Uric acid is a biomarker for heart failure, but not therapeutic target: result from a comprehensive meta-analysis.

AIMS: This systematic review and meta-analysis aimed to investigate the association between serum uric acid (SUA) levels and the incidence rate and prognosis of heart failure (HF), as well as the impact of uric acid-lowering treatment on HF patients. METHODS AND RESULTS: PubMed and Embase were searched for original articles reporting on the association between SUA and HF incidence, adverse outcomes, and the effect of uric acid-lowering treatment in HF patients. Data were pooled using random effects or fixed effects models. Univariable meta-regression analysis assessed the influence of study characteristics on research outcomes. Statistical analyses were conducted using RevMan software and STATA software version 15.0. Eleven studies on HF incidence and 24 studies on adverse outcomes in HF patients were included. Higher SUA levels were associated with an increased risk of HF (RR: 1.81, 95% CI: 1.53-2.16), all-cause mortality (RR: 1.44, 95% CI: 1.25-1.66), cardiac death (RR: 1.56, 95% CI: 1.32-1.84), and HF rehospitalization (RR: 2.07, 95% CI: 1.37-3.13) in HF patients. Uric acid-lowering treatment was found to increase all-cause mortality in HF patients (RR: 1.15, 95% CI: 1.05-1.25). CONCLUSIONS: Uric acid is an independent predictor of heart failure occurrence and adverse prognosis. Targeting uric acid lowering as a therapeutic intervention does not improve the prognosis of patients with heart failure. It may not be advisable to use traditional urate-lowering drugs in young patients with heart failure, and elderly patients should exercise caution when using them.

Correlations among the plasma concentrations of first-line anti-tuberculosis drugs and the physiological parameters influencing concentrations.

Background: The plasma concentrations of the four most commonly used first-line anti-tuberculosis (TB) drugs, isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and pyrazinamide (PZA), are often not within the therapeutic range. Insufficient drug exposure could lead to drug resistance and treatment failure, while excessive drug levels may lead to adverse reactions. The purpose of this study was to identify the physiological parameters influencing anti-TB drug concentrations. Methods: A retrospective cohort study was conducted. The 2-h plasma concentrations of the four drugs were measured by using the high-performance liquid chromatography-tandem mass spectrometry method. Results: A total of 317 patients were included in the study. The proportions of patients with INH, RMP, EMB, and PZA concentrations within the therapeutic range were 24.3%, 31.5%, 27.8%, and 18.6%, respectively. There were positive associations between the concentrations of INH and PZA and RMP and EMB, but negative associations were observed between the concentrations of INH and RMP, INH and EMB, RMP and PZA, and EMB and PZA. In the multivariate analysis, the influencing factors of the INH concentration were the PZA concentration, total bile acid (TBA), serum potassium, dose, direct bilirubin, prealbumin (PA), and albumin; those of the RMP concentration were PZA and EMB concentrations, weight, α-l-fucosidase (AFU), drinking, and dose; those of the EMB concentration were the RMP and PZA concentrations, creatinine, TBA and indirect bilirubin; and those of the PZA concentration were INH, RMP and EMB concentrations, sex, weight, uric acid and drinking. Conclusion: The complex correlations between the concentrations of the four first-line anti-TB drugs lead to a major challenge in dose adjustment to maintain all drugs within the therapeutic window. Levels of TBA, PA, AFU, and serum potassium should also be considered when adjusting the dose of the four drugs.

FIB-SEM analysis on three-dimensional structures of growing organelles in wild Chlorella pyrenoidosa cells.

To clarify dynamic changes of organelle microstructures in Chlorella pyrenoidosa cells during photosynthetic growth with CO2 fixation, three-dimensional (3D) organelle microstructures in three growth periods of meristem, elongation, and maturity were quantitatively determined and comprehensively reconstructed with focused ion beam scanning electron microscopy (FIB-SEM). The single round-pancake mitochondria in each cell split into a dumbbell and then into a circular ring, while the barycenter distance of mitochondria to chloroplast and nucleus was reduced to 45.5% and 88.3% to strengthen energy transfer, respectively. The single pyrenoid consisting of a large part and another small part in each chloroplast gradually developed to a mature state in which the two parts were nearly equal in size. The nucleolus progressively became larger with euchromatin replication. The number of starch grains gradually increased, but the mean grain volume remained nearly unchanged.

Inflammation Affects Liver Function and the Metabolism of Voriconazole to Voriconazole-N-Oxide in Adult and Elderly Patients.

