Search Results (855)

Since the initial use of biological ion channels to detect single-stranded genomic base pair differences, label-free and highly sensitive resistive pulse sensing (RPS) with nanopores has made remarkable progress in single-molecule analysis. By monitoring transient ionic current disruptions caused by molecules translocating through a nanopore, this technology offers detailed insights into the structure, charge, and dynamics of the analytes. In this work, the RPS platforms based on biological, solid-state, and other sensing pores, detailing their latest research progress and applications, are reviewed. Their core capability is the high-precision characterization of tiny particles, ions, and nucleotides, which are widely used in biomedicine, clinical diagnosis, and environmental monitoring. However, current RPS methods involve bottlenecks, including limited sensitivity (weak signals from sub-nanometer targets with low SNR), complex sample interference (high false positives from ionic strength, etc.), and field consistency (solid-state channel drift, short-lived bio-pores failing POCT needs). To overcome this, bio-solid-state fusion channels, in-well reactors, deep learning models, and transfer learning provide various options. Evolving into an intelligent sensing ecosystem, RPS is expected to become a universal platform linking basic research, precision medicine, and on-site rapid detection. Full article

The recovery and abatement of volatile organic compounds (VOCs) have received increasing attention due to their significant environmental and health impacts. Supported sulfonic acid materials have shown great potential in converting aromatic VOCs into their non-volatile derivatives through reactive adsorption. However, the anchoring state of sulfonic acid groups, which is closely related to the properties of the support, greatly affects their performance. In this study, two supported sulfonic acid materials, SZO and SMO, were prepared by treating ZrO₂ and MgO with chlorosulfonic acid, respectively, to investigate the influence of the support properties on the anchoring state of sulfonic acid groups and their reactive adsorption performance for o-xylene. The supports, adsorbents, and adsorption products were extensively characterized, and the reactivity of SZO and SMO towards o-xylene was systematically compared. The results showed that sulfonic acid groups are anchored on the ZrO₂ surface through covalent bonding, forming positively charged sulfonic acid sites ([O_1.5Zr-O]^δ−-SO3H^δ+) with a loading of 3.6 mmol/g. As a result, SZO exhibited excellent removal efficiency (≥91.3%) and high breakthrough adsorption capacity (ranging from 38.59 to 82.07 mg/g) for o-xylene in the temperature range of 130 –150 °C. In contrast, sulfonic acid groups are anchored on the MgO surface via ion-paired bonding, leading to the formation of negatively charged sulfonic acid sites ([O_0.5Mg]⁺:OSO₃H⁻), which prevents their participation in the electrophilic sulfonation reaction with o-xylene molecules. This work provides new insights into tuning and enhancing the performance of supported sulfonic acid materials for the resource-oriented treatment of aromatic VOCs. Full article

Background: Liquid chromatography-mass spectrometry (LC-MS), widely used in metabolomics, is often limited by low ionization efficiency and ion suppression, which reduce overall metabolite detectability and quantification accuracy. To address these challenges, chemical isotope labeling (CIL) LC-MS has emerged as a powerful approach, offering high sensitivity, accurate quantification, and broad metabolome coverage. This method enables comprehensive profiling by targeting multiple submetabolomes. Specifically, amine-/phenol- and hydroxyl-containing metabolites are labeled using dansyl chloride under distinct reaction conditions. While this strategy provides extensive coverage, the sequential analysis of each submetabolome reduces throughput. To overcome this limitation, we propose a two-channel mixing strategy to improve analytical efficiency. Methods: In this approach, samples labeled separately for the amine/phenol and hydroxyl submetabolomes are combined prior to LC-MS analysis, leveraging the common use of dansyl chloride as the labeling reagent. This integration effectively doubles throughput by reducing LC-MS runtime and associated costs. The method was evaluated using human urine and serum samples, focusing on peak pair detectability and metabolite identification. A proof-of-concept study was also conducted to assess the approach’s applicability in putative biomarker discovery. Results: Results demonstrate that the two-channel mixing strategy enhances throughput while maintaining analytical robustness. Conclusions: This method is particularly suitable for large-scale studies that require rapid sample processing, where high efficiency is essential. Full article

