A new scale for older resident satisfaction with residential integrated care in China: Development and validation.

The factors that affect resident satisfaction with emerging residential integrated care for older people in China have been unclear due to a lack of validated instruments. Based on psychometric assessment procedures, we developed a new scale for older resident satisfaction with residential integrated care (SORSRIC). The scale was developed using a two-step process and a sample of 16 Chinese institutions and 333 residents. Exploratory and confirmatory factor analysis was used to evaluate reliability and validity. Principal component analysis and maximum variance methods were used to orthogonally rotate the items to extract seven factors. These were: resident expectations, perceived quality (physical care), perceived quality (mental care), perceived value, resident satisfaction, resident complaints, and resident loyalty. The CR value of each dimension of the pre-tested, formal scale was greater than 0.80, and the AVE value was greater than 0.50. This 24-item instrument showed good reliability and structural validity and can be applied to improve the experience and outcomes for older people in residential care.

Phosphorothioate-modified G-quadruplex as a signal-on dual-mode reporter for CRISPR/Cas12a-based portable detection of environmental pollutants.

BACKGROUND: Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a-powered biosensor with a G-quadruplex (G4) reporter offer the benefits of simplicity and sensitivity, making them extensively utilized in detection applications. However, these biosensors used for monitoring pollutants in environmental water samples may face the problem of high background signal and easy interference due to the "signal-off" output. It is obvious that a biosensor based on the CRISPR/Cas12a system and G4 with a "signal on" output mode needs to be designed for detecting environmental pollutants. RESULTS: By using phosphorothioate-modified G4 as a reporter and catalytic hairpin assembly (CHA) integrated with Cas12a as an amplification strategy, a "signal-on" colorimetric/photothermal biosensor (psG4-CHA/Cas) for portable detection of environmental pollutants was developed. With the help of functional nucleotides, the target pollutant (kanamycin or Pb2+) triggers a CHA reaction to produce numerous double-strand DNA, which can activate Cas12a's trans-cleavage activity. The active Cas12a cleaves locked DNA to release caged psG-rich sequences. Upon binding hemin, the psG-rich sequence forms a psG4/hemin complex, facilitating the oxidation of the colorless 3,3',5,5'-tetramethylbenzidine (TMB) into the blue photothermal agent (oxTMB). The smartphone was employed for portable colorimetric detection of kanamycin and Pb2+. The detection limits were found to be 100 pM for kanamycin and 50 pM for Pb2+. Detection of kanamycin and Pb2+ was also carried out using a portable thermometer with a detection limit of 10 pM for kanamycin and 8 pM for Pb2+. SIGNIFICANCE: Sensitive, selective, simple and robust detection of kanamycin and Pb2+ in environmental water samples is achieved with the psG4-CHA/Cas system. This system not only provides a new perspective on the development of efficient CRISPR/Cas12a-based "signal-on" designs, but also has a promising application for safeguarding human health and environmental monitoring.

Eutectogel Electrolyte Constructs Robust Interfaces for High-Voltage Safe Lithium Metal Battery.

Dramatic growth of lithium dendrite, structural deterioration of LiCoO2 (LCO) cathode at high voltages, and unstable electrode/electrolyte interfaces pose significant obstacles to the practical application of high-energy-density LCO||Li batteries. In this work, a novel eutectogel electrolyte is developed by confining the nonflammable eutectic electrolyte in a polymer matrix. The eutectogel electrolyte can construct a robust solid electrolyte interphase (SEI) with inorganic-rich LiF and Li3N, contributing to a uniform Li deposition. Besides, the severe interface side reactions between LCO cathode and electrolyte can be retarded with an in situ formed protective layer. Correspondingly, Li||Li symmetrical cells achieve highly reversible Li plating/stripping over 1000 h. The LCO||Li full cell can maintain 72.5% capacity after 1500 cycles with a decay rate of only 0.018% per cycle at a high charging voltage of 4.45 V. Moreover, the well-designed eutectogel electrolyte can even enable the stable operation of LCO at an extremely high cutoff voltage of 4.6 V. This work introduces a promising avenue for the advancement of eutectogel electrolytes, the nonflammable nature and well-regulated interphase significantly push forward the future application of lithium metal batteries and high-voltage utilization of LCO cathode.

