Biomimetic Photonic Elastomer Exhibiting Stress/Moisture Reconfigurable Wrinkle-Lattice for Reversible Deformation Information Storage.

Photonic elastomers, capable of converting imperceptible deformations into visible colors, show significant potential in smart materials. However, instantaneous deformation is arduous to record accurately due to the disappearance of optical information after deformation recovery. Herein, inspired by the folding structures of iridocytes in cephalopods, a stress- and moisture-triggered wrinkling and erasure effect is proposed to be introduced in the construction of a photonic elastomer. Implemented in a dual-network polymer framework with modulatable locking, it allows for reversible deformation storage. The photonic elastomer comprises a surface one-dimensional photonic crystal (1DPC) and a poly(dimethylsiloxane) (PDMS) substrate. The deformed 1DPC lattice transforms into a wrinkled state due to a substrate deformation mismatch, preserving strain-induced structural color information through interchain hydrogen bonding and crystalline shape-locking in dual-network polymers. Reading the color provides multidimensional information about the instantaneous deformation degree and distribution. Moreover, the moisture-induced shape-memory feature of the 1DPC can be triggered with a minute amount of water, like fingertip perspiration or humidity change (35% to 80%), to restore the original color. This stress/moisture-responsive photonic elastomer, with its dynamically reconfigurable wrinkle-lattice, holds great promise for applications in mechanical sensing, inkless writing, and anticounterfeiting, significantly enhancing the versatility of photonic materials.

Bioinspired Colorimetric Double Inverse Opal Photonic Crystal Indicators for Ethanol Concentration Sensing in Fermentation Engineering.

Photonic crystal-based ethanol concentration indicators with rapid response and brilliant structural color output definitely take a place in colorimetric sensors. Here, based on the H-bond-regulated swelling of acrylate shape memory polymers (SMPs) and the solvent-induced structural color change of the double inverse opal photonic crystals (DIOPCs), new-type photonic crystals (PCs) colorimetric indicators were constructed, exhibiting a span of maximum reflection wavelength (λmax) up to ∼166 nm in response to alcohols with concentrations from 0 to 100 vol %. DIOPC indicators (DIOPCIs) show a rapid response to alcohols (<1.5 s) and output different structural colors (covering from blue to red). The colorimetric sensing mechanism includes the solvent-triggered recovery of the inverse opal skeleton, the cosolvency effect and H-bonds induced swelling/shrinkage of the polymer, the phase separation between polystyrene (PS) microsphere and polymer skeleton, and the light diffraction of DIOPCs. While ensuring a larger λmax span by regulating the H-bond interactions in polymer chains through acrylamide (AAm), AAm-modified DIOPCIs are sensitive to some specific ethanol concentrations. The real-time sensing of ethanol concentration during fermentation verified the practicability of DIOPCIs, thus establishing a visual model between structural color and corresponding fermentation kinetics. We envisage that the DIOPCIs will contribute to the intelligentization of the alcoholic fermentation and distillation industry.

Ultrathin photonic crystal based on photo-crosslinked polymer and metal-organic framework for highly sensitive detection and discrimination of benzene series vapors.

Volatile organic compounds (VOCs) have always been a major concern as a global environmental problem. As a low-cost, high-efficiency and visual sensor, photonic crystals (PCs) have been actively studied in VOCs detection. Herein, a one-dimensional PC sensor for visual sensing of highly toxic benzene series VOC vapors is prepared for the first time by integrating a new photo-crosslinked polymer-poly(styrene-benzoylphenyl acrylate) P(St-BPA) and a high specific surface area metal-organic framework (MOF) MIL-101(Cr). The PC can detect VOCs quantitatively and visually, and clearly distinguish 7 benzene series vapors. The detection limit of the benzene series VOCs is as low as 0.06-3.45 g/m3. Meanwhile, owing to the ultra-thin layer and porous structure, the PC can reach a response equilibrium to the VOCs within 1-2.6 s. Moreover, the PC has a good organic vapor tolerance and can maintain stable optical performance after 1000 times of reuse in VOCs. Besides, 4 other PCs assembled with different aryl polymers and MOFs are first fabricated and their sensing performance to benzene series VOCs are studied and compared, which provides a valuable reference for the selection of materials for the preparation of such PC sensors.

microRNA-15a-5p suppresses hypoxia-induced tumor growth and chemoresistance in bladder cancer by binding to eIF5A2.

