Clearance Rate Research Articles

#474 Features of the functional state of the kidney in patients with chronic heart failure with metabolic syndrome

Abstract Background and Aims to study the features of the functional state of the kidneys in patients with chronic heart failure with intermediate ejection fraction, depending on the representation of components of metabolic syndrome Method To achieve the objectives, 197 male patients with chronic heart failure (CHF) of ischemic origin II - III functional class (FC) according to NYHA, aged 40-60 years with a history of myocardial infarction of 6 months, were examined. up to 5 years. Depending on the presence of MS components, 3 groups of patients were identified: group I (n = 70), patients without MS (CHF FC II -38, CHF FC III - 32 patients); Group II (n = 67) patients with various combinations of dyslipidemia (HDL-C <1.03 mmol/l; LDL-C >3.0 mmol/l) with AO, hypertension and HTG (CHF FC II -35, CHF FC III - 32 patients); Group III (n = 60) patients with various combinations of dyslipoproteinemia (DLP) and type 2 diabetes mellitus (DM2) with AO, hypertension and HTG (CHF FC II -26, CHF FC III - 34 patients). When diagnosing MS, the International Diabetes Federation diagnostic criteria for MS were used (IDF, 2009). The study of the functional state of the kidneys included determination of the level of serum creatinine, urinary albumin excretion (determination of microalbuminuria (MAU ≥300 mg/l), glomerular filtration rate (GFR), calculated using the GFR EPI formula. Results when studying the parameters of the functional state of the kidneys in patients with CHF HFmrEF group 1, MAU was identified in 10 patients (35.7%) out of 28. Serum creatinine clearance in this group was 89.0 ± 8.49 μmol /l, and the GFR level was 88.58 ± 8.36 ml/min. With the development of MS in group II patients, 16 out of 28 patients had MAU (53.6%). A decrease in GFR was also found by 11.3% ( P < 0.05) with an increase in serum creatinine levels by 12.7% (P < 0.01), in contrast to the data from group I of the study. Further analysis of the parameters of renal function in group III of CHF HFmrEF revealed a significant decrease in GFR (by 23.0%; P < 0.01) with a significant increase in blood creatinine levels (by 21.8%; P < 0.01) in relation to the data Group I. Also in group III of patients with CHF and MS (+DM2 ), microalbuminuria was detected in 24 patients (85.7%) out of 32 . When comparing indicators of renal function between study groups II and III, there was a significant difference in the level of blood creatinine clearance and glomerular filtration rate by 11.3% and 10.1% (P < 0.05), respectively. Conclusion MS in patients with CHF HFmrEF aggravates renal dysfunction, which developed as one of the main pathogenetic links of CHF. Evidence of the importance of MS in the nature of the clinical manifestations of CHF HFmrEF is the established dependence of the identified disorders on the severity of MS.

