfer. Thus the assumption adopted by the previous models that mass transfer was controlled by eddies of certain sizes is no more needed. The overall kL predicted by the proposed model showed a better agreement with the reported experimental data. © 2015 American Institute of Chemical Engineers AIChE J, 62: 1007-1022, 2016 [ABSTRACT FROM AUTHOR]

The interzeolite conversion of zeolite MCM-49 into zeolite ZSM-35 in “cyclohexylamine (CHA)–hexamethyleneimine (HMI)–Na2O–H2O” systems, consisting of “CHA–Na2O–H2O”, “HMI–Na2O–H2O” and “Na2O–H2O”, was investigated in detail using X-ray diffraction (XRD), scanning electron microscopy (SEM), and nuclear magnetic resonance (NMR) characterization techniques. Both CHA and HMI play important roles in directing the interzeolite conversion of MCM-49 into ZSM-35, and the conversion speed is much faster in systems containing CHA than those containing HMI. Even in the Na2O–H2O system without any organic amine, MCM-49 can still transform into some other zeolites with more stable topological structures than itself, such as ZSM-35, ZSM-5, and mordenite, but the product of the interzeolite conversion is more complicated than that in the systems containing organic amines (CHA and/or HMI). In the Na2O–H2O system, alkalinity has been proved to be a crucial factor influencing the conversion trend of MCM-49. Zeolites ZSM-5 and mordenite will appear in the products besides ZSM-35 with the increase of the alkalinity. The conversion process of zeolite MCM-49 in the systems investigated accords well with the solution-mediated transformation mechanism. [ABSTRACT FROM AUTHOR]

Developing safe and effective nonviral gene vector ishighly crucialfor successful gene therapy. In the present study, we designed a seriesof biodegradable micelles based on hybrid polypeptide copolymers ofpoly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-leucine) (PEG-PLL-PLLeu) for efficientgene delivery. A group of amphiphilic PEG-PLL-PLLeu hybrid polypeptidecopolymers were synthesized by ring-opening polymerization of N-carboxyanhydride, and the chemical structure of each copolymerwas characterized by 1H NMR and FT-IR spectroscopy measurement.The PEG-PLL-PLLeu micelles were positively charged with tunable sizesranging from 40 to 90 nm depending on the length of PLL and PLLeusegment. Compared with PEG-PLL copolymers, PEG-PLL-PLLeu micellesdemonstrated significantly higher transfection efficiency and lesscytotoxicity. Furthermore, the transfection efficiency and biocompatibilityof the micelles can be simultaneously improved by tuning the lengthof PLL and PLLeu segments. The transfection efficiency of PEG-PLL-PLLeumicelles in vivo was two to three times higher than that of PEI25k, which was attributable to their capability of promotingDNA condensation and cell internalization as well as successful lysosomeescape. Hence well-defined PEG-PLL-PLLeu micelles would serve as highlyeffective nonviral vectors for in vivo gene delivery. [ABSTRACT FROM AUTHOR]

The spread of infectious diseases on complex networks has been a hot topic of research in recent years. In this work, we constructed multi-community networks based on the varying frequencies of social interactions between individuals in different regions, in which the frequencies of social interactions are described by the intra-community average degree. We investigated the impact of vaccine allocation in different communities on the overall spreading range of the entire network. The simulation and analysis show that to achieve the optimal control performance, all communities should be ranked from the smallest to the largest in terms of the threshold vaccine number first, and the lower the threshold vaccine number, the easier the community is to be suppressed. Secondly, we compared the total number of vaccines with the threshold number of vaccines required for each community, and if the number of vaccines is sufficient to suppress l communities, then the vaccines should be allocated among the l + 1 communities that are most likely to be suppressed. Finally, we sequentially assigned the threshold number of vaccines for each community until they are allocated to the l + 1 communities. Our findings provide theoretical support for addressing the challenge of vaccine allocation in resource-limited settings. • Proposed effective vaccine allocation scheme for multi-community networks. • Ranked communities based on critical vaccine numbers to achieve effective control performance with limited resources. • Findings provide theoretical support for vaccine allocation in resource-limited settings and have important implications for controlling infectious diseases on complex networks. [ABSTRACT FROM AUTHOR]