Curcumin-Based Ionic Liquid Hydrogel for Topical Transdermal Delivery of Curcumin To Improve Its Therapeutic Effect on the Psoriasis Mouse Model.

Psoriasis is a systemic, recurrent, chronic autoimmune skin disease. However, psoriasis drugs have poor skin permeability and high toxicity, resulting in low bioavailability and affecting their clinical application. In this study, we propose a curcumin-based ionic liquid hydrogel loaded with ilomastat (Cur-Car-IL@Ilo hydrogel), which can effectively maintain the sustained release of drugs and improve the skin permeability of drugs. We used a model of imiquimod-induced psoriasis and demonstrated that local application of Cur-Car-IL@Ilo hydrogel can improve skin lesions in mice with significantly reduced expression levels of inflammatory factors, matrix metalloproteinase 8, and collagen-I. The expressions of iron death-related proteins SLC7A11 and ASL4 were significantly decreased after treatment with Cur-Car-IL@Ilo hydrogel. Flora analysis showed that the content of anaerotruncus, proteus, and UCG-009 bacteria in the gut of psoriatic mice increased. The levels of paludicola, parabacteroides, prevotellaceae_UCG-001, escherichia-shigella, and aerococcus decreased, and the levels of some of the above bacteria tended to be normal after treatment. Therefore, the curcumin-based ionic liquid hydrogel can be used as a multifunctional, nonirritating, noninvasive, and highly effective percutaneous treatment of psoriasis.

Self-adjuvanting polymeric nanovaccines enhance IFN production and cytotoxic T cell response.

Vaccines represent one of the most powerful and cost-effective innovations for controlling a wide range of infectious diseases caused by various viruses and bacteria. Unlike mRNA and DNA-based vaccines, subunit vaccines carry no risk of insertional mutagenesis and can be lyophilized for convenient transportation and long-term storage. However, existing adjuvants are often associated with toxic effect and reactogenicity, necessitating expanding the repertoire of adjuvants with better biocompatibility, for instance, designing self-adjuvating polymeric carriers. We herein report a novel subunit vaccine delivery platform constructed via in situ free radical polymerization of C7A (2-(Hexamethyleneimino) ethyl methacrylate) and acrylamide around the surface of individual protein antigens. Using ovalbumin (OVA) as a model antigen, we observed substantial increases in both diameter (∼70 nm) and surface potential (-1.18 mV) following encapsulation, referred to as n(OVA)C7A. C7A's ultra pH sensitivity with a transition pH around 6.9 allows for rapid protonation in acidic environments. This property facilitates crucial processes such as endosomal escape and major histocompatibility complex (MHC)-I-mediated antigen presentation, culminating in the substantial CD8+ T cell activation. Additionally, compared to OVA nanocapsules without the C7A components and native OVA without modifications, we observed heightened B cell activation within the germinal center, along with remarkable increases in serum antibody and cytokine production. It's important to note that mounting evidence suggests that adjuvant effects, particularly its targeted stimulation of type I interferons (IFNs), can contribute to advantageous adaptive immune responses. Beyond its exceptional potency, the nanovaccine also demonstrated robust formation of immune memory and exhibited a favorable biosafety profile. These findings collectively underscore the promising potential of our nanovaccine in the realm of immunotherapy and vaccine development.

Plant Growth-Promoting Rhizobacteria Are Key to Promoting the Growth and Furanocoumarin Synthesis of Angelica dahurica var. formosana under Low-Nitrogen Conditions.

