Development of a UHPLC-MS/MS method for the quantification of Pristinamycin â A and â ¡A in beagle dog plasma and its pharmacokinetic application.

The aim of this study was to develop and fully validate a sensitive and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous quantification of pristinamycin ⅠA (PⅠA) and pristinamycin ⅡA (PⅡA) in plasma of beagle dogs after oral administration of pristinamycin tablets. PⅠA, PⅡA and quinupristin (internal standard, IS) were separated on an Agilent Eclipse Plus C18 column (2.1 mm × 100 mm, 3.5 µm particle size) by using gradient elution consisting of methanol and water (0.1 % formic acid) at a flow rate of 0.4 mL/min in 4.0 min. Multiple reaction monitoring (MRM) mode was performed to quantify data under monitoring precursor-product ion transitions of m/z 867.6→134.1, 548.4→287.1 and 1022.7→133.9 for PⅠA, PⅡA and IS at positive ion mode, respectively. The method was developed at linearity ranging from 1.0 to 1000 ng/mL for all analytes.The accuracy of PⅠA and PⅡA was observed to range between -10.6 % and 7.1 %, while the precision was found to be within 8.9 %. No significant matrix effect was observed. PⅠA and PⅡA demonstrated stability during sample storage, preparation and analytic procedures. Furthermore, this method was successfully applied in the investigation of the pharmacokinetic profile of PⅠA and PⅡA in beagle dogs after oral administration of pristinamycin tablets (75 mg for PⅠA and 175 mg for PⅡA). The biological half-life (t1/2) was determined to be 1.75 ± 0.07 h and 1.44 ± 0.31 h for PⅠA and PⅡA, respectively. The areas under curves (AUC0-t) of PⅠA and PⅡA were 80.7 ± 24.6 and 230 ± 94.8 µg/L·h, respectively.

Antibacterial Hydrogels for Wound Dressing Applications: Current Status, Progress, Challenges, and Trends.

Bacterial infection treatment for chronic wounds has posed a major medical threat and challenge. Bacteria at the wounded sites can compete with the immune system and subsequently invade live tissues, leading to more severe tissue damage. Therefore, there is an urgent demand for wound dressings with antibacterial and anti-inflammatory properties. Considering the concept of moist healing, hydrogels with a three-dimensional (3D) network structure are widely used as wound dressings due to their excellent hydrophilicity, water retention properties, and biocompatibility. Developing antibacterial hydrogels for the treatment of infected wounds has been receiving extensive attention recently. This article categorizes antibacterial hydrogels according to their materials and antibacterial modes, and introduces the recent findings and progress regarding their status. More importantly, with the development of emerging technologies, new therapies are utilized to prepare antibacterial hydrogels such as nanoenzymes, photothermal therapy (PTT), photodynamic therapy (PDT), metal-organic frameworks (MOFs), and other external stimuli-responsive methods. Therefore, this review also examines their progress, challenges, and future trends as wound dressings. In the following studies, there will still be a focus on antibacterial hydrogels that have a high performance, multi-functions, and intelligence, especially biocompatibility, a high and long-lasting antibacterial property, responsiveness, and on-demand therapeutic ability.

Ten Thousand Recaptures of a Single DNA Molecule in a Nanopore and Variance Reduction of Translocation Characteristics.

Nanopores have emerged as highly sensitive biosensors operating at the single-molecule level. However, the majority of nanopore experiments still rely on averaging signals from multiple molecules, introducing systematic errors. To overcome this limitation and obtain accurate information from a single molecule, the molecular ping-pong methodology provides a precise approach involving repeated captures of a single molecule. In this study, we have enhanced the molecular ping-pong technique by incorporating a customized electronic system and control algorithm, resulting in a recapture number exceeding 10,000. During the ping-pong process, we observed a significant reduction in the variance of translocation characteristics, providing fresh insights into single-molecule translocation dynamics. An inhomogeneous translocation velocity of folded DNA has been revealed, illustrating a strong interaction between the molecule and the solid-state nanopore. The results not only promise heightened experimental efficiency with reduced sample volume but also increase the precision in statistical analysis of translocation events, marking a significant stride toward authentic single-molecule nanopore sensing.

