Ionic Liquid Gating Induces Anomalous Permeation through Membrane Channel Proteins.

Membrane channel proteins (MCPs) play key roles in matter transport through cell membranes and act as major targets for vaccines and drugs. For emerging ionic liquid (IL) drugs, a rational understanding of how ILs affect the structure and transport function of MCP is crucial to their design. In this work, GPU-accelerated microsecond-long molecular dynamics simulations were employed to investigate the modulating mechanism of ILs on MCP. Interestingly, ILs prefer to insert into the lipid bilayer and channel of aquaporin-2 (AQP2) but adsorb on the entrance of voltage-gated sodium channels (Nav). Molecular trajectory and free energy analysis reflect that ILs have a minimal impact on the structure of MCPs but significantly influence MCP functions. It demonstrates that ILs can decrease the overall energy barrier for water through AQP2 by 1.88 kcal/mol, whereas that for Na+ through Nav is increased by 1.70 kcal/mol. Consequently, the permeation rates of water and Na+ can be enhanced and reduced by at least 1 order of magnitude, respectively. Furthermore, an abnormal IL gating mechanism was proposed by combining the hydrophobic nature of MCP and confined water/ion coordination effects. More importantly, we performed experiments to confirm the influence of ILs on AQP2 in human cells and found that treatment with ILs significantly accelerated the changes in cell volume in response to altered external osmotic pressure. Overall, these quantitative results will not only deepen the understanding of IL-cell interactions but may also shed light on the rational design of drugs and disease diagnosis.

Selective ion migration in a polyelectrolyte driving a high-performance flexible moisture-electric generator.

We propose a novel moisture-electric generator that utilizes the unique properties of a blended poly(4-styrene sulfonic acid) and poly(vinyl alcohol) with phytic acid by screen printing and scrape coating, achieving an impressive open-circuit voltage of 0.88 V from ambient humidity. This innovative design significantly enhances ion transport, moisture adsorption, and flexibility, making a marked improvement in converting environmental humidity to electrical energy.

Medicinal Value, Genetic Diversity, and Genetic Relationship Analysis of Auricularia cornea (Agaricomycetes) Based on ITS, ISSR, and SRAP Markers.

Wild resources of Auricularia cornea (A. polytricha) are abundant in China, and genetic diversity and genetic relationships analysis of A. cornea can provide basis for germplasm resource utilization and innovation and molecular marker-assisted breeding. In this study, 22 Auricularia strains collected were identified as A. cornea based on ITS sequence analysis, and its genetic diversity was examined by ISSR and SRAP markers. The results showed that a total of 415 bands were amplified by 11 selected ISSR primers, with an average amplification of 37.73 bands per primer, and the mean values of Ne, I, and H were 1.302, 0.368, and 0.219, respectively. A total of 450 bands were amplified by 10 SRAP primers, with an average of 45 bands per primer, and the average of Ne, I, and H were 1.263, 0.302, and 0.183, respectively. The unweighted pair-group method with arithmetic means analysis based on ISSR-SRAP marker data revealed that the genetic similarity coefficient between the tested strains was 0.73-0.97, and the strains could be divided into five groups at 0.742, which had a certain correlation with regional distribution. The results of PCOA and population structure analysis based on ISSR-SRAP data also produced similar results. These results demonstrate the genetic diversity and distinctness among wild A. cornea and provide a theoretical reference for the classification, breeding, germplasm innovation, utilization, and variety protection of A. cornea resources.

Protein Interface Regulating the Inserting Process of Imidazole Ionic Liquids into the Cell Membrane.

Ionic liquids (ILs) have shown promising potential in membrane protein extraction; however, the underlying mechanism remains unclear. Herein, we employed GPU-accelerated molecular dynamics (MD) simulations to investigate the dynamic insertion process of ILs into cell membranes containing membrane proteins. Our findings reveal that ILs spontaneously insert into the membrane, and the presence of membrane proteins significantly decelerates the rate of IL insertion into the membrane. Specifically, the relationship between the insertion rate and inserting free energy exhibits non-monotonic changes, which can be attributed to interfacial effects. The protein-water interface acts as trap for free ions and ionic clusters, while free ions preferentially insert into the membrane from the protein-lipid interface, which limits the insertion rate due to its narrowness. Thus, the insertion rate is governed by a combination of the free energy and interfacial effects. These findings provide valuable insights into the interfacial effects of protein-lipid bilayers and have implications for various biochemical-related applications.

