Tuning Electrons Migration of Dual S Defects Mediated MoS2-x/ZnIn2S4-x Toward Highly Efficient Photocatalytic Hydrogen Production.

Photocatalytic hydrogen production is a prevalent method for hydrogen synthesis. However, high recombination rate of photogenerated carriers and high activation energy barrier of H remain persistent challenge. Here, the two-step hydrothermal method is utilized to prepare dual S-defect mediated catalyst molybdenum sulfide/zinc indium sulfide (MSv/ZISv), which has high hydrogen production rate of 8.83 mmol g-1h-1 under simulated sunlight. The achieved rate is 21.91 times higher than pure ZnIn2S4 substrate. Defects in ZIS within MSv/ZISv modify the primitive electronic structure by creating defect state that retaining good reducing power, leading to the rapid separation of electron-hole pairs and the generation of additional photogenerated carriers. The internal electric field further enhances the migration toward to cocatalyst. Simultaneously, the defects introduced on the MoS2 cause electron rearrangement, leading to electron clustering on both S vacancies and edge S. Thereby MSv/ZISv exhibits the lowest activation energy barrier and |ΔGH*|. This work explores the division of synergies between different types of S defects, providing new insights into the coupling of defect engineering.

OralExplorer: a web server for exploring the mechanisms of oral inflammatory diseases.

BACKGROUND: Oral inflammatory diseases are localized infectious diseases primarily caused by oral pathogens with the potential for serious systemic complications. However, publicly available datasets for these diseases are underutilized. To address this issue, a web tool called OralExplorer was developed. This tool integrates the available data and provides comprehensive online bioinformatic analysis. METHODS: Human oral inflammatory disease-related datasets were obtained from the GEO database and normalized using a standardized process. Transcriptome data were then subjected to differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis, and visualization. The single-cell sequencing data was visualized as cluster plot, feature plot, and heatmaps. The web platform was primarily built using Shiny. The biomarkers identified in OralExplorer were validated using local clinical samples through qPCR and IHC. RESULTS: A total of 35 human oral inflammatory disease-related datasets, covering 6 main disease types and 901 samples, were included in the study to identify potential molecular signatures of the mechanisms of oral diseases. OralExplorer consists of 5 main analysis modules (differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis and single-cell analysis), with multiple visualization options. The platform offers a simple and intuitive interface, high-quality images for visualization, and detailed analysis results tables for easy access by users. Six markers (IL1ß, SRGN, CXCR1, FGR, ARHGEF2, and PTAFR) were identified by OralExplorer. qPCR- and IHC-based experimental validation showed significantly higher levels of these genes in the periodontitis group. CONCLUSIONS: OralExplorer is a comprehensive analytical platform for oral inflammatory diseases. It allows users to interactively explore the molecular mechanisms underlying the action and regression of these diseases. It also aids dental researchers in unlocking the potential value of transcriptomics data related to oral diseases. OralExplorer can be accessed at https://smuonco.shinyapps.io/OralExplorer/  (Alternate URL: http://robinl-lab.com/OralExplorer ).

Biosynthetic mechanism of the yellow pigments in the marine bacterium Pseudoalteromonas sp. strain T1lg65.