[Display omitted] • Heterostructured ZIF-8@MXene applied for the first time in CO 2 /N 2 gas separation. • The change of structure after blending shows the CO 2 permeability of 639 Barrer. • PEO/ZIF-8@MXene achieved remarkable CO 2 /N 2 selectivity of 294.1 at sub-ambient temperatures. • Mixed matrix membranes can be economically utilized for capturing CO 2 from coal-fired and blast furnace flue gases at sub-ambient temperatures. At the present time, the realm of gas separation membranes is predominantly centered on the development of membrane materials that simultaneously exhibit exceptional gas permeability and selectivity. Mixed Matrix Membranes (MMMs) hold significant promise in addressing the long-standing challenge of balancing membrane selectivity with permeability. By incorporating a molecular sieving mechanism, an enhanced gas separation process is achieved. In this research endeavor, single-layer MXene nanosheets serve as an ideal substrate for the direct growth of ZIF-8 nanoparticles, yielding heterogeneously structured nanofillers, coined ZIF-8@MXene. The composite filler, ZIF-8@MXene, maintains a two-dimensional lamellar structure reminiscent of MXene, while also integrating ZIF-8 nanoparticles with their optimal pore size of 3.4 Å. This optimal pore size efficiently facilitates the unimpeded passage of CO 2 molecules through the channels, creating a preferential pathway. Conversely, N 2 molecules encounter greater difficulty traversing these channels, effectively coupling the solubility-diffusion mechanism with the molecular sieving mechanism to enhance selectivity in gas separation processes. Consequently, the mixed matrix membrane exhibits a remarkable enhancement in gas selectivity. Particularly, under sub-ambient conditions (−20 °C), the PEO/ZIF-8@MXene-0.3 % membrane achieves an exceptional CO 2 /N 2 selectivity of 294.1, accompanied by a high CO 2 permeability of 115.58 Barrer. This outstanding performance surpasses the 2019 upper bound, underscoring the significant potential of heterostructured nanofillers to be harnessed in advancing various mixed matrix membranes (MMMs) towards high-performance gas separation capabilities. [ABSTRACT FROM AUTHOR]

Ultrafiltration membrane separation technology is considered an effective method for separating oil-water emulsions. However, oil droplets can easily deposit on the surface of the membranes, leading to severe fouling and a decrease in flux. In this study, poly (ethylene oxide)/acrylamide/sodium alginate (PEO/AM/NaAlg) hydrogel nanofibers were deposited on a poly (hydroxybutyric acid) (PHB) electrospun nanofibrous membrane. Subsequently, superhydrophilic (ethylene oxide)-poly(acrylamide)/calcium alginate hydrogel nanofiber composite filtration membranes (PEO/PAM/CaAlg-PHB) were prepared by polymerization and Ca2+ cross-linking using a PHB electrospun nanofibrous membrane as the matrix. The morphology, tensile strength, water contact angle, and oil–water emulsion separation properties of the PEO/PAM/CaAlg-PHB hydrogel filtration membrane were investigated. The results showed that the PEO/PAM/CaAlg-PHB membrane had good anti-fouling performance, with a tensile strength of 1.95 MPa. After 3 h of the filtration operation, the stable flux and oil–water emulsion rejection of the membrane reached 2925.2 L m−2 h−1 bar−1 and 98.66 %, respectively. The preparation method was simple, cost effective, and environmentally friendly, without introducing any organic pollutants. The PEO/PAM/CaAlg-PHB hydrogel filtration membrane shows promise for separating oil–water emulsions. [Display omitted] • Anti-fouling PEO/PAM/CaAlg-PHB hydrogel electrospun nanofibrous membrane was prepared. • Oil-water emulsion separation performance of PEO/PAM/CaAlg-PHB membrane was investigated. • The membrane can reject 98.66 % of oil-water emulsion, with a flux of 2925.2 L m−2 h−1 bar−1. • Flux and rejection of oil-water emulsion can be controlled by depositing time. [ABSTRACT FROM AUTHOR]