The structures of hexaammine solvated indium(III) and thallium(III) ions in liquid ammonia solution are determined by EXAFS. Both complexes have regular octahedral coordination geometry with mean In-N and Tl-N bond distances of 2.23(1) and 2.29(2) Å, respectively. Ammine solvated thallium(III) in liquid ammonia is characterized with ²⁰⁵Tl NMR measurements. Solvents such as liquid ammonia, N,N-dimethylthioformamide (DMTF), trialkyl and triphenyl phosphite and phosphine are strong electron pair donors and thereby able to form bonds with a large covalent contribution with strong electron pair acceptors. A survey of reported structures of ammine, DMTF, trialkyl and triphenyl phosphite and phosphine solvated metal ions in the solid state and solution is presented. The M-N and M-S bond distances in ammine and DMTF solvated metal ions are compared with the M-O bond distance in the corresponding metal ion hydrates, expected to form mainly electrostatic interactions with metal ions. The d¹⁰ metal ions have high ability to form bonds with a high degree of covalency with increasing ability down the group and with decreasing charge of the metal ion. The difference in M-N and M-O bond distances between ammine solvated and hydrated metal ions with the same coordination geometry decreases significantly with the increasing ability of the metal ion to form bonds with a large covalent contribution. This difference correlates well with the covalent bonding index, γ_M²*r. Full article

MicroRNA-based regulatory mechanisms show disturbances related to oxidative stress (OS) interconnected with inflammation (IFM), as well as impairments associated with gestational diabetes (GDM). The aim of this study was to assess the diagnostic and prognostic significance of the OS/IFM-related microRNA in GDM by using peripheral blood mononuclear cells (PBMCs) and serum-derived extracellular vesicles (EVs) as biological samples. We selected the known OS/IFM-associated microRNAs miR-146a-5p, miR-155-5p, and miR-21-5p as candidates for our GDM biomarker analysis. Quantitative RT-PCR was employed for relative quantification of the selected microRNAs from paired samples of PBMCs and EVs derived from patients with GDM and healthy controls (n = 50 per group). The expression levels were analyzed for correlations with lipid and glycemic status indicators; metal ion-related parameters; serum thiol content; protein carbonyl and thiobarbituric acid-reactive substances’ (TBARS) levels; glutathione reductase (GR), Superoxide dismutase (SOD), and catalase (CAT) activity; and NRF2 expression. MiR-146a-5p and miR-21-5p were significantly upregulated in both PBMCs and EVs obtained from GDM patients. EVs-miR-21-5p showed a positive correlation with glycemic status in GDM patients, while miR-155-5p from PBMCs demonstrated correlation with iron-related parameters. The expression of selected microRNAs was found to correlate with NRF2 expression and SOD activity. The level of miR-146a-5p negatively correlated with neonatal anthropometric characteristics, while a higher level of PBMCs-miR-21-5p expression was determined in GDM patients with adverse pregnancy outcomes (p = 0.012). Our data demonstrate a disturbance of OS/IFM-microRNAs in GDM and illustrate their potential to serve as indicators of the associated OS-related changes, neonatal characteristics, and adverse pregnancy outcomes. Full article