Microbiomes are the most important members involved in the regulation of soil nitrogen metabolism. Beneficial interactions between plants and microbiomes contribute to improving the nitrogen utilization efficiency. In this study, we investigated the Apiaceae medicinal plant Angelica dahurica var. formosana. We found that under a low-nitrogen treatment, the abundance of carbon metabolites in the rhizosphere secretions of A. dahurica var. formosana significantly increased, thereby promoting the ratio of C to N in rhizosphere and nonrhizosphere soils, increasing carbon sequestration, and shaping the microbial community composition, thus promoting a higher yield and furanocoumarin synthesis. Confirmation through the construction of a synthetic microbial community and feedback experiments indicated that beneficial plant growth-promoting rhizobacteria play a crucial role in improving nitrogen utilization efficiency and selectively regulating the synthesis of target furanocoumarins under low nitrogen conditions. These findings may contribute additional theoretical evidence for understanding the mechanisms of interaction between medicinal plants and rhizosphere microorganisms.

DNA hypomethylation-mediated upregulation of GADD45B facilitates airway inflammation and epithelial cell senescence in COPD.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease typically characterized by chronic airway inflammation, with emerging evidence highlighting the driving role of cellular senescence-related lung aging. Accelerated lung aging and inflammation mutually reinforce each other, creating a detrimental cycle that contributes to disease progression. Growth arrest and DNA damage-inducible (GADD45) family has been reported to involve in multiple biological processes, including inflammation and senescence. However, the role of GADD45 family in COPD remains elusive. OBJECTIVES: To investigate the role and mechanism of GADD45 family in COPD pathogenesis. METHODS: Expressions of GADD45 family were evaluated by bioinformatic analysis combined with detections in clinical specimens. The effects of GADD45B on inflammation and senescence were investigated via constructing cell model with siRNA transfection or overexpression lentivirus infection and animal model with Gadd45b knockout. Targeted bisulfite sequencing was performed to probe the influence of DNA methylation in GADD45B expression in COPD. RESULTS: GADD45B expression was significantly increased in COPD patients and strongly associated with lung function, whereas other family members presented no changes. GADD45B upregulation was confirmed in mice exposed by cigarette smoke (CS) and HBE cells treated by CS extract as well. Moreover, experiments involving bidirectional modulation of GADD45B expression in HBE cells further substantiated its positive regulatory role in inflammatory response and cellular senescence. Mechanically, GADD45B-facilitated inflammation was directly mediated by p38 phosphorylation, while GADD45B interacted with FOS to promote cellular senescence in a p38 phosphorylation-independent manner. Furthermore, Gadd45b deficiency remarkably alleviated inflammation and senescence of lungs in CS-exposed mice, as well as improved emphysema and lung function. Eventually, in vivo and vitro experiments demonstrated that GADD45B overexpression was partially mediated by CS-induced DNA hypomethylation. CONCLUSION: Our findings have shed light on the impact of GADD45B in the pathogenesis of COPD, thereby offering a promising target for intervention in clinical settings.

Spherical nucleic acids: emerging amplifiers for therapeutic nanoplatforms.

Gene therapy is a revolutionary treatment approach in the 21st century, offering significant potential for disease prevention and treatment. However, the efficacy of gene delivery is often compromised by the inherent challenges of gene properties and vector-related defects. It is crucial to explore ways to enhance the curative effect of gene drugs and achieve safer, more widespread, and more efficient utilization, which represents a significant challenge in amplification gene therapy advancements. Spherical nucleic acids (SNAs), with their unique physicochemical properties, are considered an innovative solution for scalable gene therapy. This review aims to comprehensively explore the amplifying contributions of SNAs in gene therapy and emphasize the contribution of SNAs to the amplification effect of gene therapy from the aspects of structure, application, and recent clinical translation - an aspect that has been rarely reported or explored thus far. We begin by elucidating the fundamental characteristics and scaling-up properties of SNAs that distinguish them from traditional linear nucleic acids, followed by an analysis of combined therapy treatment strategies, theranostics, and clinical translation amplified by SNAs. We conclude by discussing the challenges of SNAs and provide a prospect on the amplification characteristics. This review seeks to update the current understanding of the use of SNAs in gene therapy amplification and promote further research into their clinical translation and amplification of gene therapy.

Blood glucose and lipids are associated with sarcoidosis: findings from observational and mendelian randomization studies.