In various malignant tumors (including bladder cancer) poor prognosis is associated with hypoxia and therapeutic resistance. Evidence indicates that in bladder cancer, microRNAs (miRNAs) have vital functions in acquired drug resistance. However, the involvement of miRNAs in hypoxia-mediated bladder cancer doxorubicin (Dox) resistance is unknown. Herein, we showed that hypoxia and Dox treatment downregulated miR-15a-5p expression. Using UM-UC-3 and J82 bladder cancer cell lines and in vivo mouse models of bladder cancer, we confirmed that miR-15a-5p arrests tumor cell growth and Dox resistance in vitro and in vivo. Furthermore, we determined the interaction between miR-15a-5p and eukaryotic translation initiation factor 5A-2 (eIF5A2) using dual luciferase reporters and quantitative real-time reverse transcription polymerase chain reaction assays. We also showed that a miR-15a-5p agomir repressed EIF5A2 expression in bladder cancer cells, thereby inhibiting the epithelial-mesenchymal transition (EMT) induced by Dox or hypoxia. Moreover, ectopic expression of miR-15a-5p abrogated eIF5A2-mediated Dox resistance in bladder cancer cells. Collectively, these data indicated that hypoxia promotes tumor growth and chemoresistance through the HIF-1α/miR-15a-5p/eIFTA2/EMT pathway. This new finding not only has implications for improving our understanding of the Dox resistance process during bladder cancer progression but also indicates that the miR-15a-5p agomir is a promising tool to prevent Dox resistance in patients with bladder cancer.

Residue-Free and Recyclable Starch-Based Flocculants for Dye Wastewater Flocculation.

Flocculants are crucial agents in wastewater treatment because they can remove oppositely charged impurities effectively and swiftly. However, flocculation also inevitably causes secondary contamination due to the residual properties, nonreusability, and nondegradability of traditional flocculant molecules. Herein, an ecofriendly starch-based flocculant, i.e., 2,4-bis(dimethylamino)-[1,3,5]-triazine-6-starch, was synthesized via a preactivation-etherification strategy. The large molecular weight property of the flocculant produced by this method enhances the intermolecular hydrophobic association, achieving complete phase separation of all flocculant molecules from water and residue-free flocculation for the first time. Importantly, a large molecular weight tertiary amine starch-based flocculant (LMTS) exhibits a remarkable flocculation capacity of over 1800 mg·g-1 for dye wastewater, which is significantly higher than that of traditional polyacrylamide and polyaluminum chloride flocculants. Furthermore, the LMTS flocculant could be recycled by pH adjustment, and its structural stability ensured sustained reusability. This high-performance residue-free biomass-based flocculant offers a green advance for wastewater treatment.

Hydrogen Bond-Mediated Self-Shielded Moisture-Responsive Structural Color for Time-Temperature Indicating.

Effective monitoring of the time-temperature history of biological reagents, chemical drugs, and perishable foods during cold chain storage is crucial for ensuring their quality and efficacy. Time-temperature indicators (TTIs) are developed to assess the cumulative impact of time and temperature on product quality. However, current indicators face challenges related to complex wrapping procedures, narrow tracking ranges, susceptibility to photobleaching, and pre-use instability, hampering widespread use. Herein, the first moisture-responsive 1D photonic crystal (1DPC) TTIs featuring robust structural colors, customizable time-temperature ranges, and reliable renewability are demonstrated. The indicators exhibit distinct color-changing responsiveness toward water vapor, which remains observable after prolonged storage at low temperatures. Significantly, the moisture responsiveness gradually diminishes at elevated temperatures over time due to ambient water-induced hydrogen bond formation, effectively shielding the indicator from external stimuli. This property enables the naked-eye inspection of product efficacy during cold chain storage. Additionally, the endowed flexibility of the TTI facilitates its easy attachment to targets, functioning as a convenient indicator label. Remarkably, the indicator can be stably stored for an extended period at room temperature before use, thereby showcasing substantial market potential.

