Two types of metal–organic frameworks (MOFs) have been synthesized and evaluated in the separation of C2 and C3 olefins and paraffins. Whereas Co2(dhtp) (=Co–CPO-27 = Co–MOF-74) and Mg2(dhtp) show an ...adsorption selectivity for the olefins ethene and propene over the paraffins ethane and propane, the zeolitic imidazolate framework ZIF-8 behaves in the opposite way and preferentially adsorbs the alkane. Consequently, in breakthrough experiments, the olefins or paraffins, respectively, can be separated.
The current work addresses the understanding of the stabilization of nanoparticles in suspension. Specifically, we study ZnO in ethanol for which the influence of particle size and reactant ratio as ...well as surface coverage on colloidal stability in dependence of the purification progress was investigated. The results revealed that the well-known ζ-potential determines not only the colloidal stability but also the surface coverage of acetate groups bound to the particle surface. The acetate groups act as molecular spacers between the nanoparticles and prevent agglomeration. Next to DLVO calculations based on the theory of Derjaguin, Landau, Verwey and Overbeek using a core–shell model we find that the stability is better understood in terms of dimensionless numbers which represent attractive forces as well as electrostatic repulsion, steric effects, transport properties, and particle concentration. Evaluating the colloidal stability in dependence of time by means of UV–vis absorption measurements a stability map for ZnO is derived. From this map it becomes clear that the dimensionless steric contribution to colloidal stability scales with a stability parameter including dimensionless repulsion and attraction as well as particle concentration and diffusivity of the particles according to a power law with an exponent of −0.5. Finally, we show that our approach is valid for other stabilizing molecules like cationic dendrons and is generally applicable for a wide range of other material systems within the limitations of vanishing van der Waals forces in refractive index matched situations, vanishing ζ-potential and systems without a stabilizing shell around the particle surface.
Patients with muscle-invasive urothelial carcinoma achieving pathological complete response (pCR) upon neoadjuvant chemotherapy (NAC) have improved prognosis. Molecular subtypes of bladder cancer ...differ markedly regarding sensitivity to cisplatin-based chemotherapy and harbor FGFR treatment targets to various content. The objective of the present study was to evaluate whether preoperative assessment of molecular subtype as well as FGFR target gene expression is predictive for therapeutic outcome—rate of ypT0 status—to justify subsequent prospective validation within the “BladderBRIDGister”. Formalin-fixed paraffin-embedded (FFPE) tissue specimens from transurethral bladder tumor resections (TUR) prior to neoadjuvant chemotherapy and corresponding radical cystectomy samples after chemotherapy of 36 patients were retrospectively collected. RNA from FFPE tissues were extracted by commercial kits, Relative gene expression of subtyping markers (e.g., KRT5, KRT20) and target genes (FGFR1, FGFR3) was analyzed by standardized RT-qPCR systems (STRATIFYER Molecular Pathology GmbH, Cologne). Spearman correlation, Kruskal−Wallis, Mann−Whitney and sensitivity/specificity tests were performed by JMP 9.0.0 (SAS software). The neoadjuvant cohort consisted of 36 patients (median age: 69, male 83% vs. female 17%) with 92% of patients being node-negative during radical cystectomy after 1 to 4 cycles of NAC. When comparing pretreatment with post-treatment samples, the median expression of KRT20 dropped most significantly from DCT 37.38 to 30.65, which compares with a 128-fold decrease. The reduction in gene expression was modest for other luminal marker genes (GATA3 6.8-fold, ERBB2 6.3-fold). In contrast, FGFR1 mRNA expression increased from 33.28 to 35.88 (~6.8-fold increase). Spearman correlation revealed positive association of pretreatment KRT20 mRNA levels with achieving pCR (r = 0.3072: p = 0.0684), whereas pretreatment FGFR1 mRNA was associated with resistance to chemotherapy (r = −0.6418: p < 0.0001). Hierarchical clustering identified luminal tumors of high KRT20 mRNA expression being associated with high pCR rate (10/16; 63%), while the double-negative subgroup with high FGFR1 expression did not respond with pCR (0/9; 0%). Molecular subtyping distinguishes patients with high probability of response from tumors as resistant to neoadjuvant chemotherapy. Targeting FGFR1 in less-differentiated bladder cancer subgroups may sensitize tumors for adopted treatments or subsequent chemotherapy.
