Search

Platelet rich fibrin (PRF) is an autologous blood concentrate, that supports tissue regeneration. The effect of the centrifuge rotor angle in the fabrication of PRF is still not fully elucidated. The hypothesis of this study is: When applying the same g-force {relative centrifugal force (RCF)} and centrifugation time, PRF components and bioactivity are not modified using either a swing-out or fixed angle rotor. For this purpose, peripheral blood samples (five donors )were used to gain solid matrices (710 xg, 8 minutes) and liquid (44 xg, 8 minutes) PRF matrices using three different centrifuges (one fixed angle as a control; and two different swingout rotor centrifuges). The physical characteristics of the solid PRF were measured to evaluate the clot formation and cellular distribution. Liquid PRF was used to evaluate the cell number, bioactivity and influence on primary human osteoblasts and fibroblasts in vitro. Solid PRF clots were significantly larger in the group of fixed rotor centrifuges compared to either of the two evaluated swing-out rotor centrifuges. No differences were observed when evaluating the cellular distribution within the solid No statistically significant differences were documented in the cell's density in liquid PRF samples (platelets, lymphocytes, neutrophils, eosinophils, and basophils) among the differently gained PRF samples. No statistically significant differences were documented for the released growth factors (VEGF, EGF, TGF-β1) over 7 days. Primary human osteoblasts (pOBs) and primary human fibroblasts (pHFs) viability after treatment with PRF conditioned media showed no statistically significant differences between the evaluated groups. However, the number of adherent cells treated with PRF obtained with the use of the fixed angle rotor was significantly higher when compared to those treated with PRF obtained by using the swing-out rotors. The presented results confirmed that regardless of the centrifuge rotor used, the components and bioactivity of solid and liquid PRF matrices are modified by the applied RCF and centrifugation time. These findings are of great importance for highlighting the essential role of adapting the centrifugation protocols when using different centrifuges and to correctly report the used centrifugation protocols in scientific research to allow for reproducible results.

Phosphate is an essential macronutrient for fungal proliferation as well as a key mediator of antagonistic, beneficial, and pathogenic interactions between fungi and other organisms. In this review, we summarize recent insights into the integration of phosphate metabolism with mechanisms of fungal adaptation that support growth and survival. In particular, we highlight aspects of phosphate sensing important for responses to stress and regulation of cell-surface changes with an impact on fungal pathogenesis, host immune responses, and disease outcomes. Additionally, new studies provide insights into the influence of phosphate availability on cooperative or antagonistic interactions between fungi and other microbes, the associations of mycorrhizal and endophytic fungi with plants, and connections with plant immunity. Overall, phosphate homeostasis is emerging as an integral part of fungal metabolism and communication to support diverse lifestyles.

The reaction of 2,3-dihydropyridines with sulfonyl halides surprisingly yielded open chain dienes with sulfonylimine structure. The products were specific out of several possible isomers and, therefore, a separation of isomers was not necessary. All new compounds were characterized using FT-IR spectroscopy, HRMS, and NMR spectroscopy. A bicyclic by-product from the reaction of a 2,3-dihydropyridine with mesyl chloride was isolated and its structure elucidated using a single X-ray crystal analysis. Some biological activities, like antimicrobial and cytotoxic properties were investigated. Graphic abstract

Chlorophyll and heme are among the “pigments of life”, tetrapyrrolic structures, without which life on Earth would not be possible. Their catabolites, the phyllobilins and the bilins, respectively, share not only structural features, but also a similar story: Long considered waste products of detoxification processes, important bioactivities for both classes have now been demonstrated. For phyllobilins, however, research on physiological roles is sparse. Here, we introduce actin, the major component of the cytoskeleton, as the first discovered target of phyllobilins and as a novel target of bilins. We demonstrate the inhibition of actin dynamics in vitro and effects on actin and related processes in cancer cells. A direct interaction with G‐actin is shown by in silico studies and confirmed by affinity chromatography. Our findings open a new chapter in bioactivities of tetrapyrroles—especially phyllobilins—for which they form the basis for broad implications in plant science, ecology, and physiology., The physiological role of the degradation products of chlorophyll and heme, exogenous phyllobilins and endogenous bilins, respectively, remained an unsolved mystery for decades. We describe the influence of these tetrapyrroles on the actin cytoskeleton and introduce G‐actin as the first human target protein for phyllobilins and a novel target for bilins. This study opens up a new perspective of the importance of these ubiquitous natural products.