TBOPP, a DOCK1 Inhibitor, Potentiates Cisplatin Efficacy in Breast Cancer by Regulating Twist-mediated EMT.

BACKGROUND: DOCK1 has been reported to be involved in tumor progression and resistance. 1-(2-(30-(trifluoromethyl)-[1,10-biphenyl]-4-yl)-2-oxoethyl)-5-pyrrolidinylsulfonyl2(1H)- pyridone (TBOPP) is a selective DOCK1 inhibitor; however, the role and molecular mechanisms of DOCK1 and its inhibition in breast cancer (BC) resistance remain poorly understood. OBJECTIVE: This study aims toinvestigate the underlying mechanisms of DOCK1 in BC resistance. METHODS: DOCK1 or Twist siRNA and Twist plasmid were used to explore the function of DOCK1 in vitro experiments. A mouse xenograft model was used for in vivo experiments. RESULTS: In the present study, we demonstrated that DOCK1 siRNA promoted cisplatin sensitivity in BC cells. Moreover, TBOPP also enhances the therapeutic effect of cisplatin both in vitro and in vivo. Mechanistically, DOCK1 siRNA inhibited EMT. Twist 1 is one of the EMT-inducing transcription factors and is known to induce EMT. To further reveal the effect of DOCK in BC cells, we co-transfected with DOCK1 and Twist1 siRNA to BC cells and found that co-transfection with DOCK1 and Twist siRNA could not further enhance the cisplatin sensitivity of BC cells. Moreover, DOCK1 siRNA failed to reverse the effect of Twist 1 up-regulation. CONCLUSION: Taken together, these results demonstrate that DOCK1 may function as a potential therapeutic target in BC and that combining cisplatin with TBOPP may provide a promising therapeutic strategy for cisplatin-resistant BC patients.

Inhibition of Taurine-upregulated Gene 1 Upregulates MiR-34a-5p to Protect against Myocardial Ischemia/Reperfusion via Autophagy Regulation.

BACKGROUND: Taurine upregulated gene 1 (TUG1) has been identified on long noncoding RNA (lncRNA); however, its function in myocardial cells following ischemia/ reperfusion (I/R) injury has not been explored. This study aimed to investigate the role of LncTUG1 in I/R injury by focusing on its relationship with autophagy induction by regulating miR-34a-5p expression. METHODS: We established a myocardial I/R model and H9C2 hypoxia-ischemic and reoxygenation (HI/R) conditions to induce I/R injury. TTC, Western blot, CCK-8 assay, quantitative reverse transcription PCR, flow cytometry, and confocal microscopy were used to assess the size of myocardial infarct, level of some apoptotic-related and autophagy-associated proteins, cell viability, the level of LncRNA TUG1, apoptosis, and autophagy, respectively. RESULTS: The results revealed that a TUG1 knockdown protected against I/R-induced myocardial injury by decreasing the impairment in cardiac function. LncRNA TUG1 expression was increased in a myocardial I/R model and HI/R in H9C2 cells. Moreover, inhibition of LncTUG1 enhanced H9C2 cell viability and protected the cells from HI/R-induced apoptosis. Silencing LncRNA TUG1 promoted HI/R-induced autophagy. Furthermore, TUG1 siRNA upregulated the level of miR-34a-5p compared to the HI/R group. The protective effect of LncRNA TUG1 inhibition on H9C2 cells following HI/R was eliminated by blocking autophagy with an miR-34a-5p inhibitor. CONCLUSION: These findings indicated that inhibiting TUG1 may reduce the extent of myocardial I/R injury by regulating miR-34a-5p. Taken together, these results suggest that LncRNA TUG1 may represent a novel therapeutic target for myocardial I/R injury.

