Constructing Ultra-Strong SERS Tags in the Cellular Raman-Silent Region by Orthogonal Array Testing Strategy.

Surface-enhanced Raman spectroscopy (SERS) tags have the advantages of unique fingerprint vibration spectrum, ultranarrow spectral line widths, and weak photobleaching effect, showing great potential for bioimaging. However, SERS imaging is still hindered for further application due to its weak spontaneous Raman scattering, biomolecular signal interference, and long acquisition times. Here, we develop a novel SERS tag of the core (Au)-shell (N-doped graphene) structure (Au@NGs) with ultrastrong and stable Raman signal (2180 cm-1) in the cellular Raman-silent region (1800-2800 cm-1) through base-promoted oxidative decarboxylation of amino acids. Exploring the factors (metal salts, amino acids, catalysts, temperature, etc.) to obtain Au@NGs with the strongest Raman signal commonly requires more than 100,000 separate experiments, while that using an orthogonal array testing strategy is reduced to 56. The existence of deep charge transfer between the Au surface and C≡N-graphene is proved by theoretical calculations, which means the ultrastrong signal of Au@NGs is the joint effect of electromagnetic and chemical enhancement. The Au@NGs have a detection sensitivity down to a single-nanoparticle level, and high-speed and high-resolution cellular imaging (4453 pixels) is obtained within 10 s by global Raman imaging. The combination of Au@NGs-based tags with ultrastrong intrinsic Raman imaging capability and global imaging technology holds great promise for high-speed Raman imaging.

Dual-Targeted Graphitic Cascade Nanozymes for Recognition and Treatment of Helicobacter pylori.

Helicobacter pylori (H. pylori) is the major etiological factor of a variety of gastric diseases. However, the treatment of H. pylori is challenged by the destruction of targeted drugs by gastric acid and pepsin. Herein, a dual-targeted cascade catalytic nanozyme PtCo@Graphene@Hemin-2(L-arginine) (PtCo@G@H2A) is designed for the treatment of H. pylori. The dual-targeting ability of PtCo@G@H2A is derived from directly targeting the receptor protein of H. pylori through hemin and responding to the acidic environment to cause charge reversal (protonation of L-arginine) to capture H. pylori, achieving efficient targeting effect. Compared with the single-targeting strategy relying on hemin, the dual-targeting strategy can greatly improve the targeting rate, achieving an increase of 850% targeting rate. At the concentration of NaHCO3 in intestinal fluid, the surface potential of PtCo@G@H2A can be quickly restored to avoid side effects. Meanwhile, PtCo@G@H2A has pH-responsive oxidase-like activity, which can generate nitric oxide (NO) through a cascade catalytic process that first generates reactive oxygen species (ROS) with oxygen, and further oxidizes L-arginine through ROS, realizing a superior acid-selective bactericidal effect. Overall, it proposes a promising strategy for the treatment of H. pylori that maintains high targeting and therapeutic effects in the environment of gastric acid and pepsin.

Biomimetic Hydrogen-Bonded G ⋠C ⋠G ⋠C Quadruplex within a Tetraphenylethene-Based Octacationic Spirobicycle in Water.

In biological systems, nucleotide quadruplexes (such as G-quadruplexes) in DNA and RNA that are held together by multiple hydrogen bonds play a crucial functional role. The biomimetic formation of these hydrogen-bonded quadruplexes captured by artificial systems in water poses a significant challenge but can offer valuable insights into these complex functional structures. Herein, we report the formation of biomimetic hydrogen-bonded G ⋅ C ⋅ G ⋅ C quadruplex captured by a tetraphenylethene (TPE) based octacationic spirobicycle (1). The spirobicyclic compound possesses a three-dimensional (3D) crossing dual-cavity structure, which enables the encapsulation of four d(GpC) dinucleotide molecules, thereby realizing 1 : 4 host-guest complexation in water. The X-ray structure reveals that four d(GpC) molecules further form a two-layer G ⋅ C ⋅ G ⋅ C quadruplex with Watson-Crick hydrogen bonds, which are stabilized within the dual hydrophobic cavities of 1 through the cooperative non-covalent interactions of hydrogen bonds, CH⋅⋅⋅π interactions, and hydrophobic effect. Due to the dynamically-rotational propeller chirality of TPE units, 1 with adaptive chirality can further serve as a chiroptical sensor to exhibit opposite Cotton effects with mirror-image CD spectra for the pH-dependent hydrogen-bonded assemblies of d(GpC) including the Watson-Crick G ⋅ C ⋅ G ⋅ C (pH 9.22) and Hoogsteen G ⋅ C+ ⋅ G ⋅ C+ (pH 5.74) quartets through the host-guest chirality transfer in water.