Fuel consumption for industrial development, SO 2 gas emissions are increasing year by year and have become a focal point of air pollution. Membrane separation method photo-responsive materials and MOFs have attracted more and more attention in a variety of fields. This is because the membrane separation method uses less energy and is an uncomplicated process; MOFs have superior gas adsorption capabilities; and the photo-responsive materials are controllable. In this study, mixed matrix membranes are prepared using Uio-66-NH 2 and photo-responsive materials CE-Azo-Uio-66 as fillers and Pebax as base membranes. By improving the dissolution-diffusion mechanism for SO 2 gas molecules, SO 2 /N 2 gas separation is accomplished. More channels for the mass transport of SO 2 gas through the membrane can be created by MOFs increased porosity and larger specific surface area. Secondly, the SO 2 adsorption and dissolution-diffusion mechanism of the mixed matrix membrane are strengthened by the grafted SO 2 affinity groups on the MOF. Moreover, Pebax/CE-Azo-Uio-66 membranes is not only significantly more permeation selective than Pebax/Uio-66-NH 2 membranes, but also shows photo-responsive characteristic. The SO 2 permeability and selectivity of Pebax/CE-Azo-Uio-66 mixed matrix membranes at CE-Azo-Uio-66 content of 20 % are increased by 191 % and 179 %, respectively, compared to pure Pebax membranes. It is also found that the SO 2 permeability and SO 2 /N 2 selectivity of the membranes show regularly reversible changes at the UV–Vis photoconversion conditions of Pebax/CE-Azo-Uio-66-20 % membranes, indicating the photo-responsive characteristics of mixed matrix membranes that include Azo groups. The SO 2 permeability of the Pebax/CE-Azo-Uio-66 membrane is increased by 1300 Barrer and the SO 2 /N 2 selectivity is increased by 350 when the light source is changed from UV to Vis light, achieving a controlled separation of SO 2 /N 2. Besides, the addition of MOF particles significantly enhances the mechanical properties and stability of the membrane. [Display omitted] • Preparation of Pebax/CE-Azo-Uio-66 membranes for flue gas desulfurization. • Grafted Uio-66 has good interfacial compatibility with Pebax 1657. • Overcoming the Trade-off effect for simultaneous improvement in permeability selectivity. • The thermal stability and mechanical strength of the membrane are improved significantly. • The membrane separation process possesses dynamic photo-responsiveness. [ABSTRACT FROM AUTHOR]

