Utility of cystatin C and serum creatinine-based glomerular filtration rate equations in predicting vancomycin clearance: A population pharmacokinetics analysis in elderly Chinese patients.

Renal function is an important factor affecting the pharmacokinetics of vancomycin. The renal function in elderly patients gradually decreases with age. An accurate estimated glomerular filtration rate (GFR) is essential in drug dosing. The study aimed to determine the most appropriate renal function estimation equations to describe vancomycin pharmacokinetics in elderly patients using population pharmacokinetic analysis. Data were obtained retrospectively from elderly patients aged ≥65 years who received vancomycin for infection from September 2016 to January 2022. Renal function was estimated using the Cockcroft-Gault equation (CG), Modification of Diet in Renal Disease equation (MDRD), three Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPIcys-scr , CKD-EPIscr , and CKD-EPIcys ) and two Berlin Initiative Study equations (BIS-1 and BIS-2). The CKD-EPIcys-scr and BIS-2 equations were based on cystatin C (Cys C) and serum creatinine (Scr). The others were based on Cys C or Scr. A nonlinear mixed effects model (NONMEM) was used to develop the population pharmacokinetic model. A total of 471 serum concentrations from 313 elderly patients were used to develop the population pharmacokinetic model. Weight and GFR were identified as significant covariates affecting the pharmacokinetics of vancomycin. Cys C and Scr-based GFR (CKD-EPIcys-scr and BIS-2) yielded significant improvement performance compared with the other equations in model building. The interindividual variability of CL was reduced from 49.4% to 23.6% and 49.4% to 23.7% in CKD-EPIcys-scr and BIS-2 based models, respectively. However, greater interindividual variabilities of CL (from 26.6% to 29.0%) were represented in the other five models which were based on either Cys C or Scr. The GFR estimated by EPIcys-scr and BIS-2 equations and vancomycin CL exhibited a good correlation (r = 0.834 and 0.833). In the external validation with 124 serum concentrations, the predictive performances of the CKD-EPIcys-scr and BIS-2 based models (the mean relative prediction errors were less than 1%, the mean relative absolute prediction errors were about 23%) were also superior to the other five models (the mean relative prediction errors were about 2%, the mean relative absolute prediction errors were greater than 25%) which are based on either Cys C or Scr. In this study, we determined that the equation used to estimate GFR can affect the population pharmacokinetic model fitting result. Population pharmacokinetics model with CKD-EPIcys-scr or BIS-2 can be used to optimize vancomycin dosage in elderly Chinese patients.

Impact of different genetic mutations on granulocyte development and G-CSF responsiveness in congenital neutropenia.

ABSTRACT: Congenital neutropenia (CN) is a genetic disorder characterized by persistent or intermittent low peripheral neutrophil counts, thus increasing susceptibility to bacterial and fungal infections. Various forms of CN, caused by distinct genetic mutations, exhibit differential responses to granulocyte colony-stimulating factor (G-CSF) therapy, with the underlying mechanisms not fully understood. This study presents an in-depth comparative analysis of clinical and immunological features in 5 CN patient groups (severe congenital neutropenia [SCN]1, SCN3, cyclic neutropenia [CyN], warts, hypogammaglobulinaemia, infections and myelokathexis [WHIM], and Shwachman-Bodian-Diamond Syndrome [SBDS]) associated with mutations in ELANE, HAX1, CXCR4, and SBDS genes. Our analysis led to the identification of 11 novel mutations in ELANE and 1 each in HAX1, CXCR4, and G6PC3 genes. Investigating bone marrow (BM) granulopoiesis and blood absolute neutrophil count after G-CSF treatment, we found that SCN1 and SCN3 presented with severe early-stage disruption between the promyelocyte and myelocyte, leading to a poor response to G-CSF. In contrast, CyN, affected at the late polymorphonuclear stage of neutrophil development, showed a strong G-CSF response. WHIM, displaying normal neutrophil development, responded robustly to G-CSF, whereas SBDS, with moderate disruption from the early myeloblast stage, exhibited a moderate response. Notably, SCN1 uniquely impeded neutrophil development, whereas SCN3, CyN, WHIM, and SBDS also affected eosinophils and basophils. In addition, SCN1, SCN3, and CyN presented with elevated serum immunoglobulins, increased BM plasma cells, and higher A Proliferation-Inducing Ligand levels. Our study reveals a strong correlation between the stage and severity of granulocyte development disruption and the efficacy of G-CSF therapy.