Stable Organic Radicals Participation in Charge Transfer: A New Strategy toward Molecular Functional Materials.

Charge-transfer (CT) engineering with inter-/intramolecular CT interactions by simple compositions has emerged as a universal and efficient way to construct organic functional materials. Stable organic radicals with unique physicochemical properties that cannot be realized in closed-shell molecules, have been widely demonstrated to be ideal building blocks to construct versatile organic CT materials. This concept article provides a brief overview of the advances in the design, structure and property of stable organic radicals-based CT molecular functional materials, and the strategy for the generation of these materials is also highlighted. First, radicals are introduced as open-shell donors or acceptors, with a focus on their importance and uniqueness in improving electrical, magnetic and optical properties of CT functional materials. Additionally, CT interactions in stable radical dimers and trimers are further discussed systematically. Finally, the challenges are summarized and perspectives for future development of stable organic radicals-based CT functional materials are provided.

Heat Confinement Aerogel Enables Supramagnetothermal Effect for Triggering Nitric Oxide Generation.

Reducing heat dissipation plays an indispensable role in boosting the magnetothermal effect but has received scant attention. Herein, a magnetothermal aerogel (MA) combining an efficient magnetothermal convertor for heat generation and a highly porous aerogel for reducing heat dissipation is developed. Such a heat confinement MA shows a large thermal resistance and high infrared absorption that can effectively confine the heat by regulating interior thermal conduction and radiation, exhibiting a supramagnetothermal effect. In addition, a waterproof beeswax coated MA achieves negligible heat loss and a supramagnetothermal effect even in high-thermal-diffusion aqueous media. As a proof of concept, a synthesized heat-triggered nitric oxide (NO) precursor is integrated into an MA, and the rapid NO generation (∼22 µM/min) resulting in an antibacterial effect further verifies the supramagnetothermal effect of the MA. This work provides an efficient strategy to promote the magnetothermal effect and offers inspiration for building a heat-triggering system.

Perception and experience of altruism in graduate nursing students.

BACKGROUND: Altruism is the core of nursing professionalism. Graduate nursing education in China started late and is still developing, exploring the current state of altruistic behavior and the perceived experience of altruism among graduate nursing students may have important implications for nursing education. OBJECTIVE: Explore the current state of altruistic behavior and the perceived experience of altruism among graduate nursing students in China. RESEARCH DESIGN: This is a descriptive phenomenological qualitative research study, semi-structured in-depth interviews were conducted. Seventeen graduate nursing students from three schools were selected to participate in the study. Colaizzi's analysis method was performed with NVivo software to develop common themes from the data. ETHICAL CONSIDERATIONS: The research proposal was approved by the Research Ethic Committee of Yangzhou University, China. RESULTS: Four themes emerged from the analysis of the interviews of the 17 participants: "Definition of altruism," "Altruism in the nursing profession," "Altruism applied in practice," and "Factors influencing altruistic behavior." CONCLUSIONS: Although participants indicated that the concept of "altruism" was relatively new to them, altruistic behavior is common in both their work and life. Many factors influence the altruistic behavior of graduate nursing students, including the environment, personal factors, education, recipient factors, occupational factors, and gains and losses. Families, schools, and hospitals should create favorable environments to foster altruistic tendencies in students.

A Risk Prediction Model for Prolonged Length of Stay in Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Retrospective Study of 225 Patients in a Single Center in Kunming, China.

