Enhanced adsorption and co-adsorption of heavy metals using highly hydrophilicity amine-functionalized magnetic hydrochar supported MIL-53(Fe)-NH2: performance, kinetics, and mechanism studies.

It is a "kill two birds with one stone" method to convert invasive plants into hydrochar via hydrothermal carbonization as well as coinciding with 3R rules (reduction, recycling, and reuse). In this work, a series of hydrochars (pristine, modified, and composite) derived from invasive plants Alternanthera philoxeroides (AP) were prepared and applied to the adsorption and co-adsorption of heavy metals (HMs) such as Pb(II), Cr(VI), Cu(II), Cd(II), Zn(II), and Ni(II). The results show that MIL-53(Fe)-NH2- magnetic hydrochar composite (M-HBAP) displayed a strong affinity for HMs, which the maximum adsorption capacities for HMs were 153.80 (Pb(II)), 144.77 (Cr(VI)), 80.58 (Cd(II)), 78.62 (Cu(II)), 50.39 (Zn(II)), and 52.83(Ni(II)) mg/g (c0 = 200 mg/L, t = 24 h, T = 25 ℃, pH = 5,2,6,4,6,5). This may be because the doping of MIL-53(Fe)-NH2 enhanced the surface hydrophilicity of hydrochar, which allows hydrochar to disperse in the water within 0.12 s and possessed excellent dispersibility compared with pristine hydrochar (BAP) and amine-functionalized magnetic modified hydrochar (HBAP). Furthermore, the BET surface area of BAP was improved from 5.63 to 64.10 m2/g after doing MIL-53(Fe)-NH2. M-HBAP shows a strong adsorption effect on the single HMs system (52-153 mg/g), while it decreased significantly (17-62 mg/g) in the mixed HMs system due to the competitive adsorption. Cr(VI) can produce strong electrostatic interaction with M-HBAP, Pb(II) can react with CaC2O4 on the surface of M-HBAP for chemical precipitation, and other HMs can react with functional groups on the surface of M-HBAP for complexation and ion exchange. In addition, five adsorption-desorption cycle experiments and vibrating sample magnetometry (VSM) curves also proved the feasibility of the M-HBAP application.

Calmodulin-like protein CML24 interacts with CAMTA2 and WRKY46 to regulate ALMT1-dependent Al resistance in Arabidopsis thaliana.

ALUMINUM-ACTIVATED MALATE TRANSPORTER1 (ALMT1)-mediated malate exudation from roots is critical for aluminium (Al) resistance in Arabidopsis. Its upstream molecular signalling regulation is not yet well understood. The role of CALMODULIN-LIKE24 (CML24) in Al-inhibited root growth and downstream molecular regulation of ALMT1-meditaed Al resistance was investigated. CML24 confers Al resistance demonstrated by an increased root-growth inhibition of the cml24 loss-of-function mutant under Al stress. This occurs mainly through the regulation of the ALMT1-mediated malate exudation from roots. The mutation and overexpression of CML24 leads to an elevated and reduced Al accumulation in the cell wall of roots, respectively. Al stress induced both transcript and protein abundance of CML24 in root tips, especially in the transition zone. CML24 interacts with CALMODULIN BINDING TRANSCRIPTION ACTIVATOR2 (CAMTA2) and promotes its transcriptional activity in the regulation of ALMT1 expression. This results in an enhanced malate exudation from roots and less root-growth inhibition under Al stress. Both CML24 and CAMTA2 interacted with WRKY46 suppressing the transcriptional repression of ALMT1 by WRKY46. The study provides novel insights into understanding of the upstream molecular signalling of the ALMT1-depdendent Al resistance.

Effect of transferrin glycation induced by high glucose on HK-2 cells in vitro.