The Pseudoalteromonas genus marine bacteria have attracted increasing interest because of their abilities to produce bioactive metabolites. The pigmented Pseudoalteromonas group encodes more secondary metabolite biosynthetic gene clusters (BGCs) than the non-pigmented group. Here, we report a yellow pigmented bacterium Pseudoalteromonas sp. strain T1lg65, which was isolated from a mangrove forest sediment. We showed that the yellow pigments of T1lg65 belong to the group of lipopeptide alterochromides. Further genetic analyses of the alterochromide BGC revealed that the yellow pigments are biosynthesized by aryl-polyene synthases and nonribosomal peptide synthases. Within the gene cluster, altA encodes a tyrosine ammonia acid lyase, which catalyzes synthesis of the precursor 4-hydroxycinnamic acid (4-HCA) from tyrosine in the alterochromide biosynthetic pathway. In addition, altN, encoding a putative flavin-dependent halogenase, was proven to be responsible for the bromination of alterochromides based on gene deletion, molecular docking, and site mutagenesis analyses. In summary, the biosynthetic pathway, precursor synthesis, and bromination mechanism of the lipopeptide alterochromides were studied in-depth. Our results expand the knowledge on biosynthesis of Pseudoalteromonas pigments and could promote the development of active pigments in the future.IMPORTANCEThe marine bacteria Pseudoalteromonas spp. are important biological resources because they are producers of bioactive natural products, including antibiotics, pigments, enzymes, and antimicrobial peptides. One group of the microbial pigments, alterochromides, holds a great value for their novel lipopeptide structures and antimicrobial activities. Previous studies were limited to the structural characterization of alterochromides and genome mining for the alterochromide biosynthesis. This work focused on the biosynthetic mechanism for alterochromide production, especially revealing functions of two key genes within the gene cluster for the alterochromide biosynthesis. On the one hand, our study provides a target for metabolic engineering of the alterochromide biosynthesis; on the other hand, the 4-HCA synthase AltA and brominase AltN show potential in the biocatalyst industry.

Optimal exposure of mycophenolic acid for induction therapy of childhood lupus nephritis patients: an observational cohort study.

OBJECTIVES: Mycophenolic acid (MPA) is recommended for lupus nephritis (LN) treatment, but with large inter-individual variability in pharmacokinetics (PK). The aim of this study is to reveal the relationship between MPA exposure and disease response and adverse drug reactions in pediatric LN patients. METHOD: This was a population-based observational cohort study. A total of 86 pediatric LN patients treated with mycophenolate mofetil (MMF) for induction therapy were enrolled. The area-under the concentration-time curve (AUC) was calculated using MPA concentrations according to a limited sampling strategy. Receiver operating characteristic analysis was performed to assess the MPA-AUC threshold values. The cumulative incidence of renal remission and inactive SLE over time was evaluated by Kaplan-Meier's analysis. RESULTS: MPA-AUC was identified as an independent factor associated with renal remission and lupus activity at 6 and 12 months after MMF treatment, and the improved renal remission rates was correlated with higher MPA-AUC, with thresholds of 29.81 and 30.63 µg·h·mL - 1 at 6 and 12 months, respectively. Furthermore, the thresholds for maintaining the hypoactive state of LN were 30.96 and 31.19 µg·h·mL - 1at 6 months and 12 months, respectively. Patients reaching target thresholds for MPA-AUC achieved renal response or stable disease earlier. In addition, the MPA-AUC threshold for decreasing MMF-related adverse reactions was 50.80 µg·h·mL - 1. CONCLUSION: The initial and long-term treatments of pediatric LN patients with MMF should be individualized according to the MPA-AUC, and the recommended MPA exposure is 31.19-50.80 µg·h·mL - 1.

Sirtuin 1 in osteoarthritis: Perspectives on regulating glucose metabolism.

Osteoarthritis (OA) is a degenerative disease characterised by articular cartilage destruction, and its complex aetiology contributes to suboptimal clinical treatment outcomes. A close association exists between glucose metabolism dysregulation and OA pathogenesis. Owing to the unique environment of low oxygen and glucose concentrations, chondrocytes rely heavily on their glycolytic capacity, exhibiting distinct spatiotemporal differences. However, under pathological stimulation, chondrocytes undergo excessive glycolytic activity while mitochondrial respiration and other branches of glucose metabolism are compromised. This metabolic change induces cartilage degeneration by reprogramming the inflammatory responses. Sirtuins, a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, regulate glucose metabolism in response to energy fluctuations in different cellular compartments，alleviating metabolic stress. SIRT1, the most extensively studied sirtuin, participates in maintaining glucose homeostasis in almost all key metabolic tissues. While actively contributing to the OA progression and displaying diverse biological effects in cartilage protection, SIRT1's role in regulating glucose metabolism in chondrocytes has not received sufficient attention. This review focuses on discussing the beneficial role of SIRT1 in OA progression from a metabolic regulation perspective based on elucidating the primary characteristics of chondrocyte glucose metabolism. We also summarise the potential mechanisms and therapeutic strategies targeting SIRT1 in chondrocytes to guide clinical practice and explore novel therapeutic directions.