BACKGROUND We aimed to develop an effective prediction model of prolonged length of stay (LOS) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). MATERIAL AND METHODS We systematically enrolled 225 patients admitted for AECOPD to our hospital and divided them into a normal LOS group (≤7 days) and prolonged LOS group (>7 days). To analyze differences in laboratory data at different times, 3 logistic regression models were established. To develop the prediction model, all variables with statistical significance were included in the model. The area under the curve (AUC) was used to evaluate discrimination, and the Hosmer-Lemeshow test was used to assess the calibration of the model. RESULTS Factors found to be independently associated with the increased risk of prolonged LOS included the use of corticosteroids during hospitalization, elevated HCO3⁻, decreased pH, and reductions in platelets (PLTs) and procalcitonin (PCT) between the fourth and first day of hospitalization. The risk prediction model including these factors had an AUC of 0.795, suggesting the good discrimination of our model. The Hosmer-Lemeshow test also showed good calibration of the model, which confirmed its good predictive performance. CONCLUSIONS A clinical prediction model was developed with good predictive performance, which could help clinicians identify patients with a higher risk of prolonged LOS, help shorten hospital stay, reduce the disease burden of patients, and improve the outcomes of AECOPD.

In Situ Gastric pH Imaging with Hydrogel Capsule Isolated Paramagnetic Metallo-albumin Complexes.

Abnormal gastric pH (pH > 3) has instructive significance for early diagnosis of various diseases, including cancer. However, for low patient compliance, limited penetration depth, high dependence on physiological function or unsafety issue, in situ noninvasive monitoring gastric pH is challenged. Herein, we developed a hydrogel capsule isolated human serum albumin-manganese complex (HSA-Mn) for in situ magnetic resonance imaging (MRI) gastric pH monitoring for the first time. In this strategy, the rotation motion restriction of Mn2+ after binding to HSA significantly increased the R1 (longitudinal relaxation rate) signal, and its high correlation with protonation imparted the HSA-Mn system sensitive responsiveness to varying pH (R1(pH 7)/R1(pH 1) = 8.2). Moreover, a screw jointed hydrogel capsule with signal confinement and internal standard abilities was designed. Such a nanoporous hydrogel capsule with size selectivity to surrounding molecules enabled a stable and sensitive response to different pH simulated gastric fluid within 0.5 h. In addition, with the unique structural outline and stable MRI characteristics, the capsule could also work as an internal standard, which facilitates the collection of signals and trace of the capsule in vivo. Through validating in a rabbit model, the precise abnormal gastric pH recognition capacity of the HSA-Mn hydrogel capsule was amply confirmed. Hence, the hydrogel capsule isolated HSA-Mn system strategy with great biocompatibility could be expected to be a potent tool for in situ anti-disturbance MRI of gastric pH in future clinical application.

A dynamic nomogram for predicting the risk of asthma: Development and validation in a database study.

BACKGROUND: Asthma remains a serious health problem with increasing prevalence and incidence. This study was to develop and validate a dynamic nomogram for predicting asthma risk. METHODS: Totally 597 subjects whose age ≥18 years old with asthma, an accurate age at first cigarette, and clear smoking status were selected from the National Health and Nutrition Examination Survey (NHANES) database (2013-2018). The dataset was randomly split into the training set and the testing set at a ratio of 4:6. Simple and multiple logistic regressions were used for identifying independent predictors. Then the nomogram was developed and internally validated using data from the testing set. The receiver operator characteristic (ROC) curve was used for assessing the performance of the nomogram. RESULTS: According to the simple and multiple logistic regressions, smoking ≥40 years, female gender, the age for the first smoking, having close relative with asthma were independently associated with the risk of an asthma attack. The nomogram was thereby developed with the link of https://yanglifen.shinyapps.io/Dynamic_Nomogram_for_Asthma/. The ROC analyses showed an AUC of 0.726 (0.724-0.728) with a sensitivity of 0.887 (0.847-0.928) in the training set, and an AUC of 0.702 (0.700-0.703) with a sensitivity of 0.860 (0.804-0.916) in the testing set, fitting well in calibration curves. Decision curve analysis further confirmed the clinical usefulness of the nomogram. CONCLUSION: Our dynamic nomogram could help clinicians to assess the individual probability of asthma attack, which was helpful for improving the treatment and prognosis of asthma.

Synthesis and antitumor activity evaluation of lamiridosin A derivatives.