Supramolecular interactions between functional saccharide-based ionic liquids and cellulose macromolecules.

Interactions between polysaccharides and ionic liquids (ILs) at the molecular level are essential to elucidate the dissolution and/or plasticization mechanism of polysaccharides. Herein, saccharide-based ILs (SILs) were synthesized, and cellulose membrane was soaked in different SILs to evaluate the interactions between SILs and cellulose macromolecules. The relevant results showed that the addition of SILs into cellulose can effectively reduce the intra- and/or inter-molecular hydrogen bonds of polysaccharides. Glucose-based IL showed the intensest supramolecular interactions with cellulose macromolecules compared to sucrose- and raffinose-based ILs. Two-dimensional correlation and perturbation-correlation moving window Fourier transform infrared techniques were for the first time used to reveal the dynamic variation of the supramolecular interactions between SILs and cellulose macromolecules. Except for the typical HO⋯H interactions of cellulose itself, stronger -Cl⋯HO hydrogen bonding interactions were detected in the specimen of SILs-modified cellulose membranes. Supramolecular interactions of -Cl⋯H, HO⋯H, C-Cl⋯H, and -C=O⋯H between SILs and cellulose macromolecules sequentially responded to the stimuli of temperature. This work provides a new perspective to understanding the interaction mechanism between polysaccharides and ILs, and an avenue to develop the next-generation ILs for dissolving or thermoplasticizing polysaccharide materials.

Effect of UV/peroxymonosulfate pretreatment on disinfection byproduct (DBP) formation during post-chlorination of humic acid.

UV/peroxymonosulfate (UV/PMS) is a promising advanced oxidation technology in water treatment. This study aimed to investigate the impact of UV/PMS on humic acid (HA) and the influence of PMS dosage, pretreatment time, pH pretreatment, nitrate, nitrite, ammonium, and bicarbonate influencing factors on disinfection byproduct (DBP) formation during post-chlorination. With increased PMS dosage or pretreatment time, the UV/PMS treatment significantly reduced ultraviolet absorbance and increased mineralization. It altered the fractional constituent as humic substances were gradually transformed into building blocks and low-molecular-weight acids. However, most DBP formation increased initially and then decreased after subsequent chlorination. Rising nitrate or nitrite concentrations markedly promoted halonitromethane (HNM) formation. The presence of ammonia had a more significant impact on dichloroacetonitrile (DCAN) formation. Bicarbonate in UV/PMS pretreatment increased carbonated disinfection byproduct (C-DBP) formation, whereas it had a negligible impact on nitrogenous disinfection byproduct (N-DBP) formation. The present study revealed the impact of a series of influencing factors on DBP formation in UV/PMS reaction systems, providing comprehensive insights on applying UV/PMS in actual practice.

Photomechaelectric Nanogenerators with Different Photoisomers and Dipole Units for Harvesting UV Light Energy.

To date, transforming environmental energy into electricity through a non-mechanical way is challenging. Herein, a series of photomechaelectric (PME) polyurethanes containing azobenzene-based photoisomer units and ionic liquid-based dipole units are synthesized, and corresponding PME nanogenerators (PME-NGs) to harvest electricity are fabricated. The dependence of the output performance of PME-NGs on the structure of the polyurethane is evaluated. The results show that the UV light energy can directly transduce into alternating-current (AC) electricity by PME-NGs via a non-mechanical way. The optimal open-circuit voltage and short-circuit current of PME-NGs under UV illumination reach 17.4 V and 696 µA, respectively. After rectification, the AC electricity can be further transformed into direct-current (DC) electricity and stored in a capacitor to serve as a power system to actuate typical microelectronics. The output performance of PME-NGs is closely related to the hard segment content of the PME polyurethane and the radius of counter anions in the dipole units. Kelvin probe force microscopy is used to confirm the existence of the PME effect and the detailed mechanism about the generation of AC electricity in PME-NGs is proposed, referring to the back and forth drift of induced electrons on the two electrodes in contact with the PME polyurethanes.