Transcriptome sequencing analysis reveals miR-30c-5p promotes ferroptosis in cervical cancer and inhibits growth and metastasis of cervical cancer xenografts by targeting the METTL3/KRAS axis.

Cervical cancer is the most common malignant tumor in the female reproductive system worldwide, and its molecular mechanisms remain complex and poorly understood. Various techniques, including transcriptome sequencing, RT-qPCR, ELISA, immunofluorescence, Western blot, CCK-8 assay, Transwell assay, and xenograft models, were employed to investigate gene/miRNA expression, cellular proliferation, migration, and the interactions between miR-30c-5p, METTL3, and KRAS. Our transcriptome sequencing results demonstrated a significant downregulation of miR-30c-5p in cervical cancer cells. Further investigations using RNA pull-down, dual-luciferase reporter assay, Me-RIP, and PAR-CLIP confirmed METTL3 as one of the downstream targets of miR-30c-5p, while KRAS was identified as an iron-death suppressor gene susceptible to m6A modification. Notably, our Me-RIP analysis demonstrated the involvement of METTL3 in m6A modification of KRAS. In vitro experiments revealed that miR-30c-5p facilitated ferroptosis in cervical cancer cells by inhibiting the METTL3/KRAS axis, thus suppressing proliferation and migration. Additionally, in vivo studies demonstrated that miR-30c-5p repressed the growth and metastasis of cervical cancer xenografts through the inhibition of the METTL3/KRAS axis. Overall, this study highlights the critical role of miR-30c-5p in modulating cervical cancer progression by targeting the METTL3/KRAS axis, providing new insights into the molecular mechanisms underlying cervical cancer growth and metastasis.

Catalyst-free readily dual-recyclable acetal-based covalent adaptable cellulose networks.

Despite covalent adaptable networks (CANs) imparting the favorable features of crosslinked polymers, as well as the functionality of reprocessing, reshaping and welding, due to exchange reaction enabled topology changes; it is still a huge challenge to design catalyst-free, fast reprocessing, controlled degradation and polymer recyclable biomass base CANs. Herein, for the first time, acetal-based covalent adaptable cellulose networks (ACCs) were utilized to synthesize readily reconstructable cellulose-based thermosets with mechanical tunability. ACCs were synthesized via catalyst-free "click" addition of cellulose and divinyl ether without releasing small molecule byproducts. Different crosslinking densities and crosslinkers were used to explore the structure-property relationship, the mechanical and thermal properties of the ACCs were strongly influenced by these factors. ACCs can obtain enhanced tensile strength or elongation at break by changing the structure of the crosslinker. Furthermore, the reworking, welding and shape memory properties of these ACCs, based on the dynamic exchange reaction of acetal bonds, were investigated. In addition, these ACCs can be degraded under acidic conditions, and closed-loop utilization of polymer was possible. Thus, ACCs can be mechanically and chemically double-cycled, which will contribute to solving the white pollution problem and resource waste as a new class of sustainable plastics.

A novel and sensitive method for simultaneous determination of 6 low-calorie bulk sweeteners by HPLC-ELSD.

A novel and sensitive method for the simultaneous analysis of six low-calorie bulk sweeteners (D-allulose, D-tagatose, D-mannitol, mycose, palatinose, and erythritol) without derivatisation was developed using high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD). Chromatographic separations were carried out on a Zorbax Original NH2 (5 µm particle size, 250 mm×4.60 mm id, 70 Å) column with flow rate gradient elution with acetonitrile: water (80:20, v/v). Drift tube temperature was set at 50 ℃, the nebuliser carrier gas flow rate was 1.0 mL·min-1, and nitrogen pressure was regulated to 276 kPa with gain:3. The regression equation showed good linearity (R2 = 0.9985-0.9998) for all six low-calorie bulk sweeteners in the tested range (0.060-0.60 mg·mL-1). The limits of detection (LOD) for the six low-calorie bulk sweeteners ranged from 0.02 to 0.06 mg·mL-1. The proposed HPLC-ELSD method was validated for the quantification of the low-calorie bulk sweeteners in 14 types of foods, and the results were satisfactory. In addition, the results showed that the number of sweeteners in each food product varied. The presence of multiple low-calorie bulk sweeteners in certain foods is interesting. This method is successful in monitoring low-calorie bulk sweeteners in food.

