Radiomics features based on dual-area CT predict the expression levels of fatty acid binding protein 4 and outcome in hepatocellular carcinoma.

RATIONALE AND OBJECTIVES: To evaluate the predictive value of tumor and peritumor radiomics in the fatty acid binding protein 4 (FABP4) expression levels and overall survival in patients with hepatocellular carcinoma. MATERIALS AND METHODS: The genomic data of HCC patients were obtained from The Cancer Genome Atlas. The Dual-area CT images of corresponding patients were downloaded from The Cancer Imaging Archive, for radiomics feature extraction, model construction and prognosis analysis. Simultaneously, using patients from Sichuan Provincial People's Hospital, the prognostic value of the radiomics model in HCC patients was validated. RESULTS: In the TCIA database, the area under the curve (AUC) values of the volumes of interest (VOI)whole model in the training set and internal validation set were 0.812 and 0.754, respectively, and the AUC value of VOIwhole+periphery in the training set and internal validation set were 0.866 and 0.779, respectively. In the VOIwhole and the VOIwhole+periphery model of the independent cohort, there were significant differences in OS between the high and low rad-score groups (P = 0.009, P = 0.021, respectively). Significant positive correlations can be observed between FABP4 expression and correlations with rad-score of VOIwhole model (r = 0.691) and VOIwhole+periphery model (r = 0.732) in the independent cohort. CONCLUSION: Radiomics models of tumor and peritumor Dual-area CT images could predict stably the expression levels of FABP4 and may be helping in personalized treatment strategies.

Allograft function predicts mortality in kidney transplant recipients with severe COVID-19: a paradoxical risk factor.

Introduction: Kidney transplant recipients (KTRs) are at a higher risk of severe coronavirus disease (COVID-19) because of their immunocompromised status. However, the effect of allograft function on the prognosis of severe COVID-19 in KTRs is unclear. In this study, we aimed to analyze the correlation between pre-infection allograft function and the prognosis of severe COVID-19 in KTRs. Methods: This retrospective cohort study included 82 patients who underwent kidney transplantation at the Sichuan Provincial Peoples Hospital between October 1, 2014 and December 1, 2022 and were diagnosed with severe COVID-19. The patients were divided into decreased eGFR and normal eGFR groups based on the allograft function before COVID-19 diagnosis (n=32 [decreased eGFR group], mean age: 43.00 years; n=50 [normal eGFR group, mean age: 41.88 years). We performed logistic regression analysis to identify risk factors for death in patients with severe COVID-19. The nomogram was used to visualize the logistic regression model results. Results: The mortality rate of KTRs with pre-infection allograft function insufficiency in the decreased eGFR group was significantly higher than that of KTRs in the normal eGFR group (31.25% [10/32] vs. 8.00% [4/50], P=0.006). Pre-infection allograft function insufficiency (OR=6.96, 95% CI: 1.4633.18, P=0.015) and maintenance of a mycophenolic acid dose >1500 mg/day before infection (OR=7.59, 95% CI: 1.0853.20, P=0.041) were independent risk factors, and the use of nirmatrelvir/ritonavir before severe COVID-19 (OR=0.15, 95% CI: 0.030.72, P=0.018) was a protective factor against death in severe COVID-19. Conclusions: Pre-infection allograft function is a good predictor of death in patients with severe COVID-19. Allograft function was improved after treatment for severe COVID-19, which was not observed in patients with non-severe COVID-19.

Regulation and mechanism of pyrite and humic acid on the toxicity of arsenate in lettuce.

Pyrite and humic acid are common substances in nature, and the combined effects of pyrite and humic acid on arsenic phytotoxicity are more widespread in the actual environments than that of a single substance, but have received less attention. In this study, the interaction between pyrite and humic acid in arsenate solution was studied, and the effects of pyrite and humic acid on plant toxicity of arsenate were evaluated. The results showed that arsenate + pyrite + fulvic acid (V-PF) treatment immobilized more arsenic by forming chemical bonds such as AsS and Fe-As-O and reduced the migration of arsenic to plants. Compared to the arsenate + fulvic acid (VF), arsenate + pyrite (VP) and arsenate (V) group, the inorganic arsenic content of lettuce leaves in the V- PF group was reduced by 19.8 %, 13.4 % and 13.4 %, respectively. In addition, the V-PF group increased the absorption of Ca, Fe and Cu in plant roots, and improved the activity of superoxide dismutase (SOD) in plant leaves. Compared to the VF group, SOD and MDA in the V-PF group increased by 34.1 % in 30 days and decreased by 47.3 % in 40 days, respectively. The biomass of lettuce in V-PF group was increased by 29.3 % compared with that in VF group on day 50. The protein content of the V-PF group was 58.3 % higher than that of the VF group and 23.1 % higher than that of the VP group. Furthermore, metabolomics analysis showed that the V-PF group promoted glycolysis by up-regulating glyoxylic acid and dicarboxylic acid metabolism, thus reducing carbohydrate accumulation. Phosphocreatine metabolism was also up-regulated, which decreased the oxidative damage in lettuce induced by arsenic. This study will provide new ideas for scientifically and rationally assessing the ecological environmental risks of arsenic and regulating its toxicity.