MZB1-mediated IgA secretion suppresses the development and progression of colorectal cancer triggered by gut inflammation.

Colorectal cancer (CRC) ranks among the top causes of mortality globally. Gut inflammation is one crucial risk factor that augments CRC development since patients suffering from inflammatory bowel disease have an increased incidence of CRC. The role of immunoglobulin (Ig)A in maintaining gut homeostasis and preventing inflammation has been well established. Our earlier work demonstrated that the marginal zone and B1 cell-specific protein (MZB1) promotes gut IgA secretion and its absence results in pronounced dextran sulfate sodium salt (DSS)-induced colitis. In the present study, we explored the role of MZB1 in CRC development using the azoxymethane (AOM)/DSS-induced CRC model. We observed an increase in both the number and size of the tumor nodules in Mzb1-/- mice compared with Mzb1+/+ mice. The increase in CRC development and progression in Mzb1-/- mice was associated with reduced intestinal IgA levels, altered gut flora, and more severe gut and systemic inflammation. Oral administration of the monoclonal IgA, W27, alleviated both the gut inflammation and AOM/DSS-induced CRC. Notably, cohousing Mzb1+/+ and Mzb1-/- mice from the 10th day after birth led to similar CRC development. Our findings underscore the pivotal role of MZB1-mediated IgA secretion in suppressing the onset and progression of CRC triggered by gut inflammation. Moreover, our study highlights the profound impact of microbiota composition, modulated by gut IgA levels, on gut inflammation. Nonetheless, establishing a direct correlation between the severity of colitis and subsequent CRC development and the presence or absence of a particular microbiota is challenging.

The Extract of Pinellia Ternata-Induced Apoptosis of Leukemia Cells by Regulating the Expression of Bax, Bcl-2 and Caspase-3 Protein Expression in Mice.

The study aims to lessen the monetary burden on patients and society by decreasing the price of proprietary drugs used in leukemia therapy. Flow cytometry, reverse transcription polymerase chain reaction, western blot, and a patient-derived xenograft mouse model were used to confirm the therapeutic effect of Pinellia ternata extract on leukemia. Three types of leukemia cells (K562, HL-60, and C8166 cell lines) were found to undergo early apoptosis (P ≤ .05) after being exposed to P. ternata extract, as measured by flow cytometry. Reverse transcription polymerase chain reaction results showed that P. ternata extract at both middle (300 µg/mL) and high (500 µg/mL) concentrations was able to down-regulate Bcl-2 and upregulate mRNA expression of Bax and caspase-3. In the patient-derived xenograft mouse model formed by BALB/c-nu/nu nude mice, immunohistochemistry indicated that P. ternata extract effectively suppressed the proliferation of leukemia cells. Therefore, P. ternata extract at 300 µg/mL and 500 µg/mL could effectively inhibit myeloid and lymphocytic leukemia cell proliferation and promote leukemia cell apoptosis by regulating Bax/Bcl-2 and caspase-3.

Spectroscopy and efficient laser performances of a Tm,Ho:CaY0.9Lu0.1AlO4 crystal.