#472 Cardiorenal relations in patients with chronic heart failure

Abstract Background and Aims To study the functional state of the kidneys and cardiorenal relationships in patients with chronic heart failure, depending on the representation of components of metabolic syndrome Method To achieve the objectives, 227 male patients with chronic heart failure (CHF) of ischemic origin of functional class II-III according to NYHA, aged 40-60 years with a history of myocardial infarction of 6 months, were examined up to 5 years. Depending on the presence of MS components, 3 groups of patients were identified: group I (n=80), patients without MS (CHF FC II—42, CHF FC III—38 patients); Group II (n=77) patients with various combinations of dyslipidemia (HDL-C <1.03 mmol/l; LDL-C >3.0 mmol/l) with abdominal obesity (AO), hypertension and hypertriglyceridemia (HTG) (CHF FC II—40, CHF FC III—37 patients); Group III (n=75) patients with various combinations of dyslipoproteinemia (DLP) and type 2 diabetes mellitus (DM2) with AO, hypertension and hypertriglyceridemia (CHF) (CHF FC II—36, CHF FC III—39 patients). When diagnosing MS, the International Diabetes Federation diagnostic criteria for MS were used (IDF, 2009). The study of the functional state of the kidneys included determination of the level of serum creatinine, urinary albumin excretion (determination of microalbuminuria (MAU ≥300 mg/l) in a single morning urine using indicator strips (Biosensor AN, Russia), glomerular filtration rate (GFR), calculated by the formula GFR EPI, which takes into account race, sex, age, serum creatinine. To calculate GFR using the CKD-EPI formula, you can use special applications for mobile devices (QxMDCalculator). Results When studying the parameters of the functional state of the kidneys in patients with group 1 CHF, 20 patients (25%) out of 80 were diagnosed with MAU. Serum creatinine clearance in this group was 89.0 ± 8.49 μmol/L, and the GFR level was 88.58 ± 8.36 ml/min. With the development of MS in group II patients, 41 out of 77 patients had MAU (53.2%). A decrease in GFR by 19.3% (P<0.01) was also found with an increase in serum creatinine levels by 22.7% (P<0.01), in contrast to the data from group I of the study. Further analysis of the parameters of renal function in CHF group III revealed a significant decrease in GFR (by 29.8%; P<0.001) with a significant increase in blood creatinine levels (by 31.8%; P<0.001) in relation to the data of group I. Also in group III of patients with CHF and MS (+DM2), microalbuminuria was detected in 47 patients (74.6%) out of 75. When comparing indicators of renal function between study groups II and III, there was a significant difference in the level of blood creatinine clearance and glomerular filtration rate by 21.3% and 20.1% (P<0.005), respectively. According to the classification of CKD, in group I of patients with CHF, stage I CKD was detected in 39.3%, in group II in 28.6% and in group III in 19.4%. CKD stage II was detected in group I in 46.4%, in group II in 50% of patients. 46.9% had CKD stage II of the disease in group III of the study. Also, in group II, 21.4% and group III, 43.7% were diagnosed with stage III CKD. V In group I, 35% had a high risk, 53.6% had a moderate and 14.3% had a low combined risk of developing cardiovascular complications in cardiorenal syndrome. Conclusion Thus, MS in patients with CHF aggravates renal dysfunction, which developed as one of the main pathogenetic links of CHF. It has been established that as MS progresses (addition of type 2 diabetes to other components of MS), the phenomena of functional renal failure increase. Violation of the functional state of the kidneys, the severity and nature of this dysfunction depends on the presence and nature of the representation of MS components.

#1526 Effects of dietary intervention on diabetic nephropathy: an umbrella review of systematic review and meta-analysis of randomized controlled trials

Abstract Background and Aims To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN). Method We conducted an umbrella review of existing meta-analyses of randomized controlled trials (RCTs) that focused on the effects of dietary intervention on DN. Literature searching was performed via PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and hand searching of the reference lists. Systematic reviews and meta-analyses of RCTs that evaluated the effects of any dietary intervention on clinical outcomes of DN were included. Two reviewers evaluated the methodological quality of the included articles through AMSTAR score. In addition, according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE), evidence of each outcome was evaluated and graded as “high”, “moderate”, “low” or “very low” quality to draw conclusions. Additionally, we classified evidence of outcomes into 4 categories (class I to IV and non-significant (NS)). Results We identified 36 meta-analyses of RCTs and 55 clinical outcomes of DN from 395 unique articles (Fig. 1). Moderate quality evidence suggested that probiotics supplementation could significantly improve blood urea nitrogen (BUN), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in DN patients. Low quality evidence indicated that probiotics supplementation significantly improved serum creatinine, urinary albumin creatinine ratio (UACR), fasting blood glucose (FBG), HbA1c and high-density lipoprotein cholesterol (HDL-C) in DN patients. In addition, low quality evidence suggested that a salt restriction diet could significantly improve creatinine clearance rate (CrCl) in patients with DN. Low quality evidence suggested that vitamin D supplementation could significantly improve UACR in patients with DN. Besides, low quality evidence indicated that soy isoflavone supplementation could significantly improve BUN, FBG, TC, triglycerides (TG) and LDL-C in patients with DN. Furthermore, low quality evidence suggested that coenzyme Q10 supplementation could significantly improve HbA1c, TC and HDL-C in patients with DN, and dietary polyphenols also significantly improved HbA1c in patients with DN. Finally, low quality evidence suggested supplementation of antioxidant vitamins could significantly improve serum creatinine, systolic blood pressure, and HbA1c in patients with DN. The remaining outcomes were rated as very low quality due to significant risk of bias, significant heterogeneity, imprecision, and publication bias. Given the small sample size, all significantly associated outcomes were evaluated as class IV evidence (Fig. 2). Conclusion Moderate to low evidence suggests that supplementation with probiotics, vitamin D, soy isoflavones, coenzyme Q10, dietary polyphenols, antioxidant vitamins, and salt-restricted diets may significantly improve clinical outcomes in patients with DN.

