Pressure-Induced Enhancement and Retainability of Optoelectronic Properties in Layered Zirconium Disulfide.

Transition metal dichalcogenides (TMDs) exhibit excellent electronic and photoelectric properties under pressure, prompting researchers to investigate their structural phase transitions, electrical transport, and photoelectric response upon compression. Herein, the structural and photoelectric properties of layered ZrS2 under pressure using in situ high-pressure photocurrent, Raman scattering spectroscopy, alternating current impedance spectroscopy, absorption spectroscopy, and theoretical calculations are studied. The experimental results show that the photocurrent of ZrS2 continuously increases with increasing pressure. At 24.6 GPa, the photocurrent of high-pressure phase P21/m is three orders of magnitude greater than that of the initial phase P 3 ¯ m 1 $P\bar{3}m1$ at ambient pressure. The minimum synthesis pressure for pure high-pressure phase P21/m of ZrS2 is 18.8 GPa, which exhibits a photocurrent that is two orders of magnitude higher than that of the initial phase P 3 ¯ m 1 $P\bar{3}m1$ and displays excellent stability. Additionally, it is discovered that the crystal structure, electrical transport properties and bandgap of layered ZrS2 can also be regulated by pressure. This work offers researchers a new direction for synthesizing high-performance TMDs photoelectric materials using high pressure, which is crucial for enhancing the performance of photoelectric devices in the future.

Zirconium Oxide Doped Organosilica Nanodots as Light- and Charge-Management Cathode Interlayer for Highly Efficient and Stable Inverted Organic Solar Cells.

In this work, it is reported that zirconium oxide (ZrO2) doped organosilica nanodots (OSiNDs: ZrO2) with light- and charge-management properties serve as efficient cathode interlayers for high-efficiency inverted organic solar cells (i-OSCs). ZrO2 doping effectively improves the light harvesting of the active layer, the physical contact between the active layer, as well as the electron collection property by habiting charge recombination loss. Consequently, all devices utilizing the OSiNDs: ZrO2 cathode interlayer exhibit enhanced power conversion efficiency (PCE). Specifically, i-OSCs based on PM6:Y6 and PM6:BTP-eC9 achieve remarkable PCEs of 17.16% and 18.43%, respectively. Furthermore, the PCE of device based on PM6:Y6 maintains over 97.2% of its original value following AM 1.5G illumination (including UV light) at 100 mW cm-2 for 600 min.

Green, Safe, and Reliable Synthesis of Bimetallic MOF-808 Nanozymes With Enhanced Aqueous Stability and Reactivity for Biological Applications.

Bimetallic metal-organic frameworks (MOFs) are promising nanomaterials whose reactivity towards biomolecules remains challenging due to issues related to synthesis, stability, control over metal oxidation state, phase purity, and atomic level characterization. Here, these shortcomings are rationally addressed through development of a synthesis of mixed metal Zr/Ce-MOFs in aqueous environment, overcoming significant hurdles in the development of MOF nanozymes, sufficiently stable on biologically relevant conditions. Specifically, a green and safe synthesis of Zr/Ce-MOF-808 is reported in water/acetic acid mixture which affords remarkably water-stable materials with reliable nanozymatic reactivity, including MOFs with a high Ce content previously reported to be unstable in water. The new materials outperform analogous bimetallic MOF nanozymes, showcasing that rational synthesis modifications could impart outstanding improvements. Further, atomic-level characterization by X-ray Absorption Fine Structure (XAFS) and X-ray Diffraction (XRD) confirmed superior nanozymes arise from differences in the synthetic method, which results in aqueous stable materials, and Ce incorporation, which perturbs the ligand exchange dynamics of the material, and could ultimately be used to fine tune the intrinsic MOF reactivity. Similar rational strategies which leverage metals in a synergistic manner should enable other water-stable bimetallic MOF nanozymes able to surpass existing ones, laying the path for varied biotechnological applications.

Targeting of immune checkpoint regulator V-domain Ig suppressor of T-cell activation (VISTA) with 89Zr-labelled CI-8993.

