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Biomedical subjects

X Huang

Publications and source records attributed to X Huang.

At least 55 records · Page 3Linked to original sources

On the relationship between human all-cause mortality and age.

Many equations can be used to study the relationship between mortality rates and age: Gompertz, Weibull, logistic, polynomial and age-period-cohort equations a.o. All these equations result in highly significant correlations between ln mortality rates and age in the age range 35-84 years. This applies to all developed countries and is independent of the differences in causes of death between populations. The best fit is obtained by a second-degree polynomial equation (R2 > 0.99), closely followed by the Gompertz equation. This equation is preferred in view of its extreme simplicity. A highly significant correlation exists between the intercept and the slope of the Gompertz equations, pointing to a crossing-over age. Beyond that age, around 85 years, populations with high mortality rates have a lower mortality, due to selective survival of the strongest individuals. The polynomial age 2 term may be positive or negative, an expression of the acceleration or de-acceleration of mortality at higher ages and is significantly more often positive in women. The equations used are very useful for the study of the aging process and for examining the relationship between possible causal factors and mortality rates in populations.

Adult↗

Further studies on the role of IL-12 in Pseudomonas aeruginosa corneal infection.

PURPOSE: Previous studies have shown that in Pseudomonas aeruginosa ocular infection, IL-12 drives a Th1 T-cell response and IFN-gamma production in susceptible (cornea perforates) C57BL/6 (B6) mice, and that after similar infection of resistant (cornea heals) BALB/c mice, no IL-12 is detectable in cornea at either the mRNA or protein levels. Therefore, the purpose of this study was to test whether BALB/c mice are capable of responding to exogenous IL-12 administration, and whether disease responsiveness following P. aeruginosa challenge is modified. METHODS: Immunostaining, RT/PCR, recombinant cytokine injection, and histopathology were used. Statistical analysis was performed using an unpaired, two-tailed Student's t-test. RESULTS: Injection of BALB/c mice with recombinant (r) IL-12 converted these normally resistant animals to the susceptible phenotype as evidenced by corneal perforation within 5-7 days after infection. RT-PCR analysis of the corneas of rIL-12 vs PBS/BSA-treated mice showed a significant increase in IFN-gamma and TNF-alpha mRNA levels in the rIL-12 vs PBS/BSA (vehicle)-treated mice at 3 and 5 days p.i. In addition, similar analysis of IL-4 mRNA levels showed decreased amounts of the cytokine in rIL-12 vs vehicle-treated mice. Injection of rIL-4 into susceptible B6 mice, however, failed to rescue these animals from corneal perforation following P. aeruginosa challenge. CONCLUSIONS: These data provide evidence that BALB/c mice can respond to exogenous IL-12, that the cytokine promotes susceptibility by increasing IFN-gamma and TNF-alpha production, with a concomitant reduction in IL-4 levels; and that injected rIL-4 fails to rescue susceptible B6 mice from corneal perforation after bacterial challenge.

Animals↗

T-bet expression is upregulated in active Behçet's disease.

AIM: To investigate T-bet mRNA and protein expression on peripheral blood mononuclear cells (PBMC) in patients with Behçet's disease with active uveitis. METHODS: Blood samples were taken from 24 patients with Behçet's disease who had active uveitis and 16 healthy individuals. PBMC were subjected to analysis of T-bet mRNA and protein expression using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot, respectively. The products from PCR were sequenced. In order to determine the influence of activation on T-bet expression, the phytohaemagglutinin (PHA) stimulated PBMC from each sample were also evaluated for expression of T-bet mRNA and protein. RESULTS: A significantly increased T-bet mRNA accumulation was detected in the samples from patients with active Behçet's disease compared with that in controls. A 62 kDa band was detectable in patients with active Behçet's disease, but not in controls. No difference was found between patients with Behçet's disease who had active uveitis and normal controls concerning the expression of either T-bet mRNA or its protein after stimulation with PHA for 72 hours. CONCLUSION: Behçet's disease is associated with an upregulation of T-bet expression, which supports a role for the Th1 subset of T cells in the pathogenesis of this disease.

Adult↗

The heat-stable root-knot nematode resistance gene Mi-9 from Lycopersicon peruvianum is localized on the short arm of chromosome 6.