Comparative analysis of within-host dynamics of acute infection and viral rebound dynamics in postnatally SHIV-infected ART-treated infant rhesus macaques.

Viral dynamics of acute HIV infection and HIV rebound following suspension of antiretroviral therapy may be qualitatively similar but must differ given, for one, development of adaptive immune responses. Understanding the differences of acute HIV infection and viral rebound dynamics in pediatric populations may provide insights into the mechanisms of viral control with potential implications for vaccine design and the development of effective targeted therapeutics for infants and children. Mathematical models have been a crucial tool to elucidate the complex processes driving viral infections within the host. Traditionally, acute HIV infection has been modeled with a standard model of viral dynamics initially developed to explore viral decay during treatment, while viral rebound has necessitated extensions of that standard model to incorporate explicit immune responses. Previous efforts to fit these models to viral load data have underscored differences between the two infection stages, such as increased viral clearance rate and increased death rate of infected cells during rebound. However, these findings have been predicated on viral load measurements from disparate adult individuals. In this study, we aim to bridge this gap, in infants, by comparing the dynamics of acute infection and viral rebound within the same individuals by leveraging an infant nonhuman primate Simian/Human Immunodeficiency Virus (SHIV) infection model. Ten infant Rhesus macaques (RMs) orally challenged with SHIV.C.CH505 375H dCT and given ART at 8 weeks post-infection. These infants were then monitored for up to 60 months post-infection with serial viral load and immune measurements. We use the HIV standard viral dynamics model fitted to viral load measurements in a nonlinear mixed effects framework. We find that the primary difference between acute infection and rebound is the increased death rate of infected cells during rebound. We use these findings to generate hypotheses on the effects of adaptive immune responses. We leverage these findings to formulate hypotheses to elucidate the observed results and provide arguments to support the notion that delayed viral rebound is characterized by a stronger CD8+ T cell response.

Prospective Assessment of Adjuvant Netarsudil Use in Patients Undergoing Descemet Stripping Only.

We sought to determine whether adjuvant use of netarsudil improves corneal clearance rate and regeneration of corneal endothelial cells in patients undergoing Descemet stripping only (DSO). We conducted a prospective assessment on the use of adjuvant netarsudil in 50 eyes from 25 patients undergoing DSO at Massachusetts Eye and Ear between May 2021 and May 2023. Our comparison group was a retrospective cohort of patients (23 eyes from 15 patients) who previously underwent DSO without the use of a postoperative rho-kinase inhibitor between September 2014 and March 2020. Use of netarsudil after DSO statistically significantly reduced time to corneal clearance, improved best corrected visual acuity, reduced pachymetric thickness, and increased central endothelial cell count (ECC) at 6 months postoperatively. Importantly, central ECC continued to increase beyond 12 months after DSO with central ECC still statistically significantly greater in eyes that received netarsudil than in eyes that received no netarsudil. A rho-kinase inhibitor, such as netarsudil, after DSO should be used if available to achieve the best corneal clearance, best corrected visual acuity, and ECC after surgery.

Foraging mechanisms in excavate flagellates shed light on the functional ecology of early eukaryotes

The phagotrophic flagellates described as "typical excavates" have been hypothesized to be morphologically similar to the Last Eukaryotic Common Ancestor and understanding the functional ecology of excavates may therefore help shed light on the ecology of these early eukaryotes. Typical excavates are characterized by a posterior flagellum equipped with a vane that beats in a ventral groove. Here, we combined flow visualization and observations of prey capture in representatives of the three clades of excavates with computational fluid dynamic modeling, to understand the functional significance of this cell architecture. We record substantial differences amongst species in the orientation of the vane and the beat plane of the posterior flagellum. Clearance rate magnitudes estimated from flow visualization and modeling are both like that of other similarly sized flagellates. The interaction between a vaned flagellum beating in a confinement is modeled to produce a very efficient feeding current at low energy costs, irrespective of the beat plane and vane orientation and of all other morphological variations. Given this predicted uniformity of function, we suggest that the foraging systems of typical excavates studied here may be good proxies to understand those potentially used by our distant ancestors more than 1 billion years ago.