BACKGROUND: CI-8993 is a fully human IgG1κ monoclonal antibody (mAb) that binds specifically to immune checkpoint molecule VISTA (V-domain Ig suppressor of T-cell activation). Phase I safety has been established in patients with advanced cancer (NCT02671955). To determine the pharmacokinetics and biodistribution of CI-8993 in patients, we aimed to develop 89Zr-labelled CI-8993 and validate PET imaging and quantitation in preclinical models prior to a planned human bioimaging trial. METHODS: CI-8993 and human isotype IgG1 control were conjugated to the metal ion chelator p-isothiocyanatobenzyl-desferrioxamine (Df). Quality of conjugates were assessed by SE-HPLC, SDS-PAGE, and FACS. After radiolabelling with zirconium-89 (89Zr), radioconjugates were assessed for radiochemical purity, immunoreactivity, antigen binding affinity, and serum stability in vitro. [89Zr]Zr-Df-CI-8993 alone (1 mg/kg, 4.6 MBq) or in combination with 30 mg/kg unlabelled CI-8993, as well as isotype control [89Zr]Zr-Df-IgG1 (1 mg/kg, 4.6 MBq) were assessed in human VISTA knock-in female (C57BL/6 N-Vsirtm1.1(VSIR)Geno, huVISTA KI) or control C57BL/6 mice bearing syngeneic MB49 bladder cancer tumours; and in BALB/c nu/nu mice bearing pancreatic Capan-2 tumours. RESULTS: Stable constructs with an average chelator-to-antibody ratio of 1.81 were achieved. SDS-PAGE and SE-HPLC showed integrity of CI-8993 was maintained after conjugation; and ELISA indicated no impact of conjugation and radiolabelling on binding to human VISTA. PET imaging and biodistribution in MB49 tumour-bearing huVISTA KI female mice showed specific localisation of [89Zr]Zr-Df-CI-8993 to VISTA in spleen and tumour tissues expressing human VISTA. Specific tumour uptake was also demonstrated in Capan-2 xenografted BALB/c nu/nu mice. CONCLUSIONS: We radiolabelled and validated [89Zr]Zr-Df-CI-8993 for specific binding to huVISTA in vivo. Our results demonstrate that 89Zr-labelled CI-8993 is now suitable for targeting and imaging VISTA expression in human trials.

Cadherin-17 as a target for the immunoPET of adenocarcinoma.

PURPOSE: Cadherin-17 (CDH17) is a calcium-dependent cell adhesion protein that is overexpressed in several adenocarcinomas, including gastric, colorectal, and pancreatic adenocarcinoma. High levels of CDH17 have been linked to metastatic disease and poor prognoses in patients with these malignancies, fueling interest in the protein as a target for diagnostics and therapeutics. Herein, we report the synthesis, in vitro validation, and in vivo evaluation of a CDH17-targeted 89Zr-labeled immunoPET probe. METHODS: The CDH17-targeting mAb D2101 was modified with an isothiocyanate-bearing derivative of desferrioxamine (DFO) to produce a chelator-bearing immunoconjugate - DFO-D2101 - and flow cytometry and surface plasmon resonance (SPR) were used to interrogate its antigen-binding properties. The immunoconjugate was then radiolabeled with zirconium-89 (t1/2 ~ 3.3 days), and the serum stability and immunoreactive fraction of [89Zr]Zr-DFO-D2101 were determined. Finally, [89Zr]Zr-DFO-D2101's performance was evaluated in a trio of murine models of pancreatic ductal adenocarcinoma (PDAC): subcutaneous, orthotopic, and patient-derived xenografts (PDX). PET images were acquired over the course of 5 days, and terminal biodistribution data were collected after the final imaging time point. RESULTS: DFO-D2101 was produced with a degree of labeling of ~ 1.1 DFO/mAb. Flow cytometry with CDH17-expressing AsPC-1 cells demonstrated that the immunoconjugate binds to its target in a manner similar to its parent mAb, while SPR with recombinant CDH17 revealed that D2101 and DFO-D2101 exhibit nearly identical KD values: 8.2 × 10-9 and 6.7 × 10-9 M, respectively. [89Zr]Zr-DFO-D2101 was produced with a specific activity of 185 MBq/mg (5.0 mCi/mg), remained >80% stable in human serum over the course of 5 days, and boasted an immunoreactive fraction of >0.85. In all three murine models of PDAC, the radioimmunoconjugate yielded high contrast images, with high activity concentrations in tumor tissue and low uptake in non-target organs. Tumoral activity concentrations reached as high as >60 %ID/g in two of the cohorts bearing PDXs. CONCLUSION: Taken together, these data underscore that [89Zr]Zr-DFO-D2101 is a highly promising probe for the non-invasive visualization of CDH17 expression in PDAC. We contend that this radioimmunoconjugate could have a significant impact on the clinical management of patients with both PDAC and gastrointestinal adenocarcinoma, most likely as a theranostic imaging tool in support of CDH17-targeted therapies.

Radiolabelling and preclinical characterisation of [89Zr]Zr-Df-ATG-101 bispecific to PD-L1/4-1BB.