Highly active complexes of pyrite and organic matter regulate arsenic fate.

Arsenic (As) presents high toxicity and strong carcinogenicity, and its health risks are regulated by its oxidation state and speciation. As can form complexes with the surface of minerals or organic matter through adsorption, affecting its toxicity and bioavailability. However, the regulation effect of the interaction of coexisting minerals and organic matter on As fate remains largely unknown. Here, we discovered that minerals (e.g., pyrite) and organic matter (e.g., alanyl glutamine, AG) can form pyrite-AG complexes, promoting As(III) oxidation under simulated solar irradiation. The formation of pyrite-AG was explored in terms of the interaction of surface oxygen atoms, electron transfer and crystal surface changes. From the perspective of atoms and molecules, pyrite-AG showed more oxygen vacancies, stronger reactive oxygen species (ROS) and a higher electron transport capacity than pyrite alone. Compared with pyrite, pyrite-AG effectively promoted the conversion of highly toxic As(III) to less toxic As(V) due to the enhanced photochemical properties. Moreover, quantification and capture of ROS confirmed that hydroxyl radicals (•OH) played an important role in As(III) oxidation in the pyrite-AG and As(III) system. Our results provide previously unidentified perspectives on the effects and chemical mechanisms of highly active complexes of mineral and organic matter on As fate and provide new insights into the risk assessment and control of As pollution.

Microbial and metabolic features in renal transplant recipients with post-transplantation diabetes mellitus.

OBJECTIVE: Post-transplantation diabetes mellitus (PTDM) is a common complication in renal transplant recipients (RTRs). Gut microbiome plays important roles in a variety of chronic metabolic diseases, but its association with the occurrence and development of PTDM is still unknown. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of PTDM. METHODS: A total of 100 RTRs fecal samples were collected in our study. Among them, 55 samples were submitted to Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of RTRs were comprehensively characterized. RESULTS: The species Dialister invisus was significantly associated with fasting plasma glucose (FPG). The functions of tryptophan and phenylalanine biosynthesis were enhanced in RTRs with PTDM, while the functions of fructose and butyric acid metabolism were reduced. Fecal metabolome analysis indicated that RTRs with PTDM had unique metabolite distribution characteristics, and two differentially expressed specific metabolites were significantly correlated with FPG. The correlation analysis of gut microbiome and metabolites showed that gut microbiome had an obvious effect on the metabolic characteristics of RTRs with PTDM. Moreover, the relative abundance of microbial function is associated with the expression of several specific gut microbiome and metabolites. CONCLUSIONS: Our study identified the characteristics of gut microbiome and fecal metabolites in RTRs with PTDM, and we also found two important metabolites and a bacterium were significantly associated with PTDM, which might be used as novel targets in the research field of PTDM.

Regulation of arsenite toxicity in lettuce by pyrite and glutamic acid and the related mechanism.

Compared with the effect of a single substance on arsenic plant toxicity, the effect of coexisting pyrite and natural organic matter can better reflect actual environmental conditions. In this study, the interaction between pyrite and glutamic acid in arsenite solution was explored, the influence of pyrite and glutamic acid on arsenite plant toxicity was evaluated, and the metabolic regulation mechanism of pyrite and glutamic acid on the arsenite phytotoxic effect was clarified by metabolomics analysis. Combined pyrite and glutamic acid treatment fixed more arsenic by forming chemical bonds such as AsS, AsO, and As-O-OH in culture solution and reduced inorganic arsenic levels in plants. Compared with glutamic acid alone and pyrite alone, the combined treatment reduced the inorganic arsenic concentration in plants by 4.7 % and 40.0 %, respectively. The combined treatment limited plant ROS accumulation and maintained the leaf chlorophyll content by increasing SOD synthesis. Compared with the effect of As(III) alone, the chlorophyll content increased by 15.1-21.0 % on average under the combined treatment. The combined treatment promoted the absorption of Ca, Cu, Fe, Mo and Zn in lettuce, enhanced plant adaptation to As(III) and significantly improved plant nutritional quality. Compared with glutamic acid alone, the combined treatment increased the VC, fiber and protein contents by 128.9 %, 202.8 % and 36.7 %, respectively. Metabolomics analysis indicated that in the combined treatment group, the upregulation of tyrosine, pyruvate and N metabolism increased the plant chlorophyll content. The upregulation of S metabolism increases VC synthesis in plants and inhibits ROS accumulation, thus maintaining normal plant growth and development. The upregulation of glutathione and glycine metabolism enhances plant stress resistance. This study will provide a new way to scientifically and rationally evaluate the ecological risk of arsenic and regulate its toxicity.