Dinuclear heteroleptic alkaline-earth-metal complexes are interesting synthetic targets because the close proximity of two metals allows for cooperative effects. However, these complexes are also prone to undergoing Schlenk-type rearrangements, affording less-active homoleptic complexes. Here we present the metalation of bis(β-diketimine) ligands possessing flexible bridging groups, i.e., 1,2-ethylene, 1,3-propylene, and trans-1,2-cyclohexylene, using calcium and magnesium precursors. Four mononuclear homoleptic calcium complexes were obtained, highlighting the pronounced tendency of calcium to undergo Schlenk-like redistributions. In the case of magnesium, however, the bridging group plays a crucial role, yielding seven dinuclear heteroleptic complexes but also one mononuclear and one dinuclear homoleptic complexes. In addition, a trinuclear mixed heteroleptic-homoleptic magnesium complex, which is a rare example of an intermediate of the Schlenk equilibrium, was isolated.

Eight dinuclear methyl aluminium(III) bis(amidinate) and bis(guanidinate) complexes have been synthesized in good to very good yields and were fully characterized by means of 1H, 13C, and IR spectroscopy as well as elemental analysis. Five of them were successfully converted to the respective dinuclear aluminium iodide complexes and a dinuclear aluminium chloride bis(amidinate) complex was directly accessed by deprotonation of the ligand using ethyl aluminium dichloride. The molecular solid-state structures of eleven complexes were obtained from X-ray diffraction analysis. Furthermore, the catalytic activity of the dinuclear methyl aluminium complexes 3 and 4 has been probed in the ring-opening polymerization of e-caprolactone and L-lactide and the results highlight the impact of the metal–metal separation and the ligands’ backbone on activity and selectivity.

The MinDE proteins from E. coli have received great attention as a paradigmatic biological pattern‐forming system. Recently, it has surfaced that these proteins do not only generate oscillating concentration gradients driven by ATP hydrolysis, but that they can reversibly deform giant vesicles. In order to explore the potential of Min proteins to actually perform mechanical work, we introduce a new model membrane system, flat vesicle stacks on top of a supported lipid bilayer. MinDE oscillations can repeatedly deform these flat vesicles into tubules and promote progressive membrane spreading through membrane adhesion. Dependent on membrane and buffer compositions, Min oscillations further induce robust bud formation. Altogether, we demonstrate that under specific conditions, MinDE self‐organization can result in work performed on biomimetic systems and achieve a straightforward mechanochemical coupling between the MinDE biochemical reaction cycle and membrane transformation., We are demonstrating a new model membrane system, flat vesicles on top of a supported lipid bilayer. By reconstituting a paradigmatic biological pattern‐forming system, ATP‐dissipating MinDE proteins, dynamic “breathing” deformations of the soft membrane vesicles and progressive membrane spreading are achieved, confirming that under this specific condition, MinDE reaction cycles can result in work performed on the biological membrane.

Naturally occurring naphthoquinones (NQs) comprising highly reactive small molecules are the subject of increasing attention due to their promising biological activities such as antioxidant, antimicrobial, apoptosis-inducing activities, and especially anticancer activity. Lapachol, lapachone, and napabucasin belong to the NQs and are in phase II clinical trials for the treatment of many cancers. This review aims to provide a comprehensive and updated overview on the biological activities of several new NQs isolated from different species of plants reported from January 2013 to January 2020, their potential therapeutic applications and their clinical significance.