BACKGROUND: Several researches have demonstrated that patients with sarcoidosis accompanied with the abnormality in blood glucose and/or lipids, however, the causal relationship between them remains uncertain. To elucidate the potential association and causality of blood glucose and lipids with sarcoidosis, we conducted a propensity score matching (PSM)-based observational study combined with mendelian randomization (MR) analysis. METHODS: All subjects in this study were retrospectively collected from Tongji Hospital during 2010 and 2023. 1:1 PSM was employed to control the potential confounders as appropriate. Univariable and multivariable logistic regression analyses were performed to estimate the associations of sarcoidosis with fasting glucose, high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), total cholesterol (TC), and total triglyceride (TG). The further subtype analysis was also conducted. Afterwards, a bidirectional MR analysis based on public data deeply explored the causality among the 5 candidate traits and sarcoidosis, for which the inverse-variance weighted (IVW) method was utilized as the main inferring approach. RESULTS: In the observational study, a total number of 756 subjects were enrolled, with 162 sarcoidosis patients and 594 non-sarcoidosis participants, while 160 pairs of subjects were matched after PSM. Multivariable logistic regression analysis indicated that HDLC (OR: 0.151; 95% CI: 0.056-0.408; P < 0.001) and TC (OR: 3.942; 95% CI: 2.644-5.877; P < 0.001) were strongly associated with sarcoidosis. Subtype analysis showed that low HDLC was independently correlated to risk of lesions in bronchus and lungs, and mediastinal lymph nodes, while high TC was to cervical lymph nodes. In MR analysis, high fasting glucose, low HDLC, and high TC were identified as the causal factors of sarcoidosis. CONCLUSION: HDLC and TC had the potential to influence the risk of sarcoidosis, which could be regarded as predictors and may provide new diagnostic and therapeutic targets for sarcoidosis.

Ionic liquid-assisted synthesis of N, F, and B co-doped BiOBr/Bi2Se3 on Mo2CTx for enhanced performance in hydrogen evolution reaction and supercapacitors.

Heteroatom doping and heterojunction formation are effective strategies to enhance electrochemical performance. In this study, we present a novel approach that utilizes an ionic liquid-assisted synthesis method to fabricate a BiOBr-based material, which is subsequently loaded onto Mo2CTx via a selenization treatment to create a BiOBr/Bi2Se3 heterostructure, denoted as NBF-BiOBr/Bi2Se3/Mo2CTx. The incorporation of heteroatoms improves its hydrophilicity and electronegativity, while the formation of heterojunctions adjusts the electronic structure at the interface, resulting in lower OH-/H+ adsorption energy. The specific surface area of NBF-BiOBr/Bi2Se3/Mo2CTx is 193.1 m2/g. In hydrogen evolution reaction (HER) tests, NBF-BiOBr/Bi2Se3/Mo2CTx exhibits exceptional catalytic performance in acidic media, requiring only an overpotential of 109 mV to achieve a current density of 10 mA cm-2. Furthermore, NBF-BiOBr/Bi2Se3/Mo2CTx demonstrates superior electrochemical performance in an asymmetric supercapacitor, with an energy density as high as 55.6 Wh kg-1 at a power density of 749.9 Wh kg-1. This work provides a novel approach for heteroatom doping and heterojunction synthesis, offering promising prospects for further advancements in the field.

Enhancing Transdermal Delivery of Curcumin-Based Ionic Liquid Liposomes for Application in Psoriasis.

To improve the permeation of curcumin, we prepared curcumin-based ionic liquid (Cur-Bet-IL) (IL formed using curcumin succinic anhydride and betaine) from curcumin by combining theoretical calculation and experimental research and then prepared curcumin-based ionic liquid liposome (Cur-Bet-IL-Lip). The Cur-Bet-IL-Lip has good stability (stored for 10 days without significant changes) and biocompatibility, which encompasses not only the properties of curcumin but also the characteristics of ionic liquids and liposomes. Cur-Bet-IL-Lip can penetrate the stratum corneum and deliver curcumin to the epidermis and dermis of the skin, and the cumulative permeability of curcumin after 24 h was 49%. Compared to Cur-Bet-IL, Cur-Bet-IL-Lip has a good uptake ability on human immortalized keratinocyte (HaCaT) cells (1.87-fold), which can reduce the expression of TNF-α (1.59-fold), IL-1ß (1.19-fold), IL-17A (1.53-fold), IL-17F (1.18-fold), and IL-22 (1.49-fold) in HaCaT cells and then increase the expression of collagen-I (1.14-fold). Therefore, Cur-Bet-IL-Lip has guiding significance in improving the solubility and permeation of insoluble drugs, which also provides a potential value for the clinical application of curcumin.