PURPOSE: ATG-101, a bispecific antibody that simultaneously targets the immune checkpoint PD-L1 and the costimulatory receptor 4-1BB, activates exhausted T cells upon PD-L1 crosslinking. Previous studies demonstrated promising anti-tumour efficacy of ATG-101 in preclinical models. Here, we labelled ATG-101 with 89Zr to confirm its tumour targeting effect and tissue biodistribution in a preclinical model. We also evaluated the use of immuno-PET to study tumour uptake of ATG-101 in vivo. METHODS: ATG-101, anti-PD-L1, and an isotype control were conjugated with p-SCN-Deferoxamine (Df). The Df-conjugated antibodies were radiolabelled with 89Zr, and their radiochemical purity, immunoreactivity, and serum stability were assessed. We conducted PET/MRI and biodistribution studies on [89Zr]Zr-Df-ATG-101 in BALB/c nude mice bearing PD-L1-expressing MDA-MB-231 breast cancer xenografts for up to 10 days after intravenous administration of [89Zr]Zr-labelled antibodies. The specificity of [89Zr]Zr-Df-ATG-101 was evaluated through a competition study with unlabelled ATG-101 and anti-PD-L1 antibodies. RESULTS: The Df-conjugation and [89Zr]Zr -radiolabelling did not affect the target binding of ATG-101. Biodistribution and imaging studies demonstrated biological similarity of [89Zr]Zr-Df-ATG-101 and [89Zr]Zr-Df-anti-PD-L1. Tumour uptake of [89Zr]Zr-Df-ATG-101 was clearly visualised using small-animal PET imaging up to 7 days post-injection. Competition studies confirmed the specificity of PD-L1 targeting in vivo. CONCLUSION: [89Zr]Zr-Df-ATG-101 in vivo distribution is dependent on PD-L1 expression in the MDA-MB-231 xenograft model. Immuno-PET with [89Zr]Zr-Df-ATG-101 provides real-time information about ATG-101 distribution and tumour uptake in vivo. Our data support the use of [89Zr]Zr-Df-ATG-101 to assess tumour and tissue uptake of ATG-101.

Pertechnetate/perrhenate-capped Zr/Hf-Dihydroxide Dimers: Elucidating Zr-TcO4 Co-Mobility in the Nuclear Fuel Cycle.

Spent nuclear fuel contains heavy element fission products that must be separated for effective reprocessing for a safe and sustainable nuclear fuel cycle. 93 Zr and 99 Tc are high-yield fission products that co-transport in liquid-liquid extraction processes. Here we seek atomic-level information of this co-extraction process, as well as fundamental knowledge about ZrIV (and HfIV ) aqueous speciation in the presence of topology-directing ligands such as pertechnetate (TcO4 - ) and non-radioactive surrogate perrhenate (ReO4 - ). In this context, we show that the flat tetrameric oxyhydroxyl-cluster [MIV 4 (OH)8 (H2 O)16 ]8+ (and related polymers) is dissociated by perrhenate/pertechnetate to yield isostructural dimers, M2 (OH)2 (XO4 - )6 (H2 O)6 ⋅ 3H2 O (M=Zr/HfIV ; X=Re/TcVII ), elucidated by single-crystal X-ray diffraction. We used these model compounds to understand the pervasive 93 Zr-99 Tc coextraction with further speciation studies in water, nitric acid, and tetrabutylphosphate (TBP) -kerosene; where the latter two media are relevant to nuclear fuel reprocessing. SAXS (small angle X-ray scattering), compositional evaluation, and where experimentally feasible, ESI-MS (electrospray ionization mass spectrometry) showed that perrhenate/pertechnetate influence Zr/HfIV -speciation in water. In Zr-XO4 solvent extraction studies to simulate fuel reprocessing, we provide evidence that TcO4 - enhances extraction of ZrIV , and compositional analysis of the extracted metal-complexes (Zr-ReO4 study) is consistent with the crystallized ZrIV 2 (OH)2 (ReVII O4 - )6 (H2 O)6 ⋅dimer.

Extractive Mass Transfer of Zr(IV) into a Hydrophobic Ionic Liquid Medium Containing Diglycolamide Extractant: Solvent Extraction and Spectroscopic Analysis.