• High-performance Au NPs/PSi was successfully fabricated on a large-scale. • With the advantages of MIL, the MIL-Au NPs /PSi active substrate with strong adsorption property was prepared. • MIL-Au NPs/PSi exhibits excellent sensitivity and stability in the detection for probe molecule. • A novel method for the detection of arsenite was proposed, with the detection limit as low as 0.5 ppb. Developing a novel and simple route for the synthesis ultrasensitive and specific SERS substrates is highly desirable and technically important. Here, a magnetic ionic liquid (MIL) assisted strategy is developed, and the high-quality and ultra-sensitive MIL-gold nanoparticles/porous silicon (MIL-Au NPs/PSi) composite substrate were synthesized by a fast and cost effective strategy with the assistance of MIL (1-methyl-3-hexyl imidazole ferric tetrachloride ([C 6 mim]FeCl 4). Fundamental SERS performance of this composite substrate was evaluated using rhodamine 6G (R6G). The results showed that MIL make the Au NPs/PSi have great advantages in synergetic enhancement and stability, and the hypersensitive detection of specific substances can be realized by selecting or designing IL. Based on the particularity of MIL ([C 6 mim] FeCl 4 ′s function and structure, arsenic was detected with MIL-Au NPs/PSi substrate. The detection limit can reach 0.5 ppb, and the standard curves with regression coefficients of 0.98527 and 0.98965 were established in the linear range of 2–80 ppb and 200–800 ppb. In a word, an advanced method for the preparation of high-performance and designable SERS substrate has been developed, which will certainly show promising applications in detection technology. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel gold nanoparticles (Au NPs)-modified graphdiyne/carbon cloth (Au NPs/GDY/CC) was prepared successfully by electrodeposition. • The unique triangular pore structure in the GDY plane enables more stable anchoring of Au NPs. • The synergistic effect between Au NPs and GDY in Au NPs/GDY/CC complex material significantly enhanced the SERS signal. As a new kind of 2D carbon allotrope, graphdiyne (GDY) has the characteristics of uniform pores and large specific surface area due to its unique electronic space arrangement structure. Therefore, we fabricated a novel gold nanoparticles (Au NPs)/GDY/carbon cloth (CC) SERS substrate by a simple electrodeposition process using GDY nanowall wrapping the CC as support. The effects of electrodeposition conditions on the microstructure and SERS activity of Au NPs/GDY/CC substrate were studied. Under the condition of optimizing deposition time and deposition voltage, the prepared Au NPs/GDY/CC substrate can detect 10-13 M with rhodamine 6G (R6G) as a probe molecule. The maximum enhancement factor (EF) is 2.2 × 1012, and the concentration of R6G is logarithmically correlated with the intensity of the SERS band with a linear correlation coefficient (R2) of 0.97036. These indicate that the Au NPs/GDY/CC substrate has good sensitivity. The prepared Au NPs/GDY/CC SERS substrate was applied to the detection of organic dyes of malachite green (MG) and methyl violet (MV) in water, and the detection limits of both can reach 10-9 M. This highly sensitive and high-performance SERS substrate has broad application prospects in the detection of organic dyes. [ABSTRACT FROM AUTHOR]

As a rapid and non-destructive biological serum detection method, SERS technology was widely used in the screening and medical diagnosis of various diseases by combining the analysis of serum SERS spectrum and multivariate statistical algorithm. Because of the high complexity of serum components and the variability of SERS spectra, which often resulted in the phenomenon that the SERS spectrum of the same biological serum was significantly different due to the different test conditions. In this experiment, through the dilution treatment of the serum and the systematic test of the serum of all concentration gradients with lasers of wavelength of 785, 633 and 532 nm, the most suitable conditions for detecting the serum were investigated. The experimental results showed that only when the serum is diluted to low concentration (10 ppm), the SERS spectrum with high reproducibility and stability could be obtained, furthermore, the low concentration serum had weak tolerance to laser, and 532 nm laser was not suitable for serum detection. In this paper, a set of test scheme for obtaining highly stable serum SERS spectra was established by using high-performance gold nanoparticles (Au NPs) as the active substrate of SERS. Through comparative analysis of SERS spectrum of serum of normal people and cervical cancer, the reliability of the established low-concentration serum test program was verified, as well as its great potential advantages in disease screening and diagnosis. [Display omitted] • The reason of the variability of serum SERS spectrum was verified. • A low-concentration serum SERS detection scheme was established. • High reproducibility serum SERS spectrum can be obtained by using this scheme. • The scheme provides guarantee for the reliability of SERS technology in medical diagnosis. [ABSTRACT FROM AUTHOR]

