Quaternized antimicrobial peptide mimics based on harmane as potent anti-MRSA agents by multi-target mechanism covering cell wall, cell membrane and intracellular targets.

Infectious disease caused by methicillin-resistant Staphylococcus aureus (MRSA) seriously threatens public health. The design of antimicrobial peptide mimics (AMPMs) based on natural products (NPs) is a new strategy to kill MRSA and slow the development of drug resistance recently. Here, we reported the design and synthesis of novel AMPMs based on harmane skeleton. Notably, compound 9b exhibited comparable or even better anti-MRSA activity in vitro and in vivo with minimum inhibitory concentration (MIC) of 0.5-2 µg/mL than the positive drug vancomycin. The highly active compound 9b not only showed low cytotoxicity, no obvious hemolysis and good plasma stability, but also presented low tendency of developing resistance. Anti-MRSA mechanism revealed that compound 9b could destroy cell wall structure by interacting with lipoteichoic acid and peptidoglycan, cause membrane damage by depolarization, increased permeability and destructed integrity, reduce cell metabolic activity by binding to lactate dehydrogenase (LDH), interfere cellular redox homeostasis, and bind to DNA. Overall, compound 9b killed the MRSA by multi-target mechanism, which provide a promising light for combating the growing MRSA resistance.

Biomimetic Superwetting Fabric for Evaporation-Induced Body Sweat and Heat Management and Electricity Generation.

Solar optothermal evaporation of water possesses the potential for thermal regulation and electricity generation, which are desirable for regulating body perspiration and heat as well as improving electrical output and strain sensing. However, ordinary fabrics exhibit poor evaporation capacity and antifouling performance due to limited adsorption capacity and internal hydrophilicity. Moreover, conventional evaporation-driven generators show a low power supply without widely practical use due to limited and fluctuating evaporation rates. Herein, an antifouling cooling fabric with an evaporation-driven electricity performance is obtained by constructing Janus channels on the superomniphobic fabric. Sweat can be easily eliminated from inside to outside through Janus channels by efficient evaporation, and the green liquid metal ink (CGM/LMP-rGO@PPy) cotton fabric shows a thermal conductivity of 0.18 W m-1 K-1, suggesting a comfortable dry and cooling sense. Meanwhile, the fabric can stably output a potential of 302.20 mV when seawater flows through the ionic channels at an evaporation rate of 1.58 mL h-1 with one sun power density. In addition, the multifunctional fabric demonstrates strain sensing at high electrical conductivity for body motion monitoring. This work would offer a prospect for intelligent textile construction and energy harvesting by water evaporation.

Predictive Value of the Hb/RDW Ratio for the Risk of All-Cause Death in Patients with Heart Failure with Different Ejection Fractions.

INTRODUCTION: The prognostic value of the ratio of haemoglobin to red cell distribution width (HRR) in different types of heart failure (HF) is not well known. METHOD AND RESULTS: We analysed the long-term prognostic value of HRR in patients with HF using the Cox proportional risk model and Kaplan-Meier method. We reviewed consecutive 972 HF patients. The overall mortality rate was 45.68%. Mortality was 52.22% in the HFrEF group and 40.99% in the HFpEF + HFmrEF group. Cox regression showed that when HRR increased by 1 unit, the risk of all-cause death in all HF patients decreased by 22.8% (HR: 0.772, 95% CI: 0.724, 0.823, p < 0.001), in the HFpEF + HFmrEF group it decreased by 15.5% (HR: 0.845, 95% CI: 0.774, 0.923, p < 0.001), and in the HFrEF group it decreased by 36.1% (HR: 0.639, 95% CI: 0.576, 0.709, p < 0.0001). Subgroup analysis showed that there were interactions between the EF and HRR groups. The group in which HRR best predicted all-cause death from HF was group 1 (EF <40%, HRR <9.45), followed by group 2 (EF <40%, HRR ≥9.45), and group 3 (EF ≥40%, HRR <9.45). HRR had no predictive value in group 4 (EF ≥40%, HRR ≥9.45). CONCLUSION: HRR is an important predictor of all-cause mortality in patients with HF, especially HFrEF. There is an interaction between HRR group and LVEF group.

Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cells.

The discovery of new lead skeleton against melanoma are urgently needed due to its highly malignant and mortality. Herein, a new molecular entity (EU-5) derived from eudistomin U was synthesized with total yield of 46%, which displayed potent activity against malignant melanoma A375 cells (IC50 = 4.4 µM), no hemolytic toxicity and good physicochemical properties in silico. Colony formation and cell cycle arrest assays revealed that EU-5 suppressed cell proliferation by causing cell cycle arrest at G0/G1 phase. Wound healing and transwell assays suggested that EU-5 could effectively inhibit migration of A375 cells in a dose-dependent manner. Calcein-AM/PI staining, Annexin V-FITC/PI apoptosis detection, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), transcriptomics, quantitative real­time polymerase chain reaction (qRT­PCR), spectrometric titration and molecular docking assays indicated that EU-5 could activate p53 signaling pathway and trigger mitochondria-mediated cell apoptosis. Taken together, this study provided a promising lead structure for the design of a new generation of anti-melanoma drugs.

Interpretable prediction of 3-year all-cause mortality in patients with chronic heart failure based on machine learning.

BACKGROUND: The goal of this study was to assess the effectiveness of machine learning models and create an interpretable machine learning model that adequately explained 3-year all-cause mortality in patients with chronic heart failure. METHODS: The data in this paper were selected from patients with chronic heart failure who were hospitalized at the First Affiliated Hospital of Kunming Medical University, from 2017 to 2019 with cardiac function class III-IV. The dataset was explored using six different machine learning models, including logistic regression, naive Bayes, random forest classifier, extreme gradient boost, K-nearest neighbor, and decision tree. Finally, interpretable methods based on machine learning, such as SHAP value, permutation importance, and partial dependence plots, were used to estimate the 3-year all-cause mortality risk and produce individual interpretations of the model's conclusions. RESULT: In this paper, random forest was identified as the optimal aools lgorithm for this dataset. We also incorporated relevant machine learning interpretable tand techniques to improve disease prognosis, including permutation importance, PDP plots and SHAP values for analysis. From this study, we can see that the number of hospitalizations, age, glomerular filtration rate, BNP, NYHA cardiac function classification, lymphocyte absolute value, serum albumin, hemoglobin, total cholesterol, pulmonary artery systolic pressure and so on were important for providing an optimal risk assessment and were important predictive factors of chronic heart failure. CONCLUSION: The machine learning-based cardiovascular risk models could be used to accurately assess and stratify the 3-year risk of all-cause mortality among CHF patients. Machine learning in combination with permutation importance, PDP plots, and the SHAP value could offer a clear explanation of individual risk prediction and give doctors an intuitive knowledge of the functions of important model components.

Prognostic Significance of Serum Chloride Level Reduction in Patients with Chronic Heart Failure with Different Ejection Fractions.

Little is known regarding the prognostic value of serum chloride in patients with chronic heart failure (CHF) with different ejection fractions. We sought to determine the postdischarge outcomes associated with lower serum chloride between different CHF types.We reviewed the medical records of 1221 consecutive patients with CHF admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021. After excluding patients with in-hospital death, missing follow-up data, missing serum chloride level data, or chronic dialysis therapy, 791 patients were included. Of these patients, 343 had heart failure with reduced ejection fraction (HFrEF; i.e., left ventricular ejection fraction (LVEF) < 40%), and 448 had heart failure with preserved ejection fraction (HFpEF) or heart failure with median ejection fraction (HFmrEF; HFpEF plus HFmrEF; i.e., LVEF ≥40%). Over a median follow-up of 750 days, 344 patients (43.5%) had all-cause mortality. In the univariate analysis, serum sodium and chloride were strongly associated with mortality in both HF subgroups (P < 0.0001). A multivariable model including both serum sodium and chloride showed the highly significant association between serum chloride and survival (P < 0.0001), whereas the association between serum sodium and mortality was not reported (HFpEF plus HFmrEF, hazard ratio (HR) 0.975, 95% confidence interval [CI] 0.942-1.010, P = 0.158; HFrEF, HR 1.007, 95% CI 0.966-1.051, P = 0.734). Kaplan-Meier survival curve analysis revealed a significant difference in mortality risk with decreasing chloride levels in all patients with CHF. The optimal cutoff value of chloride in predicting all-cause mortality was 102.95 mmol/L with area under the curve value of 0.76 [HR 0.760, 95% CI 0.727-0.793, P < 0.0001], sensitivity of 60.2%, and specificity of 78.3%.Lower serum chloride is an independent predictor of death in CHF, regardless of heart failure subtype.