Solvent extraction of Zr(IV) in ionic liquid (IL) medium is less known and Zr(IV) - IL chemistry indeed needs exploration to realize the coordination approach of Zr(IV) in IL phase. In view of this, in the present work, a strongly hydrophobic imidazolium based IL: 1-methyl-3-octylimidazolium bis(trifluoromethylsulfonyl)imide ([C8mim][NTf2]) as the medium containing a diglycolamide (DGA) extractant: N,N,N',N'-tetra-n-octyldiglycolamide (TODGA) was opted to understand the extraction behavior of Zr(IV) from nitric acid medium. Different experimental parameters such as the concentration of initial nitric acid, initial feed metal concentration, equilibration time and ligand concentration were tuned to unravel the extraction efficiency of the proposed IL phase towards Zr(IV). The extraction scenario was completely dependent on the hydrophobicity of IL diluent and increasing extraction trend with an increase in feed acidity along with the coordination of two TODGA molecules ensured Zr(IV) - complex formation in a neutral solvation mechanistic pathway. The extraction trend of Zr(IV) was compared with molecular diluent (n-dodecane (n-DD)) containing TODGA and a phase modifier: N,N-dihexyloctanamide (DHOA). The coordination aspect of Zr(IV) with ligand in IL phase was ascertained spectroscopically to validate Zr(IV) loading in IL phase. Thermodynamics of Zr(IV) extraction revealed the nature of the extraction process and the complex formation.

Enhanced Theranostic Efficacy of 89Zr and 177Lu-Labeled Aflibercept in Renal Cancer: A Viable Option for Clinical Practice.

Vascular endothelial growth factor (VEGF) targeted therapy serves as an important therapeutic approach for renal cancer, but its clinical effectiveness is unsatisfactory. Moreover, there is a lack of reliable biomarkers for preoperative assessment of tumor VEGF expression. This study aimed to explore the potential for further applications of 177Lu/89Zr-labeled aflibercept (Abe), a VEGF-binding agent, in imaging visualization of VEGF expression and therapy for renal cancer. To determine specificity uptake in renal cancer, BALB/c mice with VEGF-expressing Renca tumor were intravenously injected with [89Zr]Zr-Abe, [177Lu]Lu-Abe, or Cy5.5-Abe and the blocking group was designed as a control group. PET, SPECT, and fluorescence images were acquired, and the biodistribution of [89Zr]Zr-Abe and [177Lu]Lu-Abe was performed. Additionally, the [177Lu]Lu-Abe, [177Lu]Lu-Abe-block, 177Lu only, Abe only, and PBS groups were compared for evaluation of the therapeutic effect. To assess the safety, we monitored and evaluated the body weight, blood biochemistry analysis, and whole blood analysis and major organs were stained with hematoxylin and eosin after [177Lu]Lu-Abe treatment. DOTA-Abe was successfully labeled with 177Lu and Df-Abe with 89Zr in our study. The uptake in tumor of [89Zr]Zr-Abe was significantly higher than that of [89Zr]Zr-Abe-block (P < 0.05) and provided excellent tumor contrast in PET images. [177Lu]Lu-Abe demonstrated promising tumor-specific targeting capability with a high and persistent tumor uptake. The standardized tumor volume of [177Lu]Lu-Abe was significantly smaller than those of other treatment groups (P < 0.05). [177Lu]Lu-Abe also had smaller tumor volumes and reduced expression of VEGF and CD31 compared to those of the control groups. Fluorescence images demonstrate higher tumor uptake in the Cy5.5-Abe group compared to the Cy5.5-Abe-block group (P < 0.05). In conclusion, [89Zr]Zr-Abe enables noninvasive analysis of VEGF expression, serving as a valuable tool for assessing the VEGF-targeted therapy effect. Additionally, all of the findings support the enhanced therapeutic efficacy and safety of [177Lu]Lu-Abe, making it a viable option for clinical practice in renal cancer.

Construction of [89Zr]Zr-Labeled HuL13 for ImmunoPET Imaging of LAG-3 Checkpoint Expression on Tumor-Infiltrating T Cells.