The metal-organic frameworks (MIL-125) were synthesized by the solvothermal method and the experimental parameters of preparation, purification and activation were optimized and the physicochemical properties were characterized. The adsorption capacity of MIL-125 on C 8 aromatics was tested by the intelligent gravimetric analyzer (IGA) and the toluene vapor static adsorption device. The adsorption selectivity was studied by liquid static adsorption equilibrium experiment and large-scale pulse test. The C 8 aromatics adsorption conformation and adsorption heat in MIL-125 was simulated by Materials Studio software. The characterization results show that the synthesized sample has excellent crystallinity, regular morphology with a grain size of about 1 ​μm, surface area of 1315 ​m2/g, micropore volume of 0.601 ​mL/g and a bulk density of 0.45 ​g/mL. Moreover, the vapor static adsorption results show that the synthesized sample has almost three times of adsorption capacity as large as BaX zeolite and the liquid dynamic adsorption results indicate the synthesized sample is preferentially selective to pare-xylene with the alkane desorbent. The simulation results show that the adsorption heat of pare-xylene in the synthesized sample and the binding energy of pare-xylene in the tetrahedral cage are the largest among these four isomers. The optimized synthesis of MIL-125 with tetrahedral and octahedral cages was completed and the relation between experimental parameters and surface properties was illustrated. The adsorption capacity for C8 aromatics is 500 mg/g and the adsorption heat for PX is highest calculated by MS. PX is preferentially adsorbed in tablet MIL-125 with the alkane as the desorbent measured by large-scale pulse test. Image 1 • PX preferential adsorbent with large micropore volume was synthesized • The relationship between synthesis parameters and surface properties is provided • The tablet adsorbent is utilized in a large scale by dynamic liquid pulse device • Adsorption heat and binding energy are calculated to study adsorption selectivity • Liquid and vapor static adsorption are carried out to prove the capacity. [ABSTRACT FROM AUTHOR]

Previous studies have shown that the development of age-related cataract (ARC) is involved in lens epithelium dysfunction, which is associated with abnormally expressed circular RNAs (circRNAs). The current work aims to probe the role of circSTRBP (hsa_circ_0088,427) in hydrogen peroxide (H 2 O 2 )-induced lens epitheliums. Lens epithelium tissues were harvested from ARC or normal subjects (n = 23). CircSTRBP, spermatid perinuclear RNA binding protein (STRBP), and nicotinamide adenine dinucleotide phosphate oxidase subunit 4 (NOX4) levels were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell proliferation, cycle progression, and apoptosis were assessed using 5-ethynyl-2'-deoxyuridine (EdU), Cell Counting Kit-8 (CCK-8), and flow cytometry assays. Caspase 3 activity, reactive oxygen species (ROS), malondialdehyde (MDA), and Glutathione peroxidases (GSH-PX) levels were detected using corresponding kits. NOX4 protein level was determined using Western blot. The interaction between insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and circSTRBP or NOX4 was assessed through RNA immunoprecipitation (RIP). CircSTRBP and NOX4 abundances were increased in lens epithelium samples from ARC patients and H 2 O 2 -treated SRA01/04 cells. CircSTRBP knockdown might abolish H 2 O 2 -triggered SRA01/04 cell proliferation repression and apoptosis and oxidative stress promotion. In mechanism, circSTRBP is bound with IGF2BP1 and improves the stability and expression of NOX4 mRNA in SRA01/04 cells. CircSTRBP facilitated H 2 O 2 -induced SRA01/04 cell apoptosis and oxidative stress through by enhancing NOX4 mRNA stability via recruiting IGF2BP1, providing novel insights for ARC progression and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