Background/Objectives: Leishmaniasis is a prevailing infectious disease transmitted via infected phlebotomine sandflies. The lack of an efficient vaccine with respect to immunogenic antigens and adjuvanted delivery systems impedes its control. Following the induction of immune responses in mice vaccinated with multi-epitope Leishmania peptides (LeishPts) encapsulated in doubly adjuvanted self-nanoemulsifying drug delivery systems (ST-SNEDDSs), this study aims to assess ST-SNEDDS-based nanoemulsions as vehicles for the delivery of antigenic proteins. Methods: Model antigens (e.g., BSA-FITC, OVA) were encapsulated in ST-SNEDDS after being complexed with the cationic phospholipid dimyristoyl phosphatidylglycerol (DMPG) via hydrophobic ion pairing. The nanoemulsions were characterized with respect to droplet diameter, zeta potential, stability, protein loading, protein release from the nanodroplets in different release media and cell uptake. Results: Both model antigens exhibited high encapsulation efficiency (>95%) and their release from the nanodroplets was shown to be strongly affected by the type of release medium (e.g., PBS, FBS 10% v/v) and the ratio of its volume to that of the oily phase, in agreement with predictions of protein release. Protein-loaded nanoemulsion droplets labeled with Cy-5 were found to be efficiently taken up by macrophages (J774A.1) in vitro. However, no colocalization of the labeled nanodroplets and BSA-FITC could be observed. Conclusions: It was revealed that in contrast with LeishPts, whole protein molecules may not be appropriate antigenic cargo for ST-SNEDDS formulations due to the rapid protein release from the nanodroplets in release media simulating in vitro culture and in vivo conditions such as FBS 10% v/v. Full article

The persistent contamination of aquatic environments by heavy metals, particularly Pb²⁺, Cd²⁺, and Cu^2+, poses a serious global threat due to their toxicity, persistence, and bioaccumulative behavior. In response, low-cost and eco-friendly adsorbents are being explored, among which CaCO₃-based biocomposites derived from mollusk shells have shown exceptional performance. In this study, a hybrid biocomposite composed of poly(vinyl alcohol) (PVA) and oyster shell-derived CaCO₃ was computationally investigated using Density Functional Theory (DFT) to elucidate the electronic and structural basis for its high metal-removal efficiency. Calculations were performed at the B3LYP/6-311++G(d,p), M05-2X/6-311+G(d,p), and M06-2X/6-311++G(d,p) levels using GAUSSIAN 16. Among them, B3LYP was identified as the most balanced in terms of accuracy and computational cost. The hybridization with CaCO₃ reduced the HOMO-LUMO gap by 20% and doubled the dipole moment (7.65 Debye), increasing the composite’s polarity and reactivity. Upon chelation with metal ions, the gap further dropped to as low as 0.029 eV (Cd²⁺), while the dipole moment rose to 17.06 Debye (Pb²⁺), signaling enhanced charge separation and stronger electrostatic interactions. Electrostatic potential maps revealed high nucleophilicity at carbonate oxygens and reinforced electrophilic fields around the hydrated metal centers, correlating with the affinity trend Cu²⁺ > Cd²⁺ > Pb²⁺. Fukui function analysis indicated a redistribution of reactive sites, with carbonate oxygens acting as ambiphilic centers suitable for multidentate coordination. Natural Bond Orbital (NBO) analysis confirmed the presence of highly nucleophilic lone pairs and weakened bonding orbitals, enabling flexible adsorption dynamics. Furthermore, NCI/RDG analysis highlighted attractive noncovalent interactions with Cu²⁺ and Pb²⁺, while FT-IR simulations demonstrated the formation of hydrogen bonding (O–H···O=C) and Ca²⁺···O coordination bridges between phases. Full article

Proton and heavy ion irradiation experiments were carried out on Cascode GaN HEMT devices. Results show that device degradation from heavy ion irradiation is more significant than from proton irradiation. Under proton irradiation, obvious device degradation occurred. Low-frequency noise testing revealed a notable increase in internal defect density, reducing channel carrier concentration and mobility, and causing electrical performance degradation. Under heavy ion irradiation, devices suffered from single-event burnout (SEB) and exhibited increased leakage current. Failure analysis of post-irradiation devices showed that those with leakage current increase had conductive channels without morphological changes, while burned out devices showed obvious damage between the gate and drain regions. SRIM simulation indicated that ionization energy loss-induced electron–hole pairs and displacement damage from nuclear energy loss were the main causes of degradation. Sentaurus TCAD simulation of heavy ion irradiated GaN HEMT devices confirmed the mechanisms of leakage current increase and SEB. Full article