A series of lamiridosin A derivatives were synthesized through simple procedures. Their antitumor activities were evaluated against EC9706, MGC803, and B16 cell lines in vitro. Several compounds showed potent antitumor activity, especially compound 10, with IC50 value of 2.36 µmol/L against MGC803 cell lines, is more potent than marketed positive drug 5-fluorouridine (5-FU).

[Chemical Constituents from Melissa officinalis Leaves].

OBJECTIVE: To investigate the chemical constituents of Melissa officinalis leaves. METHODS: The chemical constituents were separated by silica gel column chromatography and their structures were determined by spectroscopic experiments. RESULTS: 13 compounds were isolated and identified as protocatechuyl aldehyde(1), serratagenic acid(2), vanillin(3), 2α,3ß-dihydroxy-urs-12-en-28-oic acid(4), ursolic acid(5), oleanolic acid(6), daucosterol(7),2α,3ß,23,29-tetrahydroxyolean-12-en-28-oic acid-29-O-ß-D-gluco- pyranoside(8), luteolin(9) rosmarinic acid(10), luteolin-7-O-ß-D-glucoside (11), ß-stitosterol(12) and palmitic acid(13). CONCLUSION: Compounds 1 ~ 8 are separated from this plant for the first time and compounds 1-4 and 8 are isolated from this genus for the first time.

[Chemical constituents from Punica granatum flowers].

OBJECTIVE: To investigate the chemical constituents in the flowers of Punica granatum. METHODS: The chemical constituents were separated by silica gel column chromatography and their structures were determined by spectroscopic experiments. RESULTS: As a result, twelve compounds were isolated and identified as oleanolic acid (1), ursolic acid (2), palmitic acid (3), tricin (4), catechin (5), rutin (6), apigenin (7), apigenin-7-O-glucoside (8), 2S, 3S, 4S-trihydroxypentanoic acid (9), gallic acid (10), beta-stitosterol (11), and daucosterol (12). CONCLUSION: Compounds 3, 4, 7, 8 and 9 are separated from this plant for the first time, and compounds 3, 4 and 9 are isolated from this genus for the first time.

The Effect of Liraglutide on Lung Cancer and Its Potential Protective Effect on High Glucose-Induced Lung Senescence and Oxidative Damage.

BACKGROUND: Lung cancer is a malignant disease with high morbidity and mortality. Lung cancer and diabetes are closely related, and diabetic patients with lung tumors are common in clinical practice. Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is commonly used in the treatment of type 2 diabetes. In this study, we examined the effect of liraglutide on lung cancer and its potential protective effect on high glucose-induced lung aging. METHODS: Indirect mmunofluorescence was done to assess the expression levels of p-AKT, ki67, Caspase3, Bax and PI3K. Western blotting was conducted to determine the expression levels of BAX, BCL2, Caspase9, E-cadherin, N-cadherin, PI3K, AKT and vimentin. Cell viability, cell cycle and cell apoptosis were evaluated by colony formation, CCK-8 assay and flow cytometry. Immunohistochemistry was performed to evaluate the expression of Nf-κb, p15, p16, p21 and SMA in vivo. Besides, a high glucose-induced lung cell injury model was established to evaluate the effect of liraglutide on lung aging and oxidative damage. Sa-ß-gal staining was used to assess cellular/ tissue senescence. Cell senescence-related markers (p16, p21 and p53 ) were determined by Western-blot analysis. RESULTS: The proliferation, cell cycle, migration of lung cancer cells were significantly inhibited after treatment with liraglutide compared to control group (p < 0.05). Furthermore, Liraglutide inhibited the epithelial-mesenchymal transition process of lung cancer cell compared to control group (p < 0.05). Liraglutide also suppressed the proliferation of lung cancer in vivo. Besides, the BEAS-2B cell senescence induced by high glucose was significantly alleviated after treatment with liraglutide compared with control group (p < 0.05). The lung aging and endoplasmic reticulum stress was significantly suppressed after liraglutide treatment. CONCLUSIONS: This work indicates that liraglutide could inhibit lung cancer cell proliferation in vitro and in vivo. In addition, liraglutide exhibited anti-aging effects in vivo and in vivo. The current work has important implications for the treatment of patients with diabetes and lung cancer.

Highly efficient carbon supported Co-Ir nanozyme for the determination of total antioxidant capacity in foods.