Management of Triplet States in Modified Mononuclear Ruthenium(II) Complexes for Enhanced Photocatalysis.

Controlling the interplay between relaxation and charge/energy transfer processes in the excited states of photocatalysts is crucial for the performance of artificial photosynthesis. Metal-to-ligand charge-transfer triplet states (3MLCT*) of ruthenium(II) complexes are broadly implemented for photocatalysis, but an effective means of managing the triplets for enhanced photocatalysis has been lacking. Herein, We proposed a strategy to considerably prolong the triplet excited-state lifetime by decorating a ruthenium(II) phosphine complex (RuP-1) with pendent polyaromatic hydrocarbons (PAHs). Systematic studies demonstrate that in RuP-4 decorated with anthracene, sub-picosecond electron transfer from anthracene to 3MLCT* leads to a charge-separated state that can mediate the formation of the intra-ligand triplet state (3IL) of anthracene, resulting in an exceptionally long excited-state up to several milliseconds. This triplet management strategy enables impressive photocatalytic reduction of CO2 to CO with a turnover number (TON) of 404, an optimized quantum yield of 43 % and 100 % selectivity, which is the highest reported performance for mononuclear photocatalysts without additional photosensitizers. RuP-4 also catalyzes photochemical hydrogen generation under argon. This work opens up an avenue for regulating the excited-state charge/energy flow for the development of long-lived 3IL multi-functional mononuclear photocatalysts to boost artificial photosynthesis.

Earth-abundant Zn-dipyrrin chromophores for efficient CO2 photoreduction.

The development of strong sensitizing and Earth-abundant antenna molecules is highly desirable for CO2 reduction through artificial photosynthesis. Herein, a library of Zn-dipyrrin complexes (Z-1-Z-6) are rationally designed via precisely controlling their molecular configuration to optimize strong sensitizing Earth-abundant photosensitizers. Upon visible-light excitation, their special geometry enables intramolecular charge transfer to induce a charge-transfer state, which was first demonstrated to accept electrons from electron donors. The resulting long-lived reduced photosensitizer was confirmed to trigger consecutive intermolecular electron transfers for boosting CO2-to-CO conversion. Remarkably, the Earth-abundant catalytic system with Z-6 and Fe-catalyst exhibits outstanding performance with a turnover number of >20 000 and 29.7% quantum yield, representing excellent catalytic performance among the molecular catalytic systems and highly superior to that of noble-metal photosensitizer Ir(ppy)2(bpy)+ under similar conditions. Experimental and theoretical investigations comprehensively unveil the structure-activity relationship, opening up a new horizon for the development of Earth-abundant strong sensitizing chromophores for boosting artificial photosynthesis.

Sensing the DNA-mismatch tolerance of catalytically inactive Cas9 via barcoded DNA nanostructures in solid-state nanopores.

Single-molecule quantification of the strength and sequence specificity of interactions between proteins and nucleic acids would facilitate the probing of protein-DNA binding. Here we show that binding events between the catalytically inactive Cas9 ribonucleoprotein and any pre-defined short sequence of double-stranded DNA can be identified by sensing changes in ionic current as suitably designed barcoded linear DNA nanostructures with Cas9-binding double-stranded DNA overhangs translocate through solid-state nanopores. We designed barcoded DNA nanostructures to study the relationships between DNA sequence and the DNA-binding specificity, DNA-binding efficiency and DNA-mismatch tolerance of Cas9 at the single-nucleotide level. Nanopore-based sensing of DNA-barcoded nanostructures may help to improve the design of efficient and specific ribonucleoproteins for biomedical applications, and could be developed into sensitive protein-sensing assays.

DNA Carrier-Assisted Molecular Ping-Pong in an Asymmetric Nanopore.

