Coordination-Assembly of Lanthanide Supramolecular Hydrogels with Luminescent Multi-stimulus Response.

Luminescent supramolecular hydrogels have shown extensive potential for a variety of applications due to their unique optical properties and biocompatibility. Coordination self-assembly provides a promising strategy for the preparation of supramolecular hydrogels. In this contribution, a series of luminescent lanthanide (Ln) supramolecular hydrogels HG-Ln2nL3n1/2 are synthesized by coordination self-assembly of Ln ions and V shaped bis-tetradentate ligands (H4L1 and H4L2) with different bent angles (∠B). Two rigid conjugated ligands H4L1 and H4L2 with bent angles (∠B ≈ 150°) featuring a 2,6-pyridine bitetrazolate chelating moiety were designed and synthesized, which generated hydrogels via the deprotonation self-assembly with lanthanide ions. Characteristic Eu3+ and Yb3+ emissions were realized in the corresponding hydrogels, with intriguing multi-stimulus response behaviors. The luminescence of the HG-Eu2nL3n1 hydrogel can be enhanced or quenched when stimulated by diverse metal ions, attributed to the replacement of the coordinated lanthanide ions and changes in the intersystem crossing efficiency of the ligand. Furthermore, pH-responsive emission of the HG-Eu2nL3n1 hydrogel has also been observed. Our work provides potential strategies for the design of next-generation smart responsive hydrogel materials with variable structures.

Transcriptome analysis of differentially expressed genes in chrysanthemum MET1 RNA interference lines.

DNA methylation is the most important epigenetic modification involved in many essential biological processes. MET1 is one of DNA methyltransferases that affect the level of methylation in the entire genome. To explore the effect of MET1 gene silencing on gene expression profile of Chrysanthemum × morifolium 'Zijingling'. The stem section and leaves at the young stage were taken for transcriptome sequencing. MET1-RNAi leaves had 8 differentially expressed genes while 156 differentially expressed genes were observed in MET1-RNAi stem compared with control leaves and stem. These genes encode many key proteins in plant biological processes, such as transcription factors, signal transduction mechanisms, secondary metabolite synthesis, transport and catabolism and interaction. In general, 34.58% of the differentially expressed genes in leaves and stems were affected by the reduction of the MET1 gene. The differentially expressed genes in stem and leaves of transgenic plants went through significant changes. We found adequate amount of candidate genes associated with flowering, however, the number of genes with significant differences between transgenic and control lines was not too high. Several flowering related genes were screened out for gene expression verification and all of them were obseved as consistent with transcriptome data. These candidate genes may play important role in flowering variation of chrysanthemum. This study reveals the mechanism of CmMET1 interference on the growth and development of chrysanthemum at the transcriptional level, which provides the basis for further research on the epigenetic regulation mechanism in flower induction and development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01022-1.

The impact of a medication reconciliation programme at geriatric hospital admission: A pre-/postintervention study.

AIMS: The aim of this study was to improve medication reconciliation and reduce the occurrence of duplicate prescriptions by pharmacists and physicians within 72 hours of hospital admission using an intelligent prescription system combined with the National Health Insurance PharmaCloud system to integrate the database with the medical institution computerized physician order entry (CPOE) system. METHODS: This 2-year intervention study was implemented in the geriatric ward of a hospital in Taiwan. We developed an integrated CPOE system linked with the PharmaCloud database and established an electronic platform for coordinated communication with all healthcare professionals. Patients provided written informed consent to access their PharmaCloud records. We compared the intervention effectiveness within 72 hours of admission for improvement in pharmacist medication reconciliation, increased at-home medications documentation and decreased costs from duplicated at-home prescriptions. RESULTS: The medication reconciliation rate within 72 hours of admission increased from 44.0% preintervention to 86.8% postintervention (relative risk = 1.97, 95% confidence interval [CI]: 1.69-2.31; P < .001). The monthly average of patients who brought and took home medications documented in the CPOE system during hospitalization increased by 7.54 (95% CI 5.58-20.49, P = .22). The monthly average of home medications documented increased by 102.52 (95% CI 38.44-166.60; P = .01). Savings on the monthly average prescription expenditures of at-home medication increased by US$ 2,795.52 (95% CI US$1310.41-4280.63; P < .01). CONCLUSION: Integrating medication data from PharmaCloud to the hospital's medical chart system improved pharmacist medication reconciliation, which decreased duplicated medications and reduced in-hospital medication costs.