Background and objective: Glycation is a common post-transcriptional modification of proteins. Previous studies have shown that advanced glycation end modified transferrin (AGE-Tf) levels in diabetic rat kidney tissues were increased; however, its role in diabetic nephropathy remains unclear. In this study, differences in glycation degree and Tf sites induced by differing high glucose concentrations in vitro and the effect on total iron binding capacity (TIBC) were observed. Moreover, the effect of AGE-Tf on human renal tubular epithelial cells (HK-2) was investigated. Methods: In vitro Tf was incubated with increasing glucose concentrations (0 mM, 5.6 mM, 11.1 mM, 33.3 mM, 100 mM, 500 mM, and 1,000 mM) for AGE-Tf. Differences in AGE-Tf glycation degree and TIBC level were analyzed via colorimetric method. The AGE-Tf glycation sites were identified with LC-MS/MS. HK-2 cells were treated with AGE-Tf prepared with different glucose concentrations (33.3 mM and 500 mM) in vitro. The effects of AGE-Tf on HK-2 cell viability, proliferation, oxidative stress index, and Tf receptor expression levels were then observed. Results: With increasing glucose concentrations (100 mM, 500 mM, and 1,000 mM) in vitro, Tf glycation degree was significantly increased. The TIBC levels of AGE-Tf were decreased significantly with increasing glucose concentrations (33.3 mM, 100 mM, 500 mM, and 1,000 mM). Four glycated modification sites in Tf and 17 glycated modification sites were detected in AGE-Tf (500 mM) by LC-MS/MS. The structural types of AGEs were CML, G-H1, FL-1H2O, FL, and MG-H1. No significant differences were found in the survival rate of HK-2 cells among the AGE-Tf (500 mM), AGE-Tf (33.3 mM), and Tf groups (all p > 0.05). The apoptosis rate of HK-2 cells in the AGE-Tf (500 mM) group was significantly higher than that in the AGE-Tf (33.3 mM) group. Additionally, both of them were significantly higher than that in the Tf group (both p < 0.05). The MDA levels of HK-2 cells in the AGE-Tf (500 mM) and AGE-Tf (33.3 mM) groups were higher than that in the Tf group, but not significantly (both p > 0.05). The T-AOC level of HK-2 in the AGE-Tf (500 mM) group was significantly lower than that in the AGE-Tf (33.3 mM) and Tf groups (both p < 0.001). The GSH level of HK-2 cells in the AGE-Tf (500 mM) group was significantly lower than that in the Tf group (p < 0.05). The expression level of TfR in the AGE-Tf (500 mM) group was also significantly lower than that in the Tf group (p < 0.05). Conclusion: The degree and sites of Tf glycation were increased in vitro secondary to high-glucose exposure; however, the binding ability of Tf to iron decreased gradually. After HK-2 was stimulated by AGE-Tf in vitro, the apoptosis of cells was increased, antioxidant capacity was decreased, and TfR expression levels were downregulated.

A new pathological assessment method to assess residual lesions after neoadjuvant chemotherapy for breast cancer, residual disease in breast and nodes combined with Ki-67 (RDBN-K).

Background: The accurate assessment of residual tumor tissue after neoadjuvant chemotherapy (NAC) for breast cancer is closely related to the subsequent treatment and prognosis of patients. The objective of this study is to develop a new pathological assessment metric for breast cancer patients through combining residual disease in breast and nodes (RDBN) and the Ki-67 expression status after NAC. We call the new metric residual disease in breast and nodes combined with Ki-67 (RDBN-K) and aim to study its significance for prognosis. Methods: A total of 723 breast cancer patients with TNM staging II to III who received NAC and surgical treatment underwent residual disease evaluation by RDBN-K and RDBN. All patients were followed up for a median of 44 months. We used pairwise stratified analysis to compare the accuracy and clinical significance of the RDBN and RDBN-K. Results: Pairwise stratified analysis revealed that DFS and OS had larger difference between RDBN-K-3 and RDBN-K-4 compared to between RDBN-3 and RDBN-4. Moreover, RDBN-K also showed larger differences in OS between stage 2 and 3 compared to RDBN alone. Conclusions: Incorporating Ki-67 expression status into RDBN improved the accuracy in residual tumor burden assessment after NAC. RDBN-K is a better metric for predicting treatment outcomes and identify patients who warrant follow-up intensive treatment.

Non-Enzymatic Glycation of Transferrin and Diabetes Mellitus.

Diabetes is a metabolic disease characterized by high blood sugar. Its complications may damage multiple organs, such as eyes, kidneys, heart, blood vessels, and nerves, severely threatening human health. Transferrin (Tf) is a major iron transport protein in the body. Recent studies have shown that the degree of non-enzymatic glycated modification of Tf is increased in diabetic patients, and glycated Tf is closely related to the occurrence and development of diabetes and diabetic complications. However, the molecular mechanisms underlying this glycated modification in diabetes and diabetic complications are still unclear. It is speculated that the mechanism may be that glycated modification reduces the binding ability of Tf and its receptor TfR, followed by excessive iron accumulation in the body. Iron overload in the body may further lead to the death of pancreatic beta cells and insulin resistance by increasing oxidative stress, inducing iron death, interfering with the insulin signaling pathway, and causing autophagy deficiency. In addition, non-enzymatic glycation affects the binding of Tf with chromium and reduces the ability of Tf to transport chromium into tissues, resulting in a decrease in the levels of chromium in tissues and ultimately affecting the sensitivity of tissues to insulin. In diabetic patients, the concentrations of glycated Tf in serum were significantly correlated with those of fructosamine.Tf has a shorter half-life, and not affected by anemia or hypoalbuminemia and less negative charge under physiological conditions, while glycated modification could not change the isoelectric point of Tf, which easily passes through the negatively charged basement membrane of the glomerulus. Therefore, compared to glucosamine, HbA1C, etc., glycated Tf may be a future biomarker for evaluating short-term glycemic control and early renal damage in diabetic patients.