The tomato gene Mi-1 confers resistance to three species of root-knot nematodes, Meloidogyne spp. However, the resistance mediated by Mi-1 is inactive at soil temperatures above 28 degrees C. Previously, we identified and mapped a novel heat-stable nematode resistance gene from the wild species Lycopersicon peruvianum accession LA2157 on to chromosome 6. Here we report further characterization of this heat-stable resistance against three Mi-1-avirulent biotypes of Meloidogyne javanica, Meloidogyne arenaria and Meloidogyne incognita. Screening segregating F(2) and F(3) progenies, derived from an intraspecific cross between susceptible LA392 and resistant LA2157, for nematode resistance at 25 degrees C and 32 degrees C, revealed a simple dominant monogenic inheritance with all the biotypes tested. We designate this gene as Mi-9. As a first step towards cloning of Mi-9, we constructed a linkage map around this gene. A total of 216 F(2) progeny from the cross between LA392 and LA2157 were screened with M. javanica at 32 degrees C and with CT119 and Aps-1, markers that flank the genetic interval that contains the Mi-1 gene. DNA marker analysis indicated that these markers also flank Mi-9. Further mapping of recombinants with both RFLP and PCR-based markers localized Mi-9 to the short arm of chromosome 6 and within the same genetic interval that spans the Mi-1 region.

Chromosome Mapping↗

Measurement of the positive muon anomalous magnetic moment to 0.7 ppm.

A higher precision measurement of the anomalous g value, a(mu)=(g-2)/2, for the positive muon has been made at the Brookhaven Alternating Gradient Synchrotron, based on data collected in the year 2000. The result a(mu(+))=11 659 204(7)(5)x10(-10) (0.7 ppm) is in good agreement with previous measurements and has an error about one-half that of the combined previous data. The present world average experimental value is a(mu)(expt)=11 659 203(8)x10(-10) (0.7 ppm).

Journal Article↗

Syntaxin-3 and syntaxin-1A inhibit L-type calcium channel activity, insulin biosynthesis and exocytosis in beta-cell lines.

AIMS/HYPOTHESIS: Syntaxin-1A (Syn-1A) is known to play a negative regulatory role in insulin secretion but the precise mechanisms for its action are not clear. Syn-2, -3 and -4 are also present in islet beta cells but their functions are not known. Here, we investigated the role of these syntaxins in the insulin secretory process. METHODS: We examined the following effects of Syn-1, -2, -3 and -4 expression in insulinoma beta-cell lines. Endogenous insulin secretion was measured by batch radioimmunoassay (RIA) and single cell patch clamp capacitance measurements. The L-type Ca(2+) channel activity was studied by patch clamp electrophysiology. Insulin gene transcription was examined by Northern blotting and measurement of insulin gene promoter activity by the co-expression of cyan fluorescent protein-labelled rat insulin promoter. RESULTS: Syn-1A or -3, but not Syn-2 or -4 overexpression, inhibited K(+)-induced insulin release as determined by RIA (49.7 +/- 5.5 % and 49.1 +/- 6.2 %, respectively) and electrophysiologic membrane capacitance measurements (68.0 +/- 21.0 % and 58.0 +/- 13.2 %, respectively). Overexpressed Syn-1A and -3, but not Syn-2, inhibited Ca(2+) channel current amplitude by 39.5 +/- 11.6 % and 52.7 +/- 6.0 %, respectively. Of note, overexpression of Syn-1A and -3 also reduced single cell (by confocal microscopy) and total cellular endogenous insulin content (by RIA) by 24.8 +/- 4.2 % and 31.8 +/- 3.9 %, respectively. This correlated to a reduction in endogenous insulin mRNA by 24.5 +/- 4.2 % and 25.7 +/- 4.2 %, respectively. This inhibition of insulin biosynthesis is mainly at the level of insulin gene transcription as demonstrated by an inhibition of insulin gene promoter activity (53.3 +/- 9.15 % and 39.0 +/- 6.8 %, respectively). CONCLUSIONS/INTERPRETATION: These results demonstrate that Syn-1A and -3 possess strong inhibitory actions on both insulin exocytosis and insulin biosynthesis whereas Syn-2 and -4 do not inhibit the insulin secretory process.

Animals↗

Suppression of pyrite oxidation by iron 8-hydroxyquinoline.