The development of membranes for protein purification has stringent requirement of disinfection resistance, low protein adsorption and anti-fouling, without changing protein structure. In this study, hydrophilic titanium dioxide (TiO 2 )/calcium alginate (TiO 2 /CaAlg) hydrogel membranes were prepared by a simple ionic cross-linking method. The effects of the porogenic agent polyethylene glycol (PEG) concentration, the molecular weight of PEG, and the concentration of TiO 2 on the filtration properties were systematically investigated. The TiO 2 /CaAlg membrane exhibited excellent bovine serum albumin (BSA) rejection and anti-fouling properties. The mechanical properties and surface energy of the TiO 2 /CaAlg membrane were significantly improved. The chemical bonding mechanism of TiO 2 and NaAlg was investigated by molecular dynamic simulation. The TiO 2 /CaAlg membrane had good chlorine resistance and could be disinfected or cleaned with sodium hypochlorite. The TiO 2 /CaAlg hydrogel membrane loaded with polyhydroxybutyrate (PHB) nanofibers maintained high flux (136.7 L/m 2 h) and high BSA rejection (98.0 %) at 0.1 MPa. The results of circular dichroism and synchronous fluorescence indicated that the secondary structure of BSA was maintained after membrane separation. This study provides one method for the preparation of green and environmentally friendly membrane for protein purification., Competing Interests: Declaration of competing interest The manuscript is entitled “Characterization of a chlorine resistant and hydrophilic TiO(2)/calcium alginate hydrogel filtration membrane used for protein purification maintaining protein structure” by Ningning Gao, Wenbin Xie, Lijing Xu, Qingping Xin, Junkui Gao, Junjun Shi, Jin Zhong, Wenxiong Shi, Huiguo Wang, Kongyin Zhao and Ligang Lin. All authors declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023. Published by Elsevier B.V.)

Objective: The objectives of this study were to analyze the accuracy of contrast-enhanced ultrasonography (CE-US) in diagnosing focal hypoechogenic lesions of the thyroid (FHLT), and to explore the clinical value of CE-US in the diagnosis of FHLT., Methods: Patients undergoing CE-US and ultrasound-guided fine needle aspiration (US-FNA) of FHLT at First Hospital of China Medical University between January 2017 and December 2018 were selected for the study; this included patients with papillary thyroid carcinoma (PTC), subacute thyroiditis (SAT) and focal Hashimoto thyroiditis (FHT). All patients underwent color Doppler ultrasonography (CD-US) after which thyroid image reporting and data system (TI-RADS) grading were done. Then, each patient underwent CE-US and US-FNA. The results of the CE-US were analyzed using descriptive statistics. The cytopathological results from the US-FNAs were the gold standard used to confirm the diagnoses., Results: A total of 56 patients were selected for the study. In the PTC group (n = 16), grading was as follows: TI-RADS4a, n = 3; TI-RADS4b, n = 12; and TI-RADS4c, n = 1. More patients with PTC showed heterogeneous hypoenhancement (n = 15) than heterogeneous isoenhancement (n = 1) on CE-US. In the SAT group (n = 24), grading was as follows: TI-RADS3, n = 1; TI-RADS4a, n = 18; TI-RADS4b, n = 5. Fewer patients with SAT showed heterogeneous hypoenhancement (n = 2) than heterogeneous isoenhancement (n = 22) on CE-US. In the FHT group (n = 16), grading was as follows: TI-RADS3, n = 1; TI-RADS4a, n = 11; TI-RADS4b, n = 4. Of those in the FHT group, one patient showed heterogeneous isoenhancement, one patient showed heterogeneous hypoenhancement, and 14 showed uniform isoenhancement on CE-US. The diagnostic accuracy of CD-US alone differed significantly from that of CD-US + CE-US (p < 0.05)., Conclusion: CE-US has a high diagnostic accuracy for FHLT and can be used to identify PTC, SAT, and FHT., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Here we intended to investigate the changes in corneal endothelial cells and foveal thickness after phacoemulsification surgery on the eyes of diabetic and non-diabetic cataract patients., Material and Methods: A total of 120 cataract patients who were scheduled for phacoemulsification surgery and intraocular lens implantation were recruited and divided into 2 categories according to the diagnosis of diabetes mellitus. Changes in integrity, endothelial cell density (ECD), coefficient of variation (CV), percentage of hexagonal cells (PHC), central corneal thickness (CCT), and central foveal thickness (CFT) were all recorded at preoperative day 1 and postoperative day 3, 1 week, 1 month, 3 months and 6 months., Results: None of the recorded variables showed any difference between the nondiabetic and diabetic groups before surgery ( p > 0.05). During the postoperative 6 months, ECD and PHC decreased and CV increased in both groups (all p time < 0.05), whereas CCT and CFT fluctuated in both groups significantly (both p time < 0.05), with their individual peaks at postoperative 1 week in the diabetic group. The groups differed significantly in ECD, PHC, and CV at each time point postoperatively (all p group < 0.05). Furthermore, the diabetic group had improved CFT during the postoperative 1 month and higher CCT during the 6 months postoperatively than the nondiabetic group (all p group < 0.05). The time and group interactions were significant for ECD, CV, PHC, CCT and CFT (all p group × time < 0.05)., Conclusions: The diabetic group had more changes in corneal endothelial cells and foveal thickness than the nondiabetic group postoperatively., Competing Interests: The authors declare no conflict of interest.