Detection of BK polyomavirus-associated nephropathy using plasma graft-derived cell-free DNA: Development of a novel algorithm from programmed monitoring.

Graft-derived cell-free DNA (GcfDNA) is a promising non-invasive biomarker for detecting allograft injury. In this study, we aimed to evaluate the efficacy of programmed monitoring of GcfDNA for identifying BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant recipients. We recruited 158 kidney transplant recipients between November 2020 and December 2021. Plasma GcfDNA was collected on the tenth day, first month, third month, and sixth month for programmed monitoring and one day before biopsy. ΔGcfDNA (cp/mL) was obtained by subtracting the baseline GcfDNA (cp/mL) from GcfDNA (cp/mL) of the latest programmed monitoring before biopsy. The receiver operating characteristic curve showed the diagnostic performance of GcfDNA (cp/mL) at biopsy time and an optimal area under the curve (AUC) of 0.68 in distinguishing pathologically proven BKPyVAN from pathologically unconfirmed BKPyVAN. In contrast, ΔGcfDNA (cp/mL) had a sensitivity and specificity of 80% and 84.6%, respectively, and an AUC of 0.83. When distinguishing clinically diagnosed BKPyVAN from clinical excluded BKPyVAN, the AUC of GcfDNA (cp/mL) was 0.59 at biopsy time, and ΔGcfDNA (cp/mL) had a sensitivity and specificity of 81.0% and 76.5%, respectively, and an AUC of 0.81. Plasma ΔGcfDNA (cp/mL) was not significantly different between TCMR [0.15 (0.08, 0.24) cp/mL] and pathologically proven BKPyVAN[0.34 (0.20, 0.49) cp/mL]. In conclusion, we recommend programmed monitoring of plasma GcfDNA levels after a kidney transplant. Based on our findings from the programmed monitoring, we have developed a novel algorithm that shows promising results in identifying and predicting BKPyVAN.

Arsenite phytotoxicity and metabolite redistribution in lettuce (Lactuca sativa L.).

Arsenic (As) contamination has become a global problem, especially in developing countries, where a significant percentage of the population depends on groundwater for drinking. Arsenic toxicity depends on its chemical form. Herein, we evaluated the phytotoxicity of arsenite [As(III)], including As accumulation and adverse physiological responses (e.g., growth inhibition, oxidative stress, and metabolic disturbances). Furthermore, this result was compared with the mechanism of the phytotoxicity of arsenate [As(V)] that we previously explored. As accumulated mainly in the roots (29.33-88.73 mg/kg) of lettuce, only a small amount was transferred to the leaves (0.08-0.22 mg/kg); arsenic mainly existed in the form of As(III) in plants. As(III) was positively correlated with Mn in the leaves and roots and negatively correlated with Ca in roots and Mg in leaves, consistent with the increase in SOD activity and the destruction of the chloroplast membrane. Plants responded differently to As(III) and As(V) in terms of the antioxidant response and metabolic response. CAT activity in leaves was reduced following As(III) exposure and increased upon As(V) exposure. Furthermore, As(III) decreased the levels of some products of the tricarboxylic acid cycle and induced abnormal metabolism of secondary metabolites, such as phenol and niacin. The present study explored arsenic accumulation induced by As(III), the related physiological and biochemical responses and subsequent metabolite redistribution, and provided insights into the effects of different As species on plants.

Serum Procalcitonin Correlates With Renal Function and Immune Components in Early-Stage Renal Transplant Recipients.