Proangiogenic effect and underlying mechanism of holmium oxide nanoparticles: a new biomaterial for tissue engineering.

BACKGROUND: Early angiogenesis provides nutrient supply for bone tissue repair, and insufficient angiogenesis will lead tissue engineering failure. Lanthanide metal nanoparticles (LM NPs) are the preferred materials for tissue engineering and can effectively promote angiogenesis. Holmium oxide nanoparticles (HNPs) are LM NPs with the function of bone tissue "tracking" labelling. Preliminary studies have shown that HNPs has potential of promote angiogenesis, but the specific role and mechanism remain unclear. This limits the biological application of HNPs. RESULTS: In this study, we confirmed that HNPs promoted early vessel formation, especially that of H-type vessels in vivo, thereby accelerating bone tissue repair. Moreover, HNPs promoted angiogenesis by increasing cell migration, which was mediated by filopodia extension in vitro. At the molecular level, HNPs interact with the membrane protein EphrinB2 in human umbilical vein endothelial cells (HUVECs), and phosphorylated EphrinB2 can bind and activate VAV2, which is an activator of the filopodia regulatory protein CDC42. When these three molecules were inhibited separately, angiogenesis was reduced. CONCLUSION: Overall, our study confirmed that HNPs increased cell migration to promote angiogenesis for the first time, which is beneficial for bone repair. The EphrinB2/VAV2/CDC42 signalling pathway regulates cell migration, which is an important target of angiogenesis. Thus, HNPs are a new candidate biomaterial for tissue engineering, providing new insights into their biological application.

Expression, purification, and biological activity evaluation of cathepsin L in mammalian cells.

Cathepsin L (CTSL) could cleave and activate SARS-CoV-2 Spike protein to promote viral entry, making it a hopeful therapeutic target for COVID-19 prevention and treatment. So CTSL inhibitors are considered to be a promising strategy to SARS-CoV-2 infection. CTSL has previously been expressed in inclusion body in Escherichia coli. In order to prepare CTSL with high purity and activity in soluble active form, we transformed HEK-293T cells with a recombinant mammalian expression plasmid. CTSL was purified to a purity about 95%, found to migrate at approximately 43 kDa and exhibited substrate specificity against Z-Phe-Arg-AMC with specific activity of no less than 85 081 U/mg, characteristic of active CTSL. Although eukaryotic purified CTSL is commercially available, our study for the first time reported the details of the expression, purification, and characterization of active, recombinant CTSL in eukaryocyte system, which laid an experimental foundation for the establishment of high-throughput screening model for anti-coronavirus drugs targeting CTSL.

Design of a compact off-axis two-mirror freeform optical antenna for shaping and transmitting an elliptical beam emitted by laser diode.

Elliptical Gaussian beams generated by laser diodes (LDs) often exhibit asymmetrical divergence angle distribution, which limits their practical applications. In this study, we propose what we believe is a novel approach to shape and collimate the elliptical output beam from a LD. The design process involves the construction of two freeform reflective surfaces on a reference circle using a three-dimensional point-by-point iterative method, based on the law of conservation of energy, the vector reflection theory, and Fermat's principle. The output beam's maximum divergence angle is effectively compressed to 3.1579 mrad. The design is compact with a folded optical path and antenna size of 368.8c m 3. This paper presents a comprehensive design and optimization process, along with an in-depth analysis of the system's performance, thereby offering novel insights for emerging optical design practitioners.

Multi-focus composite spiral zone plate to generate focused vortices with the comparable intensity based on genetic algorithm.