Preparation of xylooligosaccharides from rice husks and their structural characterization, antioxidant activity, and probiotic properties

Rice husks are rich in xylan, which can be hydrolyzed by xylanase to form xylooligosaccharides (XOS). XOS are a functional oligosaccharide such as improving gut microbiota and antioxidant properties. In this study, the structure and functional characteristics of XOS were studied. The optimal xylanase hydrolysis conditions through response surface methodology (RSM) were: xylanase dosage of 3000 U/g, hydrolysis time of 3 h, hydrolysis temperature of 50 °C. Under this condition, the yield of XOS was 150.9 mg/g. The TG-DTG curve showed that XOS began to decompose at around 200 °C. When the concentration of XOS reached 1.0 g/L, the clearance rate of DPPH reached 65.76 %, and the scavenging rate of OH reached 62.10 %, while the clearance rate of ABTS free radicals reached 97.70 %, which was equivalent to the clearance rate of VC. XOS had a proliferative effect on four probiotics: Lactobacillus plantarum, Lactobacillus brucelli, Lactobacillus acidophilus, and Lactobacillus rhamnosus. However, the further experiments are needed to explore the improvement effect of XOS on human gut microbiota, laying a foundation for the effective utilization of XOS. XOS have a wide range of sources, low price, and broad development prospects. The reasonable utilization of XOS can bring greater economic benefits.

Renal Replacement Therapy as a New Indicator of Voriconazole Clearance in a Population Pharmacokinetic Analysis of Critically Ill Patients.

The pharmacokinetic (PK) profiles of voriconazole in intensive care unit (ICU) patients differ from that in other patients. We aimed to develop a population pharmacokinetic (PopPK) model to evaluate the effects of using extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and those of various biological covariates on the voriconazole PK profile. Modeling analyses of the PK parameters were conducted using the nonlinear mixed-effects modeling method (NONMEM) with a two-compartment model. Monte Carlo simulations (MCSs) were performed to observe the probability of target attainment (PTA) when receiving CRRT or not under different dosage regimens, different stratifications of quick C-reactive protein (qCRP), and different minimum inhibitory concentration (MIC) ranges. A total of 408 critically ill patients with 746 voriconazole concentration-time data points were included in this study. A two-compartment population PK model with qCRP, CRRT, creatinine clearance rate (CLCR), platelets (PLT), and prothrombin time (PT) as fixed effects was developed using the NONMEM. We found that qCRP, CRRT, CLCR, PLT, and PT affected the voriconazole clearance. The most commonly used clinical regimen of 200 mg q12h was sufficient for the most common sensitive pathogens (MIC ≤ 0.25 mg/L), regardless of whether CRRT was performed and the level of qCRP. When the MIC was 0.5 mg/L, 200 mg q12h was insufficient only when the qCRP was <40 mg/L and CRRT was performed. When the MIC was ≥2 mg/L, a dose of 300 mg q12h could not achieve ≥ 90% PTA, necessitating the evaluation of a higher dose.

Effectiveness of Combined Hemodialysis-Hemadsorption Therapy in Improving Uremic Toxin Clearance, Inflammatory Markers, and Symptoms in Maintenance Hemodialysis Patients

Introduction: Combined hemodialysis (HD) and hemadsorption (HA) therapy has shown the highest clearance rates for middle and large-sized uremic toxin molecules and reduced mortality rates among maintenance HD (MHD) patients. This study aimed to investigate the effectiveness of combined HD and HA therapy in patients undergoing MHD. Methods: Forty patients with end-stage renal disease (ESRD) were divided into three groups: HD only (14), HD + biweekly HA (14), and HD + weekly HA (12). The duration of the study was 8 weeks. Uremic toxins (β2-microglobulin, leptin, parathyroid hormone), inflammatory markers (interleukin-6, C-reactive protein), and symptoms (appetite, pruritus, sleep quality) were assessed before the start and at the completion of therapy. Changes in the parameters were compared between the three groups. Mean differences of parameters in each group were also compared between before and after therapy. Results: Decrease in BUN level (−61.34 mg/dL [95% CI: −71.33 to −51.34], p < 0.0001) and pruritus score (−3.93 [95% CI: −6.89 to −0.97], p = 0.013) was significantly larger in HD + biweekly HA group compared to the others. Only HD + biweekly HA group showed significant reductions in CRP level (−0.10 mg/L [95%: −0.18 to −0.01], p = 0.034), VAS appetite score (10.43 [95% CI: 4.99–15.87], p = 0.001), and pruritus score (−3.93 [95% CI: −6.89 to −0.97], p = 0.013) after therapy. Both HD + biweekly HA (−2.79 [95% CI: −4.97 to −0.60], p = 0.016) and HD + weekly HA group (−2.33 [95% CI: −4.59 to −0.08], p = 0.044) exhibited a significant improvement in sleep quality score after therapy. Conclusions: HD combined with a biweekly HA is associated with a greater reduction in BUN level and better improvement of pruritus in ESRD patients compared to HD alone. HD + biweekly HA can significantly reduce CRP levels, alleviate pruritus, improve appetite, and enhance sleep quality.