Inspired by natural metalloenzymes that efficiently catalyze a variety of transformations, chemists have developed large numbers of dinuclear transition-metal complexes with extraordinary properties and reactivity patterns. For main-group element compounds, however, metal-metal cooperativity is much less explored. Here we present the synthesis and characterization of a room-temperature-stable compound with two separated two-coordinated gallium(I) centers possessing both a lone pair of electrons and a vacant orbital, reminiscent of singlet carbenes. This species displays enhanced reactivity compared to its mononuclear counterpart due to bimetallic cooperativity that allows for the facile activation of strong C-F bonds across the gallium-gallium bond. Two mechanistic scenarios of the cooperative bond activation have been identified by DFT and DLPNO-CCSD(T) calculations.

Background and aims [177Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) is a new therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). However, identification of reliable prognostic factors is hampered by heterogeneous treatment regimens applied in previous studies. Hence, we sought clinical factors able to predict response and survival to PSMA-RLT in a homogenous group of patients, all receiving 7400 MBq every 4 weeks. Patients and methods Data of 61 patients (mean age 71.6 ± 6.9 years, median basal PSA 70.7 [range 1.0–4890 μg/L]), pretreated with abiraterone/enzalutamide (75.4%) and docetaxel/cabazitaxel (68.9%), received three cycles of PSMA-RLT (mean 7321 ± 592 MBq) at four weekly intervals and were analyzed retrospectively. General medical conditions and laboratory parameters of every patients were regularly assessed. Response to therapy was based on PSA levels 1 month after the 3rd cycle. Binary logistic regression test and Kaplan-Meier estimates were used to evaluate predictors and overall survival (OS). Results Forty-nine (80.3%) patients demonstrated a therapy response in terms of any PSA decline, while 21 (19.7%) patients showed increase or no changes in their PSA levels. Baseline hemoglobin (Hb) significantly predicted PSA reductions of ≥ 50% 4 weeks after receiving the 3rd PSMA-RLT (P = 0.01, 95% CI: 1.09–2.09) with an AUC of 0.68 (95% CI: 0.54–0.81). The levels of basal Hb and basal PSA were able to predict survival of patients, both P P = 0.016). Also, patients with basal PSA levels ≤ 650 μg/L had a significantly longer survival than patients with basal PSA levels > 650 μg/L (median survival not reached vs. 97 weeks, P = 0.031). Neither pretreatments with abiraterone/enzalutamide or docetaxel/cabazitaxel nor distribution of metastasis affected survival and rate of response to PSMA-RLT. Conclusion Basal Hb level is an independent predictor for therapy response and survival in patients receiving PSMA-RLT every 4 weeks. Both baseline PSA ≤ 650 μg/L and normal Hb levels were associated with longer survival.

Density functional theory (DFT) calculations demonstrate that the previously reported reaction of [(BDI)Mgn-Bu] (BDI = HC{(Me)CN-Dipp}2; Dipp – 2,6-di-iso-propylphenyl) with the silaborane, Me2PhSi-Bpin, provides the magnesium silanide derivative, [(BDI)MgSiMe2Ph], through the intermediacy of a short lived silyl-pinacolato-organoborate species. The nucleophilic character of the resultant silanide anion is assayed through a series of reactions with RN=C=NR (R = i-Pr, Cy, t-Bu) and p-tolN=C=Np-tol. When performed in a strict 1:1 stoichiometry, all four reactions result in silyl addition to the carbodiimide carbon center and formation of the corresponding beta-diketiminato magnesium sila-amidinate complexes. Although performance of the reaction of [(BDI)MgSiMe2Ph] with two equivalents of p-tolylcarbodiimide also results in the formation of a sila-amidinate anion, the second equivalent is observed to engage with the nucleophilic gamma-methine carbon of the BDI ligand to provide a tripodal di-imino-iminoamidate ligand. This behaviour is judged to be a consequence of the enhanced electrophilicity of the N-aryl substituted carbodiimide reagent, a viewpoint supported by a further reaction with the N-isopropyl sila-amidinate complex, [(BDI)Mg(i-PrN)2CSiMe2Ph]. This latter reaction not only provides an identical di-imino-iminoamidate ligand but also results in twofold insertion of p-tolN=C=Np-tol into a Mg-N bond between the magnesium center and the sila-amidinate anion.