A promising perovskite primary explosive.

A primary explosive is an ideal chemical substance for performing ignition in military and commercial applications. For over 150 years, nearly all of the developed primary explosives have suffered from various issues, such as troublesome syntheses, high toxicity, poor stability or/and weak ignition performance. Now we report an interesting example of a primary explosive with double perovskite framework, {(C6H14N2)2[Na(NH4)(IO4)6]}n (DPPE-1), which was synthesized using a simple green one-pot method in an aqueous solution at room temperature. DPPE-1 is free of heavy metals, toxic organic components, and doesn't involve any explosive precursors. It exhibits good stability towards air, moisture, sunlight, and heat and has acceptable mechanical sensitivities. It affords ignition performance on par with the most powerful primary explosives reported to date. DPPE-1 promises to meet the challenges existing with current primary explosives, and this work could trigger more extensive applications of perovskite.

A smartphone-integrated portable platform based on polychromatic ratiometric fluorescent paper sensors for visual quantitative determination of norfloxacin.

The emergence of "superbugs" due to antibiotics overuse poses a significant threat to human health and security. The development of sensitive and effective antibiotics detection is undoubtedly a prerequisite for addressing antibiotics overuse-associated issues. However, current techniques for monitoring antibiotics typically require costly equipment and well-trained professionals. Hence, we developed herein a rapid, instrument-free, and on-site detection method for antibiotic residues such as norfloxacin (NOR) based on a ratiometric sensing platform utilizing "on-off-on" response properties of polychromatic fluorescence for direct visual quantitative NOR analysis. Specifically, this platform integrated iron ions (Fe3+)-chelated blue carbon dots (BCDs) for signal sensing and red carbon dots (RCDs) as an internal reference. The sensor mechanism is selective quenching of BCDs' blue fluorescence by Fe3+ via an inner filter effect with unaffected RCDs' red fluorescence. Further NOR addition led to competitive binding with BCDs due to Fe3+ shedding from the BCDs' surface for a recovered blue fluorescence signal. Notably, the ratiometric fluorescence sensor demonstrated rapid and highly sensitive NOR detection in a concentration range of 1-70 µM with an impressive detection limit of 6.84 nM. The ratiometric fluorescence sensing platform was constructed by integrating smartphone and paper-based strategies, which exhibited exceptional sensitivity, selectivity, and rapid response for portable, instrument-free, visual quantification of NOR in real samples.

Hg2+-triggered cascade strand displacement assisted CRISPR-Cas12a for Hg2+ quantitative detection using a portable glucose meter.

CRISPR-Cas12a is a powerful and programmable tool that has revolutionized the field of biosensing. However, the construction of a CRISPR-Cas12a-mediated portable system for on-site and quantitative detection of mercury ion (Hg2+) has yet to be explored. By integrating a target-triggered cascade toehold-mediated strand displacement reaction (TSDR) and CRISPR-Cas12a, we herein construct a portable on-site biosensor for the quantitative, sensitive, and selective detection of Hg2+ with a glucose meter. The Hg2+ initiates two cascade TSDRs through the T-Hg2+-T interaction to produce multiple double-stranded DNAs that can activate Cas12a's trans-cleavage activity. The Cas12a cleaves the sucrase-modified DNA on the electrode, resulting in the liberation of sucrase into the solution. The freed sucrase can catalyze sucrose to generate glucose, which can be quantitatively monitored by a glucometer. The developed portable biosensor provides a dynamic range of 5 orders of magnitude with a detection limit of 40 fM. This biosensor also displays excellent selectivity and stability for detecting Hg2+. Moreover, environmental water samples are utilized to further verify the robustness and effectiveness of the developed biosensor, highlighting its potential application in environmental monitoring and food safety analysis.