In this study, we introduce an optical element, named Multi-focus Composite Spiral Zone Plate (MFCSZP), to generate multi focused vortices with approximately equal intensity along the optical axis. The genetic algorithm (GA) is used to optimize the parameters of the MFCSZP, which avoids manual parameter adjustment and improves computational efficiency. We analyze the focusing properties of the constructed MFCSZP theoretically and experimentally. The results provide evidence for its capability to generate multiple focused vortices with comparable peak intensities verified through experiment. This work shows the powerful ability of intelligent algorithms in the optimization of complex optical elements. The proposed optical element showcases potential applications within research areas of optical trapping and laser machining.

Design of a compact optical antenna system with high transmission efficiency utilizing a ring-like VCSEL array.

Vertical cavity surface-emitting lasers (VCSELs) with gigahertz bandwidth and good beam quality possess great potential for multi-wavelength free-space optical communication. In this Letter, a compact optical antenna system utilizing a ring-like VCSEL array that can realize the parallel transmission of multi-channel and multi-wavelength collimated laser beams and has the advantages of aberration elimination and high transmission efficiency is proposed. Ten different signals can be transmitted simultaneously, greatly increasing the channel capacity. Based on the vector theory of reflection, ray tracing and the performance of the proposed optical antenna system are demonstrated. This design method has a certain reference value for designing complex optical communication systems with high transmission efficiency.

AKAP12 inhibits esophageal squamous carcinoma cell proliferation, migration, and cell cycle via the PI3K/AKT signaling pathway.

Esophageal squamous cell carcinoma (ESCC) consistently ranks as one of the most challenging variants of squamous cell carcinomas, primarily due to the lack of effective early detection strategies. We herein aimed to elucidate the underlying mechanisms and biological role associated with A-kinase anchoring protein 12 (AKAP12) in the context of ESCC. Bioinformatic analysis had revealed significantly lower expression level of AKAP12 in ESCC tissue samples than in their non-cancerous counterparts. To gain deeper insights into the potential role of AKAP12 in the progression of ESCC, we conducted a single-gene set enrichment analysis of AKAP12 on ESCC datasets. Our findings suggested that AKAP12 exhibits functions inhibiting cell cycle progression, tumor proliferation, and epithelial-mesenchymal transition. To further validate our findings, we subjected ESCC cell lines to AKAP12 overexpression using CRISPR/Cas9-SAM. In vitro analyses demonstrated that increased expression of AKAP12 significantly reduced cell proliferation, migration, and cell cycle progression. Simultaneously, genes associated with this biological role undergo corresponding regulatory shifts. These observations provided valuable insights into the biological role played by AKAP12 in ESCC progression. In summary, AKAP12 shows promise as a new potential biomarker for early ESCC diagnosis, offering potential advantages for subsequent therapeutic intervention and disease management.

Anti-Biofilm Activity of Cocultimycin A against Candida albicans.

Candida albicans (C. albicans), the most common fungal pathogen, has the ability to form a biofilm, leading to enhanced virulence and antibiotic resistance. Cocultimycin A, a novel antifungal antibiotic isolated from the co-culture of two marine fungi, exhibited a potent inhibitory effect on planktonic C. albicans cells. This study aimed to evaluate the anti-biofilm activity of cocultimycin A against C. albicans and explore its underlying mechanism. Crystal violet staining showed that cocultimycin A remarkably inhibited biofilm formation in a dose-dependent manner and disrupted mature biofilms at higher concentrations. However, the metabolic activity of mature biofilms treated with lower concentrations of cocultimycin A significantly decreased when using the XTT reduction method. Cocultimycin A could inhibit yeast-to-hypha transition and mycelium formation of C. albicans colonies, which was observed through the use of a light microscope. Scanning electron microscopy revealed that biofilms treated with cocultimycin A were disrupted, yeast cells increased, and hypha cells decreased and significantly shortened. The adhesive ability of C. albicans cells treated with cocultimycin A to the medium and HOEC cells significantly decreased. Through the use of a qRT-PCR assay, the expression of multiple genes related to adhesion, hyphal formation and cell membrane changes in relation to biofilm cells treated with cocultimycin A. All these results suggested that cocultimycin A may be considered a potential novel molecule for treating and preventing biofilm-related C. albicans infections.