Simple, ultrasensitive detection of superoxide anion radical mutations in melanoma mice with SERS microneedles.

Elevated levels of superoxide anion radicals (O2·-) have been implicated in the pathogenesis of a variety of diseases, such as cancer, inflammatory diseases and autoimmune diseases. To determine the O2·- concentration for assisting disease detection, a method based on surface-enhanced Raman scattering (SERS) combined with transparent polymer microneedles has been developed. Photocrosslinked NOA61 is used to prepare microneedles with sulfhydryl group, which can contribute to anchor gold nanoparticles (Au NPs) functionalized by p-mercaptobenzoic acid (PATP). This work successfully constructed SERS microneedles for in situ detection. A REDOX reaction occurred between PATP and O2·-, resulting in the formation of dimethylaminoborane (DMAB) and a subsequent change in Raman signal. Based on the quantitative relationship between the change of peak area ratio at 1042 cm-1 and 1077 cm-1 and the concentration change of O2·-, a standard curve with a linear range of 0-480 ng/mL was constructed. The SERS microneedles were effectively employed to track melanoma progression in mice, establishing a fundamental correlation between O2·- concentration and melanoma stage, as confirmed by ELISA. The benefits of this approach, including convenience, in situ applicability, and low cost, are anticipated to offer novel insights for non-invasive in situ detection, potentially enhancing disease monitoring and diagnosis.

SERS-Based Microneedle Biosensor for In Situ and Sensitive Detection of Tyrosinase.

Tyrosinase (TYR) emerges as a key enzyme that exerts a regulatory influence on the synthesis of melanin, thereby assuming the role of a critical biomarker for the detection of melanoma. Detecting the authentic concentration of TYR in the skin remains a primary challenge. Distinguished from ex vivo detection methods, this study introduces a novel sensor platform that integrates a microneedle (MN) biosensor with surface-enhanced Raman spectroscopy (SERS) technology for the in situ detection of TYR in human skin. The platform utilized dopamine (DA)-functionalized gold nanoparticles (Au NPs) as the capturing substrate and 4-mercaptophenylboronic acid (4-MPBA)-modified silver nanoparticles (Ag NPs) acting as the SERS probe. Here, the Au NPs were functionalized with mercaptosuccinic acid (MSA) for DA capture. In the presence of TYR, DA immobilized on the MN is preferentially oxidized to dopamine quinone (DQ), a process that results in a decreased density of SERS probes on the platform. TYR concentration was detected through variations in the signal intensity emitted by the phenylboronic acid. The detection system was able to evaluate TYR concentrations within a linear range of 0.05 U/mL to 200 U/mL and showed robust anti-interference capabilities. The proposed platform, integrating MN-based in situ sensing, SERS technology, and TYR responsiveness, holds significant importance for diagnosing cutaneous melanoma.

SOX-1 antibodies positive Lambert-Eaton myasthenic syndrome with occult small cell lung cancer: A case report.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare paraneoplastic neurological syndrome of the neuromuscular transmission. The symptoms often progress slowly and can be misdiagnosed in early stage. Seropositive SOX-1 antibodies are support for the diagnosis of LEMS and have high specificity for small cell lung cancer (SCLC). In this paper, we report a case of a 56-year-old man with smoking history who was admitted to hospital with progressive muscle weakness of the proximal legs. LEMS was diagnosed by repetitive nerve stimulation (RNS) testing and seropositive SOX-1 antibodies. Primary screening with chest computed tomography (CT) and integrated PET/CT did not reveal any tumor. After continuous follow-up, SCLC was found by chest CT and confirmed with pathological examination 10 months after the diagnosis of LEMS. Long-term follow-up and screening for occult SCLC in LEMS patients with positive SOX-1 antibodies are very important.

Granulin in renal tubular epithelia is associated with interstitial inflammation and activates the TLR9-IFN-α pathway in lupus nephritis.