BACKGROUND: In renal transplantation, monitoring procalcitonin (PCT) in the early post-transplant period can be a promising method for early tracking of infectious complications. However, the correlation between PCT and infection-related factors and immune components and renal function remains unclear. PATIENTS AND METHODS: Between November 2017 and December 2018, 62 early-stage renal transplant recipients were selected, and 4 mL peripheral blood samples were collected to detect the changes of specific immune cells and cytokines. Our study was in compliance with the Helsinki Congress and the Declaration of Istanbul; no prisoners were used, and participants were neither paid nor coerced in our study. RESULTS: According to serum PCT levels, recipients were divided into a high group (PCT ≥ 0.5 ng/mL) and a low group (PCT < 0.5 ng/mL). Compared with the low group, creatinine, cystatin C, urea, T helper type (Th) 22 cells, IL-22 + Th17 cells, interleukin (IL)-22, tumor necrosis factor alpha, and IL-17A increased while estimated glomerular filtration rate (eGFR) was decreased in the high group. In addition, PCT was significantly correlated with eGFR in the high group. CONCLUSIONS: Serum PCT is related with renal function and seems to be associated with immune components in early-stage renal transplant recipients.

Arsenate phytotoxicity regulation by humic acid and related metabolic mechanisms.

The use of irrigation water containing arsenic (As) had led to large areas of As-contaminated farmland, and as a result, plants and food have become severely poisoned. Humic acid (HA) can be complexed with metals, which in turn affects the metals' behavior. Herein, we explored the accumulation of arsenate in lettuce treated with different concentrations of arsenate and studied the effects of HA on the accumulation and toxicity of arsenate. The addition of HA did not cause significant changes in the arsenate content in lettuce but had a significant effect on the activity of antioxidant enzymes, which improved the antioxidant capability of the lettuce plants. Furthermore, HA promoted the accumulation of nutrients, such as magnesium (Mg), calcium (Ca), molybdenum (Mo) and manganese (Mn), in the leaves. Arsenate disrupted metabolic pathways, such as amino acid metabolism, carbohydrate metabolism, and aminoacyl-tRNA biosynthesis. The addition of HA increased the contents of amino acids and sugars, thereby improving lettuce growth. The present study explored the effects of HA on As accumulation and related physiological changes (antioxidant enzyme activities, absorption of nutrients and metabolic mechanisms) and provided insights into the regulation of As contamination by HA, which is relatively inexpensive.

Using pH as a single indicator for evaluating/controlling nitritation systems under influence of major operational parameters.

This study focused on using pH as a single indicator to evaluate/control the performance of the nitritation system under the influence of three major operational parameters, and a total of fifteen batch tests were conducted. Results indicated that there were important interactions among different operational parameters and pH in the nitritation system; it was possible to propose the optimal nitritation operation scheme to compensate for negative changes in operational parameters. The optimal carbon to nitrogen (C/N) ratio was kept at 2.0 to ensure efficient removal of ammonium. The reaction time was the lowest (150 min) with the temperature = 20 °C, C/N = 0, and sludge/water ratio = 1:1. However, the C/N ratio could be adjusted to close to zero by reducing the temperature to about 10 °C, weakening the heterotrophic bacteria, and supplying sufficient biomass. The C/N ratio and sludge/water ratio could also be set at 4.0 and 1:3 respectively to deal with the impact of low temperature and organic matter. Results of this study might be useful to explain the optimal conditions and process control schemes with pH as a single indicator.

Hypochlorite and visible-light irradiation affect the transformation and toxicity of graphene oxide.

Graphene oxide (GO) that has many advanced properties, has been applied in various fields, such as water treatments and removal of contaminations. Hypochlorite is widely used in water treatments. However, the effects of hypochlorite on the transformations and risks of GO, and the toxicological responses remain largely unknown, especially under visible-light irradiation. The present work found that visible-light irradiation promoted the breakdown of sp2 structures of GO by hypochlorite, producing alkanes and arenes with short carbon skeletons. Compared to oxygen-containing radicals, chlorine-related radicals contributed to the breakdown of carbon atomic rings of GO. Compared to pristine GO, the transformed GO inhibited algal reproduction, reduced photosynthesis, and promoted oxidative stress and membrane permeability. Substantial plasmolysis and increased numbers of starch grains were observed in the exposure groups. Metabolomics analysis found that oxidative stress and increased membrane permeability linked to downregulated proline. The downregulated pathways of alanine, aspartate and glutamate metabolism were associated with the inhibition of algal reproduction. The downregulated pathways related to protein synthesis and the secondary metabolism explained the strong toxicity induced by GO with hypochlorite and visible-light irradiation. The above results provide insight into the safety assessment of GO.