Background: Phytoremediation is an efficient approach for remediating heavy metal-contaminated soils. Heavy metal-associated isoprenylated plant proteins (HIPPs)—crucial for metal ion homeostasis—are unique to vascular plants, featuring a heavy metal-associated (HMA) domain and an isoprenylated CaaX motif. However, ZmHIPP genes have not been systematically or functionally characterized in maize. Methods: This study characterizes ZmHIPP at the genome-wide level, including phylogenetic classification, motif/gene structure, chromosome location, gene duplication events, promoter elements, and tissue expression patterns. Cadmium (Cd) responses were evaluated by specific ZmHIPP expression and Cd accumulation in shoots and roots under Cd treatment. Results: A total of 66 ZmHIPPs were distributed unevenly across ten chromosomes, classified into five phylogenetic groups phylogenetically. Gene collinearity revealed 26 pairs of segmental duplications in ZmHIPPs. Numerous synteny genes were detected in rice and sorghum, but none in Arabidopsis, suggesting high conservation of HIPP genes in crop evolution. Transcriptomic analysis revealed tissue-specific expression patterns of ZmHIPP members in maize. Cis-acting element analysis linked several binding elements to abscisic acid, MeJA response, and MYB and MYC transcription factors. Under Cd stress, 53 out of 66 ZmHIPP genes were significantly induced, exhibiting three expression patterns. Cd exposure confirmed that the expression of ZmHIPP11, ZmHIPP30, and ZmHIPP48 was generally higher in shoots than roots, while ZmHIPP02 and ZmHIPP57 exhibited the opposite. Cd accumulation was higher in roots than shoots, peaking at 72 h (96 mg/kg) in shoots and exceeding 1000 mg/kg in roots after 120 h. Conclusions: This study not only provides fundamental genetic and molecular insights into HIPP function in maize but also identifies specific ZmHIPP genes as promising genetic resources for breeding Cd-tolerant maize, aiding in phytoremediation of Cd-contaminated soils. Full article

Background/Objectives: Refractory community-acquired pneumonia (r-CAP) has become a thorny issue in clinical practice, especially after the COVID-19 pandemic, even in immunocompetent patients, as conventionally defined. In this study, we aimed to identify the risk factors for immunocompetent patients with r-CAP. Methods: This was a single-center retrospective study. In total, we collected clinical data from 82 patients with r-CAP in whom the first-line antibiotic therapy failed and 82 patients with general CAP (g-CAP) who recovered with first-line antibiotics, matched at a ratio of 1:1, admitted to Beijing Shijitan Hospital, Capital Medical University, from 1 January 2022, to 31 December 2023. The differences between the two groups (clinical characteristics, peripheral blood cell count, lymphocyte subsets, and regular laboratory indicators) were analyzed using paired t, paired Wilcoxon, Chi-square, or Fisher’s exact tests, and univariate and multivariate logistics regression analyses were conducted to identify the independent risk factors. A model for predicting indicators with statistical significance was established and proved with the receiver operating characteristic (ROC) curve. Results: Warm season, a history of chronic obstructive pulmonary disease, longer time from onset to admission (T_O-A), higher percentages of CD4⁺ T, CD8⁺ T, and double-negative T (DNT) lymphocytes, as well as higher levels of C-reactive protein (CRP), low-density lipoprotein cholesterin (LDL-C), serum sodium ion (Na⁺), and free-calcium ion (FCa²⁺) were regarded as independent risk factors, while T lymphocyte percentage (T%) and total cholesterol (TC) were identified as protective factors. The combined multivariate model using all the above factors proved to be sensitive and specific (AUC = 0.8711, p < 0.0001, R² = 0.4235), and thus better than the respective univariate models. Conclusions: Increased CD4⁺ T%Lym, CD8⁺ T%Lym, and DNT%Lym, warm season, a history of COPD, longer T_O-A, and increased levers of CRP, LDL-C, Na⁺, and FCa²⁺ potentially cause CAP to be refractory, while the T lymphocyte count, namely, the overall cellular immunity, was impaired in r-CAP patients, and increased TC levels could be beneficial to pneumonia recovery. Full article