One of the important approaches to prevent pyrite (FeS(2)) oxidation and subsequent formation of acid mine drainage (AMD) is to create a surface coating on pyrite. In this study, a coating of iron 8-hydroxyquinoline was formed by leaching pyrite with a 0.10 M H(2)O(2)/0.0034 M 8-hydroxyquinoline solution; stability of the coated pyrite was tested under various pH and temperature conditions. The results showed that iron 8-hydroxyquinoline coating could significantly suppress further pyrite oxidation by both chemical (H(2)O(2)) and biological ( e.g., Thiobacillus ferrooxidans) processes. At pH from 3.0 to 5.0 and temperature from 10-40 degrees C, the amount of SO(4)(2-) leached out by 0.10 M H(2)O(2) from the coated pyrite samples was 54.8-70.1% less than that from the uncoated controls. The oxidation of pyrite followed a pseudo-zero-order kinetics under the constant concentration of H(2)O(2). In the presence of microorganisms, sulfate leached out of the uncoated pyrite in 1 year accounted for 5.32% of the total pyrite in the system, with a concurrent pH drop to 2.35 under the ambient room temperatures. In contrast, the amount leached out from the coated samples was only 0.15% of the total pyrite and the final pH was 5.48. Thus, the coating decreased the leachability of pyrite by 97% in the inoculated systems. In comparison to the more widely studied iron phosphate coating, the advantage of iron 8-hydroxyquinoline coating was that it inhibited both chemical and biological pyrite oxidation, whereas iron phosphate coating could only inhibit chemical pyrite oxidation.

Equipment Design↗

Mechanisms involved in development of resistance to adenovirus-mediated proapoptotic gene therapy in DLD1 human colon cancer cell line.

To evaluate resistance that develops in cancer cells during treatment with adenoviral vectors expressing proapoptotic genes, we repeatedly treated the human colon cancer cell line DLD1 with adenoviral vectors expressing the human Bax gene and the human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene. DLD1 cells resistant to the Bax- or TRAIL-expressing adenoviral vectors were then selected and designated as DLD1/Bax-R or DLD1/TRAIL-R cells, respectively. Further study showed that resistance in DLD1/Bax-R cells was caused by resistance to adenoviral infection, which can be overcome by dose escalation of the adenoviral vectors. However, resistance in DLD1/TRAIL-R cells was caused by resistance to the TRAIL gene. Therefore, different mechanisms are involved in the development of resistance during adenovirus-mediated proapoptotic gene therapy. A survey of molecules involved in TRAIL- or Bax-mediated apoptotic pathways showed no significant change in expression of death receptors, death decoy receptors; FLIP; Bcl-2; Bcl-xS; Bax; Bak; XIAP or caspase-2, -7, -8, or -9 in either DLD1/Bax-R or DLD1/TRAIL-R cells. Bcl-xL expression detected in both mRNA and protein level assays was three times higher in DLD1/TRAIL-R cells than in parental or DLD1/Bax-R cells. However, transfection of DLD1 cells with the Bcl-xL gene showed that overexpression of Bcl-xL is not sufficient for the resistance. Moreover, DLD1/Bax-R cells were sensitive to adenoviral vectors that expressed the TRAIL gene, but resistant to adenoviral vectors that expressed the Bak gene. In contrast, DLD1/TRAIL-R cells were sensitive to adenoviral vectors that expressed either Bax or Bak gene. Thus, alternative application of adenoviral vectors that expressed proapoptotic genes in different pathways or different cell killing models may delay or prevent development of resistance in adenovirus-mediated proapoptotic gene therapy.

Adenoviridae↗

Combined TRAIL and Bax gene therapy prolonged survival in mice with ovarian cancer xenograft.