Surgery combined with 125I brachytherapy for treatment of carcinoma ex pleomorphic adenoma of the parotid gland.

OBJECTIVE: The aim of this study was to investigate the effectiveness and safety of surgery combined with 125I seed brachytherapy for treatment of carcinoma ex pleomorphic adenoma (CXPA) of the parotid gland and to identify the factors associated with prognosis. STUDY DESIGN: We conducted a retrospective analysis of data of patients with CXPA of the parotid gland treated with surgery plus 125I seed brachytherapy at the Peking University School of Stomatology Hospital between December 2003 and July 2018. RESULTS: Fifty-five patients (median age, 51 years) were included in the study. Median follow-up was 50.5 months. The 3-, 5-, and 10-year overall survival rates were 91.1%, 91.1%, and 81.5%, respectively. The 3-, 5-, and 10-year local control rates were all 85.2%. Grades 1-3 adverse effects occurred in 22 patients; no grade 4 reactions occurred. T stage, N stage, tumor invasiveness, perineural invasion, and surgical margins significantly affected local control rates. Lymph node metastasis and perineural invasion were independent predictors of poor local control. Lymph node metastasis was an independent predictor of poor survival. CONCLUSIONS: Surgery plus 125I seed brachytherapy appears to be an effective and safe treatment for CXPA of the parotid gland. T stage, N stage, tumor invasiveness, and perineural invasion are factors influencing prognosis.

Endocrine Adverse Events Caused by Different Types and Different Doses of Immune Checkpoint Inhibitors in the Treatment of Solid Tumors: A Meta-Analysis and Systematic Review.

The aim of this meta-analysis was to assess the risks of endocrine adverse events in patients with malignancies treated with different types and different doses of immune checkpoint inhibitors (ICIs). PubMed and Embase were searched for randomized controlled trials on ICIs and endocrine adverse events since 2000, and meta-analysis was carried out. Twenty-six randomized controlled trials comprising 13 824 patients with malignancies were included. Compared with the other tumor therapies (used as a control group), patients treated with programmed death-1 inhibitors appeared to be at higher risks of hypothyroidism, hyperthyroidism, thyroiditis, hypophysitis or hypopituitarism, and type 1 diabetes mellitus, while there was no difference in the risk of primary adrenal insufficiency. It was also found that patients treated with cytotoxic T-lymphocyte-associated protein-4 inhibitors were at higher risk of hypophysitis or hypopituitarism, primary adrenal insufficiency, and hypothyroidism. In comparison, patients treated with programmed death-ligand 1 inhibitors were at higher risk of hyperthyroidism and hypothyroidism. Compared with the control group, both low-dose and high-dose ICI groups were at higher risk of hypothyroidism and hyperthyroidism, and the low-dose group had increased risk of thyroiditis and primary adrenal insufficiency. There was no significant difference in the risk of type 1 diabetes between the low-dose group and the high-dose group. The risk of hypophysitis or hypopituitarism in the high-dose group (relative risk, 20.12; 95% confidence interval, 8.02-50.46) was significantly higher than that in the low-dose group (relative risk, 4.92; 95% confidence interval, 2.11-11.47). The risk of endocrine adverse events was increased in patients treated with ICIs. Different types and doses of ICIs have varying characteristics of endocrine adverse events.

Assisted computer and imaging system improve accuracy of breast tumor size assessment after neoadjuvant chemotherapy.