Nanozyme-based colorimetric assays have aroused extensive attention in biosensing due to quick response, low cost and simplicity. However, their practical applications are limited by the unsatisfactory stability and catalytic activity of nanozymes in complex detection environments. Herein, using the one-pot chemical vapor deposition method, we successfully prepare a highly efficient and stable carbon supported Co-Ir nanozyme (termed as Co-Ir/C nanozyme) for the determination of total antioxidant capacity (TAC) in food samples. The Co-Ir/C nanozyme shows excellent durability under extensive pH ranges, high temperature and high salt concentration due to the protection of carbon supporter. It can be recycled by simple magnetic separation, and its catalytic activity remains stable after long-term operation and storage. Taking full advantage of the superior peroxidase-like activity of Co-Ir/C nanozyme, it is used for colorimetric detection of ascorbic acid (or known as vitamin C), an important vitamin to adjust body's normal physiological function, with results showing higher sensitivity (detection limit of 0.27 µM) than most of the recently published works. Moreover, the determination of TAC in vitamin C tablets and fruits are further achieved, which are in good agreement with those of commercial colorimetric test kits. This study helps guide the rational preparation of versatile and highly stable nanozymes, and develops a robust TAC determination platform for future food quality monitoring.

Dual Charge Transfer Generated from Stable Mixed-Valence Radical Crystals for Boosting Solar-to-Thermal Conversion.

Realizing dual charge transfer (CT) based on stable organic radicals in one system is a long-sought goal, however, remains challenging. In this work, a stable mixed-valence radical crystal is designed via a surfactant-assisted method, namely TTF-(TTF+• )2 -RC (where TTF = tetrathiafulvalene), containing dual CT interactions. The solubilization of surfactants enables successful co-crystallization of mixed-valence TTF molecules with different polarity in aqueous solutions. Short intermolecular distances between adjacent TTF moieties within TTF-(TTF+• )2 -RC facilitate both inter-valence CT (IVCT) between neutral TTF and TTF+• , and inter-radical CT (IRCT) between two TTF+• in radical π-dimer, which are confirmed by single-crystal X-ray diffraction, solid-state absorption, electron spin resonance measurements, and DFT calculations. Moreover, TTF-(TTF+• )2 -RC reveals an open-shell singlet diradical ground state with the antiferromagnetic coupling of 2J = -657 cm-1 and an unprecedented temperature-dependent magnetic property, manifesting the main monoradical characters of IVCT at 113-203 K while the spin-spin interactions in radical dimers of IRCT are predominant at 263-353 K. Notably, dual CT characters endow TTF-(TTF+• )2 -RC with strong light absorption over the full solar spectrum and outstanding stability. As a result, TTF-(TTF+• )2 -RC exhibits significantly enhanced photothermal property, an increase of 46.6 °C within 180 s upon one-sun illumination.

Cyclin D1 mediated by the nuclear translocation of nuclear factor kappa B exerts an oncogenic role in lung cancer.

The relevance of cyclin D1 (CCND1) has been implicated in lung cancer progression. Nevertheless, the mechanism by which CCND1 supports lung cancer development is yet to be expounded. Here, we established that CCND1 is overexpressed in clinical lung cancer specimens and various lung cancer cells. Importantly, CCND1 overexpression enhanced lung cancer cell proliferation, invasion and migration, and arrested the cell cycle at the S phase. In vivo, overexpression of CCND1 promoted lung cancer growth and metastasis. The nuclear translocation of nuclear factor kappa B (NF-κB) promoted p65 protein expression and CCND1 transcription. Meanwhile, PI3K/AKT pathway activity was significantly reduced when NF-κB nuclear translocation was decreased. PI3K/AKT pathway activity was significantly elevated upon CCND1 overexpression. Inhibition of PI3K/AKT pathway activity or suppression of NF-κB translocation in cells with high CCND1 expression was found to significantly reduce the activity of lung cancer cells in vitro and in vivo. Our data revealed that NF-κB/CCND1/PI3K/AKT axis could act as a prospective diagnostic biomarker and a therapeutic option for lung cancer.

Metal Graphitic Nanocapsules for Theranostics in Harsh Conditions.