We evaluated the antitumor activity of the Bax gene and green fluorescent protein/tumor necrosis factor-related apoptosis-inducing ligand (GFP/TRAIL) fusion gene driven by the human telomerase reverse transcriptase promoter both separately and combined in the human ovarian cancer lines SKOV3ip and DOV13 and human lung cancer line H1299. In vitro study showed that both TRAIL- and Bax-expressing vectors elicited significant cell killing in H1299 and SKOV3ip cells, but only the GFP/TRAIL gene elicited significant cell killing in DOV13 cells. Combined TRAIL and Bax therapy also produced more profound cell killing in SKOV3ip and H1299 cells, but not DOV13 cells without escalation of the vector doses. To further evaluate the combined effects of Bax and TRAIL, abdominally spread tumors were established in nude mice via intraperitoneal inoculation of SKOV3ip cells followed by that of adenoviral vectors. Tumor growth, ascites formation, survival duration and toxicity were evaluated after treatment. We found that treatment using the Bax- or TRAIL-expressing vector alone significantly suppressed tumor growth and ascites formation, and prolonged animal survival when compared with that of using PBS or a control vector. Combined TRAIL and Bax therapy further prolonged survival significantly when compared with therapy using the TRAIL or Bax gene alone. Transgene expression and apoptosis induction were not detected in normal human ovarian epithelial cells in vitro or normal mouse tissues in vivo after intraperitoneal vector administration. Also, liver toxicity was not detected after either treatment. Thus, combined TRAIL and Bax gene therapy may be useful for treatment of abdominally spread tumors.

Animals↗

Phosphorus removal and greenhouse gas N2O emission in a lime-induced aerobic sludge granule process.

Aerobic sludge granulation was achieved in an activated sludge process continuously fed with lime (Ca2+ 100 mg l(-1) influent) every other day. Eighteen days after lime addition, activated sludge granules with the size of 0.5-2.2 mm were formed, which occupied 10-25% of total sludge volume. Sludge volume index (SVI) was reduced to an average of 50 ml g(-1), which increased average sludge concentration to 3.6-5.0 g VSS l(-1), 1.6-2.1 times of that of control. Greenhouse gas N2O emission was also significantly reduced: N2O concentration from the lime-addition reactor was 5-15 ppmv, 47-61% of that of control, Effluent PO4-P concentration was generally lower than 1 mg l(-1) when average influent PO4-P concentration was 6.07-6.37 mg l(-1). Total phosphorus (TP) and total nitrogen (TN) removal efficiencies were around 89.6% and 14.5-16.1%, over 3.5 and 1 times higher than those of control, respectively. COD removal rate in the lime-addition reactor was 2.05-2.48 kg COD m(-3) d(-1), higher than 1.34-1.61 kg COD m(-3) d(-1) in the control.

Air Pollution↗

Development and evaluation of an enzyme-linked immunosorbent assay with recombinant SAG2 for diagnosis of Toxoplasma gondii infection in cats.

Cats are pivotal in the transmission of Toxoplasma gondii. To develop a sensitive and specific serodiagnostic method for feline toxoplasmosis, surface antigen 2 (SAG2) of T. gondii was expressed in Escherichia coli and its diagnostic potential evaluated in an enzyme-linked immunosorbent assay (ELISA). The ELISA with recombinant SAG2 (rSAG2) was able to differentiate very clearly between sera from cats experimentally infected with T. gondii and sera from normal cats. Serum samples collected from domestic cats in Japan were investigated by the ELISA, and the results were compared with those of a commercially available latex agglutination test (LAT) kit. Of the 192 samples screened, 42 (21.9%) were positive by ELISA. Among the 42 ELISA-positive samples, 39 were positive by LAT. There was a significant correlation between ELISA and LAT titers. All the 150 ELISA-negative samples were negative by LAT. These results indicate that the ELISA with rSAG2 expressed in E. coli should be a useful method for detection of T. gondii infection in cats.

Animals↗

Identification of two novel human dynein light chain genes, DNLC2A and DNLC2B, and their expression changes in hepatocellular carcinoma tissues from 68 Chinese patients.