Lymphocyte activation gene 3 (LAG-3) has attracted much attention as a potentially valuable immune checkpoint. Individual identification of LAG-3 expression at screening and during treatment could improve the successful implementation of anti-LAG-3 therapies. HuL13 is a human IgG1 monoclonal antibody that binds to the LAG-3 receptor in T cells. Here, we used [89Zr]Zr-labeled HuL13 to delineate LAG-3+ T-cell infiltration into tumors via positron emission tomography (PET) imaging. A549/LAG-3 cells, which stably express LAG-3, were generated by infection with lentivirus. The uptake of [89Zr]Zr-DFO-HuL13 in A549/LAG-3 cells was greater than that in the negative control (A549/NC) cells at each time point. The equilibrium dissociation constant (Kd) of [89Zr]Zr-DFO-HuL13 for the LAG-3 receptor was 8.22 nM. PET imaging revealed significant uptake in the tumor areas of A549/LAG-3 tumor-bearing mice from 24 h after injection (SUVmax = 2.43 ± 0.06 at 24 h). As a proof of concept, PET imaging of the [89Zr]Zr-DFO-HuL13 tracer was further investigated in an MC38 tumor-bearing humanized LAG-3 mouse model. PET imaging revealed that the [89Zr]Zr-DFO-HuL13 tracer specifically targets human LAG-3 expressed on tumor-infiltrating lymphocytes (TILs). In addition to the tumors, the spleen was also noticeably visible. Tumor uptake of the [89Zr]Zr-DFO-HuL13 tracer was lower than its uptake in the spleen, but high uptake in the spleen could be reduced by coinjection of unlabeled antibodies. Coinjection of unlabeled antibodies increases tracer activity in the blood pool, thereby improving tumor uptake. Dosimetry evaluation of the healthy mouse models revealed that the highest absorbed radiation dose was in the spleen, followed by the liver and heart wall. In summary, these studies demonstrate the feasibility of using the [89Zr]Zr-DFO-HuL13 tracer for the detection of LAG-3 expression on TILs. Further clinical evaluation of the [89Zr]Zr-DFO-HuL13 tracer may be of significant help in the stratification and management of patients suitable for anti-LAG-3 therapy.

Preclinical ImmunoPET Imaging Using a Zr-89-Labeled Anti-CD146 Monoclonal Antibody for Diagnosis of Melanoma.

The aim of this study was to evaluate the preclinical efficacy of [89Zr]Zr-DFO-Ab253 as a novel positron emission tomography (PET) tracer for CD146-positive malignant melanoma imaging. Considering the high expression of CD146 in malignant melanoma, this study investigated the effect of different CD146 expression levels on the tumor uptake of [89Zr]Zr-DFO-Ab253. CD146 selectivity was investigated by using the CD146-positive human melanoma cell A375 and the CD146-negative human alveolar epithelial cell A549. The cell uptake of [89Zr]Zr-DFO-Ab253 tracers was investigated, and receptor-binding affinities were measured by radioactive enzyme-linked immunosorbent assay. Biodistribution studies and micro-PET imaging of the radiotracers were performed on mice bearing A375 and A549 xenografts under baseline and blocking conditions. An immunohistochemical test was performed using A375 and A549 tissue sections for CD146 expression level analysis. [89Zr]Zr-DFO-Ab253 was obtained with a high radiochemical yield (87.86 ± 4.66%) and a satisfactory radiochemical purity (>98.0%). The specificity and affinity of [89Zr]Zr-DFO-Ab253 were confirmed in melanoma A375 cells and in vivo PET imaging of A375 tumor models. [89Zr]Zr-DFO-IgG and A549 lung tumors were prepared as control radiotracers and negative models to verify the specificity of [89Zr]Zr-DFO-Ab253 on CD146. [89Zr]Zr-DFO-Ab253 has a Kd of 4.01 ± 0.50 nM. PET imaging and biodistribution showed a higher uptake of [89Zr]Zr-DFO-Ab253 in A375 melanomas than that in A549 tumors (42.1 ± 4.04% vs 7.87 ± 1.30% ID/g at 120 h, P < 0.05). A low tumor uptake of [89Zr]Zr-DFO-IgG was observed with uptakes of 1.91 ± 0.41 and 2.80 ± 0.14 ID%/g when blocked at 120 h. The radiation-absorbed dose was calculated to be 0.13 mSv/MBq. This study demonstrates the synthesis and preclinical evaluation of [89Zr]Zr-DFO-Ab253 and indicates that the novel tracer has promising applications in malignant melanoma-specific PET imaging because of its high uptake and long-time retention in malignant melanoma. It also provides feasibility for the development of integrated molecular probes for diagnosis and treatment based on the CD146 target.

Hyperkalemia treatment standard.