Preliminary study on a novel biological scaffold loaded with Apelin-13 sustained-release microcapsules for promoting fallopian tube recanalization in rabbits. / è½½Apelin-13ç¼“é‡Šå¾®å›Šçš„æ–°åž‹ç”Ÿç‰©æ”¯æž¶ä¿ƒå ”è¾“åµç®¡å†é€šçš„åˆæ­¥ç ”ç©¶.

OBJECTIVES: Tubal factor infertility severely impairs the natural fertility of women, and there is for genuine tubal recanalization, including restoration of both the anatomy and function of the diseased fallopian tubes. Currently, there is no effective treatment available. This study aims to explore methods for promoting the repair and recanalization of fallopian tubes from these 2 aspects. METHODS: Apelin-13 sustained-release microspheres and poly (lactic-co-glycolic acid) (PLGA) three-dimensional (3D) biodegradable scaffolds were prepared. The basic characteristics and in vivo degradation (mass loss rate) of the biodegradable scaffolds were tested, along with the in vitro drug release (cumulative release rate), the in vivo drug release (Apelin-13 plasma concentration), and in vitro degradation (degradation rate) of the microspheres. The Apelin-13 microspheres (microsphere group)/PLGA 3D scaffolds loaded with Apelin-13 sustained-release microspheres (scaffold-microcapsule group) were injected/placed into the fallopian tubes of New Zealand rabbit of chronic salpingitis models. The patency, microscopic structure, and positive expression of estrogen receptor and progesterone receptor of the fallopian tubes in the control group, the model group, the microcapsule group, and the scaffold-microcapsule group was observed and compared. RESULTS: At the 4th week post-operation, the mass loss rate of the PLGA 3D scaffolds, the degradation rate of the microspheres, and the Apelin-13 sustained-release microspheres-generated cumulative release rate in vitro over 30 days were 98.66%, 70.58%, and 98.68% respectively. The plasma concentration of Apelin-13 reached its peak within 5 days and remained stable for 25 days. Compared with the model and microsphere groups, the scaffold-microsphere group showed a milder inflammatory reaction within the tubal lumen, a higher rate of fallopian tube patency, and higher expression levels of estrogen and progesterone receptors (all P<0.05). The indicators of the scaffold-microsphere group were close to those of the control group. CONCLUSIONS: The PLGA 3D scaffolds loaded with Apelin-13 sustained-release microspheres can comprehensively repair the anatomical structure and physiological function of the fallopian tubes and hold promise for truly effective tubal recanalization.

Crack Patterns of Environmental Plastic Fragments.

Secondary microplastics usually come from the breakdown of larger plastics due to weathering and environmental stress cracking of plastic wastes. In the present study, 5013 plastic fragments were collected from coastal beaches, estuary dikes, and lake banks in China. The fragment sizes ranged from 0.2 to 17.1 cm, and the dominant polymers were polypropylene and polyethylene. Cracks were observed on the surfaces of 49-56% of the fragments. Based on the extracted crack images, we proposed a general crack pattern system including four crack types with specific definitions, abbreviations, and symbols. The two-dimensional spectral analysis of the cracks suggests that the first three patterns showed good regularity and supported the rationality of the pattern system. Some crack metrics (e.g., line density) were closely correlated with the carbonyl index and additives (e.g., phthalate esters) of fragments. For crack investigation in field, we proposed a succinct protocol, in which five crack ranks were established to directly characterize the degree of cracking based on the line density values. The system was successfully applied to distinguish the differences in crack features at two representative sites, which indicates that crack pattern is a useful tool to describe the morphological changes of plastic surfaces in the environment.

Gut-derived fungemia due to Kodamaea ohmeri combined with invasive pulmonary aspergillosis: a case report.