Visual Recognition of Volatile Organic Compounds by Photonic Nose Integrated with Multiple Metal-Organic Frameworks.

The photonic nose inspired by the olfactory system is an integrated detection platform constructed by multiple sensing units as channels. However, in the detection of volatile organic compounds (VOCs), the sensing results that cannot be directly readable and the poor ability to distinguish analytes with similar chemical properties are the main challenges faced by this sensor. Here, 8 metal-organic frameworks (MOF)-based photonic crystals are used as the basic sensing units to construct a photonic nose detection platform. The microscopic adsorption of VOCs by MOFs enables the photonic crystals (PCs) to produce macroscopic structural color output, and further makes the photonic nose have specific color fingerprints for different VOCs, the response time of all PCs to VOCs can be within 1 s. Through the color fingerprint, the visual identification of VOCs produced by 5 common solvent vapors is realized, and 9 VOCs with similar chemical properties are further distinguished. In addition, the application potential of the photonic nose in the actual environment is verified by identifying different contents of benzene in the paint. It is envisaged that the MOF-based photonic nose has great reference value for the development of intelligent and multi-component synergistic functional gas sensors.

2D Information Security System Based on Polyurethane Inverse Photonic Glass Structure.

Information security has become a major global problem in recent years. Thus, people continue to exert much effort in developing new information security technologies based on encryption and storage. In this study, a 2D information security technology based on polyurethane optical devices with inverse photonic glass structure (PU-IPG) is introduced. Based on 1) the swelling and plasticizing effects of various solvents on PU-IPG and 2) the capillary force that can produce geometric deformation on micro/nanostructures when solvents evaporate, a 2D information security system with two modules of decryption (structural color information display) and anticounterfeiting (structural color transformation) is successfully constructed. The spraying method adopted can be simple and fast and can provide a large area to build photonic glass templates, which greatly improves the capacity and category of information in the encryption system. The prepared PU-IPG optical devices can produce large-area multicolor output capability of information. These devices also have excellent mechanical properties, strong cycle stability, environmental friendliness, and low price. Therefore, the preparation strategy has great reference value and application prospects in the field of information security.

Correlation Between Persistent HPV Infection and Vaginal Microecological Imbalance After Treatment of Cervical High-Grade Squamous Intraepithelial Lesion.

Objective: To analyze the association between persistent human papillomavirus (HPV) infection and vaginal microecological imbalance after surgical treatment of cervical high-grade squamous intraepithelial lesion (HSIL). Methods: This is a retrospective study, 180 cervical HSIL patients admitted to our hospital from May 2019 to May 2021 were selected, of these, 84 were treated with loop electrosurgical excision procedure (LEEP) and 96 with cold knife conization (CKC). Patients were followed up for HPV infection 1 year after surgery. There is a division into a persistent infection group (positive group) and a negative group based on the presence or absence of HPV, the detection technique was PCR amplification. The two groups were compared regarding preoperative HPV infection, vaginal micro-ecological indicators 1 year after surgery, and the correlation between persistent HPV infection and vaginal microecological imbalance. Results: At 1 year after surgery, among 180 cervical HSIL patients, 64 (35.56%) were persistently infected with HPV, with an age of (40.20 ± 4.85) years, including 36 (56.25%) with cervical intraepithelial neoplasia (CIN) grade II, 28 (43.75%) with cervical intraepithelial neoplasia (CIN) grade III, 116 (64.44%) with HPV negative, with an age of (40.22 ± 5.15) years, including 67 (57.76%) with CIN grade II and 49 (42.24%) with CIN grade III, the differences in age and CIN classification between the two groups were not statistically significant (P > .05). Preoperatively, 53 people (82.81%) with HPV viral load >100 RLU/CO in the HPV persistent infection group and 76 people (65.52%) with HPV viral load >100 RLU/CO in the HPV negative group, with statistically significant differences between the two groups (P < .05); The difference in HPV virus typing and HPV infection type between the two groups was not statistically significant (P > .05). At 1 year after surgery, the composition ratio of flora density class IV and flora diversity class IV were significantly higher in the HPV persistent infection group than in the HPV negative group, and the dominant bacteria were mainly gram-positive large bacillus, accounting for 83.33%, the difference between the two groups was statistically significant (P < .05); The differences in Nugent scores and pH values between the two groups were not statistically significant (P > .05). Logistic regression analysis showed that flora density, flora diversity, and dominant bacteria were all independent risk factors for persistent HPV infection after treatment in patients with HSIL (P < .05). Conclusion: After treatment of HSIL patients, clinical attention should be paid to monitoring of HPV infection but also to the changes in vaginal microecology, as timely correction of vaginal microecology can facilitate HPV regression and improve the patient's prognosis.