The microporous zeolitic imidazolate framework ZIF-4 has been synthesized, and its ethylene/ethane and propylene/propane separation potentials have been evaluated by single-component adsorption ...isotherms and breakthrough experiments of the respective binary mixtures. In all experiments, a higher selectivity for the paraffin is observed that is manifested by a steeper equilibrium isotherm as well as a later breakthrough in the fixed-bed adsorber experiments. Microporous adsorbents with paraffin selectivity are rare but highly interesting for cyclic adsorption processes such as pressure-swing adsorption (PSA).
The synthesis of ZIF-11 in N,N-Diethylformamide (DEF) at varying reaction temperatures, times and different molar compositions of the reaction mixture was investigated in detail in order to identify ...ranges of the formation of phase-pure ZIF-11. Since it is known that water in the solvent DEF leads to the formation of the phase impurity ZIF-7-III during the ZIF-11 synthesis, all reactions were carried out in DEF exhibiting water contents below 0.1 wt%. The variations of the molar ratio of substrates Zn:bIm:DEF = 1:x:y as well as the synthesis temperature and time revealed a number of phase transitions within the ZIF-11 synthesis. Highly crystalline ZIF-11 was obtained for a molar ratio Zn:bIm:DEF of 1:15:1400 already after 3 h of reaction at 60 °C and 100 °C. Depending on the reaction vessel, the water content of the solvent as well as the temperature, ZIF-11 transformed to the dense phase ZIF-7-III within different reaction times. It was concluded that ZIF-11 represents a metastable reaction product. SEM images of the samples obtained after different synthesis times showed that ZIF-11 undergoes successive dissolution-recrystallization cycles in combination with heterogeneous nucleation. For a reduced amount of solvent, the formation of ZIF-11 proceeded faster, but ZIF-11 with lower maximum relative crystallinity was formed. For lower ratios of solvent to zinc, the time range of stable ZIF-11 formation was smaller as compared to higher solvent amounts. The variations of the ratio of zinc to the linker benzimidazole showed that ZIF-11 formation was slower for lower molar ratios, e.g. 1:2:1400 and 1:4:1400. ZIF-11 with the highest relative crystallinity and a pore volume of 0.43 cm3 g−1 was formed after 3–12 h of reaction at molar ratios Zn:bIm:DEF of 1:8:1400 and 1:12:1400. Another phase transition was observed for synthesis times of 6–96 h for a molar ratio of 1:2:1400. Under those conditions, an unidentified layered crystalline product was found and similarities to the layered ZIF-L were identified.
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•A systematic study on ZIF-11 formation at different synthesis conditions in N,N-Diethylformamide is provided.•Phase-transition products occuring during the ZIF-11 synthesis are characterized in detail.•Optimum parameters for obtaining highly crystalline, pure-phase ZIF-11 are given.