BACKGROUND: Kodamaea ohmeri is a rare pathogen with high mortality and is found among blood samples in a considerable proportion; however, gastrointestinal infection of K. ohmeri is extremely rare. Invasive pulmonary aspergillosis is also an uncommon fungal; these two fungal infections reported concomitantly are unprecedented. CASE PRESENTATION: We described a case of a 37-year-old male who got infected with K. ohmeri and invasive pulmonary aspergillosis. We used the mass spectrometry and histopathology to identify these two fungal infections separately. For the treatment of K. ohmeri, we chose caspofungin. As for invasive pulmonary aspergillosis, we used voriconazole, amphotericin B, and then surgery. The patient was treated successfully through the collaboration of multiple disciplines. CONCLUSIONS: We speculate that the destruction of the intestinal mucosa barrier can make the intestine one of the ways for certain fungi to infect the human body.

Low-intensity-low-temperature stability assessment of perovskite solar cells operating on simulated Martian surface conditions.

Immigration to Mars, which is expected to be powered mainly by photovoltaics, is one of the greatest dreams of humanity. However, the extreme temperature difference and high-energy cosmic radiation on the surface of Mars make it difficult for conventional photovoltaics to operate steadily over time. With their advantages of being lightweight, having a high irradiation tolerance, and an outstanding power conversion efficiency (PCE), perovskite solar cells (PSCs) have shown themselves to be a promising candidate for Martian applications. In this study, we simulated the low-intensity-low-temperature (LILT) environment of the Mars surface, and monitored the in situ device performance of PSCs. Surprisingly, the device PCE was not only maintained at a high level but was even improved slightly. Further investigation revealed that the self-healing effect of perovskites under LILT conditions could be attributed to the light-induced decomposition of the perovskite film and the ß-phase perovskite recrystallization process at the perovskite/hole transport layer interface. Interfacial ß-phase perovskites are stable at low temperatures, which can facilitate charge extraction and protect the perovskite bulk from long-term light damage. This study demonstrated the feasibility of PSCs and provides a reference for Martian applications.

Identification of HMGB2 associated with proliferation, invasion and prognosis in lung adenocarcinoma via weighted gene co-expression network analysis.

BACKGROUND: High mobility group protein B2 (HMGB2) is a multifunctional protein that plays various roles in different cellular compartments. Moreover, HMGB2 serves as a potential prognostic biomarker and therapeutic target for lung adenocarcinoma (LUAD). METHODS: In this study, the expression pattern, prognostic implication, and potential role of HMGB2 in LUAD were evaluated using the integrated bioinformatics analyses based on public available mRNA expression profiles from The Cancer Genome Atlas and Gene Expression Omnibus databases, both at the single-cell level and the tissue level. Further study in the patient-derived samples was conducted to explore the correlation between HMGB2 protein expression levels with tissue specificity, (tumor size-lymph node-metastasis) TNM stage, pathological grade, Ki-67 status, and overall survival. In vitro experiments, such as CCK-8, colony-formation and Transwell assay, were performed with human LUAD cell line A549 to investigate the role of HMGB2 in LUAD progression. Furthermore, xenograft tumor model was generated with A549 in nude mice. RESULTS: The results showed that the HMGB2 expression was higher in the LUAD samples than in the adjacent normal tissues and was correlated with high degree of malignancy in different public data in this study. Besides, over-expression of HMGB2 promoted A549 cells proliferation and migration while knocking down of HMGB2 suppressed the tumor promoting effect. CONCLUSIONS: Our study indicated that HMGB2 was remarkably highly expressed in LUAD tissues, suggesting that it is a promising diagnostic and therapeutic marker for LUAD in the future.

Anti-GQ1b Antibody Syndrome with Visual Impairment: A Retrospective Case Series.

