Abstract: (1) Background: No consensus has been reached on indicators and protocols for monitoring drug concentrations in organ transplant recipients for the immunosuppressant mycophenolic acid (MPA) in clinical therapy.In this study, we propose to establish a Ultra Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC-MS/MS) for quantitative determination of MPA and its metabolites ( mycophenolic acid carboxybutoxyether, MPAG and mycophenolic acid carboxyglucuronide, AcMPAG) concentrations in peripheral blood mononuclear cells (PBMCs) and to assess the clinical application of PBMCs concentration detection of MPA and its metabolites in infection prediction in Chinese kidney transplant recipients(KTRs); (2) Methods: PBMCs were isolated with Ficoll-Paque solution, and cells were counted. Acetonitrile precipitated proteins to extract the target compounds.Waters ACQUITY UPLC BEH C18 column of 1.7μm (2.1 mm*50 mm) and an ACQUITY-Xevo TQ-S UPLC-MS/MS system were used for the detection with mobile phases: water and methanol (containing 2 mmol/L NH4Ac + 0.1% formic acid); flow rate: 0.3 mL/min. After gradient elution, the samples were positively ionized by an electrospray positive ion source (ESI) and then quantitatively analyzed by a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode. The performance of the established method was evaluated through a series of validation experiments according to the requirements of the relevant guidelines. We enrolled 7 KTRs with stable conditions and 8 KTRs with infection from August to November 2022, who were treated at the West China Hospital of Sichuan University.Their peripheral blood samples were collected and detected MPA, MPAG, and AcMPAG concentrations in PBMCs using the methods mentioned above and evaluated for their clinical application in the prediction and monitoring of infections in KTRs; (3) Results: After validation of the methodology, the UPLC-MS/MS method established in this study for the determination of MPA, MPAG, and AcMPAG concentrations in PBMCs showed good linearity in the quantitative ranges of 0.0625-50 ng/ml, 0.5-50 ng/ml and 0.1-20 ng/ml, and the selectivity, specificity, matrix effect, carry-over contamination, reproducibility, precision and accuracy all satisfied the requirements.AcMPAG in PBMCs was poorly stabilized and showed significant degradation after -80°C storage for 24 h or 3 cycles of freeze-thaw.There was a large variability in MPA and MPAG concentrations in PBMCs of KTRs and it correlated poorly with plasma MPA concentrations (rs=0.206,p=0.117).Subgroup analysis showed that the correlation between MPA in plasma and PBMCs was still poor in the infected group(rs=0.201,p=0.116), but significant correlation in the stable group (rs=0.643,p=0.001). A significantly higher level of MPA in PBMCs was observed in the infected group than those in the stable group at 2h and 4h after drug dosing (p<0.05).AcMPAG concentrations in PBMCs of KTRs were extremely low and virtually undetectable.ROC curve analysis (area under the curve, AUC) was performed for infection after renal transplantation with indicators of significant difference showed that the area AUC for PBMCs-MPA-C4 was 0.928 ,for PBMCs-MPA-C2 was 0.875,and for Plasma-MPA-C4 was 0.803; (4) Conclusions: In this study, a method based on UPLC-MS/MS was developed and validated for the simultaneous determination of MPA, MPAG, and AcMPAG concentrations in PBMCs.With easy operability and good stability, this method provides a reliable analytical method for the clinical implementation of the detection of MPA, MPAG, and AcMPAG concentrations in PBMCs.The concentrations of MPA and MPAG in PBMCs from KTRs were highly variable and were closely associated with the development of infections after renal transplantation.Monitoring MPA and MPAG in PBMCs may be useful indicators for mycophenolic acid therapeutic drug concentration monitoring (TDM) in KTRs.

Patterns of age and growth of a sedentary damsel fish Acanthochromis polyacanthus were tested over a latitudinal range of approximately 10 degrees (1,200 km) on the Great Barrier Reef, Australia. Within latitudes these patterns were also compared on reefs across a continental shelf that ranged in width from 52 to 128 km. Although variation in length-max, growth, age-max and the von-Bertalanffy metrics of L, and K were found within and among latitudes, greatest variation in some demographic characteristics were found across the shelf regardless of latitude. Fish were always smaller at inner shelf reefs and grew more slowly when compared to mid and outer shelf reefs. The oldest fish collected was 11 years old and, there were no consistent variation in age-max among distances from shore. On outer reefs, there was a linear relationship with age-max and latitude. This ‘tropical gradient’ of age only explained 34% of the variation, further this was not found when the oldest 10% of fish were considered. Fish only reached an age-max of 6 years on the southern-most reefs. There was a trend for a smaller L with latitude but, it was not significant and L did not vary predictably with water temperature. The sampling of MPAs did not confound the resultant patterns. Instantaneous mortality rates were 0.245-0.685, highest at inner reefs and showed no consistent MPA-related patterns. Our study suggested that the mid and outer shelf waters of the GBR appeared best suited for growth of A. polyacanthus. In conclusion, position on continental shelves and related local environmental conditions needs to be considered in spatial models of growth.

A novel configuration for a super-wide impedance planar antenna is presented based on a 2 × 2 microstrip patch antenna (MPA). The antenna comprises a symmetrical arrangement of four-square patches that are interconnected to each other with cross-shaped high impedance microstrip lines. The antenna array is exciting through a single feedline connected to one of the patches. The proposed antenna array configuration overcomes the main drawback of conventional MPA of narrow bandwidth that is typically <5%. The antenna exhibits a super-wide frequency bandwidth from 20 GHz to 120 GHz for S₁₁<−15 dB, which corresponds to a fractional bandwidth of 142.85%. The antenna’s performance of bandwidth, impedance match, and radiation gain were enhanced by etching slots on the patches. The slotted microstrip patch essentially acts like a left-handed capacitance to exhibit metamaterial properties over a given frequency range. With the inclusion of the slot the maximum radiation gain and efficiency of the MPA have increased to 15.11 dBi and 85.79% at 80 GHz, which show an improvement of 2.58 dBi and 12.54%, respectively. The dimension of each patch antenna is 30 × 30 mm². The results show that the proposed MPA is useful for various communications existing and emerging systems such as ultra-wideband (UWB) communications, RFID systems, massive multiple-output multiple-input (MIMO) for 5G, and radar systems.