Mechanistic Insights into Formation of Residual Solid in Lignin Depolymerization.

Current techniques of lignin conversion are challenged by the low carbon utilization efficiency resulting from the severe generation of residual solid (char). Therefore, a better understanding of pathway for char formation is significant and highly desired for lignin valorization. In this work, we propose a fundamental mechanistic insight into char formation in lignin depolymerization, using hydrothermal decomposition as model reaction. The results demonstrate that the char featuring a multi-layer construction of coke and oligomer contains mainly G units, primarily generated from native G-lignin and demethoxylation of S-lignin. Instead, H-lignin contributes to the formation of volatile monophenols. Furthermore, new methylene bridges form between the benzene rings in lignin, which consequently results in the formation of recalcitrant char. Based on these observations, a plausible mechanism for char formation is proposed and verified by the density functional theory calculation.

LLZTO Nanoparticle- and Cellulose Mesh-Coreinforced Flexible Composite Electrolyte for Stable Li Metal Batteries.

Composite electrolytes have been regarded as the most prospective electrolytes for commercial application because they acquire the advantages of both polymer and inorganic electrolytes, commonly exhibiting appreciated flexibility and suitable ionic conductivity. Nevertheless, the conventional solution-casting method with toxic solvent and poor interfacial contact still hamper their commercialization process. Moreover, electrolytes with higher ionic conductivity and transference number are urgently needed for satisfying fast-charging batteries. Herein, a novel composite electrolyte (LZEC) reinforced by mechanically robust LLZTO nanoparticles and flexible cellulose mesh was fabricated by a simple and advanced in situ thermal polymerization method, with adding of highly ion-conductive liquid plasticizer. Consequently, the rationally designed LZEC composite electrolyte exhibits superior flexibility and remarkable electrochemical properties in the form of high ionic conductivity, wide electrochemical stability window, and high Li+ transference number. Importantly, the in situ synthesis method is expected to help construct an enhanced electrolyte/electrode interface inside the battery, and the LZEC composite electrolyte is capable of suppressing Li dendrite growth effectively, as evidenced by the prolonged stable cycling of the Li/Li symmetric cell. Therefore, the LFP/LZEC/Li full cell exhibits superior rate performance and long cyclic life. These attractive properties make LZEC a potential composite electrolyte for boosting the practical application of safe and long-life Li metal batteries.

Engineering of An Aptamer-Functionalized Fluorescent DNA Sensor for Cu(II) Responding in Living Tumor Cells.

Copper ions play vital roles in regulating life processes and being closely involved in several diseases such as cancer. Although detection methods based on fluorescent sensors or other strategies have been developed, it still remains a challenge to simultaneously realize the convenience, specificity, and accuracy in intracellular copper ion analysis. Herein, we propose an aptamer-functionalized DNA fluorescent sensor (AFDS) for accurate and specific detection of Cu(II) both in vitro and in cells by engineering the linkage of two DNA aptamers, namely, Lettuce aptamer and AS1411 aptamer, to achieve the manner of recognition response. Taking advantage of the functions of each aptamer, the tumor cell recognition capability and the high-contrast detection performance are simultaneously equipped in the AFDS. Furthermore, the AFDS shows high specificity and selectivity in Cu(II) response to avoid interference from common metal ions, chelators, and reactants by being associated with the irreversible interaction between nucleobases and Cu(II), which can destroy the topological structures and switch off the fluorescence of the AFDS. It also enables a sensitive in vitro detection of Cu(II) with a detection limit as lower as 0.1 µM and a wide detection linear range from 0.1 to 300 µM. The feasibility and superiority of the AFDS provide an opportunity to reveal both concentration-dependent and time-dependent intracellular Cu(II) responses in living cells. Therefore, the AFDS has achieved the novel detection performance of Cu(II) to exhibit great potential in exploring copper-related biological and pathological research.