We report on the spectral properties and laser performances of a novel, to the best of our knowledge, Tm,Ho:CaY0.9Lu0.1AlO4 (Tm,Ho:CYLA) crystal. The polarized absorption spectra, luminescence spectra, and fluorescence lifetime are systematically investigated, presenting a broad and smooth luminescence band. Furthermore, a maximum continuous wave (CW) laser output power of 0.51 W at 2092 nm is obtained under an absorbed pump power of 2.89 W, corresponding to a slope efficiency of 20.4%. The beam quality factors (M2) are measured to be 1.04 in both the x and y axes. A tuning range of 123.4 nm, from 2017.8 nm to 2141.2 nm, is achieved in the CW regime by using a birefringent filter (BF). A stable passively Q switched Tm,Ho:CYLA laser employing Cr2+:ZnSe as a saturable absorber (SA) is realized for the first time, delivering the shortest pulse width of 560 ns with a transmittance of 1%. The results indicate that the Tm,Ho:CYLA crystal is an excellent laser medium for generating high-efficiency laser at ∼2 µm and has a potential in ultrafast laser generation.

Report from a randomized control trial: improved alignment between circadian biology and sleep-wake behavior as a mechanism of depression symptom improvement in evening-type adolescents with depressive symptoms.

STUDY OBJECTIVES: An evening circadian preference is common among adolescents. It is characterized by a behavioral predilection for later sleep and wake timing and is associated with higher rates of Major Depressive Disorder (MDD). The present study aims to (a) test the effectiveness of a cognitive behavioral sleep intervention (Transdiagnostic Sleep and Circadian Intervention; TranS-C) in a sample of adolescents with an evening circadian preference and clinically significant depressive symptoms and (b) evaluate improved alignment between circadian biology and sleep-wake behavior as a potential mechanism in the relationship between sleep and depression symptom improvement. METHODS: Adolescents with an evening circadian preference and clinically significant depressive symptoms were randomized to receive TranS-C (n = 24) or a psychoeducation condition (PE; n = 18). Alignment between circadian biology and sleep-wake behavior was measured using objective biological measurement. Measures of sleep and circadian rhythm were taken at pre- and posttreatment, and depression symptoms were measured at pre- and posttreatment and 6- and 12-month follow-up. RESULTS: Mixed effects modeling revealed that compared with an active control condition, TranS-C resulted in a significant reduction in MDD severity at 12-month follow-up. A MacArthur mediation analysis conducted to explore alignment between circadian biology and sleep-wake behavior as a mediator of depression severity reduction through 12-month follow-up revealed a significant interaction between change in alignment between circadian biology and sleep-wake behavior and treatment arm, indicating that improved alignment between circadian biology and sleep-wake behavior at posttreatment was associated with improvements in depression outcomes at 12-month follow-up under the treatment condition. CONCLUSIONS: These results provide novel evidence for improved alignment between circadian biology and sleep-wake behavior as a specific mechanism of depression improvement, provide key clues into the complex relationship between sleep and depression, and have significant clinical implications for adolescents with depression.

Theoretical and experimental investigation on rapid and efficient adsorption characteristics of microplastics by magnetic sponge carbon.

Microplastic pollution control has always been a thorny problem all over the world. Magnetic porous carbon materials have shown a good development prospect in microplastic adsorption due to their excellent adsorption performance and easy magnetic separation from water. However, the adsorption capacity and rate of magnetic porous carbon on microplastics are still not high, and the adsorption mechanism is not fully revealed, which hinders its further development. In this study, magnetic sponge carbon was prepared using glucosamine hydrochloride as the carbon source, melamine as the foaming agent, iron nitrate and cobalt nitrate as the magnetizing agents. Among them, Fe-doped magnetic sponge carbon (FeMSC) exhibited excellent adsorption performance for microplastics due to its sponge-like morphology (fluffy), strong magnetic properties (42 emu/g) and high Fe-loading (8.37 Atomic%). FeMSC could adsorb to saturation within 10 min, and the adsorption capacity of polystyrene (PS) reached as high as 369.07 mg/g in 200 mg/L microplastic solution, which was almost the fastest adsorption rate and highest adsorption capacity reported so far in the same condition. The performance of the material against external interference was also tested. FeMSC performed well in a wide pH range and different water quality, except in the strong alkaline condition. This is because the surface of microplastics and adsorbents will have many negative charges under strong alkalinity, significantly weakening the adsorption. Furthermore, theoretical calculations were innovatively used to reveal the adsorption mechanism at the molecular level. It was found that Fe-doping could form chemisorption between PS and the adsorbent, thereby significantly increasing the adsorption energy between the adsorbent and PS. The magnetic sponge carbon prepared in this study has excellent adsorption performance for microplastics and can be easily separated from water, which is a promising microplastic adsorbent.