Objective To investigate the synergistic anti-breast cancer effect of Toll-like receptor 7 agonist T7-ethacrynic acid conjugate (T7-EA) in combination with receptor-tyrosine-kinase-like orphan receptor 1 (ROR1). Methods ROR1 cytotoxic T lymphocyte (CTL) epitope was predicted using Syfpeithi online software. Mouse spleen lymphocytes and bone marrow dendritic cells (DCs) were separately stimulated with 4 μmol/L T7-EA and 4 μmol/L ROR1 alone or in combination. ELISA assay was used to measure the levels of interferon-γ (IFN-γ), interleukin 12 (IL-12) and tumor necrosis factor-α (TNF-α). Xenograft model was established via subcutaneous injection of mouse breast cancer 4T1 cells. The mice were weekly treated through intraperitoneal administration of 3 mg/kg T7-EA, 15 mg/kg ROR1 or the combination of T7-EA and ROR1. After four rounds of treatment, tumor tissues were weighed. Serum level of anti-4T1 tumor protein IgG was measured by ELISA. Specific CTL activity was detected by lactate dehydrogenase (LDH) assay. Results The peptide PYCDETSSV was chosen as an antigen epitope of breast cancer. The T7-EA highly activated in vitro lymphocytes in a dose-dependent manner, which wasn't affected by other relevant peptides. The combination of T7-EA and ROR1 stimulated the secretion of IFN-γ and IL-12 by lymphocytes and TNF-α by bone marrow DCs. The growth of tumor in vivo was significantly inhibited by T7-EA combined with ROR1 compared with T7-EA or ROR1 alone. The specific CTL activity triggered by T7-EA combined with ROR1 was much stronger than that triggered by T7-EA or ROR1 alone. The titer of anti-4T1 tumor protein IgG induced by T7-EA combined with ROR1 was higher than that induced by T7-EA or ROR1. Conclusion The combination of T7-EA and ROR1 has a better killing effect on breast cancer.

Immunotherapy is emerging as a powerful and active tumor-specific approach against cancer via triggering the immune system. Toll-like receptors (TLRs) are fundamental elements of the immune system, which facilitate our understanding of the innate and adaptive immune pathways. TLR agonists used as single agents can effectively eradicate tumors due to their potent stimulation of innate and adaptive immunity. We examined the effects of a novel adenine type of TLR7 agonists on both innate and adaptive immune activation in vitro and in vivo. We established the local and distant tumor‑bearing mice derived from murine mammary carcinoma cell line (4T1) to model metastatic disease. Our data demonstrated that SZU101 was able to stimulate innate immune cells to release cytokines at the very high level compared with LPS at the same or lower concentration. Locally intratumoral SZU101 injection can elicit a systemic antitumor effect on murine breast tumor model. SZU101 affected the frequency of intratumoral immune cell infiltration, including the percentage of CD4+ and CD8+ increase, and the ratio of Tregs decrease. Our data reveal that the antitumor effect of SZU101 is associated with multiple mechanisms, inducing tumor‑specific immune response, activation of innate immune cells and modulation of the tumor microenvironment.