Robust Janus Superwetting Textile with Large Pore Sizes for Oil-in-Water Emulsion Separation.

Developing advanced oil-water separation technology is significant for environmental conservation. According to the synergetic effects of the size-sieving mechanism, superwetting materials with small pore sizes have been designed to realize high-efficiency separation for oil-water emulsions. However, the separation flux limited by the pore size and the weakness of the superwetting material impede its practical application severely. Herein, we construct a robust Janus superwetting textile with large pore sizes for oil-in-water emulsion separation. The pristine textile is coated by the as-prepared CuO nanoparticles as the bottom layer with superhydrophilicity and then grafted by 1-octadecanethiol as the top layer with superhydrophobicity to construct the Janus textile. When used as a filter, the superhydrophobic layer acts as the nucleation site to coalesce the small oil droplets facilely. Then, the coalesced oil fills the pores of the superhydrophobic layer and selectively permeates it but is blocked by the superhydrophilic layer with large pore sizes. Utilizing the unique separation mechanism, the Janus textile realizes efficient and rapid separation. Even after multicycle separation, hot liquid immersion for 24 h, tribological test for 60 min, and sandpaper abrasion for 500 cycles, the Janus textile still retains the superwettability and excellent separation performance, manifesting outstanding stability to resist severe damage. This separation strategy provides a novel guideline for high-efficiency and high-flux emulsion separation and practical application.

Janus Fabric with Asymmetric Wettability for Switchable Emulsion Separation and Controllable Droplets with Low Friction.

Superwetting surfaces have recently attracted extensive attention in oil-water emulsion separation and droplet manipulations, which are widely used in various situations ranging from wastewater treatment, to flexible electronics, to biochemical diagnosis. However, it still remains challenging to obtain asymmetric materials with high efficiency during oil-water separation. Meanwhile, excellent robustness of the superhydrophobic surface is of significance but retards the mobility of droplets due to increased lateral adhesion of small spacing between solid protrusions. Herein, a facile approach is demonstrated to obtain the excellent robustness of Janus fabrics with asymmetric wettability. As for one side of water-in-oil emulsion separation, mimicking the soft earthworm with periodically wrinkled skin, an adaptive superhydrophobic fabric was fabricated by wrapping soft wrinkled poly(dimethylsiloxane) (PDMS) polymer with a cross-linking structure on woven fabric fibers induced by Ar plasma treatment. In addition, inspired by the desert beetle's structure but with reversed wettability, the other side of the Janus fabric was constructed for treating emulsion of oil-in-water. In addition, the underwater superoleophobic surface consisting of magnetically responsive PDMS microcilia with slippery heads, which shows robustness against pH, improved water drop mobility and lowered the resistance of fluid friction similar to the intrinsic hydrophobic Salvinia molesta with additional slippery performance. Hence, we propose a novel and easy approach that optimizes enhanced emulsion separation and reduced fluid drag properties simultaneously, which actively broadens their widespread applications.

A naphthalimide-derived hypochlorite fluorescent probe from ACQ to AIE effect transformation.

In this work, by installing a free-rotating benzene ring to suppress the intermolecular π-π stacking effect in the aggregated state, a naphthalimide-derived hypochlorite (ClO-) fluorescent probe, Probe A, with the aggregation-caused quenching (ACQ) effect was successfully transformed into Probe B possessing typical aggregation-induced emission (AIE) characteristics. The experimental results indicated that Probe B with good selectivity and a low detection limit (LOD) of 0.02 µM can also exhibit a significant ratiometric fluorescence color change from cyan to dark blue within 2 min in a nearly pure water solvent system after the addition of ClO-. Finally, by virtue of the good photophysical properties and ClO- sensing performance, Probe B and the Probe B loaded portable test paper were successfully applied to live cell imaging and the naked eye recognition of ClO-, respectively.