B cell abnormalities and autoantibody production in patients with partial RAG deficiency.

Mutations in the recombination activating gene 1 (RAG1) and RAG2 in humans are associated with a broad spectrum of clinical phenotypes, from severe combined immunodeficiency to immune dysregulation. Partial (hypomorphic) RAG deficiency (pRD) in particular, frequently leads to hyperinflammation and autoimmunity, with several underlying intrinsic and extrinsic mechanisms causing a break in tolerance centrally and peripherally during T and B cell development. However, the relative contributions of these processes to immune dysregulation remain unclear. In this review, we specifically focus on the recently described tolerance break and B cell abnormalities, as well as consequent molecular and cellular mechanisms of autoantibody production in patients with pRD.

Fluorescence enhancement of surface plasmon coupled emission by Au nanobipyramids and its modulation effect on multi-wavelength radiation.

Surface plasmon coupled emission (SPCE), a novel surface-enhanced fluorescence technique, can generate directional and amplified radiation by the intense interaction between fluorophores and surface plasmons (SPs) of metallic nanofilms. For plasmon-based optical systems, the strong interaction between localized and propagating SPs and "hot spot" structures show great potential to significantly improve the electromagnetic (EM) field and modulate optical properties. Au nanobipyramids (NBPs) with two sharp apexes to enhance and restrict the EM field were introduced through electrostatic adsorption to achieve a mediated fluorescence system, and the emission signal enhancement was realized by factors over 60 compared with the normal SPCE. It has been demonstrated that the intense EM field produced by the NBPs assembly is what triggered the unique enhancement of SPCE by Au NBPs, which effectively overcomes the inherent signal quenching of SPCE for ultrathin sample detection. This remarkable enhanced strategy offers the chance to improve the detection sensitivity for plasmon-based biosensing and detection systems, and expand the range of applications for SPCE in bioimaging with more comprehensive and detailed information acquisition. The enhancement efficiency for various emission wavelengths was investigated in light of the wavelength resolution of SPCE, and it was discovered that enhanced emission for multi-wavelength could be successfully detected through the different emission angles due to the angular displacement caused by wavelength change. Benefit from this, the Au NBP modulated SPCE system was employed for multi-wavelength simultaneous enhancement detection under a single collection angle, which could broaden the application of SPCE in simultaneous sensing and imaging for multi-analytes, and expected to be used for high throughput detection of multi-component analysis.

[Wernekink Commissure Syndrome With Hallucinations and Involuntary Groping:Report of One Case].

Wernekink commissure syndrome is a rare midbrain syndrome with bilateral cerebellar dysfunction,eye movement disorder,and palatal myoclonus.Few cases of this syndrome have been reported in China,let alone those combined with hallucinations and involuntary groping.This paper reports the diagnosis and treatment of a case of Wernekink commissure syndrome with hallucinations and involuntary groping,aiming to enrich the knowledge about this disease for clinicians.

Diode-pumped mode-locked Yb:Sc2SiO5 laser generating 38 fs pulses.

We report on sub-40 fs pulse generation from a Yb:Sc2SiO5 laser pumped by a spatially single-mode fiber-coupled laser diode at 976 nm. A maximum output power of 545 mW was obtained at 1062.6 nm in the continuous-wave regime, corresponding to a slope efficiency of 64% and a laser threshold of 143 mW. A continuous wavelength tuning across 80 nm (1030 -1110 nm) was also achieved. Implementing a SESAM for starting and stabilizing the mode-locked operation, the Yb:Sc2SiO5 laser delivered soliton pulses as short as 38 fs at 1069.5 nm with an average output power of 76 mW at a pulse repetition rate of ∼79.8 MHz. The maximum output power was scaled to 216 mW for slightly longer pulses of 42 fs, which corresponded to a peak power of 56.6 kW and an optical efficiency of 22.7%. To the best of our knowledge, these results represent the shortest pulses ever achieved with any Yb3+-doped rare-earth oxyorthosilicate crystal.