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Background: Patients with muscle invasive urothelial carcinoma achieving pathological complete response upon neoadjuvant chemotherapy (NACT) have improved prognosis. Previously we did show ...that luminal tumors respond better to NACT, while FGFR1 expression is associated with NACT resistance (Ecke et al. 2022). Interestingly the expression of the radioligand targets CXCR4 and FAP is found in chemoresistant, stroma-associated tumors. The objective of this study was to prospectively validate the predictive value of molecular target typing from TUR biopsy samples and compare PET CT imaging by FDG and FAP radioligand imaging in selected patients after two cycles of NACT to justify subsequent adaptive trial concepts within the "Bladder BRIDGister." Methods: Formalin fixed paraffin embedded tissues (FFPE) from transurethral resections (TUR) before chemotherapy and cystectomy samples after NACT of 36 patients were retrospectively collected and 650 TURB samples were prospectively collected as part of the Bladder BRIDGister. RNA from FFPE tissues were extracted by commercial kits, relative gene expression of subtyping markers (KRT5, KRT20, FGFR1) and radioligand target genes (CXCR4, FAP) were analyzed by standardized RT-qPCR systems (STRATIFYER Molecular Pathology GmbH, Cologne). PET CT Imaging by FDG and FAP was performed after two cycles cisplatinum based NACT. Results: The neoadjuvant cohort consisted of 36 patients (median age 69, male 83%, female 17%) with 92% of patients being node negative. Hierarchical clustering revealed CXCR4 and FAP to be elevated in stromal rich, KRT5 & KRT20 negative tumors not responding to NACT. Elevated FAP mRNA expression was sig. associated with resistance to NACT (chi
2
4.314 p=0,0378). Combining elevated FAP and CXCR4 mRNA expression did identify 1/3 of the patients to be at high risk of NACT resistance (90%). Exemplarily one pT3 G3 patient was selected for PET CT imaging after two cycles that was predicted to be unresponsive to NACT by molecular subtyping. FDG PET CT revealed a hepatic metastatic lesion. In contrast FAP PET CT indicated multiple hepatic and a pancreatic metastatic lesion indicating tumor progression under NACT. Therapy was switched to MVAC with persistent non response. Then pembrolizumab monotherapy was administered due to PD-L1 positivity of the initial TURB (10% TPS /CPC 15). However there still was fulminant progression of the liver metastasis so that ICI therapy had to be stopped. Conclusions: Expression of the radioligand targets CXCR4 and FAP has been shown to be associated with aggressive stromal associated tumors and being resistant to NACT. This could be validated by selecting patients after two cycles of NACT for PET/CT imaging. Stratified FAP PET/CT turned out to be more sensitive than conventional FDG PET CT and may enable future theranostic treatment combinations in patients unresponsive to standard chemo- or immunotherapies.
Studying complex processes in solid phases such as adsorption or phase transitions in situ is the best way to obtain detailed and realistic insights on a molecular level. Besides in situ X-ray ...diffraction techniques, magic angle spinning (MAS) solid-state NMR spectroscopy is one of the most powerful analytical techniques. The implementation of in situ and operando MAS NMR is however challenging and requires dedicated hardware. We introduce here a new 4.0 mm wide-bore probe that allows for a continuous and well-distributed flow of gaseous adsorbates or reactants through the packed sample, as well as uniform heating of the sample and spinning of the rotor at the magic angle. The combination of both in situ MAS NMR and in situ powder X-ray diffraction allowed us to obtain new insights into two phase transformation mechanisms in crystalline, porous materials, viz. that of aluminophosphate VPI-5 into AlPO4-8 and that of metal–organic frameworks from the MIL-53 family during water adsorption and desorption.
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Background: Patients with muscle invasive urothelial carcinoma achieving pathological complete response (pCR) upon neoadjuvant chemotherapy (NACT) have improved prognosis. Molecular subtypes of ...bladder cancer differ markedly with regard to sensitivity to cisplatinum based chemotherapy. Previously we did show that luminal tumors respond better to NACT, while FGFR1 expression is associated with chemo resistance (Ecke et al. 2022). The objective of this study was to determine which patients may benefit from Antibody Drug Conjugate (ADC) treatment in addition to NACT to justify subsequent prospective analysis within the "Bladder BRIDGister". Methods: Formalin fixed paraffin embedded (FFPE) tissues from transurethral resections (TUR) before chemotherapy and cystectomy samples after NACT of 36 patients were retrospectively collected. RNA from FFPE tissues were extracted by commercial kits, relative gene expression of subtyping markers (KRT5, KRT20, FGFR1) and radioligand target genes (NECTIN4, TROP2) were analyzed by standardized RT-qPCR systems (STRATIFYER Molecular Pathology GmbH, Cologne). Spearman correlation, hierarchical clustering, Kruskal-Wallis, chi square and contingency tests were done by JMP 9.0.0 (SAS software). Results: The neoadjuvant cohort consisted of 36 patients (median age: 69, male 83% vs. female 17%) with 92% of patients being pathohistologically node negative. When comparing pretreatment with post treatment samples the median expression of KRT20 dropped 128fold, while FGFR1 expression increased 6.8 fold. Interestingly, TROP2 and NECTIN4 mRNA expression also dropped significantly upon NACT by 5.7 fold and 7.1 fold, respectively. TROP2 and NECTIN4 were positively associated with the response marker KRT20 in therapy naïve TUR biopsies (r=0.5562 p=0.0004; r=0.5833 p=0.0002), but negatively associated with the resistance marker FGFR1 (r=-0.2903 p=0,0858; r=-0.3396 p=0,0427). However, TROP2 and NECTIN4 were not associated with pCR in spearman analysis with minor trend for TROP2 (r=0,2139 p=0,2103). Cluster analysis revealed a subgroup of KRT20 positive and FGFR1 negative tumors expression TROP2 and NECTIN4, which achieved 80% pCR. In addition elevated TROP2 and NECTIN4 expression was found in KRT20 positive tumors coexpressing FGFR1 and being resistant to NACT. Conclusions: Expression of the ADC targets TROP2 and NECTIN4 is associated with KRT20 positive, luminal tumors being highly sensitive to neoadjuvant chemotherapy alone. KRT5 positive, basal tumors do exhibit only very low expression of TROP2 and NECTIN4 mRNA. In view of toxicities the addition of TROP2 and NECTIN4 treatment to NACT might be considered only in luminal tumors exhibiting elevated FGFR1 expression as resistance mechanism and therefore do not respond to NACT.
