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Objective To develop liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the content determination of voriconazole (VRCZ) and its N-oxide (VNO) in human plasma, and to apply it to clinical samples. Methods Ketoconazole was used as the internal standard (IS). The plasma samples were treated with methanol to precipitate protein and analyzed by HPLC-MS/MS. The detection was accomplished with electrospray ionization (ESI) operated in positive ionization mode, and ion reaction pairs were selected to be m/z350.1→m/z127.0 (VRCZ), m/z366.1→m/z224.0 (VNO) and m/z531.0→m/z82.1 (Ketoconazole). Chromatographic separation had been achieved on Inertsil ODS-3 (50/2.1) with methanol-10 mmol/L ammonium acetate (90:10) as the mobile phase. Plasma concentrations of VRCZ and VNO in 23 patients were determined. Results Both VRCZ and VNO were linear (r>0.999) over the concentration ranges of 0.4~10.0 μg/mL, inter- and intra-batch relative standard deviations (RSDs) and matrix effect were all less than 15%. The 2 compounds remained stable during sample storage and handling progress. Plasma concentrations of VRCZ in 23 patients ranged from 0.4 to 14.3 μg/mL, and those of VNO ranged from 0.5 to 7.2 μg/mL. Significant variance was found among these patients. Conclusion LC-MS/MS is simple, quick and sensitive for detection of VRCZ and VNO, and can be used for drug monitoring in clinical practice.

The blood-brain barrier (BBB) remains a formidable obstacle in medicine, preventing efficient penetration of chemotherapeutic and diagnostic agents to malignant gliomas. Here, a transactivator of transcription (TAT) peptide-modified gold nanoparticle platform (TAT-Au NP) with a 5 nm core size is demonstrated to be capable of crossing the BBB efficiently and delivering cargoes such as the anticancer drug doxorubicin (Dox) and Gd(3+) contrast agents to brain tumor tissues. Treatment of mice bearing intracranial glioma xenografts with pH-sensitive Dox-conjugated TAT-Au NPs via a single intravenous administration leads to significant survival benefit when compared to the free Dox. Furthermore, it is demonstrated that TAT-Au NPs are capable of delivering Gd(3+) chelates for enhanced brain tumor imaging with a prolonged retention time of Gd(3+) when compared to the free Gd(3+) chelates. Collectively, these results show promising applications of the TAT-Au NPs for enhanced malignant brain tumor therapy and non-invasive imaging.

Photothermal applications, such as therapy, imaging, and catalysis, necessitate heat sources capable of generating high temperatures under mid‐infrared (mid‐IR) illumination. However, commonly used metal nanostructures suffer from low efficiency due to their high carrier concentrations, resulting in shallow surface heating and optical range restrictions. To overcome these limitations, this work proposes a novel approach employing materials that support phonon polaritons (PhPs) as a promising paradigm for light‐controllable heat sources. The theoretical demonstration reveals that hexagonal boron nitride (hBN) nanorods can produce up to 46 times more heat compared to plasmonic gold counterparts under resonant monochromatic light. This superior heating capability stems from the unique properties of PhPs, which enable stronger field confinement and deeper penetration within the nanostructure, leading to higher efficiency by circumventing the electrostatic shielding effect associated with plasmonic heating. Furthermore, this work demonstrates that the heating performance of hBN antennas can be optimized by manipulating their size, geometry, and material loss. Notably, the use of isotopically pure hBN can triple the heat power. These findings highlight the tremendous potential of hBN antennas as light‐controllable heat sources, opening up new possibilities for IR photothermal applications by harnessing materials that support PhPs. [ABSTRACT FROM AUTHOR]

The study was to establish a method for the simultaneous determination of six growth promoting antibacterial agents in premixes by ultra-high performance liquid chromatography. An acetonitrile-0.25% formic acid aqueous solution (50: 50) was used as the solvent, and the samples were pretreated by ultrasonic extraction. A 0.05 mol/L ammonium formate aqueous solution (pH value adjusted to 3.8 with formic acid)-acetonitrile was used as the mobile phase, and the samples were separated by gradient elution and C18 column. The results showed that the detection limit of six antibacterial agents was 1~10 mg/g. In the range of 2~100 mg/g of the added concentration, the peak areas of the main components of the six growth promoting antibacterial agents detected by the method had a good linear relationship, and the correlation coefficient R2 was 0.999 4~1.000 0. The average recoveries of six antibacterial agents were 92.2%~104.6%. The study indicates that the proposed method is efficient, reliable and sensitive, which can be used for the detection of growth promoting antibacterial agents in premixes. [ABSTRACT FROM AUTHOR]

Methylation of adenosine at N1 position yields N1-methyladenosine (m1A), which is an epitranscriptomic modification that regulates mRNA metabolism. Recent studies showed that altered m1A methylation promotes acute and chronic neurological diseases. We currently evaluated the effect of focal ischemia on cerebral m1A methylome and its machinery. Adult male C57BL/6J mice were subjected to transient middle cerebral artery occlusion, and the peri-infarct cortex was analyzed at 12 h and 24 h of reperfusion. The bulk abundance of m1A was measured by mass spectrometry and dot blot, and transcriptome-wide m1A alterations were profiled using antibody-independent m1A-quant-seq. Expression of the m1A writers and erasers was estimated by real-time PCR. Ischemia significantly decreased m1A levels and concomitantly upregulated m1A demethylase alkB homolog 3 at 24 h of reperfusion compared to sham. Transcriptome-wide profiling showed differential m1A methylation at 14 sites (8 were hypo- and 6 were hypermethylated). Many of those are located in the 3′-UTRs of unannotated transcripts proximal to the genes involved in regulating protein complex assembly, circadian rhythms, chromatin remodeling, and chromosome organization. Using several different approaches, we show for the first time that m1A epitranscriptomic modification in RNA is highly sensitive to cerebral ischemia. [ABSTRACT FROM AUTHOR]