Design, expression, and characterization of a novel dendritic cell-targeted proteins.

In vivo approaches to inducing an effective immune response focus on targeted antigen (Ag) delivery to dendritic cells (DCs). In this study, we developed a new method of targeting plasmid DNA and/or the antigen (Ag)-antibody (Ab) complex to DCs via the DC receptor DEC-205, also known as cluster of differentiation CD205. We cloned and expressed a recombinant protein composed of mouse DEC-205-specific single-chain fragment variable region (mDEC-205-scFv), the streptococcal protein G (SPG) IgG-binding domain and cationic peptide (CP), which named mDEC205-scFv-SPG-CP (msSC). In vitro, the recombinant protein msSC can specifically bind to DCs through the section of mDEC-205-scFv, and bound the Ag-Ab complex via SPG as well as plasmid DNA through electrostatic bonding with CP in vitro. In addition, msSC functioned in a manner similar to anti-DEC-205 monoclonal Ab and bound to mouse bone marrow-derived DCs. It was demonstrated in vivo that msSC can target plasmid DNA to DCs, resulting in efficient uptake and expression. Moreover, msSC can form a complex with pGL3-CMV and transport it to draining lymph nodes when injected in vivo. These results indicate that msSC can be used as a carrier protein for vaccine delivery to DCs via formation of plasmid DNA-Ag-Ab ternary complexes.

Sensitivity of initial biopsy or transurethral resection of bladder tumor(s) for detecting histological variants on radical cystectomy.

BACKGROUND: To investigate the efficacy of initial biopsy or transurethral resection of bladder tumor for detecting histological variants on radical cystectomy and to assess the prognostic significance of variant histology on urothelial carcinoma outcomes after radical cystectomy. METHODS: Clinical and histopathological characteristics of 147 patients with variant histology who underwent radical cystectomy for urothelial carcinoma between 2006 and 2012 were assessed. Sensitivity was calculated as the proportion of radical cystectomy specimens with a particular variant that also presented the variant in the biopsy or transurethral resection specimen. The Kaplan-Meier method and multivariate Cox proportional hazard regression analysis were used to estimate cancer-specific survival. RESULTS: Of the 147 patients, 116 (79 %) were diagnosed with a single variant histology, and 31 (21 %) had multiple patterns. Squamous differentiation (31 %) was the most common single variant histology, followed by glandular differentiation (28 %). Except for small cell variant (100 %), the sensitivity of biopsy and transurethral resection was most effective for the diagnosis of squamous differentiation, 19 % vs. 40 % respectively, followed by glandular differentiation, 11 % vs. 21 % respectively. A total of 6 % and 49 % patients could be variant-free partially due to biopsy or complete resection(s) respectively. Presence of variant differentiation in urothelial carcinoma at cystectomy was significantly associated with inferior survival both in univariate analysis (P = 0.005) and multivariate analysis (HR4.48, 95 % CI:1.03-19.53). CONCLUSIONS: Overall sensitivity of biopsy or transurethral resection to detect variant differentiation on cystectomy is relatively low. Patients with variant differentiation on cystectomy specimens have inferior survival.

SLC12A5 promotes hepatocellular carcinoma growth and ferroptosis resistance by inducing ER stress and cystine transport changes.