Compound Glycyrrhizin tablets (CGTs) are a combination of glycyrrhizin, glycine and methionine. Glycine and methionine have relatively high polarity and lack chromophore; therefore, it is difficult to simultaneously determine the various components using traditional reversed-phase chromatography and ultraviolet detectors. In addition, it is even more challenging to obtain a comprehensive and systematic impurity profiling for the CGTs. In this study, an ion-pair high-performance liquid chromatography (HPLC)–charged aerosol detection (CAD) method was established to determine the content of glycyrrhizin, glycine and methionine. The impurities of CGTs were also identified using mass spectrometry. By optimizing the content of trifluoroacetic acid (TFA) in the mobile phase and optimizing the CAD parameter settings, the developed method was verified in accordance with the guidelines outlined in ICH Q2 (R2). The results indicated that the method demonstrated high accuracy and sensitivity. Glycine, methionine and glycyrrhizin all showed a good linear relationship within the labeled range of 50–200%, and the average recoveries of the three components were 97.62–100.6%. The impurity detection was quantified via the principal component control method. The limit of detection (LOD) method showed an equivalent to 0.05% of the glycyrrhizin in CGTs, approximately 12.5 ng. The ion-pair HPLC–CAD method developed in this study simultaneously determined the content of the main component and the impurities of CGTs, without necessitating derivatization. This has provided a research basis for further improving the quality standards of CGTs. Full article

Nickel’s durability and catalytic properties make it essential in the aerospace, automotive, electronics, and fuel cell technology industries. Wastewater analysis typically relies on sensitive but costly techniques such as ICP-MS, AAS, and ICP-AES, which require complex equipment and are unsuitable for on-site testing. This study introduces a novel screen-printed electrode array with 16 chemically and, optionally, electrochemically coated Au electrodes. Its electrochemical response to Ni²⁺ was tested using Na₂SO₃ and ChCl-EG deep eutectic solvents as electrolytes. Ni²⁺ solutions were prepared from NiCl₂·6H₂O, NiSO₄·6H₂O, and dry NiCl₂. In Na₂SO₃, the linear detection ranges were 20–196 mM for NiCl₂·6H₂O and 89–329 mM for NiSO₄·6H₂O. High Ni²⁺ concentrations (10–500 mM) were used to simulate industrial conditions. Two linear ranges were observed, likely due to differences in electrochemical behaviour between NiCl₂·6H₂O and NiSO₄·6H₂O, despite the identical Na₂SO₃ electrolyte. Anion effects (Cl⁻ vs. SO₄²⁻) may influence response via complexation or ion pairing. In ChCl-EG, a linear range of 0.5–10 mM (R² = 0.9995) and a detection limit of 1.6 µM were achieved. With a small electrolyte volume (100–200 µL), nickel detection in the nanomole range is possible. A key advantage is the array’s ability to analyze multiple analytes simultaneously via customizable electrode configurations. Future research will focus on nickel detection in industrial wastewater and its potential in the multiplexed analysis of toxic metals. The array also holds promise for medical diagnostics and food safety applications using thiol/Au-based capture molecules. Full article