BACKGROUND: Anti-GQ1b antibody syndrome referred to a clinical spectrum characterized by acute onset of ataxia, ophthalmoplegia and areflexia, while visual deterioration was rarely reported in terms of ocular disorders. This study aimed to describe the clinical characteristics of anti-GQ1b antibody syndrome with visual impairment. METHODS: The database at the First Affiliated Hospital of Sun Yat-sen University was searched from 2014 to 2020. Patients with anti-GQ1b IgG were identified and divided into two groups according to the existence of optic neuropathy. Clinical and laboratory data of these subjects between the two groups were collected and analyzed. All patients were followed up by telephone to assess the outcome. RESULTS: A total of 12 patients with seropositive anti-GQ1b antibody were included, 75% of which got antecedent infection. Of these cases, 3 showed visual deterioration accompanied by abnormal orbital magnetic resonance imaging or visual evoked potentials, and the other 9 didn't show any evidence of vision impairment. Patients in the optic neuropathy group presented prominent visual impairments as initial symptoms and were more likely to suffer from facial weakness. There were 4 patients in normal visual acuity group complaining of blurred vision due to intraocular muscle paralysis, which was distinguished by subsequent examination. The combination of glucocorticoids and intravenous immunoglobulin was applied to treat patients with optic neuropathy. CONCLUSIONS: This study provides strong evidence that anti-GQ1b antibody syndrome can exhibit visual impairment, which helps further expand the clinical spectrum of anti-GQ1b antibody syndrome. More attention should be paid to the physical and supplementary ophthalmological examination to explore the pathogenesis and treatment of anti-GQ1b antibody syndrome.

Long-Term Radiologic Evaluation of Microaspirations among Patients after Esophagectomy.

OBJECTIVES: Aspirations are common after esophagectomy. Data are lacking regarding its long-term radiological manifestations. The purpose of this study is to determine the incidence and radiological patterns of aspirations among long-term survivors and evaluate their clinical significance. METHODS: The records of all patients who underwent esophagectomy between October 2003 and December 2011 and survived more than 3 years were reviewed. Preoperative, first routine postoperative, and latest chest computed tomography (CT)scans were reviewed. Imaging studies were reviewed for radiological signs suspicious of aspirations, conduit location, anastomotic site, and maximal intrathoracic diameter. Data regarding patients' complaints during clinic visits were also collected. RESULTS: A total of 578 patients underwent esophagectomy during the study period. One-hundred twenty patients met the inclusion criteria. Median follow-up was 83.5 months. Cervical and intrathoracic anastomoses were performed in 103 and 17 patients, respectively. A higher rate of CT findings was found in postoperative imaging (n = 51 [42.5%] vs. n = 13 [10.8%] respectively, p < 0.05). Most of these were found in the lower lobes (61%). A higher rate of lesions was found among patients in whom the conduit was bulging to the right hemithorax compared with totally mediastinal or completely in the right hemithorax (54.5 vs. 35.2% and 34.6%, respectively, p < 0.05). No correlation was found with conduit diameter or anastomotic site. These lesions were more prevalent among patients who complained of reflux or cough during meals (NS). CONCLUSIONS: A significantly higher rate of new CT findings was found in postoperative imaging of this post-esophagectomy cohort, suggesting a high incidence of aspirations. The locations of the conduit, rather than anastomosis site, seem to play a role in the development of these findings. Further research is needed to evaluate the clinical significance of these findings.

Validated LC-MS/MS method for quantitation of total and free mycophenolic acid concentration and its application to a pharmacokinetic study in pediatric renal transplant recipients.

A simple and sensitive LC-MS/MS method was established to quantify total and free mycophenolic acid (MPA) plasma concentrations during immunosuppressive medication for pediatric renal transplantation. The chromatographic separation was performed with the Hypersil GOLD C18 column, using a mobile phase consisting of 0.1% formic acid in water and acetonitrile (60:40, v/v) at an isocratic flow rate of 0.4 ml/min. An Agilent 6420 triple quadrupole mass spectrometer was operated via a positive electrospray ionization interface using the transitions m/z 321.14 → 206.9 for MPA and m/z 324.15 → 209.9 for MPA-d3 (internal standard). The linearity was 0.1-50 µg/ml for total MPA and 0.0025-0.5 µg/ml for free MPA. The within-run and between-run precisions were all <5% and accuracy was within 96.23-107.63%. The validated method was successfully aspplied to a pharmacokinetic study in 28 pediatric renal recipients. The mean free fraction of MPA in our patients was 0.89% (ranging from 0.62 to 1.25%) and albumin level played a major role in the variability of free fraction of MPA, thus, in pediatric patients with hypoproteinemia, close free drug monitoring and dose adjustments should be considered to prevent toxicity.