OBJECTIVE: This study aimed to investigate the possible role of granulin (GRN) in activating the TLR9-IFN-α pathway in renal tubular epithelial cells (RTECs) and explore clues that RTECs regulate the micro-environment of inflammatory response in lupus nephritis (LN). METHODS: Renal sections from 57 LN patients and 30 non-LN patients were sampled for histological study, and GRN overexpression RTECs were applied for cytological study. RESULTS: In the histological study, GRN is highly expressed in LN RTECs with tubulointerstitial inflammation (TII) and well co-localized with TLR9. ROC analysis suggested a potential relationship between GRN expression in RTECs and therapeutic response. Moreover, IFN-α also highly expressed in LN RTECs with TII, and the intensity of IFN-α is positively correlated with the co-localization intensity of GRN and TLR9. In the cytological study, LN serum, especially serum from LN with TII, activates the expression of TLR9 in RTECs, and GRN engages the interaction of TLR9 to activate the expression of IFN-α in RTECs. While TLR9 inhibitors can suppress the expression of IFN-α in RTECs, the degree of inhibition is dose-dependent. CONCLUSION: The expression of GRN in RTECs is associated with interstitial inflammation and therapeutic response. GRN may mediate the activation of the TLR9-IFN-α pathway in RTECs and involve in the micro-environment of inflammatory response in LN.

Multi-target field control for matrix gradient coils.

OBJECTIVE: Conventional single-target field control for matrix gradient coils will add control complexity in MRI spatial encoding, such as designing specialized fields and sequences. This complexity can be reduced by multi-target field control, which is realized by optimizing the coil structure according to target fields. METHODS: Based on the principle of multi-target field control, the X, Y and Z gradient fields can be set as target fields, and all coil elements can then be divided into three groups to generate these fields. An improved simulated annealing algorithm is proposed to optimize the coil element distribution of each group to generate the corresponding target field. In the improved simulated annealing process, two swapping modes are presented, and randomly selected with certain probabilities that are set to 0.25, 0.5 and 0.75, respectively. The flexibility of the final designed structure is demonstrated by a spherical harmonic basis up to the full second order with single-target field control. An experimental platform is built to measure the gradient fields generated by the designed structure with multi-target target control. RESULTS: With three probabilities of swapping modes, three similar coil element distributions are optimized, and their maximum magnetic field errors for generating X, Y and Z gradients are all below 5%. The structure selected for the final design is the one with a probability of 0.75, considering the coil performance and structural symmetry. The maximum error for all target fields generated by single-target field control is also below 5%. The experimental results show that the measured gradient fields along the axes have enough strength and high linearity. CONCLUSIONS: With the proposed improved simulated annealing algorithm and swapping modes, multi-target field control for matrix gradient coils is verified and achieved in this study by optimizing the coil element distribution. Moreover, this study provides a solution to simplify the complexity of controlling the matrix gradient coil in spatial encoding.

Water-induced strong isotropic MXene-bridged graphene sheets for electrochemical energy storage.

Graphene and two-dimensional transition metal carbides and/or nitrides (MXenes) are important materials for making flexible energy storage devices because of their electrical and mechanical properties. It remains a challenge to assemble nanoplatelets of these materials at room temperature into in-plane isotropic, free-standing sheets. Using nanoconfined water-induced basal-plane alignment and covalent and π-π interplatelet bridging, we fabricated Ti3C2Tx MXene-bridged graphene sheets at room temperature with isotropic in-plane tensile strength of 1.87 gigapascals and moduli of 98.7 gigapascals. The in-plane room temperature electrical conductivity reached 1423 siemens per centimeter, and volumetric specific capacity reached 828 coulombs per cubic centimeter. This nanoconfined water-induced alignment likely provides an important approach for making other aligned macroscopic assemblies of two-dimensional nanoplatelets.

Classification, Diagnosis, and Treatment of Obesity-Related Heart Diseases.