Purpose Urinary stones can be successfully treated using a Holmium: Yttrium-Aluminum-Garnet (Ho: YAG) laser. Regarding success rates, laser pulse energy, frequency, and pulse width are well-known contributing factors. Whether the pulse shape might be a further factor influencing the laser efficiency is unclear. This study aimed to evaluate different modes of laser pulse shapes in a real-world setting. Materials and methods The Dornier Medilas® H Solvo (Wesling, Germany) was used in the treatment of ureter and kidney stones. Patients were randomized into standard pulse shape (SPS) and new pulse shape groups (NPS1; ureter) and (NPS2; kidney pelvis), depending on the stone localization. The primary endpoint was laser efficiency defined as mm³ stone destruction per overall operating time. Secondary endpoints encompassed number of stone recoveries and stone-free rate. Results Altogether 145 patients (24 SPS vs. 32 NPS1; 51 SPS vs. 38 NPS2) were included. No differences in sex, age, body mass index, stone localization and stone composition were found, except for preoperative stone size (133±95 [SPS] vs. 197±139 [NPS1] mm³; p=0.023) and (348±298 [SPS] vs. 525±429 [NPS2] mm³; p=0.042). Regarding the primary endpoint, a significant increase in laser efficiency could be detected for the NPS1 and NPS2 groups compared to the SPS groups (39.9±44.9 vs. 28.8±30.2 and 51.7±61.3 vs. 22.4±24.2 mm³/min [mean±standard deviation]). No statistically significant differences were found for secondary endpoints and perioperative complication rates. Conclusions Efficiency of the Ho: YAG laser can be positively influenced by different pulse shapes. This adds the variable of individualized intraoperative decision making.

Ni‐rich layered lithium metal oxides are the cathode active materials of choice for high‐energy‐density Li‐ion batteries. While the high content of Ni is responsible for the excellent capacity, it is also the source of interfacial instability, limiting the material's lifetime due to a variety of correlated in‐ and extrinsic factors. Hence, reconciling the opposing trends of high Ni content and long‐term cycling stability by modifying the material's surface is one of the challenges in the field. Here, we review various studies on surface modification of Ni‐rich (≥ 80 %) layered cathode active materials in order to categorize current research efforts. Broadly, the three strategies of coating, surface doping and washing are discussed, each with their advantages and shortcomings. In conclusion, we highlight new directions of research that could bring Ni‐rich layered lithium metal oxide cathodes from the laboratory to the real world.

Dissolved neodymium (Nd) isotopes (expressed as εNd) have been widely used as a water mass tracer in paleoceanography. However, one aspect of the modern biogeochemical cycle of Nd that has been sparsely investigated is the interplay between dissolved and particulate phases in seawater. We here present the first regional data set on particulate Nd isotope compositions (εNdp) and concentrations ([Nd]p) from five stations in the western North Atlantic Ocean along the GEOTRACES GA02 transect, in conjunction with previously published dissolved Nd isotope compositions (εNdd) and concentrations ([Nd]d)1. Key observations and interpretations from our new particulate data set include the following: (1) A low fractional contributions of [Nd]p to the total Nd inventory per volume unit of seawater (~5%), with significant increases of up to 45% in benthic boundary layers. (2) Increasing Nd concentrations in suspended particulate matter ([Nd]SPM) and fractions of lithogenic material with water depth, suggesting the removal of Nd poor phases. (3) Different provenances of particulates in the subpolar and subtropical gyres as evidenced by their Nd isotope fingerprints reaching from εNdp ≈ -20 near the Labrador Basin (old continental crust), over εNdp ≈ -4 between Iceland and Greenland (young mafic provenance), to values of εNdp ≈-13 in the subtropics (similar to African dust signal). (4) Vertical heterogeneity of εNdp, as well as large deviations from ambient seawater values in the subpolar gyre, indicate advection of lithogenic particles in this area. (5) Vertically homogenous εNdp values in the subtropical gyre, indistinguishable from εNdd values, are indicative of predominance of vertical particulate supply. The process of reversible scavenging only seems to influence particulate signatures below 3 km. Overall, we do not find evidence on enhanced particle dissolution, often invoked to explain the observed increase in dissolved Nd in the North Atlantic.