BACKGROUND: Hepatocellular carcinoma (HCC) has a poor prognosis and new effective treatments are needed. SLC12A5 plays important roles in multiple complex pathological states and is overexpressed in a variety of malignancies. However, the effects of SLC12A5 in HCC have not been determined. METHODS: SLC12A5 expression was assessed by immunostaining and western blotting. A cell viability assay was used to detect cell proliferation. Flow cytometry was used to evaluate the intracellular calcium concentration and cell cycle. Ferroptosis was detected by transmission electron microscopy, lipid peroxidation, and glutathione assays. Subcutaneous tumor formation experiments were used to validate the tumorigenic effect of SLC12A5 in vivo. RNA-seq was used to evaluate the molecular mechanisms underlying the effects of SLC12A5. The therapeutic efficacy of targeting SLC12A5 was assessed in a patient-derived xenograft (PDX) model. RESULTS: High SLC12A5 expression was strongly associated with a poor clinical prognosis and promoted HCC growth. Mechanistically, SLC12A5 promoted ER stress to enhance calcium release and upregulated PNCK expression levels. Concomitantly, PNCK was significantly activated by calcium ions released from the ER. PNCK activated and induced the phosphorylation of PI3K/AKT/mTOR pathway components. Furthermore, SLC12A5 inhibited ferroptosis in HCC by upregulating the expression of xCT, a cystine transporter. CONCLUSION: High SLC12A5 levels were correlated with a poor prognosis, promoted tumorigenesis, and inhibited ferroptosis in HCC. These findings suggested that SLC12A5 is a therapeutic target and provide insight into the link between ER stress and ferroptosis in HCC.

Cation modulated spin state and near room temperature transition within a family of compounds containing the same [FeL2]2- center.

Spin-crossover (SCO) active compounds have received much attention due to their potential application in molecular devices. Herein, a family of solvent-free FeII compounds, formulated as (A)2[FeL2], (H2L = pyridine-2,6-bi-tetrazolate, A = (Me)4N+1, Et2NH2+2, iPr2NH2+3 and iPrNH3+4), were synthesized and characterized. Single-crystal X-ray diffraction studies reveal that 1-4 are all supramolecular frameworks containing the same [FeL2]2- center, which is arranged into two packing modes via inter-molecular interactions, that is, a 3D architecture in 1 and 1D chain in 2-4. The spin states of 1-4 at different temperatures are assigned on the basis of the single-crystal X-ray diffraction data. Solid state magnetic investigations indicate that 1 and 4 exhibit a low spin state (below 350 K) and high spin state (2-400 K), respectively. 2 and 3 display clear SCO behavior in the measured temperature, but with different profiles and critical temperatures. 2 undergoes a complete gradual SCO with a critical temperature of T1/2 = 260 K. 3 has an abrupt near room temperature transition between T1/2 cooling = 278 K and T1/2 warming = 286, centered at 282 K (9 °C). This study reveals the importance of organic cations in the modulation of SCO behavior and offers a new insight for the design of SCO compounds with near room temperature spin transitions.

Detection of urothelial carcinoma, upper tract urothelial carcinoma, bladder carcinoma, and urothelial carcinoma with gross hematuria using selected urine-DNA methylation biomarkers: A prospective, single-center study.

INTRODUCTION: Hematuria is the most common symptom of urothelial carcinomas (UC) but is often idiopathic. Cystoscopy is expensive which involves considerable patient discomfort, and conventional urine cytology for noninvasive UC detection and disease monitoring suffers from poor sensitivity. We aim to evaluate the performance of genes selected from a previous study in detecting UC, especially among patients with gross hematuria, as well as upper tract urothelial carcinoma (UTUC) and bladder carcinoma separately, in voided urine samples. METHODS: Using methylation-specific polymerase chain reaction, we examined the promoter methylation status of 10 genes in voided urine samples among 473 patients at our institution, including 217 UC patients and 256 control subjects. RESULTS: The final combination of VIM, CDH1, SALL3, TMEFF2, RASSF1A, BRCA1, GDF15, and ABCC6 identified UC with a sensitivity of 0.83 and a specificity of 0.60. Additionally, a panel of selected genes (CDH1, HSPA2, RASSF1A, TMEFF2, VIM, and GDF15) identified UTUC with a sensitivity of 0.82 and a specificity of 0.68, while a panel of selected genes (VIM, RASSF1A, GDF15, and TMEFF2) identified bladder carcinoma with a sensitivity of 0.82 and a specificity of 0.53. Remarkably, a different panel (CDH1, SALL3, THBS1, TMEFF2, VIM, and GDF15) identified UC in patients with gross hematuria with 0.89 sensitivity and 0.74 specificity, and sensitivity (0.91) and specificity (0.92) could be achieved when cytology was included. CONCLUSIONS: The selected urine-DNA methylation biomarkers are reliable, noninvasive, and cost-effective diagnostic tools for bladder carcinoma and UTUC, especially among patients with gross hematuria.