Nanopore analysis relies on ensemble averaging of translocation signals obtained from numerous molecules, requiring a relatively high sample concentration and a long turnaround time from the sample to results. The recapture and subsequent re-reading of the same molecule is a promising alternative that enriches the signal information from a single molecule. Here, we describe how an asymmetric nanopore improves molecular ping-pong by promoting the recapture of the molecule in the trans reservoir. We also demonstrate that the molecular recapture could be improved by linking the target molecule to a long DNA carrier to reduce the diffusion, thereby achieving over 100 recapture events. Using this ping-pong methodology, we demonstrate its use in accurately resolving nanostructure motifs along a DNA scaffold through repeated detection. Our method offers novel insights into the control of DNA polymer dynamics within nanopore confinement and opens avenues for the development of a high-fidelity DNA detection platform.

Effect of Fabric Substrate and Introduction of Silk Fibroin on the Structural Color of Photonic Crystals.

Monodispersed polystyrene (PS) particles were prepared and deposited onto various kinds of textile fabrics using a gravity sedimentation method. The monodispersed PS particles were self-assembled on fabrics to form a photonic crystal, which has an iridescent structural color. The structural color of fabrics was determined by the bandgaps of photonic crystals. Moreover, the effect of the fabric substrate, including the raw materials, base color, and fabric weave, etc., on the structural color of the photonic crystals was studied. Scanning electron microscopy and UV-vis spectrometry were adopted to characterize the structure and optical performance of photonic crystals. The results indicate that the silk fabric with a black base color and satin weave contribute to a bright and pure textile structural color. In order to solve the problem of low color fastness of the structural color on the fabric surface, silk fibroin (SF) was introduced to the PS microsphere solution. Results show that the addition of SF slightly affects the brightness of the structural color, while it has a certain reinforcing effect on the structural color fastness to rubbing and washing.

The Optimized Preparation Conditions of Cellulose Triacetate Hollow Fiber Reverse Osmosis Membrane with Response Surface Methodology.

Reverse osmosis (RO) membrane materials play a key role in determining energy consumption. Currently, CTA is regarded as having one of the highest degrees of chlorine resistance among materials in the RO process. The hollow fiber membrane has the advantages of a large membrane surface area and a preparation process without any redundant processes. Herein, response surface methodology with Box-Behnken Design (BBD) was applied for optimizing the preparation conditions of the cellulose triacetate (CTA) hollow fiber RO membrane. There were four preparation parameters, including solid content, spinning temperature, post-treatment temperature, and post-treatment time, which could affect the permeability of the membrane significantly. In this study, the interaction between preparation parameters and permeability (permeate flux and salt rejection) was evaluated by regression equations. Regression equations can be applied to obtain the optimized preparation parameters of hollow fiber RO membranes and reasonably predict and optimize the permeability of the RO membranes. Finally, the optimized preparation conditions were solid content (44%), spinning temperature (167 °C), post-treatment temperature (79 °C), and post-treatment time (23 min), leading to a permeability of 12.029 (L·m-2·h-1) and salt rejection of 90.132%. This study of reinforced that CTA hollow fiber membrane may promote the transformation of the RO membrane industry.

Simultaneous identification of viruses and viral variants with programmable DNA nanobait.

Respiratory infections are the major cause of death from infectious disease worldwide. Multiplexed diagnostic approaches are essential as many respiratory viruses have indistinguishable symptoms. We created self-assembled DNA nanobait that can simultaneously identify multiple short RNA targets. The nanobait approach relies on specific target selection via toehold-mediated strand displacement and rapid readout via nanopore sensing. Here we show that this platform can concurrently identify several common respiratory viruses, detecting a panel of short targets of viral nucleic acids from multiple viruses. Our nanobait can be easily reprogrammed to discriminate viral variants with single-nucleotide resolution, as we demonstrated for several key SARS-CoV-2 variants. Last, we show that the nanobait discriminates between samples extracted from oropharyngeal swabs from negative- and positive-SARS-CoV-2 patients without preamplification. Our system allows for the multiplexed identification of native RNA molecules, providing a new scalable approach for the diagnostics of multiple respiratory viruses in a single assay.