The effect of vorticity on the feeding of a freshwater grazer

AbstractThe transfer of energy through zooplankton grazing on phytoplankton is one of the most important interactions in aquatic ecosystems, yet the role of hydrodynamic forces is not fully understood. Factors that influence these interactions include algal size and shape and the interactions between grazer and alga dictated by hydrodynamic forces. Hydrodynamic forcing lead to unimodal relationships in grazer clearance rates (CR) because water motion and turbulence increases encounters but interferes with feeding at high levels. We expect higher CR on small algae due to increased encounter rates caused by vorticity generated in a horizontally oriented rotating cylinder to model increasing turbulence, whereas longer cells, tumbling in the flow, may be more difficult to handle. Ultimately, we expect that increased vorticity will interfere with zooplankton swimming. The CR of Daphnia magna followed the unimodal trend, with higher CR on the small, spherical Chlorella vulgaris than on larger, elongated, and colonial Scenedesmus quadricauda. This was likely due to lower handling time and higher concentration of the smaller cells in the feeding radius around D. magna. The normal hop‐sink swimming behavior of the Daphnia was affected by increasing vorticity; hop frequency decreased, displacement increased, and there was a loss of vertical orientation. This pattern in feeding and swimming were predicted by vorticity. These results for Daphnia differ from those obtained for copepods, which do not respond to vorticity. Given the importance of vorticity in nature, it is relevant to examine grazer feeding interactions under ecologically relevant hydrodynamic conditions.

Role of lactate and lactate metabolism in liver diseases (Review).

Lactate is a byproduct of glycolysis, and before the Warburg effect was revealed (in which glucose can be fermented in the presence of oxygen to produce lactate) it was considered a metabolic waste product. At present, lactate is not only recognized as a metabolic substrate that provides energy, but also as a signaling molecule that regulates cellular functions under pathophysiological conditions. Lactylation, a post‑translational modification, is involved in the development of various diseases, including inflammation and tumors. Liver disease is a major health challenge worldwide. In normal liver, there is a net lactate uptake caused by gluconeogenesis, exhibiting a higher net lactate clearance rate compared with any other organ. Therefore, abnormalities of lactate and lactate metabolism lead to the development of liver disease, and lactate and lactate metabolism‑related genes can be used for predicting the prognosis of liver disease. Targeting lactate production, regulating lactate transport and modulating lactylation may be potential treatment approaches for liver disease. However, currently there is not a systematic review that summarizes the role of lactate and lactate metabolism in liver diseases. In the present review, the role of lactate and lactate metabolism in liver diseases including liver fibrosis, non‑alcoholic fatty liver disease, acute liver failure and hepatocellular carcinoma was summarized with the aim to provide insights for future research.

Lactate dynamics in paediatric patients with severe sepsis: insights from a prospective cohort study

BackgroundSepsis is an infection-related systemic inflammatory response that often leads to elevated lactate levels. Monitoring lactate levels during severe sepsis is vital for influencing clinical outcomes. The aim of this study was to assess the association between plasma lactate levels and mortality in children with severe sepsis or septic shock.MethodsThe current prospective study was conducted in the PICU of University Children’s Hospital. The International Paediatric Sepsis Consensus Conference criteria for Definitions of Sepsis and Organ Failure in 2005 were used to diagnose patients with sepsis. We measured plasma lactate levels upon admission (Lac H0) and 6 h later (Lac H6). The static indices included the absolute lactate values (Lac H0 and Lac H6), while the dynamic indices included the delta-lactate level (ΔLac) and the 6-hour lactate clearance. The 6-hour lactate clearance was calculated using the following formula: [(Lac H0–Lac H6)100/Lac H0]. ΔLac was calculated as the difference between the Lac H0 and Lac H6 levels. Patient survival or death after a PICU stay was the primary outcome.ResultsA total of 46 patients were included in this study: 25 had septic shock, and 21 had severe sepsis. The mortality rate was 54.3%. The Lac H0 did not significantly differ between survivors and nonsurvivors. In contrast, the survivors had significantly lower Lac H6 levels, higher ΔLac levels, and higher 6-hour lactate clearance rates than nonsurvivors. Lactate clearance rates below 10%, 20%, and 30% were significantly associated with mortality. The best cut-off values for the lactate clearance rate and Lac H6 for the prediction of mortality in the PICU were < 10% and ≥ 4 mmol/L, respectively. Patients with higher Lac H6 levels and lower lactate clearance rates had significantly higher PICU mortality based on Kaplan–Meier survival curve analysis.ConclusionsThis study highlights the significance of lactate level trends over time for the prediction of mortality in the PICU in patients with severe sepsis or septic shock. Elevated lactate levels and decreased lactate clearance six hours after hospitalisation are associated with a higher mortality rate.