Antimicrobial peptides (AMPs) are an important part of the human innate immune system for protection against bacterial infections, however the AMPs display varying degrees of activity against Staphylococcus aureus. Previously, we showed that inactivation of the ATP synthase sensitizes S. aureus towards the AMP antibiotic class of polymyxins. Here we wondered if the ATP synthase similarly is needed for tolerance towards various human AMPs, including human β-defensins (hBD1-4), LL-37 and histatin 5. Importantly, we find that the ATP synthase mutant (atpA) is more susceptible to killing by hBD4, hBD2, LL-37 and histatin 5 than wild type cells, while no changes in susceptibility was detected for hBD3 and hBD1. Administration of the ATP synthase inhibitor, resveratrol, sensitizes S. aureus towards hBD4-mediated killing. Neutrophils rely on AMPs and reactive oxygen molecules to eliminate bacteria and the atpA mutant is more susceptible to killing by neutrophils than the WT, even when the oxidative burst is inhibited.These results show that the staphylococcal ATP synthase enhance tolerance of S. aureus towards some human AMPs and this indicates that inhibition of the ATP synthase may be explored as a new therapeutic strategy that sensitizes S. aureus to naturally occurring AMPs of the innate immune system.

Purpose To report a single surgeon experience with one year follow-up after open ureteroplasty with buccal mucosa graft (OUBMG) in the rare situation of long segment proximal ureteral strictures. Materials and methods Four patients with long segment proximal ureteral stricture underwent OU-BMG between February and July 2017. Functional outcome was assessed by pre- and postoperative serum creatinine, ultrasound and renal scintigraphy as well as patient reported outcomes. Results Four patients with an average stricture length of 4 cm underwent OU-BMG between February and July 2017. No major postoperative complications occurred. Retrograde uretero-pyelography 6 weeks postoperatively revealed a watertight anastomosis followed by immediate emptying of the renal pelvis and ureter in all four patients. Ureteroscopy at this time showed a wide lumen with well-vascularized pink mucosa. After a mean follow-up time of 12.5 (12-14) months, postoperative serum creatinine was unimpaired. Renal scintigraphy revealed no signs of renal obstruction. With regard to intraoral surgery, no difficulties with mouth opening or intraoral dryness or numbness were reported. Conclusions For patients with long segment ureteral strictures OU-BMG is a safe technique with excellent surgical and functional outcomes. Hence, the application of this technique should be encouraged and regarded as one of the standard options in case of this rare problem.

The reaction pathways of the cooperative activation of protic, hydridic, and apolar H-X bonds by electron-precise Al and Ga beta-diketiminates have been probed by means of DFT calculations. Different mechanistic scenarios have been identified and range from concerted bimolecular to associative termolecular mechanisms depending on the nature of the H-X bond. The importance of distortion in the transition-state structure for catalyst design is emphasised.