Organic solvent-free constructing of stable zeolitic imidazolate framework functional layer enhanced by halloysite nanotubes and polyvinyl alcohol on polyvinylidene fluoride hollow fiber membranes for treating dyeing wastewater.

In this study, zeolitic imidazolate framework (ZIF-8)/polyvinylidene fluoride (PVDF) loose nanofiltration (NF) hollow fiber membranes were fabricated by constructing ZIF-8 functional layer on the PVDF supporting membranes based on the vacuum-assisted assembly process. The ZIF-8 synthesis was completed in a water system, and the synthesized ZIF-8 suspension was directly added to polyvinyl alcohol (PVA) and halloysite nanotubes (HNTs) aqueous solution system without drying to prepare the casting solution, which could solve the agglomeration and poor dispersion problem of ZIF-8 particles. In addition, the embedded HNTs and the loaded PVA among the ZIF-8 layer could improve the bonding strength between the ZIF-8 layer and the supporting membranes. After constructing ZIF-8 functional layer, the pore size of supporting membranes decreased from more than 300 nm to several nanometers. Furthermore, the water contact angle reduced from 91.1° to 54.2°. Applied to treat dye wastewater, the prepared ZIF-8/PVDF membranes maintained high dye rejection (˃99.0 %) for Congo red (CR), but low salt rejection for NaCl (about 2 %). In addition, the flux could reach 21.6 L m-2h-1 after continuous filtration 360 min, exhibiting a potential for treating the dye/salt wastewater. In particular, there were no organic solvents used in the work, which provided a promising idea for solvent-free fabrication of loose NF membranes.

Super-Resolution Detection of DNA Nanostructures Using a Nanopore.

High-resolution analysis of biomolecules has brought unprecedented insights into fundamental biological processes and dramatically advanced biosensing. Notwithstanding the ongoing resolution revolution in electron microscopy and optical imaging, only a few methods are presently available for high-resolution analysis of unlabeled single molecules in their native states. Here, label-free electrical sensing of structured single molecules with a spatial resolution down to single-digit nanometers is demonstrated. Using a narrow solid-state nanopore, the passage of a series of nanostructures attached to a freely translocating DNA molecule is detected, resolving individual nanostructures placed as close as 6 nm apart and with a surface-to-surface gap distance of only 2 nm. Such super-resolution ability is attributed to the nanostructure-induced enhancement of the electric field at the tip of the nanopore. This work demonstrates a general approach to improving the resolution of single-molecule nanopore sensing and presents a critical advance towards label-free, high-resolution DNA sequence mapping, and digital information storage independent of molecular motors.

A two-sample mendelian randomization analysis excludes causal relationships between non-alcoholic fatty liver disease and kidney stones.

Objectives: Non-alcoholic fatty liver disease (NAFLD) has been linked to an increased risk of kidney stones in prior observational studies, However, the results are inconsistent, and the causality remains to be established. We aimed to investigate the potential causal relationship between NAFLD and kidney stones using two-sample Mendelian randomization (MR). Methods: Genetic instruments were used as proxies for NAFLD. Summary-level data for the associations of exposure-associated SNPs with kidney stones were obtained from the UK Biobank study (6536 cases and 388,508 controls) and the FinnGen consortium (9713 cases and 366,693 non-cases). MR methods were conducted, including inverse variance weighted method (IVW), MR-Egger, weighted median, and MR-PRESSO. MR-Egger Regression Intercept and Cochran's Q test were used to assess the directional pleiotropy and heterogeneity. Results: cALT-associated NAFLD did not exhibit an association with kidney stones in the Inverse variance weighted (IVW) methods, in both the FinnGen consortium (OR: 1.02, 95%CI: 0.94-1.11, p = 0.632) and the UKBB study (OR: 1.000, 95%CI: 0.998-1.002, p = 0.852). The results were consistent in European ancestry (FinnGen OR: 1.05, 95%CI: 0.98-1.14, p = 0.144, UKBB OR: 1.000, 95%CI: 0.998-1.002, p = 0.859). IVW MR analysis also did not reveal a significant causal relationship between NAFLD and the risk of kidney stone for the other three NAFLD-related traits, including imaging-based, biopsy-confirmed NAFLD, and more stringent biopsy-confirmed NAFLD. The results remained consistent and robust in the sensitivity analysis. Conclusions: The MR study did not provide sufficient evidence to support the causal associations of NAFLD with kidney stones.