Solid foam composite derived from cement and jujube core activated carbon: a sustainable adsorbent for textile wastewater treatment

The textile industry is responsible for a significant amount of environmental damage caused by the use of dyes, which puts the health of humans and the ecosystems in the surrounding area in dire danger. The conventional approaches to wastewater treatment can be rather expensive and demand a significant amount of energy. Regrettably, these techniques are not very efficient when it comes to dealing with the substantial quantities of coloured wastewater that are generated by the textile sector. The utilisation of cement-activated carbon solid foam composite technology is a viable option that offers significant advantages in terms of both efficiency and environmental impact. These solid foam adsorbents are produced by the utilisation of a manufacturing process that is environmentally friendly and ingredients that are sourced locally, such as jujube cores. Even at low initial dye concentrations, they had clearance rates of over 98%, which is an impressively high percentage from their dye retention capabilities. In order to demonstrate the composite's potential for use in wastewater treatment applications, characterization techniques such as scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and EDX are utilised. After conducting in-depth research, it has been established that the mass of the adsorbent and the length of time that it is in contact with the substance have a significant impact on the removal efficiency. The most favourable conditions have been seen to occur within a time range of ninety minutes, according to those observations. Methylene blue can be effectively removed with the help of the solid foam Composite, which is a sorbent that is not only readily available but also practical, cost-effective, and readily available. According to the findings of equilibrium research, the Temkin isotherm model is the one that is most suitable for understanding the behaviour of adsorption. As an additional point of interest, desorption experiments have shown that there are strong bindings between the dye and the composite, which indicates that there is minimal reversibility.

Bioaccumulation and biological effects of hydrogenated cement particles in the marine bivalve, Mytilusgalloprovincialis

The decommissioning and normal functioning of nuclear facilities can result in the production and release of airborne particles in the environment. Aquatic biota are expected to be exposed to these particles considering that nuclear facilities are often located near water bodies. Aerosols, such as cement dust, can interact with radionuclides as well as with heavy metals, and therefore elicit not only radiological impacts but also chemical toxicity. In the present study, we aimed to determine the effects of hydrogenated cement particles (HCPs) as a first step before evaluating any radiotoxicity of tritiated cement particles in the marine mussels, Mytilus galloprovincialis. Responses at different levels of biological organisation were assessed, including clearance rate (CR), tissue specific accumulation, DNA damage and transcriptional expression of key stress related genes. Acute (5 h) and medium-term, chronic (11 d) exposures to 1000 μg L−1 HCPs showed that bioaccumulation, assessed using Cu as a proxy and determined by inductively coupled plasma mass spectrometry, was time and tissue dependent. The highest levels of Cu were found in the digestive gland (DG) after 11 d. HCP exposure caused changes in the expression of oxidative and other stress-related genes, including mt20 in DG and gst and sod in the gill after 5 h exposure, while an overexpression of hsp70 in the gill was observed after 11 d. Genotoxic effects in haemocytes were observed after 11 d of HCP exposure. Multivariate analysis indicated that oxidative stress is the most probable factor contributing to overall physiological dysfunction. Our results provide a baseline to perform further studies employing tritiated cement particles. Specifically, future work should focus on the DG since only this tissue showed significant bioaccumulation when compared to the negative control.

Hypoxia impairs blood glucose homeostasis in naked mole-rat adult subordinates but not queens.