ZusammenfassungDas retinale Pigmentepithel (RPE) ist eine hochpolarisierte Einzelschicht quaderförmiger Epithelzellen, die dicht mit Melanin gepackt sind. Sie liegt zwischen den lichtempfindlichen Außensegmenten der Photorezeptoren und der Aderhaut (Choroidea), spielt eine essenzielle Rolle bei der Entwicklung der Photorezeptoren und übernimmt wichtige Funktionen in Bezug auf Nährstoffversorgung und Erhaltung, im Retinalstoffwechsel und bei der Abschirmung von der Blutversorgung der Aderhaut. Die Photorezeptoren durchlaufen täglich einen Erneuerungsprozess, bei dem 10% der äußeren Segmente durch das retinale Pigmentepithel phagozytiert werden. Dies erfordert eine enge Wechselwirkung zwischen dem retinalen Pigmentepithel und der Retina. Daher kann eine Störung oder eine Verzögerung der Reifung des RPE erhebliche krankheitsauslösende Auswirkungen auf die Netzhaut haben, die zu einer Degeneration der Photorezeptoren führen. Auch die Alterung des RPE beeinträchtigt die unterstützenden Funktionen, was zum fortschreitenden Verlust von Photorezeptoren und Sehvermögen beiträgt. Wie viele okuläre Zelltypen bildet auch das RPE während seiner Entwicklung eine Primärzilie, eine auf Mikrotubuli basierende Ausstülpung der Zellmembran. Sie wird mit einigen wichtigen zellulären Prozessen und verschiedenen Signalwegen in Verbindung gebracht, die wichtige Funktionen in der Entwicklung unterschiedlicher Gewebe haben. Unter anderem ist der WNT-Signalweg (WNT: wingless-related integration site) essenziell für die Polarisation und Reifung des RPE und dadurch ausschlaggebend für die Funktion dieses Epithels. Der kanonische WNT-Signalweg ist zunächst für das Zellschicksal unabdingbar. Jedoch ist dessen Herunterregulieren, was von der Lokalisation von Inversin an der Basis des Ziliums und dadurch auch von der Funktionalität der ziliären BBS-Proteine (BBS: Bardet-Biedl-Syndrom) abhängt, unerlässlich für die Umstrukturierung des Zytoskeletts und den RPE-Phänotyp. Die Zilie und ihre regulatorische Funktion sind im RPE nur transient vertreten und bilden sich im Laufe der Entwicklung wieder zurück. Durch Eingriffe in den WNT-Signalweg können die Reifung und Polarisation des RPE in vitro manipuliert werden, sodass dessen Ausdifferenzierung gewährleistet und schlussendlich möglicherweise transplantierfähiges Gewebe hergestellt werden kann. Außerdem kann die Applikation von Substanzen, die in den Signalweg eingreifen, in vivo die Differenzierung des RPE verbessern und zu einer Verbesserung des Phänotyps führen, was die retinale Degeneration aufhalten kann. Diese Literaturrecherche soll die Wichtigkeit des retinalen Pigmentepithels und die Relevanz des Zusammenspiels mit dem WNT-Signalweg für die Entwicklung des Auges deutlich machen und einen Überblick über den derzeitigen Forschungsstand geben.

The synthesis of 3,4-ethylene-bridged 1,1,2,5-tetrasubstituted biguanides is reported, which are accessible by three alternative routes. Exemplary molecular structures of the ligand and an observed side product have been elucidated by X-ray diffraction analysis. Mono- and dinuclear complexes of the biguanide in both its neutral and monoanionic forms were obtained, including examples of aluminum, copper, magnesium, potassium, tin, and zinc, indicating a versatile coordination behavior, as evidenced by means of single-crystal X-ray diffraction analysis.

Salt metathesis, i.e. the reaction of sodium β-diketiminate with (AlCp*)4 and GaCp*, respectively, is a valuable pathway to access the respective aluminium(i) and gallium(i) β-diketiminates I and II. The protocol gives better yields compared to the established procedures and avoids the use of strong reducing agents such as metallic potassium. Furthermore, the aluminium(i) β-diketiminate I was found to react with itself and yields upon C-N bond cleavage and hydrogen-atom transfer the asymmetric dinuclear aluminium(iii) complex V that is readily separated from I by crystallisation. The reaction mechanism has been probed by means of DFT and DLPNO-CCSD(T) calculations and the computational findings are in good agreement with the experimental observations.

The synthesis of two different types of bis(N,N′,N′-substituted 1,2-ethanediamine)s, bridged either through the secondary (type 1) or tertiary (type 2) amine groups is reported. Selected protio-ligands have been applied in subsequent metallation reactions using aluminium, magnesium, tin, and zinc sources allowing to isolate five mononuclear and eight dinuclear complexes. All complexes have been fully characterized and their solid-state structures have been studied by means of single-crystal X-ray diffraction analysis. Nine of the 13 complexes carry reactive alkyl, amide or hydride groups, which indicates their potential as catalysts or supports for (transition) metals.