Hyperkalemia is a common electrolyte disturbance in both inpatient and outpatient clinical practice. The severity and associated risk depends on the underlying cause and rate of potassium (K+) increase. Acute hyperkalemia requires immediate attention due to potentially life-threatening manifestations resulting from the rapid increase in plasma K+ concentration. Treatment is initially focused on stabilizing the cardiac membrane, followed by maneuvers to shift K+ into the cells, and ultimately initiating strategies to decrease total body K+ content. Chronic hyperkalemia develops over a more extended period of time and manifestations tend to be less severe. Nevertheless, the disorder is not benign since chronic hyperkalemia is associated with increased morbidity and mortality. The approach to patients with chronic hyperkalemia begins with a review of medications potentially responsible for the disorder, ensuring effective diuretic therapy and correcting metabolic acidosis if present. The practice of restricting foods high in K+ to manage hyperkalemia is being reassessed since the evidence supporting the effectiveness of this strategy is lacking. Rather, dietary restriction should be more nuanced, focusing on reducing the intake of nonplant sources of K+. Down-titration and/or discontinuation of renin-angiotensin-aldosterone inhibitors should be discouraged since these drugs improve outcomes in patients with heart failure and proteinuric kidney disease. In addition to other conservative measures, K+ binding drugs and sodium-glucose cotransporter 2 inhibitors can assist in maintaining the use of these drugs.

Potassium-lowering effects of sodium zirconium cyclosilicate in the early post-transplant period.

PROBLEM: Hyperkalemia is a serious condition among intra-abdominal transplant recipients, and the safety and efficacy of sodium zirconium cyclosilicate (SZC) for its management during the early post-transplant period are not well-established. METHODS: Adults who received at least one 10-g dose of SZC within 14 days after an intra-abdominal transplant between January 2020 and July 2022 were included in our study. The primary outcome was the change in potassium (K+) levels following the first SZC dose. Other analyses explored adjunctive potassium-lowering therapies, potential gastrointestinal complications, and patient subgroups based on therapy and transplant type. RESULTS: Among the recipients (n = 46), 11 were kidney recipients, 26 were liver recipients, seven were simultaneous liver/kidney recipients, and two were simultaneous pancreas/kidney recipients. The mean time to first dose post-transplant was 7.6 (±4) days, and the mean change in serum K+ after the initial SZC dose was -.27 mEq (p = .001). No gastrointestinal complications were observed following the SZC dose. The mean increase in serum bicarbonate was .58 mEq (p = .41) following the first dose of SZC. Four kidney recipients required dialysis following the SZC dose. CONCLUSION: This study represents the largest investigation on the use of SZC in transplant recipients. A single 10-g dose of SZC reduced serum K+ levels in all subgroups, while the use of adjunctive K+-lowering therapies did not provide additional reduction beyond the effects of SZC. Importantly, no gastrointestinal complications were observed. These findings suggest that SZC may be a safe and promising therapeutic option for hyperkalemia management following solid organ transplantation.

Ti4+ functionalized zirconium metal-organic frameworks with polymer brushes for specific identification of phosphopeptides in human serum and skimmed milk.

In the present study, click chemistry and Schiff base reactions were simultaneously applied to prepare polymer brush (PEG)-functionalized MOF materials (UiO-66-NH2) and immobilized with Ti4+ (MOF-Brush-THBA-Ti4+) for phosphopeptide analysis. The material has a detection limit of 0.5 fmol, a selectivity of 2000:1, and a loading capacity of 133 mg/g for phosphopeptides. It also demonstrated great repeatability (10 cycles) and recovery rate (96.7 ± 1.4%). During the analysis of bio-samples, 4 specific phosphopeptides were identified in endogenous breast cancer serum, while 11 phosphopeptides were identified in skimmed milk. Moreover, 47 phosphopeptides correlated with 29 phosphorylated proteins were selectively identified from normal control serum, and 66 phosphopeptides correlated with 26 phosphorylated proteins were identified from breast cancer serum. Further analysis of gene ontology (GO) revealed that the detected phosphorylated proteins associated with breast cancer included positive regulation of receptor-mediated endocytosis, proteolysis, extracellular exosome, heparin binding, and chaperone binding. These findings suggest that these associated pathways might contribute to the etiology of breast cancer. Overall, this application exhibits enormous potential in the identification of phosphorylated peptides within bio-samples.

Hyperkalaemia in Cardiological Patients: New Solutions for an Old Problem.