Naked mole-rats (NMRs) are among the most hypoxia-tolerant mammals and metabolize only carbohydrates in hypoxia. Glucose is the primary building block of dietary carbohydrates, but how blood glucose is regulated during hypoxia has not been explored in NMRs. We hypothesized that NMRs mobilize glucose stores to support anaerobic energy metabolism in hypoxia. To test this, we treated newborn, juvenile and adult (subordinate and queen) NMRs in normoxia (21% O2) or hypoxia (7, 5 or 3% O2), while measuring metabolic rate, body temperature and blood [glucose]. We also challenged animals with glucose, insulin or insulin-like growth factor-1 (IGF-1) injections and measured the rate of glucose clearance in normoxia and hypoxia. We found that: (1) blood [glucose] increases in moderate hypoxia in queens and pups, but only in severe hypoxia in adult subordinates and juveniles; (2) glucose tolerance is similar between developmental stages in normoxia, but glucose clearance times are 2- to 3-fold longer in juveniles and subordinates than in queens or pups in hypoxia; and (3) reoxygenation accelerates glucose clearance in hypoxic subordinate adults. Mechanistically, (4) insulin and IGF-1 reduce blood [glucose] in subordinates in both normoxia but only IGF-1 impacts blood [glucose] in hypoxic queens. Our results indicate that insulin signaling is impaired by hypoxia in NMRs, but that queens utilize IGF-1 to overcome this limitation and effectively regulate blood glucose in hypoxia. This suggests that sexual maturation impacts blood glucose handling in hypoxic NMR queens, which may allow queens to spend longer periods of time in hypoxic nest chambers.

Assessment of the Safety and Probiotic Properties of Enterococcus faecium B13 Isolated from Fermented Chili

Enterococcus faecium B13, selected from fermentation chili, has been proven to promote animal growth by previous studies, but it belongs to opportunistic pathogens, so a comprehensive evaluation of its probiotic properties and safety is necessary. In this study, the probiotic properties and safety of B13 were evaluated at the genetic and phenotype levels in vitro and then confirmed in vivo. The genome of B13 contains one chromosome and two plasmids. The average nucleotide identity indicated that B13 was most closely related to the fermentation-plant-derived strain. The strain does not carry the major virulence genes of the clinical E. faecium strains but contains aac(6′)-Ii, ant (6)-Ia, msrC genes. The strain had a higher tolerance to acid at pH 3.0, 4.0, and 0.3% bile salt and a 32.83% free radical DPPH clearance rate. It can adhere to Caco-2 cells and reduce the adhesion of E. coli to Caco-2 cells. The safety assessment revealed that the strain showed no hemolysis and did not exhibit gelatinase, ornithine decarboxylase, lysine decarboxylase, or tryptophanase activity. It was sensitive to twelve antibiotics but was resistant to erythromycin, rifampicin, tetracycline, doxycycline, and minocycline. Experiments in vivo have shown that B13 can be located in the ileum and colon and has no adverse effects on experiment animals. After 28 days of feeding, B13 did not remarkable change the α-diversity of the gut flora or increase the virulence genes. Our study demonstrated that E. faecium B13 may be used as a probiotic candidate.

Photothermal/photodynamic synergistic antibacterial study of MOF nanoplatform with SnFe2O4 as the core

Drug-resistant bacterial infections cause significant harm to public life, health, and property. Biofilm is characterized by overexpression of glutathione (GSH), hypoxia, and slight acidity, which is one of the main factors for the formation of bacterial resistance. Traditional antibiotic therapy gradually loses its efficacy against multi-drug-resistant (MDR) bacteria. Therefore, synergistic therapy, which regulates the biofilm microenvironment, is a promising strategy. A multifunctional nanoplatform, SnFe2O4-PBA/Ce6@ZIF-8 (SBC@ZIF-8), in which tin ferrite (SnFe2O4, denoted as SFO) as the core, loaded with 3-aminobenzeneboronic acid (PBA) and dihydroporphyrin e6 (Ce6), and finally coated with zeolite imidazole salt skeleton 8 (ZIF-8). The platform has a synergistic photothermal therapy (PTT)/photodynamic therapy (PDT) effect, which can effectively remove overexpressed GSH by glutathione peroxidase-like activity, reduce the antioxidant capacity of biofilm, and enhance PDT. The platform had excellent photothermal performance (photothermal conversion efficiency was 55.7 %) and photothermal stability. The inhibition rate of two MDR bacteria was more than 96 %, and the biofilm clearance rate was more than 90 % (150 μg/mL). In the animal model of MDR S. aureus infected wound, after 100 μL SBC@ZIF-8+NIR (150 μg/mL) treatment, the wound area of mice was reduced by 95 % and nearly healed. The serum biochemical indexes and H&E staining results were within the normal range, indicating that the platform could promote wound healing and had good biosafety. In this study, we designed and synthesized multifunctional nanoplatforms with good anti-drug-resistant bacteria effect and elucidated the molecular mechanism of its anti-drug-resistant bacteria. It lays a foundation for clinical application in treating wound infection and promoting wound healing.