Construction of interfacial crystallized oleogel emulsion with improved thermal stability.

In this study, we reported a facile strategy to produce an interfacial crystallized oleogel emulsion for improved thermal stability. The interfacial crystallization of ceramide (non-interfacial active oleogelator) was achieved by addition of a surface active compound, which was demonstrated by interfacial rheology tests and polarized light microscopy. For successfully prepared interfacial crystallized emulsions, smaller particle size was observed when the gelator concentration was lower. However, better thermal stability was achieved when oleogelator concentration was higher than 1 wt%. Results from differential scanning calorimetry, X-ray diffraction and Fourier transform infrared spectroscopy suggested that the interfacial adsorption of ceramide was due to its co-crystallization with the emulsifier driven by hydrogen bonds formed by multiple sites. It provided appropriate crystallinity and steric repulsion for oleogel emulsions against oil droplet coalescence during heating process. This strategy greatly enriches oleogel emulsion formulations and their potential applications in food products involved with thermal treatment.

A Review of the Regulatory Mechanisms of N-Myc on Cell Cycle.

Neuroblastoma has obvious heterogeneity. It is one of the few undifferentiated malignant tumors that can spontaneously degenerate into completely benign tumors. However, for its high-risk type, even with various intensive treatment options, the prognosis is still unsatisfactory. At the same time, a large number of research data show that the abnormal amplification and high-level expression of the MYCN gene are positively correlated with the malignant progression, poor prognosis, and mortality of neuroblastoma. In this context, this article explores the role of the N-Myc, MYCN gene expression product on its target genes related to the cell cycle and reveals its regulatory network in promoting tumor proliferation and malignant progression. We hope it can provide ideas and direction for the research and development of drugs targeting N-Myc and its downstream target genes.

A case report of hypertrophic olivine degeneration complicated with OSAHS exacerbation: Case report and retrospective analysis.

RATIONALE: Hypertrophic subolivine degeneration (HOD) was destroyed by Guillain-Mollaret triangle (GMT) due to various injuries, resulting in anterograde cavity-like degeneration of the lower olive nucleus. In addition, the brain stem is related to the muscle coordination of the upper respiratory tract. Obstructive sleep apnea hypopnea syndrome may affect the respiratory center due to the injury of the brain stem. Brain stem hemorrhage damage GMT, resulting in transsynaptic neuronal degeneration. Clinical manifestations can be complex, and enhanced magnetic resonance imaging can be helpful in distinguishing them. PATIENT CONCERNS: HOD is a self-limiting disease with no effective treatment and a long course of disease. Most patients can improve their symptoms after symptomatic treatment, and some patients can relieve their symptoms by themselves after 3 to 4 years. DIAGNOSIS INTERVENTIONS: The limbs wobble involuntarily. His clinical symptoms and signs are consistent with HOD. Imaging with a clear primary lesion confirmed HOD. After treatment with antiepileptic drugs, the patient's symptoms were relieved. Moreover, the patient had snoring and apnea, and respiratory sleep monitoring showed moderate obstructive sleep apnea hypopnea syndrome, which was treated with noninvasive ventilator. OUTCOMES: After treatment with antiepileptic drugs and noninvasive ventilator, the patient's symptoms were significantly relieved. LESSONS: HOD is a rare clinical disorder. Therefore, for similar patients, more attention should be paid to early diagnosis and treatment to avoid missed diagnosis, misdiagnosis and unnecessary intervention measures. The diagnosis can be confirmed by primary disease, clinical symptoms, and imaging based on GMT.

Enhanced ultrasonic spray ionization for direct mass spectrometry analysis of aqueous solution and complex samples using a single-orifice piezoelectric atomizer.