Two full-length cDNAs, DNLC2A and DNLC2B, were cloned and characterized. Their open reading frames respectively encode 96 amino acids which are most closely homologous to roadblock/LC7, one member of an ancient dynein light chain protein family, conserved in nematode, fruit fly, mouse and rat. The DNLC2A was expressed in 12 of 16 human tissues examined, with especially strong expression in heart, liver and brain, whereas there was weak expression in lung, prostate, testis, small intestine and colon. The expression of DNLC2B was generally high compared with that of DNLC2A except in liver. Northern blotting and/or semi-quantitative RT-PCR analysis examined the expression changes of DNLC2A and DNLC2B in 68 hepatocellular carcinoma tissue samples. It was revealed that DNLC2A was up-regulated (45 out of the 68 cases) while DNLC2B was down-regulated (44 out of 68 cases), compared with their adjacent tumor-free liver tissues. Interestingly, among the total 68 liver cancer samples tested, DNLC2A was up-regulated while DNLC2B was down-regulated in 28 cases; DNLC2A was up-regulated while no obvious change was observed for DNLC2B in 10 cases; no obvious change was observed for DNLC2A while DNLC2B was down-regulated in 14 cases. Although the underlying mechanism is not clear to date, the apparent up-regulation of DNLC2A and down-regulation of DNLC2B suggest that these genes might be involved in tumor progression. On the other hand, the different expression changes of the two homologous genes indicate that hepatocellular carcinomas are caused by different pathological mechanisms. In addition, DNLC2A was assigned to human chromosome 20q12-q13.11 near the marker D20S106 by radiation hybrid mapping.

Adult↗

Serodiagnosis of Toxoplasma gondii infection in cats by enzyme-linked immunosorbent assay using recombinant SAG1.

The gene encoding surface antigen 1 (SAG1, P30) of Toxoplasma gondii (T. gondii) was cloned into the plasmid pGEX-4T-3 and subsequently expressed in Escherichia coli (E. coli) as a glutathione-S-transferase (GST) fusion protein. The recombinant SAG1 (rSAG1) was refolded using 8M urea solution followed by dialysis and thereafter evaluated in an enzyme-linked immunosorbent assay (ELISA) for serological diagnosis of toxoplasmosis. The test sera were adsorbed with GST to block non-specific reactivity to the GST-SAG1 fusion protein. The ELISA with rSAG1 was able to differentiate very clearly between sera from cats or mice experimentally infected with T. gondii and sera from normal cats or mice. The ELISA detected no cross-reactivity with sera from mice experimentally infected with the closely related parasite Neospora caninum (N. caninum). Some 193 cat sera were tested for antibodies to T. gondii, out of which 40 (20.7%) reacted positively by ELISA with the rSAG1 while another 79.3% cats reacted negative to the assay. Both positive and negative sera were confirmed by Western blot analysis. The results of ELISA were in agreement with those of a commercially available latex agglutination test (LAT) kit, although the former had higher titers than the latter.

Animals↗

Importance of complete DNA digestion in minimizing variability of 8-oxo-dG analyses.

Estimates of 8-oxo-2'-deoxyguanosine (8-oxo-dG) in DNA vary at least one order of magnitude using different quantitative methods or even the same method. Our hypothesis is that an incomplete DNA hydrolysis to nucleosides by the conventional nuclease P1 (NP1) and alkaline phosphatase (AP) digestion system plays an important role in contributing to the variability of measurements using HPLC coupled with UV and electrochemical (EC) detection. We show here that factors, such as the amount of DNA, choice of enzymes, their activities, and incubation time, can affect DNA digestion and, thus, cause variability in 8-oxo-dG levels. The addition of DNase I and phosphodiesterases I and II to the NP1 + AP system improves the DNA digestion by completely releasing normal nucleosides and 8-oxo-dG, thereby reducing the interday variations of 8-oxo-dG levels. Diethylenetriamine pentaacetic acid (DTPA), an iron chelator, prevented background increases of 8-oxo-dG during DNA digestion, as well as during the waiting period in the autosampler when a batch of DNA samples is analyzed by HPLC. After optimization of the DNA digestion conditions, the interday variability of 8-oxo-dG measurements using commercially available salmon testes DNA (ST DNA) were 26% over a period of 2 years. Under these optimal conditions, our laboratory variability may contribute as little as 13% to the overall variability as shown by assessment of oxidative DNA damage in a population of smokers. Based on our results, we believe that the modified DNA digestion conditions will provide much more accurate 8-oxo-dG determinations and, thus, more reliable estimates of cancer risk.

8-Hydroxy-2'-Deoxyguanosine↗

The constitutive photomorphogenesis 9 signalosome directs vascular endothelial growth factor production in tumor cells.