Large-Area Rewritable Paper Based on Polyurethane Inverse Photonic Glass with Durable High-Resolution Information Storage and Structural Stability.

To alleviate the negative effects of resource waste and environmental pollution caused by the excessive use of paper, technologies for rewritable paper have received widespread attention and in-depth research. Despite the growing interest in rewritable paper, meeting the requirements of large-scale preparation, long-lasting information storage time, high reversibility, and good environmental stability remains a huge challenge for this technology. This study developed a solvent-responsive copolymerized polyurethane-based rewritable paper with an inverse photonic glass structure (co-PUIPG paper). Comprehensive writing modes, including handwriting, spraying, and printing, were realized by using the swelling effect of different solvents and the local force field formed by capillary force to control the deformation degree of the inverse photonic glass structure. Co-PUIPG paper can persistently store high-resolution information and has a green and environmentally friendly "write-erase" method. Meanwhile, it exhibits good rewritability, as well as high mechanical strength and exceptional resistance to environmental factors, such as friction, high temperature, and sunlight. Because the spraying method can prepare templates quickly and extensively and polyurethane materials are economical, co-PUIPG rewritable paper possesses great potential as a substitute for commercial fiber paper and its industrialization is full of great possibilities.

Inhibition of GPR30 sensitized gefitinib to NSCLC cells via regulation of epithelial-mesenchymal transition.

Introduction: G-protein coupled receptor 30 (GPR30) is associated with cell metastasis and drug resistance in many different cancer cells. The present study aimed to reveal the sensitivity of GPR30 to gefitinib in non-small cell lung cancer (NSCLC) cells.Methods: Cell viability and proliferation were detected using cell counting kit 8 and 5-ethynyl-2'-deoxyuridine assays, respectively. Western blotting and quantitative real-time reverse transcription PCR were used to detect GPR30 or epithelial-mesenchyme transition (EMT)-related mRNA and protein expression.Results: The results showed that GPR30 expression is associated with gefitinib sensitivity. G15, as a GPR30 antagonist, reduced GPR30 expression. We chose the maximum concentration of G15 with minimal cytotoxicity to detect cell viability after combined treatment with gefitinib in NSCLC cells, which indicated that G15 could increase sensitivity to gefitinib. However, the effect of G15 on gefitinib sensitivity disappeared after treatment with a small interfering RNA targeting GPR30. Further research showed that G15 or GPR30 siRNA treatment could upregulate E-cadherin and downregulate vimentin levels.Conclusion: Taken together, these data suggested that G15 could enhance NSCLC sensitivity to gefitinib by inhibition of GPR30 and EMT.

GSH-Responsive Polymeric Micelles for Remodeling the Tumor Microenvironment to Improve Chemotherapy and Inhibit Metastasis in Breast Cancer.