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Background: Patients with muscle invasive urothelial carcinoma achieving pathological complete response (pCR) upon neoadjuvant chemotherapy (NACT) have improved prognosis. Molecular subtypes of ...bladder cancer differ markedly with regard to sensitivity to cisplatinum based chemotherapy and harbour FGFR treatment targets to various content. Previously we did show that lumina tumors respond better to NACT, while FGFR1 expression is associated with chemo resistance (Ecke et al. 2022). The objective of this study was to determine wether radioligand therapy may be an appropriate option in chemoresistent tumors to justify subsequent prospective validation within the "Bladder BRIDGister". Methods: Formalin fixed paraffin embedded (FFPE) tissues from transurethral resections (TUR) before chemotherapy and cystectomy samples after NACT of 36 patients were retrospectively collected. RNA from FFPE tissues were extracted by commercial kits, relative gene expression of subtyping markers (KRT5, KRT20, FGFR1) and radioligand target genes (CXCR4, FAP) were analyzed by standardized RT-qPCR systems (STRATIFYER Molecular Pathology GmbH, Cologne). Spearman correlation, hierarchical clustering, Kruskal-Wallis, chi square and contingency tests were done by JMP 9.0.0 (SAS software). Results: The neoadjuvant cohort consisted of 36 patients (median age: 69, male 83% vs. female 17%) with 92% of patients being histopathologically node negative. When comparing pretreatment with post treatment samples the median expression of KRT20 dropped 128fold, while FGFR1, CXCR4 and FAP mRNA expression increased 6,8fold, 1,9 fold and 2,9 fold, respectively. FAP was positively associated with KRT5, FGFR1 and CXCR4 in treatment naïve TUR biopsies (r=0.4051 p=0.0141, r=0.6458 p<0.0001 and r=0.7586 p<0.0001, respectively), but negatively associated with KRT20 (r=-0.3879 p=0.0194). As previously described, FGFR1 was negatively associated with pCR (r=-0.6418 p<0.0001). Similarly, CXCR4 and FAP trended to be negatively associated with pCR (r=-0.3181 p=0.0586; r=-0.3072 p=0.0684). Hierarchical clustering revealed that CXCR4 and FAP are elevated in stromal rich, KRT5 & KRT20 negative tumors not responding to NACT. Elevated FAP above median mRNA expression was significantly associated with resistance to NACT (chi
2
4.314 p=0,0378). Combining elevated FAP and CXCR4 mRNA expression did identify 28% of the patients to be at high risk of NACT resistance (90%). Conclusions: Expression of the radioligand targets CXCR4 and FAP are associated with basal/stromal enriched tumors and resistance to NACT. Theranostic targeting of CXCR4 and FAP before NACT might increase response towards NACT in this poor prognosis group.
An organic imidazolium salt of terephthalic acid has been utilized as a linker precursor for the synthesis of an aluminum-based metal organic framework (MOF) with MIL-53(ht) structure. This material ...shows the predicted porosity in terms of nitrogen and hydrogen sorption without exhibiting the breathing effect typical for MIL-53(Al) materials.
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