BACKGROUND: The use of neoadjuvant therapy (NAT) in patients with early breast cancer is becoming increasingly common. The purpose of this study was to explore the combined use of breast pathology cabinet X-ray system (CXS) to accurately assess the response to neoadjuvant treatment of breast cancer and establish a standard evaluation system. METHODS: A total of 100 patients with breast cancer after neoadjuvant treatment were randomly selected. Preoperative imaging evaluation of tumor masses were significantly degenerated, and they were randomly divided into experimental and control groups of 50 cases each. Compared with the traditional two methods of material extraction, the effective material extraction rate is comparative. Take the two largest diameters of the largest two-dimensional surface of the tumor bed as the measurement object, the macro-description value is D1/D2, the radiographic system description measurement value is the experimental group d1/d2, and the correction under the microscope is worth the true size of the tumor bed H1/H2 as the final test standard, calculate the difference between D1/D2 and d1/d2 with H1 and H2, and compare the difference between d1- H1, d2 - H2 and D1- H1, D2 - H2. RESULTS: The average group of tissue samples in the experimental group was 16.4, and the average group of tissue samples in the control group was 16.7, and there was no difference between the two groups; The effective tissue blocks of tumor bed samples in the experimental group were11.8, and the control group was 7.5. There is difference between the two groups. The average effective percentage of tumor bed in the experimental group was 72%, and the average effective percentage of tumor bed in the control group was 44.8%. The difference was also statistically significant; d1- H1, d2 - H2 and D1- H1, D2 - H2 are all different. CONCLUSIONS: CXS assists the collection of breast tumor bed, which can significantly improve the efficiency of tumor bed collection and save the cost of collection. Compared with the maximum diameter of the tumor bed by eyes, the CXS mapping value is closer to the value measured under the microscope.

Influential factors and prognostic analysis of blood vessel invasion in advanced gastric cancer.

The purpose of this study was to analyze the influencing factors of BVI in advanced gastric cancer and explore the factors affecting the prognosis of advanced gastric cancer, so as to accurately evaluate the disease status and enable patients to receive effective treatment. We retrospectively analyzed 622 cases with complete data and successful follow-up. BVI was found in 144 of the 622 patients with advanced gastric cancer, with a detection rate of 23.15%. BVI was closely related to the differentiation degree, infiltration depth and lymph node metastasis of advanced gastric cancer, (P <  0.05). Gender, age, tumor location, tumor size, Lauren classification, tumor M stage, and clinical TNM stage were not the influencing factors of BVI in patients with advanced gastric cancer (P >  0.05). The 5-year survival rate of patients in the positive group of BVI was 34.72%. The 5-year survival rate of patients with advanced gastric cancer was correlated with BVI, Lauren classification, depth of invasion, lymph node metastasis, and clinical TNM staging, (P <  0.05). The 5-year survival rate was independent of gender, age, tumor location, tumor size, tumor tissue differentiation, and M stage (P >  0.05). The results of multi-factor analysis showed that BVI, N stage and clinical TNM stage were independent predictors of prognosis in patients with advanced radical gastric cancer. By analyzing the stage and related prognostic factors of resectable advanced gastric cancer, we found that BVI was not only closely related to lymph node metastasis, but also an independent predictor of prognosis of advanced gastric cancer. As this study was only a single-center retrospective study, there may be a selective bias in clinical data. So large-scale and multi-center collaboration is needed to further explore the influencing factors of BVI in the progression of gastric cancer.

Predictors of poor outcomes in 488 patients with herb-induced liver injury.

BACKGROUND/AIMS: Herb-induced liver injury (HILI) can lead to chronic liver injury, liver transplantation, or even death. This study aimed to identify the predictors of poor HILI outcomes, especially chronic HILI. MATERIALS AND METHODS: Clinical data of 488 patients with HILI were retrospectively analyzed from a Chinese center between January 2010 and January 2014. Logistic regression and C-statistic were used to identify risk factors and prognostic models for HILI outcomes. RESULTS: In all patients, 69 (14.1%) developed chronic HILI, and 20 (4.1%) died due to liver injury or underwent liver transplantation. To predict the fatal HILI prognosis, the model for end-stage liver disease (MELD) with a C-statistic of 0.981 (95%CI 0.968-0.995) was better than Hy's law (C-statistic 0.569; 95%CI 0.449-0.689). The latency, course of peak alanine aminotransferase decreasing >50% after discontinuation of herb application, peak triglyceride value, and platelet count at liver injury onset were identified as independent risk factors for chronicity with the adjusted odds ratios of 1.268 (95% confidence interval [CI] 1.034-1.554), 2.303 (95%CI 1.588-3.340), 0.580 (95%CI 0.343-0.978), and 0.183 (95%CI 0.091-0.368), respectively. A prognostic model for chronic HILI based on these four factors yielded the best prediction with a C-statistic of 0.812 (95%CI 0.755-0.868), compared with MELD (C-statistic 0.506; 95%CI 0.431-0.581) and Hy's law (C-statistic 0.418; 95%CI 0.343-0.492). CONCLUSION: Model for end-stage liver disease can be used to predict the fatal prognosis of HILI. A long latency, slow recovery, and low triglyceride value and platelet counts are important determinants for chronic HILI.