Broadband and strong visible-light-absorbing cuprous sensitizers for boosting photosynthesis.

Rational construction of broadband and strong visible-light-absorbing (BSVLA) earth-abundant complexes is of great importance for efficient and sustainable solar energy utilization. Herein, we explore a universal Cu(I) center to couple with multiple strong visible-light-absorbing antennas to break the energy level limitations of the current noble-metal complexes, resulting in the BSVLA nonprecious complex (Cu-3). Systematic investigations demonstrate that double "ping-pong" energy-transfer processes in Cu-3 involving resonance energy transfer and Dexter mechanism enable a BSVLA between 430 and 620 nm and an antenna-localized long-lived triplet state for efficient intermolecular electron/energy transfer. Impressively, Cu-3 exhibited an outstanding performance for both energy- and electron-transfer reactions. Pseudo-first-order rate constant of photooxidation of 1,5-dihydroxynaphthalene with Cu-3 can achieve a record value of 190.8 × 10-3 min-1 among the molecular catalytic systems, over 30 times higher than that with a noble-metal photosensitizer (PS) [Ru(bpy)3]2+. These findings pave the way to develop BSVLA earth-abundant PSs for boosting photosynthesis.

Design of Robust FEP Porous Ultrafiltration Membranes by Electrospinning-Sintered Technology.

Perfluoropolymer membranes are widely used because of their good environmental adaptability. Herein, the ultrafine fibrous FEP porous membranes were fabricated with electrospinning-sintered technology. The effects of PVA content and sintering temperature on the fabricated membranes' morphologies and properties were investigated. The results indicate that a kind of dimensionally stable network structure was formed in the obtained ultrafine fibrous FEP porous membranes after sintering the nascent ultrafine fibrous FEP/PVA membranes. The optimal sintering conditions were obtained by comparing the membranes' performance in terms of membrane morphology, hydrophobicity, mechanical strength, and porosity. When the sintering temperature was 300 °C for 10 min, the porosity, water contact angle, and liquid entry pressure of the membrane were 62.7%, 124.2° ± 2.1°, and 0.18 MPa, respectively. Moreover, the ultrafine fibrous FEP porous membrane at the optimal sintering conditions was tested in vacuum membrane distillation with a permeate flux of 15.1 L·m-2·h-1 and a salt rejection of 97.99%. Consequently, the ultrafine fibrous FEP porous membrane might be applied in the seawater desalination field.

Simple Fabrication of Polyvinylidene Fluoride/Graphene Composite Membrane with Good Lipophilicity for Oil Treatment.

Graphene (GE) is an emerging type of two-dimensional functional nanoparticle with a tunable passageway for oil molecules. Herein, polyvinylidene fluoride (PVDF)/GE composite membranes with controllable pore structure were fabricated with a simple non-solvent-induced phase separation method. The change of crystallinity and crystal structure (α, ß, γ, etc.) generated is due to the addition of GE, which benefits the design of a suitable pore structure for oil channels. Meanwhile, the hydrophobicity and thermal stability of the composite membrane were obviously enhanced. With 3 wt % GE, the contact angle was 124.6°, which was increased greatly compared to that of the GE-0 sample. Moreover, the rate of the phase transition process was affected by the concentration of casting solution, temperature, and composition of the coagulation bath. For example, the composite membrane showed better oil-water separation properties when the coagulation bath was dioctyl phthalate. In particular, the oil flux and separation efficiencies were up to 2484.08 L/m2·h and 99.24%, respectively. Consequently, PVDF/GE composite membranes with excellent lipophilicity may have good prospects for oily wastewater treatment.