[Analysis on processing mechanism of calamine].

OBJECTIVE: To study processing method and mechanism of Calamine. METHOD: Thermogravimetry analysis method and nano-technology were adopted to analyze and synthesize the components in Calamine, Tetracycline was took as the comparison drug to determine the antibacterial activity of Calamine and its components. RESULT: A part of zinc carbonate in Calamine was decomposed into zinc oxide when processing, and the particle size was smaller than before. The antibacterial activity of Calamine is decided by the content and particle size of zinc oxide, and has nothing with zinc carbonate. The more content and the smaller particle size of zinc oxide, the more powerful antibacterial activity of Calamine. CONCLUSION: The content and the particle size of zinc oxide can be the important targets in the processing of Calamine.

Aberrant Methylation of the 1p36 Tumor Suppressor Gene RIZ1 in Renal Cell Carcinoma.

BACKGROUND: Retinoblastoma protein-interacting zinc finger gene 1(RIZ1) functions as a tumor suppressor. Hypermethylation-mediated RIZ1 silencing has been reported in several cancers, but not in renal cell carcinoma (RCC) yet. MATERIALS AND METHODS: We examined the RIZ1 expression and methylation in a panel of RCC cell lines and 50 primary tumors using semiquantitative/quantitative polymerase chain reaction (PCR), methylation specific PCR, and bisulfite sequencing genomic. We also explored the relationship between methylation status of RIZ1 and clinicopathological features in RCC patients. RESULTS: RIZ1 expression was down-regulated or lost in OS-RC-2, 769-P, Caki-1, 786-O and A498 RCC cell lines. Restored expression of RIZ1 was detected after addition of 5-aza-2'-deoxycytidine with/without trichostatin A, suggesting that DNA methylation directly mediates its silencing. The RIZ1 expression was significantly reduced in RCCs compared to adjacent non-malignant renal samples (P<0.001). Aberrant methylation was detected in 15 of 50 (30%) RCCs and in 2 of 28 (7%) adjacent non- malignant renal samples (P=0.02). No statistically significant correlation between methylated and unmethylated cases with regard to age, gender, pathological stage and grade was observed. CONCLUSIONS: RIZ1 expression is down-regulated in human RCC, and this down-regulation is associated with methylation. RIZ1 methylation may play a role in renal carcinogenesis.

Mechanisms of hypercoagulability in nephrotic syndrome associated with membranous nephropathy as assessed by thromboelastography.

INTRODUCTION: Thromboelastography (TEG) was performed to assess potential hypercoagulability in Nephrotic syndrome (NS) patients with membranous nephropathy (MN) and to explore correlated factors contributing to hypercoagulable status MATERIALS AND METHODS: 101 MN patients, 61 minimal change disease (MCD) patients and 20 healthy controls met the inclusion criteria. The MN and MCD patients were stratified into two layers according to serum albumin (SALB) levels (<20g/l or 20-30g/l). Primary outcome measures included reaction time (R), α-angle, maximum amplitude (MA) and coagulation index (CI). TEG parameters of four patient subgroups were analyzed in factorial designed ANOVA with factors disease and SALB. RESULTS: By linear regression analysis, TEG parameters in MN patients correlated with SALB (P<0.01) and the ANOVA for factorial designed data confirmed that the main effects of factors SALB and disease were both statistically significant. Besides, comparison between control group and patient subgroups showed that R value in normal controls was significantly higher than that in MN subgroups, but was not statistically different from that in MCD subgroups. NS patients (MCD, MN) had significantly higherα-angle, MA and CI values than healthy controls (p<0.05). CONCLUSIONS: MN patients tend to be more hypercoagulable than normal and MCD patients. Hypercoagulability in MN patients involves the whole thrombotic processes acceleration (activated intrinsic pathway, fibrinogen, platelet function and fibrin-platelet interaction), whereas hypercoagulable state in MCD patients may be that the coagulation factors are not fully activated. Greater efforts should be made to prevent hypercoagulability especially for MN patients with severe hypoalbuminemia.