Association of postabsorptive glucose and acetate metabolism with feed intake, growth, and efficiency in finishing beef heifers

The objective of this experiment was to determine whether acetate and glucose metabolism and insulin response to glucose are associated with the growth, feed intake, and feed efficiency of finishing heifers. Charolais heifers ( n = 18; initial body weight = 415.7 ± 45.17 kg) were acclimated to restraint with a halter and fed a finishing diet ad libitum using an Insentec feeding system. Following a 12 h fast, a jugular catheter was inserted, and an acetate clearance test was performed followed by a glucose clearance test. Four days after the metabolic tests, heifers began an 84-day DMI and ADG test period. Heifers gained 1.69 ± 0.03 kg/day and consumed 10.4 ± 0.19 kg/day. Acetate and glucose clearance rates were not associated with any production trait ( P ≥ 0.40). Insulin time to peak concentration after the glucose challenge was associated ( r = 0.69; P = 0.003) with G:F, but not peak concentration ( P = 0.45). The increased time to insulin peak could indicate that efficient heifers have pancreatic β-cell dysfunction, which is a contributor to insulin resistance. These data indicate that insulin resistance early in the finishing period could be related to improved feed efficiency in finishing heifers.

High-risk acute myeloid leukemia with DEK-NUP214 rearrangement and eyelid infiltration: a case report

Objective: This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD(+) R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. Methods: The clinical data of 26 patients with FLT3-ITD(+) R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. Results: A total of 26 patients with FLT3-ITD(+) R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95%CI 2.2-4.3 months, P=0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment (P=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; P=0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. Conclusion: The Gilt-based combination therapy is highly effective in treating FLT3-ITD(+) R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients' survival. Furthermore, the clearance rate of FLT3-ITD mutation is notably high. Additionally, implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients' survival. Closely monitoring and managing any adverse event that may occur during treatment are crucial.

Albumin Nanoparticles Increase the Efficacy of Doxorubicin Hydrochloride Liposome Injection Based on Threshold Theory.

One of the most significant reasons hindering the clinical translation of nanomedicines is the rapid clearance of intravenously injected nanoparticles by the mononuclear phagocyte system, particularly by Kupffer cells in the liver, leading to an inefficient delivery of nanomedicines for tumor treatment. The threshold theory suggests that the liver's capacity to clear nanoparticles is limited, and a single high dose of nanoparticles can reduce the hepatic clearance efficiency, allowing more nanomedicines to reach tumor tissues and enhance therapeutic efficacy. Building upon this theory, researchers have conducted numerous validation studies based on the same nanoparticle carrier systems. These studies involve the use of albumin nanoparticles to improve the therapeutic efficacy of albumin nanomedicines as well as polyethylene glycol (PEG)-modified liposomal nanoparticles to enhance the efficacy of PEGylated liposomal nanomedicines. However, there is no research indicating the feasibility of the threshold theory when blank nanoparticles and nanomedicine belong to different nanoparticle carrier systems currently. In this study, we prepared two different sizes of albumin nanoparticles by using bovine serum albumin. We used the marketed nanomedicine liposomal doxorubicin hydrochloride injection (trade name: LIBOD, manufacturer: Shanghai Fudan-zhangjiang Biopharmaceutical Co., Ltd.), as the representative nanomedicine. Through in vivo experiments, we found that using threshold doses of albumin nanoparticles still can reduce the clearance rate of LIBOD, prolong its time in vivo, increase the area under the plasma concentration-time curve (AUC), and also lead to an increased accumulation of the drug at the tumor site. Furthermore, evaluation of in vivo efficacy and safety further indicates that threshold doses of 100 nm albumin nanoparticles can enhance the antitumor effect of LIBOD without causing harm to the animals. During the study, we found that the particle size of albumin nanoparticles influenced the in vivo distribution of the nanomedicine at the same threshold dose. Compared with 200 nm albumin nanoparticles, 100 nm albumin nanoparticles more effectively reduce the clearance efficiency of LIBOD and enhance nanomedicine accumulation at the tumor site, warranting further investigation. This study utilized albumin nanoparticles to reduce hepatic clearance efficiency and enhance the delivery efficiency of nonalbumin nanocarrier liposomal nanomedicine, providing a new avenue to improve the efficacy and clinical translation of nanomedicines with different carrier systems.