Small molecule inhibitors that target the E3 ligase activity of MDM2-MDM4 have been explored to inhibit the oncogenic activity of MDM2-MDM4 complex. MMRi62 is a small molecule that was identified using an MDM2-MDM4 E3 ligase-based high throughput screen and a cell-death-based secondary screen. Our previous studies showed that MMRi62 promotes MDM4 degradation in cells and induces p53-independent apoptosis in cancer cells. However, MMRi62 activity in solid tumor cells such as melanoma cells, especially in BRAF inhibitor resistant melanoma cells, have not been explored. Although its promotion of MDM4 degradation is clear, the direct MMRi62 targets in cells are unknown. In this report, we show that MMRi62 is a much more potent p53-independent apoptosis inducer than conventional MDM2 inhibitors in melanoma cells. A brief structure-activity study led to development of SC-62-1 with improved activity. SC-62-1 potently inhibits and eliminates clonogenic growth of melanoma cells that acquired resistance to BRAF inhibitors. We developed a pair of active and inactive SC-62-1 probes and profiled the cellular targets of SC-62-1 using a chemical biology approach coupled with IonStar/nano-LC/MS analysis. We found that SC-62-1 covalently binds to more than 15 hundred proteins in cells. Pathways analysis showed that SC-62-1 significantly altered several pathways including carbon metabolism, RNA metabolism, amino acid metabolism, translation and cellular response to stress. This study provides mechanistic insights into the mechanisms of action for MMRi62-like quinolinols. This study also suggests multi-targeting compounds like SC-62-1 might be useful for overcoming resistance to BRAF inhibitors for improved melanoma treatment. Full article

Negative air ions (NAIs) can purify the atmosphere and maintain human health. In this study, we selected six tree species, Pinus tabuliformis, Pinus bungeana, Acer truncatum, Sophora japonica, Koelreuteria paniculata, Quercus variabilis, Robinia pseudoacacia, and Populus tomentosa, and we established for the first time five “capacity indicators” to characterize and judge the capacity of plants to release negative ions: they comprised the release contribution rate L, release coefficient n, release rate s, instantaneous current number v, and total level of release Z. These indicators were used to assess the ability of the plants to release NAIs by themselves. The results showed the following. (1) The daily variations in L and n show “W” and “concave” shapes, respectively, and the contribution capacity at night is significantly higher than that during the day. The diurnal variations in s, v, and Z all showed a “bimodal” pattern. The NAI release rate and release level of each tree species during the day were significantly higher than those at night. (2) The trees released the most NAIs during the day at approximately 10:00, while Robinia pseudoacacia and Populus tomentosa peaked with a 2 h lag (12:00). The NAI release capacity of each tree species was the worst at 13:00. (3) During the growing season, the self-contribution effects L and n of the plants were the strongest in May. The release rates and release levels s, v, and Z were the lowest in August. The coniferous plants released NAIs at the fastest rate in September and broad-leaved plants in July, with the highest release levels. In this study, the plants released the most NAIs from 10:00 a.m. to 11:00 a.m., which is the best time to travel. Quercus variabilis was preferentially recommended in the pairing of species of tree with the quickest NAI release and the highest total number released, followed by Koelreuteria paniculata and Sophora japonica. Full article

The recovery of radiation damage induced by 231-MeV xenon ions with varying fluence (from 5 × 10¹¹ to 2 × 10¹⁴ cm⁻²) in α-Al₂O₃ (corundum) single crystals has been studied by means of isochronal thermal annealing of radiation-induced optical absorption (RIOA). The integral of elementary Gaussians (product of RIOA spectrum decomposition) OK has been considered as a concentration measure of relevant oxygen-related Frenkel defects (neutral and charged interstitial-vacancy pairs, F-H, F⁺-H⁻). The annealing kinetics of these four ion-induced point lattice defects has been modelled in terms of diffusion-controlled bimolecular recombination reactions and compared with those carried out earlier for the case of corundum irradiation by fast neutrons. The changes in the parameters of interstitial (mobile component in the recombination process) annealing kinetics—activation energy E and pre-exponential factor X—in ion-irradiated crystals are considered. Full article