The tumor microenvironment (TME) of breast cancer is hypoxic, which can promote tumor progression, including invasion and metastasis, and limit the efficacy of anti-tumor treatment. Nitric oxide (NO) can dilate blood vessels, effectively alleviate hypoxia, and regulate the TME, which has the potential to improve the anti-tumor therapeutic efficacy. Here, chitosan (CO) and octadecylamine (ODA) were linked by the disulfide bond, and the LinTT1 peptide was linked onto CO-SS-ODA for targeting tumor cells and endothelial cells in tumors. The NO donor S-nitroso-N-acetylpenicillamine (SNAP) was connected to CO. Doxorubicin (DOX) was encapsulated, and GSH hierarchically responsive polymer micelles (TSCO-SS-ODA/DOX) were constructed for the treatment of breast cancer. The micelles had differently responsive drug release in different GSH concentrations. In endothelial cells, the micelles rapidly responded to release NO. In tumor cells, the disulfide bond rapidly broke and released DOX to effectively kill tumor cells. The disulfide bond was not sensitive to GSH concentration in endothelial cells, which had less release of DOX. The killing effect of the micelles to endothelial cells was much lower than that to tumor cells. The cell selective drug release of the drug delivery systems enabled safe and effective treatment of drugs. TSCO-SS-ODA/DOX, which had the excellent ability to target tumors, can alleviate tumor hypoxia, decrease the infiltration of M2 macrophages in tumors, increase the infiltration of M1 macrophages in tumors, and remodel the TME. Notably, TSCO-SS-ODA/DOX can significantly inhibit the growth of the primary tumor and effectively inhibit tumor metastasis. The drug delivery system provided a potential solution for effectively treating breast cancer.

[Simultaneous determination of six rare sugars in solid foods by high performance liquid chromatography-evaporative light-scattering detection].

Excessive sugar consumption is associated with metabolic health problems. Rare sugars are gradually being used as substitutes for sugar, and their consumption is increasing daily, raising food-safety issues such as false advertising, adulteration, and overdosing. The determination of rare-sugar compounds has attracted considerable attention in recent years. However, no standard method for the simultaneous determination of six rare sugars (allulose, tagatose, trehalose, isomaltulose, erythritol, and mannitol) in solid foods is available. Therefore, establishing a suitable analytical method for these sugars is necessary. In this study, high performance liquid chromatography coupled with evaporative light-scattering detection was used to determine rare sugars in solid foods. The optimum chromatographic and detector conditions were determined by evaluating the instrument parameters. Analysis was carried out on a Zorbax Original NH2 column (250 mm×4.6 mm, 5 µm) via flow-rate gradient elution (0-15 min, 1.0 mL/min; 15-18 min, 1.0-2.0 mL/min; 18-25 min, 2.0 mL/min) with acetonitrile-water (80∶20, v/v) as the mobile phase. Sharp and symmetric chromatographic peaks were obtained under these conditions. The resolutions for all the six rare sugars were greater than 1.5. Optimization of the evaporative light-scattering detector was extremely important to the responses of the rare-sugar compounds. The two most significant parameters were the nebulizer carrier gas flow rate and drift tube temperature. The detection system was operated under the following conditions: the drift tube temperature was set to 50 ℃, the nebulizer carrier gas was high-purity nitrogen, the carrier gas flow rate was 1.0 mL/min, the nitrogen pressure was regulated to 275.79 kPa, and the gain factor was set to 3. The sample was extracted with 25 mL of water, shaken and vortexed for 10 min, purified with 200 µL of zinc acetate solution and 200 µL of potassium ferricyanide solution, and centrifuged at 4500 r/min for 10 min. Next, 1 mL of the supernatant was passed through a 0.22 µm aqueous-phase filter membrane, and the filtrate obtained was analyzed using the evaporative light-scattering detector. The six rare sugars were quantitatively analyzed using the external standard method and showed good linearity with coefficients of determination (R2) greater than 0.9985. The limits of detection and quantification were 0.020-0.60 and 0.60-1.8 g/100 g, respectively. In addition, when blank solid food samples were spiked with the analytes at three levels, the average recoveries of the six rare sugars were 92.6%-103.2%, with relative standard deviations (RSDs) of 0.7%-4.4%. An RSD of <5% indicated that the method had good precision. Interference experiments were performed to determine whether the sugars and artificial sweeteners commonly found in solid foods affected the targets. The method established in this study was used to analyze the contents of the six rare sugars in actual solid food samples. The experimental results showed various levels of rare glycoconjugates in different solid foods. Moreover, the actual compositions and labeled of rare glycoconjugates in the solid foods were generally consistent. The proposed method features simple operation, rapid results, high sensitivity, and good reproducibility; thus, it meets the requirements for the detection of the six rare sugars in solid foods. It also provides technical support for the development of methodological standards and detection limits for rare sugars in Chinese foods. The results of this study are of great relevance for the daily monitoring of the levels of the six rare sugars in solid foods.