Background: The inner association of inflammation with voriconazole (VCZ) metabolism has not been fully investigated. We intend to investigate the effects of inflammation on liver function, VCZ trough concentration (C0), C0/dose ratio and the ratio of VCZ to VCZ-N-oxide concentration (C0/CN) in adult and elderly patients. Methods: A single-center retrospective study was conducted among patients who were treated in our hospital between January 2018 and December 2021. For each eligible patient, demographic details, medical history, laboratory parameters, procalcitonin (PCT), C reactive protein (CRP), and interleukin-6 (IL-6) were collected from the medical chart. VCZ CN, TNF-α, IL-1ß, IL-8, and IL-10 concentrations were detected in blood samples. Results: A total of 356 patients were included in our study, with 195 patients in the adult cohort (<60 years) and 161 patients in the elderly cohort (≥60 years). In adult patients, CRP and IL-8 levels showed moderate association with VCZ C0/CN ratio (CRP: r = 0.512, p < 0.001; IL-8: r = 0.476, p = 0.002). IL-6 level shallowly associated with VCZ C0/CN ratio both in adult and elderly patients (r = 0.355, p = 0.003; r = 0.386, p = 0.001). A significantly higher VCZ C0, C0/dose ratio and C0/CN ratio was observed in adult patients with severe inflammation compared with patients with moderate inflammation and no to mild inflammation, as reflected by PCT levels (p < 0.05). However, there was no significant difference observed among different inflammation degrees in elderly patients. Lower albumin (AL) and higher total bilirubin (TBIL) were observed along with the degree of inflammation in both adult and elderly patients, as reflected by CRP and PCT levels (p < 0.05). Conclusion: Inflammation may affect the metabolism of VCZ to VCZ-N-oxide both in adult and elderly patients, and decreased plasma AL levels and increased TBIL levels under inflammatory conditions may also alter VCZ metabolism.

Impact of acceleration of agricultural and industrial waste conditioning on thermal drying of sewage sludge.

Improving the dewatering performance of sludge is a necessary advancement for collaborative sludge disposal and energy-efficient utilization in power plants. Herein, the effects of temperature changes and the addition of drying accelerators derived from agricultural and industrial waste on the drying characteristics of sewage sludge (SS) were investigated from the perspectives of drying kinetics and micromorphology. According to the results, the drying time for sludge significantly showed a clear downward trend via medium-low temperature (160 °C) thermal drying, which subsequently reduced the energy input substantially. When the drying temperature was 160 °C, the ideal addition proportions of rice husk (RH), sludge ash (SA), and coal ash (CA) comprised 15%. The addition of SA prominently boosted the drying rate constant of the original sludge by 48%. Additionally, SEM images along with the spectral dimension obtained via fractal theory explicitly clearly demonstrated that SS + SA had more loose pore channels than other mixed samples. This provided a convenient approach to ensure the evaporation and migration of moisture and thereby shorten the drying time effectively. Consequently, the addition of sludge ash as a drying accelerator can promote the deep dewatering of sludge.

Novel hyaluronic acid-modified temperature-sensitive nanoparticles for synergistic chemo-photothermal therapy.

This study has developed a versatile nano-system with the combined advantages of photothermal effect, active tumor-targeting, temperature-sensitive drug release, and photoacoustic imaging. The nano-system consists of the core of the phase change material (PCM), the outer polypyrrole (PPY) shell and the hyaluronic acid (HA) modified in the PPY shell. The obtained composite nanoparticles (denoted as DTX/PPN@PPY@HA) were spherical with a mean diameter of about 232.7 nm. In vivo and in vitro photoacoustic imaging experiments show that DTX/PPN@PPY@HA is an effective photoacoustic contrast agent, which can be used for accurate localization of tumor region and real-time guidance of photothermal chemotherapy. DTX/PPN@PPY@HA shows good photothermal effects and temperature-sensitive drug release. In addition, cellular experiments showed that DTX/PPN@PPY@HA could be efficiently internalized into tumor cells and produce significant cytotoxicity with the help of near-infrared (NIR) laser. Furthermore, the remarkable inhibition of DTX/PPN@PPY@HA against tumor growth was achieved in 4T1 tumor-bearing mice model.

Simulations on Monitoring and Evaluation of Plasticity-Driven Material Damage Based on Second Harmonic of S0 Mode Lamb Waves in Metallic Plates.

In this study, a numerical approach-the discontinuous Meshless Local Petrov-Galerkin-Eshelby Method (MLPGEM)-was adopted to simulate and measure material plasticity in an Al 7075-T651 plate. The plate was modeled in two dimensions by assemblies of small particles that interact with each other through bonding stiffness. The material plasticity of the model loaded to produce different levels of strain is evaluated with the Lamb waves of S0 mode. A tone burst at the center frequency of 200 kHz was used as excitation. Second-order nonlinear wave was extracted from the spectrogram of a signal receiving point. Tensile-driven plastic deformation and cumulative second harmonic generation of S0 mode were observed in the simulation. Simulated measurement of the acoustic nonlinearity increased monotonically with the level of tensile-driven plastic strain captured by MLPGEM, whereas achieving this state by other numerical methods is comparatively more difficult. This result indicates that the second harmonics of S0 mode can be employed to monitor and evaluate the material or structural early-stage damage induced by plasticity.