Expression of YAP/TAZ in Keratocystic Odontogenic Tumors and Its Possible Association with Proliferative Behavior.

The aim of this study is to clarify whether YAP/TAZ is involved in the pathogenesis and proliferative growth of keratocystic odontogenic tumor (KCOT). The expression levels of YAP/TAZ and downstream proteins and genes in normal oral mucosa (OM) and KCOT were determined and compared by immunohistochemistry and real-time quantitative PCR. The results showed that the expression of YAP/TAZ and downstream proteins (Cyr61, CTGF) was significantly upregulated in KCOT with upregulation of Ki-67 compared to OM. Importantly, the mRNA levels of transcription factors (TEAD1, TEAD4, and RUNX2) and cell cycle related genes (CDK2, PCNA), which interact with the transcriptional coactivators YAP/TAZ, are also upregulated in the KCOT. In addition, the results from Spearman rank correlation test revealed the close relationship between YAP/TAZ and Ki-67, which was further evidenced by double-labelling immunofluorescence that revealed a synchronous distribution for YAP/TAZ with Ki-67 in KCOT samples. All the data suggested YAP/TAZ might be involved in the proliferative behavior of KCOT.

Jasmonic Acid Enhances Al-Induced Root Growth Inhibition.

Phytohormones such as ethylene and auxin are involved in the regulation of the aluminum (Al)-induced root growth inhibition. Although jasmonate (JA) has been reported to play a crucial role in the regulation of root growth and development in response to environmental stresses through interplay with ethylene and auxin, its role in the regulation of root growth response to Al stress is not yet known. In an attempt to elucidate the role of JA, we found that exogenous application of JA enhanced the Al-induced root growth inhibition. Furthermore, phenotype analysis with mutants defective in either JA biosynthesis or signaling suggests that JA is involved in the regulation of Al-induced root growth inhibition. The expression of the JA receptor CORONATINE INSENSITIVE1 (COI1) and the key JA signaling regulator MYC2 was up-regulated in response to Al stress in the root tips. This process together with COI1-mediated Al-induced root growth inhibition under Al stress was controlled by ethylene but not auxin. Transcriptomic analysis revealed that many responsive genes under Al stress were regulated by JA signaling. The differential responsive of microtubule organization-related genes between the wild-type and coi1-2 mutant is consistent with the changed depolymerization of cortical microtubules in coi1 under Al stress. In addition, ALMT-mediated malate exudation and thus Al exclusion from roots in response to Al stress was also regulated by COI1-mediated JA signaling. Together, this study suggests that root growth inhibition is regulated by COI1-mediated JA signaling independent from auxin signaling and provides novel insights into the phytohormone-mediated root growth inhibition in response to Al stress.

Spatial-temporal analysis of polyethylene glycol-reduced aluminium accumulation and xyloglucan endotransglucosylase action in root tips of common bean (Phaseolus vulgaris).

BACKGROUND AND AIMS: Aluminium (Al) toxicity and drought are two major limiting factors for common bean (Phaseolus vulgaris) production on tropical acid soils. Polyethylene glycol (PEG 6000)-induced osmotic stress (OS) simulating drought stress reduces Al accumulation in the entire root tips of common bean by alteration of cell-wall (CW) porosity, which might be regulated by two genes encoding xyloglucan endotransglucosylase/hydrolase, PvXTH9 and PvXTHb The aim of this research was to understand the spatial and temporal regulation of both XTH genes in PEG-mediated Al accumulation in the root tips. METHODS: In this study the spatial and temporal expression patterns of Al-inhibited root elongation, Al accumulation, XTH gene expression and xyloglucan endotransglucosylase (XET) enzyme action in the root tips were analysed under PEG-induced OS by a combination of physiological and molecular approaches such as quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and in situ fluorescence detection of XET in root tips. KEY RESULTS: The results showed that Al accumulation, expression of XTH genes and XET action were distinctly reduced in the apical 0-2, 2-7 and 7-12 mm zones under OS, implying a potential regulatory role of XTH genes and XET enzyme in CW Al accumulation in these zones. CONCLUSIONS: The results provide novel insights into the physiological and molecular mechanisms of CW structure modification as a response of plant roots to OS, which will contribute to mitigate Al and drought stresses, severely limiting crop yields on acid soils.