Metal nanoparticles (NPs) with superior physicochemical properties and biocompatibility have shown great potential in theranostics. However, metal NPs show poor stability in some harsh conditions such as strong acid, oxidation, corrosion and high-temperature conditions, which limits their extensive bioapplications. To address such issue, a variety of superstable metal graphitic nanocapsules with the metal cores confined in the nanospace of few-layer graphitic shell have been developed for biodetection and therapy in harsh conditions. In this mini-review, we summarize the recent advances in metal graphitic nanocapsules for bioapplications in harsh conditions. Firstly, their theranostic performance in non-intrinsic physiological harsh environment, including oxidation, corrosion and high-temperature conditions, is systematically discussed. Then, we highlight their theranostic performance in the harsh stomach condition that is strong acidic and pepsin-rich. It is expected that this review will offer inspiration to facilitate the exploitation of novel theranostic agents that are stable in harsh conditions.

Comprehensive Analysis of ABCA Family Members in Lung Adenocarcinoma with Prognostic Values.

ATP-binding cassette subfamily A (ABCA) has received wide recognition because it possesses the capacity to translocate its derivatives, xenobiotics, vitamins, and cholesterol across biological membranes. Some ABCA members have causative relevance to inborn diseases, and a number of studies have explored their functions in cancer progression and metastasis. Here, we explored the interrelation between ABCA genes and lung adenocarcinoma (LUAD). We specified the expression and functions of ABCA members in LUAD using the GEPIA, GEO, Human Protein Atlas, UALCAN, TIMER, and Kaplan-Meier Plotter databases. ABCA5, ABCA6, ABCA8, ABCA9, and ABCA10 were found to be significantly less expressed in LUAD and correlated with TP53 mutation in patients with LUAD. Furthermore, ABCA5, ABCA6, and ABCA8 were relevant to overall survival of patients with LUAD. In conclusion, this study showed that ABCA members may be related to the TP53 mutation of LUAD. Moreover, it may serve as a potential marker for the prognosis of LUAD.

Outcomes of Visualized Puncture Needle and Small Needle-Knife Therapy in Primary Frozen Shoulder Based on Multimodal Ultrasound Imaging.

OBJECTIVE: To compare the outcomes of visualized puncture needle and small needle-knife therapy in 68 patients with primary frozen shoulder. METHOD: Sixty-eight patients with primary frozen shoulder were recruited and randomly divided into two groups, with 34 patients in each group. In the treatment group, an ultrasound-guided 18G-PTC puncture needle was inserted into the joint space, followed by a liquid injection until complete lysis and dissociation of the intraarticular adhesion were achieved. Then, the lesser tuberosity of the coracoid and humerus, the intertubercular groove of the humerus, and the greater tuberosity of the humerus were stripped, first vertically and then horizontally, by an amplitude ≦ 0.5 cm per treatment. This treatment procedure was performed once per week, and each cycle covered three treatments. The small needle-knife therapy was set as a control, and the efficacy was observed. RESULT: The visualized puncture needle significantly outperformed the small needle-knife therapy in overall efficacy, UCLA scores of the shoulder joint, shoulder mobility, and muscle elasticity and thickness. CONCLUSION: The efficacy of the visualized puncture needle for primary frozen shoulder was better compared to the small needle-knife therapy. The former was safer and more convenient, which caused less pain to patients and took effect more quickly. In a word, the visualized puncture needle for primary frozen shoulder is worthy of clinical popularization.

Advances in metal graphitic nanocapsules for biomedicine.

Metal graphitic nanocapsules have the advantages of both graphitic and metal nanomaterials, showing great promise in biomedicine. On one hand, the chemically inert graphitic shells are able to protect the metal core from external environments, quench the fluorescence signal from the biological system, offer robust platform for targeted molecules or drugs loading, and act as stable Raman labels or internal standard molecule. On the other hand, the metal cores with different compositions, sizes, and morphologies show unique physicochemical properties, and further broaden their biomedical functions. In this review, we firstly introduce the preparation, classification, and properties of metal graphitic nanocapsules, then summarize the recent progress of their applications in biodetection, bioimaging, and therapy. Challenges and their development prospects in biomedicine are eventually discussed in detail. We expect the versatile metal graphitic nanocapsules will advance the development of future clinical biomedicine.