Safety, efficacy and biomarkers analysis of mesenchymal stromal cells therapy in ARDS: a systematic review and meta-analysis based on phase I and II RCTs.

BACKGROUND: Mesenchymal stromal cells (MSCs) therapy for acute respiratory distress syndrome (ARDS) is an emerging treatment, but most of the current trials of MSCs stay in the animal experimental stage, and the safety and efficacy of MSCs in clinical application are not clear. We aimed to analyze the safety, efficacy and biomarkers of mesenchymal stromal cells in the treatment of ARDS. METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of science, CNKI, VIP and Wan Fang data, studies published between database inception and Mar 17, 2022. All randomized controlled trials (RCT) of stem cell interventions for ARDS were included, without language or date restrictions. We did separate meta-analyses for mortality, subjects with adverse events (AEs) and subjects with serious adverse events (SAEs). Since the trials data are dichotomous outcomes, the odds ratio (OR) is adopted for meta-analysis. The quality of the evidence was assessed with the Cochrane risk of bias tool. FINDINGS: In total, 5 trials involving 171 patients with ARDS were included in this meta-analysis. A total of 99 individuals were randomly assigned to receive MSCs treatment, and 72 were randomly assigned to receive placebo treatment. Treatment with MSCs appeared to increase the occurrence of adverse events, but this result was not statistically significant (OR, 1.58; 95%CI, 0.64-3.91; P = 0.32). The occurrence of serious adverse events was lower in the MSCs group than in the placebo group (OR, 0.57; 95%CI, 0.14-2.32; P = 0.43); there seems to be no significant difference between the two groups in terms of 28 days mortality (OR, 0.93; 95%CI, 0.45-1.89); oxygenation index and biomarkers showed a tendency to improve in treatment, but there was a lack of more statistically significant clinical evidence to support them. INTERPRETATION: Based on the current clinical trials, MSCs intervention has some safety for ARDS patients, but its effectiveness and predictive value of airspace biomarkers need to be determined by more large-scale, standard randomized controlled trials.

Lifetime of glass nanopores in a PDMS chip for single-molecule sensing.

Nanopore sensing is an emerging technology that has many biosensing applications ranging from DNA sequencing using biological pores to biomolecular analysis using solid-state pores. Solid-state nanopores that are more stable are an attractive choice for biosensing applications. Still, biomolecule interactions with the nanopore surface reduce nanopore stability and increase usage costs. In this study, we investigated the biosensing capability for 102 quartz glass nanopores with a diameter of 11-18 nm that were fabricated using laser-assisted capillary pulling. Nanopores were assembled into multiple microfluidic chips that were repeatedly used for up to 19 weeks. We find that using vacuum storage combined with minimal washing steps improved the number of use cycles for nanopores. The single-molecule biosensing capability over repeated use cycles was demonstrated by quantitative analysis of a DNA carrier designed for detection of short single-stranded DNA oligonucleotides.

A Stretchable Expanded Polytetrafluorethylene-Silicone Elastomer Composite Electret for Wearable Sensor.

Soaring developments in wearable electronics raise an urgent need for stretchable electrets. However, achieving soft electrets simultaneously possessing excellent stretchability, longevity, and high charge density is still challenging. Herein, a facile approach is proposed to prepare an all-polymer hybrid composite electret based on the coupling of elastomer and ePTFE membrane. The composite electrets are fabricated via a facile casting and thermal curing process. The obtained soft composite electrets exhibit constantly high surface potential (-0.38 kV) over a long time (30 days), large strain (450%), low hysteresis, and excellent durability (15,000 cycles). To demonstrate the applications, the stretchable electret is utilized to assemble a self-powered flexible sensor based on the electrostatic induction effect for the monitoring of human activities. Additionally, output signals in the pressure mode almost two orders of magnitude larger than those in the strain mode are observed and the sensing mechanism in each mode is investigated.