An efficient and superior soft ionization approach for direct mass spectrometry analysis of a variety of samples such as aqueous solution, raw biological sample and proteins, was developed based on commercially available piezoelectric atomizers. A single conical orifice (5 µm in diameter) was created on the atomizer, which resulted in generation of uniform fine droplets and long-duration of MS signal. The two electrodes of piezoelectric atomizer were connected to the two sides of ceramic ring which was insulated from the metallic substrate. The unique design allowed an additional high voltage input towards the spray reagents, which facilitated direct analysis of more complex samples without sample pre-treatment, such as biological samples (tomato tissue). The ionization was driven by an extremely low electrical power (3.5 V rechargeable battery) yet providing an efficient and superior soft ionization. The method displayed a better thermal and pH stability than nano electrospray ionization (nanoESI) and electrospray ionization (ESI) on direct analysis of Vitamin B and protein aqueous solutions. Quantitative analysis of Vitamin B and Rhodamine B aqueous solutions was also investigated, showing a good linearity (R2 > 0.99). In addition, our results suggested that compared with ESI and nanoESI, the method not only could be used for direct analysis of intact protein, but also provide more information concerning the association between intact protein and the subunits.

Surfactant-free oleogel-based emulsion stabilized by co-assembled ceramide/lecithin crystals with controlled digestibility.

BACKGROUND: There is increasing interest in the development of oleogel-based emulsions. However, they usually contained surfactants for stabilization, especially small-molecular weight surfactants, which may have adverse health impacts. RESULTS: Herein, a surfactant-free oleogel-based emulsion stabilized by co-assembled ceramide/lecithin (CER/LEC) crystals was developed. The formation and stabilization mechanisms were explored. The different molar ratios of gelator (LEC and CER) in emulsions resulted in different crystal morphology, crystallinity as well as different emulsion properties. This suggested that appropriate crystallinity, crystal size, and interfacial distribution of these crystals provided higher surface coverage against droplets coalescence, thus better emulsion stabilization. Both X-ray diffractograms and contact angle results confirmed that the crystals which were primarily responsible for emulsion stabilization, are co-assembled crystals consisted of both gelators (CER and LEC). Furthermore, the percentage of free fatty acids (FFAs%) results revealed a negative relationship between lipid digestibility and crystal concentration. CONCLUSIONS: This strategy greatly enriched surfactant-free oleogel-based emulsion formulations, as well as their potential applications in healthy lipid-based products and novel food delivery systems with controlled lipid digestibility. © 2022 Society of Chemical Industry.

Determination of valproic acid and its six metabolites in human serum using LC-MS/MS and application to interaction with carbapenems in epileptic patients.

Valproic acid (VPA) is a classic medication for several types of epilepsy and mood disorders, and some of its effectiveness and toxicity is associated with metabolites. Although many reports have reported the drug-drug interactions of VPA, no study has focused on the influence of carbapenems (CBPMs) on VPA's active metabolites. An LC-MS/MS method for determining VPA and its six metabolites (3-hydroxy valproic acid, 4-hydroxy valproic acid, 2-propyl-2-pentenoic acid, 2-propyl-4-pentenoic acid, 3-keto valproic acid, and 2-propylglutaric acid) in human serum was established and applied to evaluate the drug-drug interaction with CBPMs in epileptic patients. The stable isotope valproic acid-d6 was used as an internal standard. Analytes in serum samples (50 µl) were isolated using a Kinetex C18 column (3 × 100 mm, 2.6 µm) and detected via negative electrospray ionization after protein precipitation. It was linear (r > 0.99) over the calibration range for different analytes. The accuracy was 91.44-110.92%, and the precision was less than 9.98%. The matrix effect, recovery, and stability met the acceptance criteria. According to the data collected from 150 epileptic patients, the concentration-dose ratio for VPA and its metabolites decreased with CBPM polytherapy. This method is simple and rapid with great accuracy and precision. It is suitable for routine clinical analysis of VPA and its metabolites in human serum.