5′-18O labeled RNA oligos are important probes to investigate the mechanism of 2′-O-transphosphorylation reactions. Here we describe a general and efficient synthetic approach to the phosphoramidite derivatives of 5′-18O labeled nucleosides starting from the corresponding commercially available 5′-O-DMT protected nucleosides. Using this method, we prepared 5′-18O-guanosine phosphoramidite in 8 steps (13.2% overall yield), 5′-18O-adenosine phosphoramidite in 9 steps (10.1% overall yield) and 5′-18O-2′-deoxyguanosine phosphoramidite in 6 steps (12.8% overall yield). These 5′-18O labeled phosphoramidites can be incorporated into RNA oligos by solid phase synthesis for determination of heavy atom isotope effects in RNA 2′-O-transphosphorylation reactions. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of ginsenoside Rg3 (Rg3) in improving fatigue resistance and functionality of skeletal muscle mitochondria in rats at a simulated high altitude. Methods Forty adult male SD rats were randomly divided into 4 groups (n=10), namely the normal group (NG), Rg3-treated normal group (NG+Rg3), model group (MG), and Rg3-treated model group (MG+Rg3). In the latter 2 groups, the rats were exposed to a stimulated altitude of 5 000 m in a hypobaric chamber, and on a daily basis, the rats were taken from the chamber for intragastric administration of 20 mg/kg Rg3 (completed in 1 h). After 15 d of treatment, forced swimming test was performed and 30 min later blood samples were collected from the abdominal aorta for testing the levels of total cholesterol (TC), plasma triglyceride (TG), lactate dehydrogenase (LDH), blood glucose (GLU), blood ammonia (BA) and blood urea nitrogen (BUN); The quadriceps were quickly isolated for detecting malondialdehyde (MDA), Mn-superoxide dismutase (Mn-SOD) and the activity of compound Ⅲ and Ⅳ in the respiratory chain. Results Rg3 treatment significantly increased the swimming time (P < 0.05 or 0.01) and serum levels of TC, TG, LDH and GLU (P < 0.05 or 0.01) and enhanced Mn-SOD activity and mitochondrial respiratory chain complex Ⅲ and Ⅳ activities (P < 0.01) both in rats kept in normal conditions and in those exposed to the simulated high altitude. Rg3 also significantly decreased serum BUN level and MDA content in the skeletal muscle mitochondria in rats exposed to the simulated high altitude (P < 0.01). Conclusion Rg3 can extend forced swimming time, improve the biochemical indexes related to fatigue, and enhance free radical clearance and energy supply of skeletal muscle mitochondria of rats.

Objective To evaluate pharmacokinetics after administration of ranolazine sustained release tablets at a single and multiple dose to healthy Chinese volunteers. Methods A self-controlled trial design was used. In the single-time group, 10 healthy volunteers, half male and half female, were included, and 500, 1 000 and 1 500 mg ranolazine sustained-release tablets were taken sequentially in 3 cycles. For the multiple-dose group, 10 individuals of both sexes were enrolled, and 500 and 1 000 mg ranolazine sustained-release tablets were sequentially administered in 2 cycles. The concentration of ranolazine in plasma samples was determined by LC-MS-MS, and the main pharmacokinetic parameters were calculated. Results The linear concentration of ranolazine in plasma ranged from 40 to 4 000 μg/L, and the LLOQ was 40 μg/L. The intra-assay and inter-assay precision were less than 15%. After single dose, the main parameters in doses 500, 1 000, 1 500 mg were Cmax: 774±157, 1 818±554 and 2 762±1 099 μg/L, respectively; tmax: 4.9±1.8, 4.9±2.6 and 4.9±1.5 h, respectively; t1/2z: 8.2±6.8, 10.3±8.7 and 9.7±12.0 h, respectively; AUC0-t: 8 470±2 765, 20 936±6 957 and 32 554±17 780 μg·h/L, respectively. After multiple dose, the main parameters in doses 500, 1 000 mg were Cmaxss: 1 826±904 and 3 635±620 μg/L; Cminss: 1 022±3 and 2 282±163 μg/L; Cav: 1 253±634 and 2 615±536 μg/L; AUC0-t: 22 452±12 359 and 53 232±15 909 μg·h/L; MRT0-t: 8.7±2.3 and 10.6±2.6; RAUC: 3.11±2.60 and 2.86±1.54. Conclusion In a single administration trial, Cmax and AUC are increased proportionally to the dose, and there is a good linear relationship between the three doses. Multiple dose tests have found that ranolazine has a certain accumulation in the body.

The flow stress behavior of 5083 aluminum alloy was investigated under hot compression deformation at 523-723K,strain rates of 0.01-10s-1 and true strains of 0-0.7 with Gleeble-3800 thermal simulator. Based on the heat transfer effect on alloy deformation heat effect, the flow stress curves were corrected. The results show that influence of heat conduction can not be neglected and becomes more obvious with the increase of true strain. The corrected flow stress has little influence on the peak stress, but the steady flow stress softening trends to be diminished to some degree. The flow stress can be predicted by the Zener-Hollomon parameters in the constitutive equation. The corrected measured value exhibits a good agreement with the flow stress predicted by the constitutive equation, and the average relative error is only 5.21%.