Protective effect of salidroside on contrast-induced nephropathy in comparison with N-acetylcysteine and its underlying mechanism.

OBJECTIVE: To study the prevention effect of salidroside on contrast-induced-nephropathy (CIN) and its underlying mechanism. METHODS: A total of 24 Wistar rats were randomly divided into 4 groups with 6 in each group. Rats were firstly administrated with normal saline (control and model groups), N-acetylcysteine (NAC, NAC group) and salidroside (salidroside group) for 7 days before model establishment in each group, respectively. Histopathological analysis was performed by periodic acid-Schiff (PAS) staining. Oxidative stress related parameters including superoxide dismutase (SOD) and methane dicarboxylic aldehyde (MDA), nitric oxide (NO), angiotensin II (Ang II), 8-hydroxy-2'-deoxyguanosine (8-OHdG), mRNA and protein levels of endothelial nitric oxide synthase (eNOS), and nitric oxide synthase (NOS) activity were measured. RESULTS: Compared with the control group, the levels of MDA, Ang II and 8-OHdG were all significantly increased and levels of SOD, NO, and eNOS mRNA and protein were decreased significantly in the model group (P<0.05). Meanwhile, the NOS activity was also significantly decreased in the model group (P<0.05). In addition, the levels of these parameters were all improved in the NAC (P<0.05) and salidroside groups and no significant different was found between these two groups (P>0.05). CONCLUSION: Salidroside can be the potential substitute of NAC to prevent CIN. The underlying mechanism may be associated with oxidative stress damage caused by contrast agents.

Effect of probucol on insulin resistance in patients with non-diabetic chronic kidney disease.

BACKGROUND: Insulin resistance (IR) is present at all stages of chronic kidney disease (CKD) and is associated with CKD progression. Probucol can improve the prognosis of IR in diabetes mellitus (DM) patients. This study aimed to observe the effect of probucol on IR and kidney protection in non-diabetic CKD patients. METHODS: This was an open-label, non-placebo-controlled, randomized study. A total of 59 patients were randomized to the probucol group (0.5 g, twice daily) or the control group using a 1: 1 treatment ratio. IR was determined using a homeostatic model assessment-IR (HOMA-IR) index. An Excel database was established to analyze follow-up data at weeks 0, 12, and 24. The primary outcome of interest was changes in the HOMA-IR, and the secondary outcomes of interest were changes in the estimated glomerular filtration rate (eGFR), body mass index (BMI), cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and 24-h urinary protein. RESULTS: The HOMA-IR index of the probucol group after 24 weeks was significantly decreased (P < 0.001) compared to the value before treatment (average decrease: 1.45; range: -2.90 to -0.43). The HOMA-IR index in the control group increased (average increase: 0.54; range: -0.38 to 1.87). For the secondary outcomes of interest, the changes between these two groups also exhibited significant differences in eGFR (P = 0.041), cholesterol (P = 0.001), fasting insulin (P < 0.001), and fasting C-peptide (P = 0.001). CONCLUSIONS: Compared to angiotensin receptor blockers alone, the combination with probucol ameliorates IR in non-diabetic CKD patients and delays disease progression.

A meta-analysis of the effects of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers on insulin sensitivity in hypertensive patients without diabetes.