Hyperkalaemia is one of the most common electrolyte disorders in patients with cardiovascular disease (CVD). The true burden of hyperkalaemia in the real-world setting can be difficult to assess, but in population-based cohort studies up to 4 in 10 patients developed hyperkalaemia. In addition to drugs interfering with potassium metabolism and food intake, several conditions can cause or worsen hyperkalaemia, such as advanced age, diabetes, and chronic kidney disease. Mortality, cardiovascular morbidity, and hospitalisation are higher in patients with hyperkalaemia. Hyperkalaemia represents a major contraindication or a withholding cause for disease-modifying therapies like renin-angiotensin-aldosterone inhibitors (RAASi), mainly mineralocorticoid receptor antagonists. Hyperkalaemia can be also classified as acute and chronic, according to the onset. Acute hyperkalaemia is often a life-threatening emergency requiring immediate treatment to avoid lethal arrhythmias. Therapy goal is cell membrane stabilisation by calcium administration, cellular intake, shift of extracellular potassium to the intracellular space (insulin, beta-adrenergic agents, sodium bicarbonate), and increased elimination with diuretics or dialysis. Chronic hyperkalaemia was often managed with dietary counselling to prevent potassium-rich food intake and tapering of potassium-increasing drugs, mostly RAASi. Sodium polystyrene sulphonate, a potassium binder, was the only therapeutic option. Recently, new drugs such as patiromer and sodium zirconium cyclosilicate give new opportunities for the treatment of hyperkalaemia, as they proved to be safe, well tolerated, and effective. Aim of this review is to describe the burden of hyperkalaemia in cardiovascular patients, its direct and indirect effects, and the therapeutic options now available in the acute and chronic setting.

Antiperspirant-related zirconium and aluminum-containing granulomas; histopathology and in situ chemical analysis.

The potential adverse health effects of antiperspirant use are of interest to patients, primary care providers, dermatologists, and pathologists. In rare instances, antiperspirants containing aluminum-zirconium complexes have been associated with granulomatous dermatoses despite being deemed non-sensitizing in experiments. In this case study, we present a detailed examination of an axillary granuloma in a 28-year-old female who had been using an aluminum-zirconium-based antiperspirant for several years and presented with a left axillary nodule that was excised and analyzed using scanning electron microscopy with energy-dispersive x-ray analysis (SEM/EDXA). Histopathological examination revealed a foreign body-type reaction with amphophilic granular material within giant cells that corresponded to collocated zirconium and aluminum on SEM/EDXA elemental maps. Our case adds to the limited reports of axillary granulomas related to aluminum-zirconium complexes. It illustrates the histopathological appearance and in situ distribution of the aluminum-zirconium complexes, supporting the formation of foreign body-type granulomas. Additionally, our case study illustrates the potential role of these compounds in such reactions and aims to increase awareness among pathologists and clinicians.

Safety and efficacy of sodium zirconium cyclosilicate for the management of acute and chronic hyperkalemia in children with chronic kidney disease 4-5 and on dialysis.

BACKGROUND: Sodium zirconium cyclosilicate (SZC), an ion-exchange resin, is effective in the control of hyperkalemia in adults with chronic kidney disease (CKD); reports of use in children are limited. Prolonged therapy with SZC to relax dietary potassium restriction in CKD has not been examined. METHODS: We conducted a retrospective chart review of patients 6 months to 18 years of age with CKD stage 4-5 or on dialysis (5D) administered SZC for sustained hyperkalemia (potassium ≥ 5.5 mEq/L, three consecutive values). Patients received SZC (0.5-10 g per dose; age-based) either short-term (< 30 days) or long-term (> 30 days). RESULTS: Twenty patients with median age 10.8 (inter-quartile range 3.9, 13.4) years were treated with SZC. Short-term SZC, for 5 (3, 19) days, was associated with safe management of dialysis catheter insertions (n = 5) and access dysfunction (n = 4), and was useful during palliative care (n = 1). Serum potassium levels decreased from 6.7 (6.1, 6.9) to 4.4 (3.7, 5.2) mEq/L (P < 0.001). Long-term SZC for 5.3 (4.2, 10.1) months achieved decline in serum potassium from 6.1 (5.8, 6.4) to 4.8 (4.2, 5.4) mEq/L (P < 0.001). SZC use was associated with liberalization of diet (n = 6) and was useful in patients with poor adherence to dietary restriction (n = 3). Adverse events or edema were not observed; serum sodium and blood pressure remained stable. CONCLUSIONS: SZC was safe and effective for the management of acute and chronic hyperkalemia in children with CKD4-5/5D. Its use was associated with relaxation of dietary potassium restriction. Studies to examine its routine use to improve diet and nutritional status in children with CKD are required.

Discomfort/pain due to peri-implant probing at titanium and zirconium implants: A cross-sectional study.