Evidence-based medicine shows that obesity is associated with a wide range of cardiovascular (CV) diseases. Obesity can lead to changes in cardiac structure and function, which can lead to obese cardiomyopathy, subclinical cardiac dysfunction, and even heart failure. It also increases the risk of atrial fibrillation and sudden cardiac death. Many invasive and noninvasive diagnostic methods can detect obesity-related heart disease at an early stage, so that appropriate measures can be selected to prevent adverse CV events. However, studies have shown a protective effect of obesity on clinical outcomes of CV disease, a phenomenon that has been termed the obesity paradox. The "obesity paradox" essentially refers to the fact that the classification of obesity defined by body mass index (BMI) does not consider the impact of obesity heterogeneity on CV disease prognosis, but simply puts subjects with different clinical and biochemical characteristics into the same category. In any case, indicators such as waist-to-hip ratio, ectopic body fat qualitative and quantitative, and CV fitness have been shown to be able to distinguish different CV risks in patients with the same BMI, which is convenient for early intervention in an appropriate way. A multidisciplinary approach, including lifestyle modification, evidence-based generic and novel pharmacotherapy, and surgical intervention, can improve CV outcomes in overweight/obese patients.

Nanofluid-Guided Janus Membrane for High-Efficiency Electricity Generation from Water Evaporation.

Harvesting electricity from widespread water evaporation provides an alternative route to cleaner power generation technology. However, current evaporation power generation (EPG) mainly depends on the dissociation process of certain functional groups (e.g., SO3 H) in water, which suffers from low power density and short-term output. Herein, the Janus membrane is prepared by combining nanofluid and water-grabbing material for EPG, where the nanoconfined ionic liquids (NCILs) serve as ion sources instead of the functional groups. Benefiting from the selective and fast transport of anions in NCILs, such EPG demonstrates excellent power performance with a voltage of 0.63 V, a short-circuit current of 140 µA, and a maximum power density of 16.55 µW cm-2 while operating for at least 180 h consistently. Molecular dynamics (MD) simulation and surface potential analysis reveal the molecular mechanism, that is, the diffusion of Cl- anions during evaporation is much faster than that of cations, generating the voltage and current across the membrane. Furthermore, the device performs well in varying environmental conditions, including different water temperatures and sources of evaporating water, showcasing its adaptability and integrability. Overall, the nanofluid-guided Janus membrane can efficiently transform low-grade thermal energy in evaporation into electricity, showing a competitive advantage over other sustainable applied approaches.

Prognostic value of left atrial reverse remodelling in heart failure with preserved ejection fraction.

OBJECTIVES: Left atrial reverse remodelling (LARR) reflects an improvement in the function or structure. However, it is unclear whether the presence of LARR is associated with better outcomes in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: The study was a monocentric retrospective cohort one. Consecutive HFpEF patients admitted to the hospital between 1 January 2018 and 30 June 2020 were included. This cohort was divided into LARR and non-LARR groups based on the recovery of the left atrium. The primary endpoints were all-cause mortality, rehospitalization for heart failure, and the composite of death or readmission. Significant predictors of LARR were examined. RESULTS: A total of 409 patients were enrolled, including 90 cases in the LARR group and 319 in the non-LARR group. Kaplan-Meier analysis showed that compared with the non-LARR group, the LARR group had a lower incidence of rehospitalization for heart failure and the composite of death or readmission but not all-cause mortality. Similar results were observed in a subgroup analysis of patients with and without atrial fibrillation. Cox regression analysis demonstrated that the non-LARR group experienced higher risks of heart failure-related readmission [hazard ratio: 1.785, 95% confidence interval (CI) 1.236-3.215, P  = 0.037] and the composite outcome (hazard ratio: 1.684, 95% CI 1.254-2.865, P  = 0.044), but not all-cause mortality (hazard ratio: 1.475, 95% CI: 0.481-3.527, P  = 0.577) compared with the LARR group after adjusting for significant confounders. Logistic regression analysis showed that mild mitral regurgitation and the use of loop diuretics were two positive predictors of LARR in patients with HFpEF. CONCLUSION: LARR is an effective echocardiographic index that can be used to predict heart failure-related readmission in HFpEF. Therefore, regular assessment of left atrial size can provide a useful marker for risk stratification of heart failure.

Differential expression of zinc finger CCHC-type superfamily proteins in thyroid carcinoma and their associations with tumor immunity.