AIMS: This study sought to compare the effects of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) on insulin sensitivity (IS) in hypertensive patients without diabetes. METHODS: Studies on the observation of IS in hypertensive patients without diabetes who received ACEI and ARB prior to December 2013 was collected using computer-based retrieval of the PUBMED, EMBASE, and COCHRANE databases. The primary indicators included IS, fasting plasma glucose (FPG), and fasting plasma insulin (FPI). The secondary indicators included systolic blood pressure (SBP) and diastolic blood pressure (DBP). A meta-analysis was performed using the STATA and Review Manager 5.2 software. The effects of these two drugs on IS in hypertensive patients without diabetes were analyzed using the fixed effect model and the random effect model. RESULTS: A total of 203 cases of patients involved in 4 clinical studies were included. As compared to ARB, ACEI treatment resulted in more effective improvement of IS in hypertensive patients without diabetes (SMD: 0.45, 95% CI 0.17-0.73), although these two drugs did not show significant differences with regards to FPG (WMD: 0.00, 95% CI -0.19-0.20), FPI (WMD: -0.34, 95% CI -1.31-0.63), SBP (WMD: 2.85, 95% CI -1.55-7.24), and DBP (WMD: 0.81, 95% CI -1.12-2.75). CONCLUSION: In patients showing no significant difference in blood pressure control, the comparison between ACEI and ARB showed that the former type of drug more effectively relieved IS in hypertensive patients without diabetes.

Cryopreservation of shoot-tips of citrus using vitrification: effect of reduced form of glutathione.

A commercial citrus scion cultivar, '439' tangor [C. Suavissima Hort. et Tanaka x C. sinensis (L.) Osbesk cv.Gailiangcheng] was used to investigate whether GSH (reduced form of glutathione) could improve survival of a vitrification procedure. The optimal pre-growth treatment was a 3-day pre-culture on basal pre-culture medium (BPM: MT basal medium containing 0.5 mol/L glycerol and 5 % sucrose at pH 5.8). GSH of 40 mg/L in the pre-culture medium improved shoot tip survival after cryopreservation. GSH in the recovery medium also improved survival, with 10 mg/L giving the best result. GSH of 40 mg/L in the loading and vitrification solutions also improved survival. The optimal cryopreservation protocol was successfully applied to 12 other citrus cultivars. This is the first report on the successful cryopreservation of shoot-tips from commercial citrus scion cultivars.

A meta-analysis of the effect of angiotensin receptor blockers and calcium channel blockers on blood pressure, glycemia and the HOMA-IR index in non-diabetic patients.

OBJECTIVE: This study compared the efficacy of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) in the effect of insulin resistance (IR) as assessed using the homeostasis model assessment of insulin resistance (HOMA-IR) in non-diabetic patients. METHODS: The MEDLINE, EMBASE, and Cochrane Library databases were searched to identify studies published before December 2012 that investigated the use of ARBs and CCBs to determine the effect on the HOMA-IR index in non-diabetics. Parameters on IR and blood pressure were collected. Review Manager 5.2 and Stata 12.0 were used to perform the meta-analysis. Fixed and random effects models were applied to various aspects of the meta-analysis, which assessed the therapeutic effects of the two types of drug using the HOMA-IR index in non-diabetic patients. RESULTS: The meta-analysis included five clinical trials. Patient comparisons before and after treatment with ARBs and CCBs revealed that ARBs reduced the HOMA-IR index (weighted mean difference (WMD) -0.65, 95% confidence interval (CI) -0.93 to -0.38) and fasting plasma insulin (FPI) (WMD -2.01, 95% CI -3.27 to -0.74) significantly more than CCBs. No significant differences in the therapeutic effects of these two types of drug on blood pressure were observed. CONCLUSION: Given that there are no significant differences in the therapeutic effects of ARBs and CCBs on blood pressure, as ARBs are superior to CCBs in their effect on the HOMA-IR index in non-diabetics, they might be a better choice in hypertension patients without diabetes.