Rational design of AIE-based fluorescent probes for hypochlorite detection in real water samples and live cell imaging.

As one kind of important disinfectant and reactive oxygen species (ROS), hypochlorite (ClO-), plays vital roles in both water treatment and cell homeostasis. In this work, by decorating a series of groups with different electron donating and withdrawing properties on tetraphenylethene (TPE), four aggregation-induced emission (AIE)-based fluorescent probes containing CË­C double bonds as the potential reaction sites named Probe A, B, C and D were constructed, and their sensing performance for ClO- was systematically studied. The results showed that the substituents can not only effectively tune the photophysical properties of the probes, but also make a significant impact on their sensing performance for ClO-. Combined with the theoretical calculation results, it can be inferred that the reactivity of the probes for ClO- can be greatly enhanced with the increase of electron cloud density on the CË­C double bonds by the introduction of strong electron-donating group (EDG) and electron-withdrawing group (EWG) adjacent to the double bonds. Finally, the best performing Probe D was selected and then successfully applied to ClO- detection in real water samples and live cell imaging.

Artificial Leaf for Switchable Droplet Manipulation.

Droplet manipulation plays an important role in scientific research, daily life, and practical production such as biological and chemical analysis. Inspired by the structure and function of three typical leaf veins, the bionic texture was replicated by the template method, and the artificial leaf was selectively treated by nanoparticles to obtain a quasi-three-dimensional hybrid superhydrophobic-hydrophilic surface. When the droplet touches the surface of the leaf, it will be attracted to the bottom of the main vein from different directions even in horizontal conditions due to the Laplace pressure gradient and energy gradient. The simulation analysis demonstrates that the reason for directional transportation is the energy gradient of the droplets on the different levels of veins, including the thin veins, lateral veins, and main vein. Meanwhile, the experimental result of water collection also showed an outstanding directional transportation effect and excellent water collection efficiency. In addition, when the sample is tilted upside down, the droplet will flow back to the main vein along the lateral vein and then flow down the main vein, showing a good droplet pumping effect. Therefore, the directional and polydirectional transportation of droplets on the same sample is successfully realized, and the conversion between executing single and multiple tasks simultaneously can be realized only by upright and inverted samples. This work provided a new strategy for directional and polydirectional water manipulation, water collection, directional drainage, and microfluidic devices.

A dual-responsive fluorescent probe for detection of fluoride ion and hydrazine based on test strips.

Hydrazine (N2H4) and fluoride ion (F-) are regarded as environmental pollutants and potential carcinogens. A dual-functional fluorescent probe (probe 1) was developed for both F- and N2H4 with high selectivity and sensitivity. 1 was based on nucleophilic aromatic substitution reaction for N2H4 detection and selective cleavage of 4-nitrobenzenesulphonyl group for the determination of F-. The limits of detection of probe for F- and N2H4 were 77.82 nM and 29.34 nM, respectively, which are far below the threshold limit value (TLV) of United States Environmental Protection Agency (EPA). The home-made test strips of 1 provided the positive tool for F- and gaseous N2H4 in different system. And the confocal fluorescence images indicated that 1 can quantitatively detect N2H4 in living PC12 cells. Promisingly, 1 has great prospects for N2H4 imaging and determining in living system.

A highly selective fluorescent probe for the detection of hypochlorous acid in tap water and living cells.

A turn-on fluorescent probe (DAME) for sensing hypochlorous acid (HClO) with excellent selectivity was presented. The fluorescent probe was composed of coumarin derivative as the fluorophore and dimethylcarbamothioic chloride group with a sulfide moiety as modulator. Additionally, the sulfide moiety would be oxidized by HClO, and then free dye of coumarin derivate was released and exhibited significant fluorescence. In addition, the probe could respond to HClO in solutions within 60 s and the limit of detection was down to 34.75 nM. Moreover, the probe was used for the detection of HClO in tap water through the home-made test paper. And confocal images confirmed that probe DAME could be used for recognizing HClO in living cells.