BACKGROUND: The zinc-finger CCHC-type (ZCCHC) superfamily proteins are characterized by the shared sequence CX2-CX4-HX4-C and thought to own high affinity to single-stranded nucleic acids, particularly RNAs. In humans, a total of 24 ZCCHC proteins have been annotated in the HUGO Gene Nomenclature Committee (HGNC, https://www.genenames.org/ ) database with most of these members involved in multiple steps of RNA metabolism. Many studies have indicated that the ZCCHC genes play a regulatory role in the development and progression of solid tumors. To date, the expression pattern and prognostic value of ZCCHC factors in thyroid carcinomas have not been reported. METHODS: Bioinformatics analyses on the functions of ZCCHC factors in thyroid carcinoma (THCA) patients were performed based on various databases, i.e., TCGA, GEPIA, Kaplan-Meier Plotter, and TIMER. RESULTS: Compared with normal tissues, the expression of ZCCHC12 mRNA was significantly increased in THCA tissues. And it was associated with the overall survival of THCA patients, based on the Kaplan-Meier Plotter database. Furthermore, the expression levels of all ZCCHCs were correlated with tumor stages, implying its high relevance to THCA, specifically its immunity. CONCLUSION: The ZCCHC genes, represented by ZCCHC12, are differentially expressed in THCA staging. These genes are associated with immune infiltration of THCA and identified as the potential therapeutic targets for immunotherapy in THCA patients, which are possible novel biomarkers for the treatment of THCA.

Electron Density Learning of Z-Bonds in Ionic Liquids and Its Application.

Ionic liquids (ILs) exhibit fascinating properties due to special Z-bonds and have been widely used in electrochemical systems. The local Z-bond networks potentially cause a discrepancy in electrochemical properties. Understanding the correlations between the Z-bond energy (EZ-bond) and the electrochemical properties is helpful to identify appropriate ILs. It is difficult to estimate the correlations from single density functional theory calculations or molecular dynamic simulations. In this work, a machine learning model targeting the electronic density (ρBCP) of Z-bonds has been trained successfully, as expected for use in systems above the nanoscale size. The connection between the EZ-bond and the electrochemical potential window in ILs@TiO2, as well as that between the EZ-bond and the charge carrier mobility in ILs-PEDOT:Tos@SiO2, was separately investigated. This study highlights an efficient model for predicting ρBCP in nanoscale systems and anticipates exploring the connection between Z-bonds and the electrochemical properties of IL-based systems.

Low-grade wind-driven directional flow in anchored droplets.

Low-grade wind with airspeed Vwind < 5 m/s, while distributed far more abundantly, is still challenging to extract because current turbine-based technologies require particular geography (e.g., wide-open land or off-shore regions) with year-round Vwind > 5 m/s to effectively rotate the blades. Here, we report that low-speed airflow can sensitively enable directional flow within nanowire-anchored ionic liquid (IL) drops. Specifically, wind-induced air/liquid friction continuously raises directional leeward fluid transport in the upper portion, whereas three-phase contact line (TCL) pinning blocks further movement of IL. To remove excessive accumulation of IL near TCL, fluid dives, and headwind flow forms in the lower portion, as confirmed by microscope observation. Such stratified circulating flow within single drop can generate voltage output up to ~0.84 V, which we further scale up to ~60 V using drop "wind farms". Our results demonstrate a technology to tap the widespread low-grade wind as a reliable energy resource.

Three-Electron Transfer-Based High-Capacity Organic Lithium-Iodine (Chlorine) Batteries.

Conversion-type batteries apply the principle that more charge transfer is preferable. The underutilized electron transfer mode within two undermines the electrochemical performance of halogen batteries. Here, we realised a three-electron transfer lithium-halogen battery based on I- /I+ and Cl- /Cl0 couples by using a common commercial electrolyte saturated with Cl- anions. The resulting Li||tetrabutylammonium triiodide (TBAI3 ) cell exhibits three distinct discharging plateaus at 2.97, 3.40, and 3.85 V. Moreover, it has a high capacity of 631 mAh g-1 I (265 mAh g-1 electrode , based on entire mass loading) and record-high energy density of up to 2013 Wh kg-1 I (845 Wh kg-1 electrode ). To support these findings, experimental characterisations and density functional theory calculations were conducted to elucidate the redox chemistry involved in this novel interhalogen strategy. We believe our paradigm presented here has a foreseeable inspiring effect on other halogen batteries for high-energy-density pursuit.