Normalizing Tumor Blood Vessels to Improve Chemotherapy and Inhibit Breast Cancer Metastasis by Multifunctional Nanoparticles.

The abnormal tumor blood vessels with high leakage can promote tumor cells to infiltrate into the systemic circulation and increase the risk of tumor metastasis. In addition, chemotherapy may destroy tumor blood vessels and further aggravate metastasis. Normalizing tumor blood vessels can reduce vascular leakage and increase vascular integrity. The simultaneous administration of vascular normalization drugs and chemotherapy drugs may resist the blood vessels' destruction of chemotherapy. Here, multifunctional nanoparticles (CCM@LMSN/DOX&St), which combined chemotherapy with tumor blood vessel normalization, were prepared for the treatment of breast cancer. The results showed that CCM@LMSN/DOX&St-loaded sunitinib (St) promoted the expression of junction proteins Claudin-4 and VE-cadherin of endothelial cells, reversed the destruction of DOX to the endothelial cell layer, protected the integrity of the endothelial cell layer, and inhibited the migration of 4T1 tumor cells across the endothelial cell layer. In vivo experiments showed that CCM@LMSN/DOX&St effectively inhibited tumor growth in situ; what is exciting was that it also inhibited distal metastasis of breast cancer. CCM@LMSN/DOX&St encapsulated with St can normalize tumor blood vessels, reverse the damage of DOX to tumor blood vessels, increase the integrity of blood vessels, and prevent tumor cell invasion into blood vessels, which can inhibit breast cancer spontaneous metastasis and reduce chemotherapy-induced metastasis. This drug delivery platform effectively inhibited the progression of tumors and provided a promising solution for effective tumor treatment.

Chitosan-based nano-micelles for potential anti-tumor immunotherapy: Synergistic effect of cGAS-STING signaling pathway activation and tumor antigen absorption.

Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway is an essential DNA-sensing pathway to regulate the innate and adaptive immune response, which plays an important role in tumor immunotherapy. Although the STING agonists can be used, they are limited by their inability to target immune cells and systemic immunotoxicity, calling for novel strategies to accurately and effectively activate the cGAS-STING signaling pathway. Herein, mannose-modified stearic acid-grafted chitosan (M-CS-SA) micelles with the ability to activate the cGAS-STING signaling pathway and absorb tumor antigens were constructed. The chitosan-based nano-micelles showed valid dendritic cell (DCs) targeting and could escape from lysosomes leading to the activation of the cGAS-STING signaling pathway and the maturation of DCs. In addition, a combinatorial therapy was presented based on the programmed administration of oxaliplatin and M-CS-SA. M-CS-SA adsorbed tumor antigens released by chemotherapy to construct an autologous tumor vaccine and built a comprehensive antitumor immune response. In vivo, the combinatorial therapy achieved a tumor inhibition rate of 76.31 % at the oxaliplatin dose of 5 mg/kg and M-CS-SA dose of 15 mg/kg, and increased the CD3+ CD8+ T cell infiltration. This work demonstrated that M-CS-SA and its co-treatment with oxaliplatin showed great potential in tumor immunotherapy.