OBJECTIVE: This study was designed to compare discomfort/pain after periodontal and peri-implant probing in patients with titanium compared with zirconium implants. METHODS: One examiner recruited and examined 70 patients, each of whom had a dental implant with a contralateral tooth; 37 patients had titanium implants of various types and 33 patients had zirconium implants; one implant was analyzed for each patient. Periodontal and peri-implant probing pocket depth (PPD) and clinical attachment level (CAL) were assessed. Immediately after probing, patients rated their discomfort/pain with a visual analog scale (VAS). The emergence profiles of implant crowns were assessed on periapical radiographs of the implants. RESULTS: Seventy patients with a median age of 55 years (interquartile range [IQR]: 42-65 years), including 43 females and 16 current smokers, were examined. The mean PPD and bleeding on probing (BOP) were higher around implants than around teeth (p < .001). CAL and suppuration were well-balanced between implants and teeth. Peri-implant probing caused significantly more discomfort/pain than periodontal probing [median VAS score: 12.5 (IQR 4-22) vs. 9 (2-15); p < .001]. Logistic regression revealed that discomfort/pain after peri-implant probing was less intense in patients who had taken analgesic medication (p = .021) and around titanium implants (p = .037). CONCLUSIONS: Peri-implant probing caused significantly more discomfort/pain than periodontal probing. Patients who had taken analgesic medication experienced less discomfort and pain with peri-implant probing than those who had not; furthermore, titanium implants were associated with less pain than zirconium implants.

Clinical, radiographic and patient-reported outcomes of zirconia and titanium implants in the posterior zone after 1 year of loading-A randomized controlled trial.

OBJECTIVE: To assess the clinical, radiographic and patient-reported outcomes (PROMs) of posterior zirconia and titanium implants at 1 year of implant loading. MATERIALS AND METHODS: Forty-two patients with two adjacent missing teeth were enrolled in a randomized controlled trial with a within-subject controlled design. Each patient received one zirconia (Zr) and one titanium (Ti) implant, with the mesial and distal positions randomized. The implant restoration consisted of multiple layered zirconia, with the buccal aspect veneered. In group Zr, the restoration was intraorally cemented onto the one-piece Zr implant, whereas in group Ti, the restoration was extraorally cemented onto the titanium base abutment and intraorally screw-retained onto the Ti implant. Examinations were performed following restoration delivery at baseline (BL) and at 1 year. Measurements included clinical parameters, radiographic outcomes (MBL) and PROMs. RESULTS: Bleeding on probing showed an increase from BL to 1 year (34 ± 30% for Zr; 25 ± 21% for Ti). MBL remained stable with minimal changes from BL to 1 year, measuring 0.1 ± 0.4 mm (mean ± SD) for Zr and -0.1 ± 0.7 mm for Ti. Veneering fractures were the most frequent technical complication and amounted to 17.5% in group Zr and 5% in group Ti (p = .100). Patients preferred Zr implants for their soft tissue color, with a significant difference in perception between patients and clinicians (p < .017). CONCLUSION: The study showed that both Zr and Ti implants had similar clinical outcomes, despite a high prevalence of mucositis and a few technical complications. Both implant types demonstrated stable marginal bone levels and similar patient-reported outcome measures.

Do the number of zirconia implants and the thickness of CBCT image reconstruction affect the detection of peri-implant bone defect? A diagnostic accuracy ex vivo study.

OBJECTIVES: To evaluate the influence of multiplanar reconstruction thickness on the detection of peri-implant bone defects with a standalone zirconia implant and compare it to when another implant is in the vicinity using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Five dry human mandibles were used to create twenty implant sites in the second premolar and first molar regions. The OP300 Maxio was used to acquire CBCT images (90 kVp, 6.3 mA, 5 × 5 cm FOV, and 0.125 mm3 voxel size) before and after creating 3 mm peri-implant bone defects in the buccal aspect of the premolar region. Half of the scans featured a single zirconia implant in the premolar region, while the others had two implants in the premolar and molar regions. Three reconstruction thicknesses (0.125 mm, 1 mm, and 2 mm) were considered for the multiplanar reconstruction analyses. Five oral and maxillofacial radiologists assessed the detection of peri-implant bone defects using a 5-point scale. Diagnostic parameters were calculated and compared using Two-way ANOVA (α = .05). RESULTS: The studied factors showed no significant influence on the diagnosis of peri-implant bone defects (p > .05). Diagnostic performance was notably higher with a single implant, especially with a 2-mm reconstruction thickness (AUC = 0.88, sensitivity = 0.68, specificity = 0.94). Although the differences were not statistically significant, the results were more modest when two implants were present (AUC = 0.80, sensitivity = 0.58, specificity = 0.82). CONCLUSIONS: The presence of an adjacent zirconia implant and variations in reconstruction thickness did not influence the detection of 3 mm buccal peri-implant bone defects on CBCT images.