Angiogenesis is a prerequisite for solid tumor growth and metastasis. Elucidation of the signaling pathways that control tumor angiogenesis constitutes the basis for a rational antiangiogenic tumor therapy. Here we show that the production of vascular endothelial growth factor (VEGF) in HeLa and HL-60 cells is directed by the constitutive photomorphogenesis 9 signalosome (CSN). The CSN is a kinase complex that cooperates with the ubiquitin/26S proteasome system in regulating the stability of proteins involved in signal transduction. VEGF expression is controlled by the transcription factors activator protein (AP)-1, AP-2, SP-1, and hypoxia-inducible factor 1. Inhibition of CSN kinase activity by 50 microM curcumin for 2 h decreases the cellular c-Jun concentration, resulting in a reduction of the VEGF production by approximately 75%. The removal of the inhibitor from the cells led to a time-dependent recovery of endogenous c-Jun that is paralleled by increasing VEGF production. Elevated cellular CSN activity induced by CSN subunit 2 overexpression causes increased VEGF production in HeLa cells. A competitor of CSN-dependent c-Jun phosphorylation, the NH(2)-terminal c-Jun fragment Deltac-Jun(1-226), inhibits VEGF production in HeLa cells. The transcription factors AP-2 and SP-1 act independently of the CSN. They contribute less than a quarter to basal VEGF production. Under our experimental conditions, hypoxia-inducible factor 1alpha protein was not detected. Overexpression of the tumor suppressor p53 reduces VEGF production in HeLa cells. p53 competes with c-Jun for CSN-specific phosphorylation with the consequence of c-Jun destabilization. We conclude that CSN-directed c-Jun signaling mediates high VEGF production in HeLa and HL-60 cells. The data provide an explanation for the known antiangiogenic and antitumorigenic activities of curcumin. Because the CSN regulates the major part of VEGF production in the tested tumor cells, it constitutes a potentially important target for tumor therapy.

COP9 Signalosome Complex↗

[Allogeneic peripheral blood stem cell transplantation for high-risk leukemia].

OBJECTIVE: To study the effects of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in high-risk leukemia. METHODS: From October 1995 to December 2000, 25 patients with high-risk leukemia (median age 34 years, range 5.5-52 years) were transplanted with peripheral blood stem cells from their HLA-identical sibling donors. Among them, 15 patients suffered from acute leukemia (ALL) (one ph+ ALL in CR1, seven in CR2 or greater, and seven in relapse, including two in relapse after the first all-BMT), four patients suffered from chronic myelocytic leukemia (CML) (in CP2, AP, BC, and relapse after BMT respecively), 6 patients suffered from myelodys plastic syndrome (MDS), including one case of refractory anemia with excess of blasts (REAB), one case of refractory anemia with excess of blasts in trransformation (REAB-T), and 4 cases of acute leukemia secondary to MDS. The graft versus host disease (GVHD) prophylaxis included administration of cyclosporine and methotrexate. RESULTS: All patients were successfully engrafted. The median times (range) for their neutrophil returning to > or = 0.5 x 10(9)/L and for platelet returning to > or = 20 x 10(9)/L were 14 (10-18) days and 11 (7-45) days after transplantation resprctively. Grade II acute GVHD occurred in 12 patients with an incidence rate of 48%. Grade III GVHD was found in one patient (4%). No grade IV GVHD was seen. Among the 23 evaluable patients, 16 were diagnosed as chronic GVHD (70%). The actual transplant-related mortality was 16%. Leukemia relapse occurred in 6 patients, four of them received donor lymphocyte infusion (DLI) and achieved remission again. Nineteen patients were alive and disease-free with a median follow-up time of 304 (94-1,963) days. The two-year probability of overall survival, disease-free survival (DFS), and relapse rates were 64%, 58%, and 25% respectively. CONCLUSION: Allo-PBSCT decreases the relapse rate, increases the disease-free survival rate for patients with high-risk leukemia. All-PBSCT may be a better choice for patients with high-risk hematological maligmancies.

Adolescent↗

Potassium silver tin selenide, K(2)Ag(2)Sn(2)Se(6).

The title compound was synthesized by a reactive salt reaction at 773 K over a period of 5 d. It has a one-dimensional chain structure consisting of K(+) cations and one-dimensional [Ag(2)Sn(2)Se(6)](2-) anions. The chain is constructed by edge-sharing bitetrahedral [Sn(2)Se(6)] units connected in a 1:2 ratio via linear Ag(+) ions.

Journal Article↗