Highly Stable Potassium Metal Anodes with Controllable Thickness and Area Capacity.

K metal battery is a kind of high-energy-density storage device with economic advantages. However, due to the dendrite growth and difficult processing characteristics, it is difficult to prepare stable K metal anode with thin thickness and fixed area capacity, which severely limits its development. In this work, a multi-functional 3D skeleton (rGCA) is synthesized by simple vacuum filtration and thermal reduction, and K metal anodes with controllable thickness and area capacity (K content) can be fabricated by changing the raw material mass and graphene layer spacing of rGCA. Moreover, the graphene sheet layer of rGCA can relax stress and relieve volume expansion; carbon nanotubes can serve as the fast transport channel of electrons, reducing internal impedance and local current density; Ag nanoparticles can induce the uniform nucleation and deposition of K+ . The K metal composite anodes (rGCA-K) based on the conductive skeleton can effectively suppress dendrites and exhibit excellent electrochemical performance in symmetric and full cells. The controllable fabrication process of stable K metal anode is expected to help K metal batteries move toward the stage of commercial production.

Multistage-Responsive Dual-Enzyme Nanocascades for Synergistic Radiosensitization-Starvation Cancer Therapy.

Radiotherapy is a common cancer treatment approach in clinical practice, yet its efficacy has been restricted by tumor hypoxia. Nanomaterials-mediated systemic delivery of glucose oxidase (GOx) and catalase (CAT) or CAT-like nanoenzymes holds the potential to enhance tumor oxygenation. However, they face the challenge of intermediate (hydrogen peroxide [H2 O2 ]) escape during systemic circulation if the enzyme pair is not closely placed to largely decompose H2 O2 , leading to oxidative stress on normal tissues. In the present study, a oxygen-generating nanocascade, n(GOx-CAT)C7A , constructed by strategically placing an enzymatic cascade (GOx and CAT) within a polymeric coating rich in hexamethyleneimine (C7A) moieties, is reported. During blood circulation, C7A remains predominantly non-protonated , achieving prolonged blood circulation due to its low-fouling surface. Once n(GOx-CAT)C7A reaches the tumor site, the acidic tumor microenvironment (TME) induces protonation of C7A moieties, resulting in a positively charged surface for enhanced tumor transcytosis. Moreover, GOx and CAT are covalently conjugated into close spatial proximity (<10 nm) for effective H2 O2  elimination. As demonstrated by the in vivo results, n(GOx-CAT)C7A achieves effective tumor retention and oxygenation, potent radiosensitization and antitumor effects. Such a dual-enzyme nanocascade for smart O2  delivery holds great potential for enhancing the hypoxia-compromised cancer therapies.

Oral Ionic Liquid for Transdermal Delivery and Obesity Treatment.

Obesity is currently a prerequisite for more than 70% of adults, including chronic obesity and long-term obesity. With the increase of diabetes patients in the world, it is urgent to develop effective oral drugs to replace insulin. However, the gastrointestinal tract is a main obstacle to oral drug preparations. Here, a highly effective oral drug was developed, mainly formulated as an ionic liquid (IL) prepared by l-(-)-carnitine and geranic acid. Density functional theory (DFT) calculations showed that l-(-)-carnitine and geranic acid can exist stably through hydrogen bonding. IL can significantly enhance the transdermal transport of drugs. In vitro study of intestinal permeability showed that particles formed by IL can prevent the absorption of intestinal fat. Compared with the control group, oral administration of IL (10 mL kg-1) significantly reduced blood glucose, white adipose tissue in the liver and epididymis, and the expression of SREBP-1c and ACC in IL. Therefore, these results and high-throughput sequencing analysis showed that IL can effectively reduce the intestinal absorption of adipose tissue to reduce blood glucose. IL has good biocompatibility and stability. Therefore, IL has a certain application value in the field of oral drug-delivery carriers, which provides an effective means for the treatment of diabetes and is a potential tool to solve the epidemic of obesity.