An analysis of codon utilization patterns in the chloroplast genomes of three species of Coffea.

BACKGROUND: The chloroplast genome of plants is known for its small size and low mutation and recombination rates, making it a valuable tool in plant phylogeny, molecular evolution, and population genetics studies. Codon usage bias, an important evolutionary feature, provides insights into species evolution, gene function, and the expression of exogenous genes. Coffee, a key crop in the global tropical agricultural economy, trade, and daily life, warrants investigation into its codon usage bias to guide future research, including the selection of efficient heterologous expression systems for coffee genetic transformation. RESULTS: Analysis of the codon utilization patterns in the chloroplast genomes of three Coffea species revealed a high degree of similarity among them. All three species exhibited similar base compositions, with high A/T content and low G/C content and a preference for A/T-ending codons. Among the 30 high-frequency codons identified, 96.67% had A/T endings. Fourteen codons were identified as ideal. Multiple mechanisms, including natural selection, were found to influence the codon usage patterns in the three coffee species, as indicated by ENc-GC3s mapping, PR2 analysis, and neutral analysis. Nicotiana tabacum and Saccharomyces cerevisiae have potential value as the heterologous expression host for three species of coffee genes. CONCLUSION: This study highlights the remarkable similarity in codon usage patterns among the three coffee genomes, primarily driven by natural selection. Understanding the gene expression characteristics of coffee and elucidating the laws governing its genetic evolution are facilitated by investigating the codon preferences in these species. The findings can enhance the efficacy of exogenous gene expression and serve as a basis for future studies on coffee evolution.

Convenient and Controllable Synthesis of Poly(2-oxazoline)-Conjugated Doxorubicin for Regulating Anti-Tumor Selectivity.

Polyethylene glycol (PEG)-doxorubicin (DOX) conjugation is an important strategy to improve toxicity and enhance clinically therapeutic efficacy. However, with the frequent use of PEG-modified drugs, the accumulation of anti-PEG antibodies has become a tough issue, which limits the application of PEG-drug conjugation. As an alternative solution, poly(2-oxazoline) (POX)-DOX conjugation has shown great potential in the anti-tumor field, but the reported conjugation process of POX with DOX has drawbacks such as complex synthetic steps and purification. Herein, we propose a convenient and controllable strategy for the synthesis of POX-DOX conjugation with different chain lengths and narrow dispersity by N-boc-2-bromoacetohydrazide-initiated 2-ethyl-oxazoline polymerization and the subsequent deprotection of the N-Boc group and direct reaction with DOX. The DOX-PEtOx conjugates were firstly purified, and the successful conjugations were confirmed through various characterization methods. The synthetic DOX-PEtOxn conjugates reduce the toxicity of DOX and increase the selectivity to tumor cells, reflecting the promising application of this POX-DOX conjugation strategy in drug modification and development.

A Versatile Disorder-to-Order Technology to Upgrade Polymers into High-Performance Bioinspired Materials.

Biodegradable polymer as traditional material has been widely used in the medical and tissue engineering fields, but there is a great limitation as to its inferior mechanical performance for repairing load-bearing tissues. Thus, it is highly desirable to develop a novel technology to fabricate high-performance biodegradable polymers. Herein, inspired by the bone's superstructure, a versatile disorder-to-order technology (VDOT) is proposed to manufacture a high-strength and high-elastic modulus stereo-composite self-reinforced polymer fiber. The mean tensile strength (336.1 MPa) and elastic modulus (4.1 GPa) of the self-reinforced polylactic acid (PLA) fiber are 5.2 and 2.1 times their counterparts of the traditional PLA fiber prepared by the existing spinning method. Moreover, the polymer fibers have the best ability of strength retention during degradation. Interestingly, the fiber tensile strength is even higher than those of bone (200 MPa) and some medical metals (e.g., Al and Mg). Based on all-polymeric raw materials, the VDOT endows bioinspired polymers with improved strength, elastic modulus, and degradation-controlled mechanical maintenance, making it a versatile update technology for the massive industrial production of high-performance biomedical polymers.