Metabolomics deals with the large-scale analysis of metabolites, belonging to numerous compound classes and showing an extremely high chemical diversity and complexity. Lipidomics, being a subcategory of metabolomics, analyzes the cellular lipid species. Both require state-of-the-art analytical methods capable of accessing the underlying chemical complexity. One of the major techniques used for the analysis of metabolites and lipids is Liquid Chromatography-Mass Spectrometry (LC-MS), offering both different selectivities in LC separation and high sensitivity in MS detection. Chromatography can be divided into different modes, based on the properties of the employed separation system. The most popular ones are Reversed-Phase (RP) separation for non- to mid-polar molecules and Hydrophilic Interaction Liquid Chromatography (HILIC) for polar molecules. So far, no single analysis method exists that can cover the entire range of metabolites or lipids, due to the huge chemical diversity. Consequently, different separation methods have been used for different applications and research questions. In this review, we explore the current use of LC-MS in metabolomics and lipidomics. As a proxy, we examined the use of chromatographic methods in the public repositories EBI MetaboLights and NIH Metabolomics Workbench. We extracted 1484 method descriptions, collected separation metadata and generated an overview on the current use of columns, eluents, etc. Based on this overview, we reviewed current practices and identified potential future trends as well as required improvements that may allow us to increase metabolite coverage, throughput or both simultaneously.

The energy density of layered oxide cathode materials increases with their Ni content, while the stability decreases and degradation becomes more severe. A common strategy to mitigate or prevent degradation is the application of protective coatings on the particle surfaces. In this article, a room-tem-perature, liquid-phase reaction of trimethylaluminum (TMA) and tetraethyl orthosilicate (TEOS) with adsorbed moisture on either LiNi0.85Co0.10Mn0.05O2or LiNiO2, yielding a hybrid coating that shows synergetic benefits compared to coatings from TMA and TEOS individually, is reported. The surface layer is investigated in long-term pouch full-cell studies as well as by electron micros-copy, X-ray photoelectron spectroscopy, and differential electrochemical mass spectrometry, demonstrating that it prevents degradation primarily by a fluorine-scavenging effect, and by reducing the extent of rock salt-type phase formation.

Background and purpose Aerobic glycolysis is a unique feature of tumour cells that entails several advantages for cancer progression such as resistance to apoptosis. The low MW compound, dichloroacetate, is a pyruvate dehydrogenase kinase inhibitor, which restores oxidative phosphorylation and induces apoptosis in a variety of cancer entities. However, its therapeutic effectiveness is limited by resistance mechanisms. This study aimed to examine the role of the anti-apoptotic hyaluronan (HA) matrix in this context and to identify a potential add-on treatment option to overcome this limitation. Experimental approach The metabolic connection between dichloroacetate treatment and HA matrix augmentation was analysed in vitro by quantitative PCR and affinity cytochemistry. Metabolic pathways were analysed using Seahorse, HPLC, fluorophore-assisted carbohydrate electrophoresis, colourimetry, immunoblots, and immunochemistry. The effects of combining dichloroacetate with the HA synthesis inhibitor 4-methylumbelliferone was evaluated in 2D and 3D cell cultures and in a nude mouse tumour xenograft regression model by immunoblot, immunochemistry, and FACS analysis. Key results Mitochondrial reactivation induced by dichloroacetate metabolically activated HA synthesis by augmenting precursors as well as O-GlcNAcylation. This process was blocked by 4-methylumbelliferone, resulting in enhanced anti-tumour efficacy in 2D and 3D cell culture and in a nude mouse tumour xenograft regression model. Conclusions and implications The HA rich tumour micro-environment represents a metabolic factor contributing to chemotherapy resistance. HA synthesis inhibition exhibited pronounced synergistic actions with dichloroacetate treatment on oesophageal tumour cell proliferation and survival in vitro and in vivo suggesting the combination of these two strategies is an effective anticancer therapy.

Context The assessment of “soft” endpoints such as health-related quality of life (HRQOL) is increasingly relevant when evaluating the optimal treatment sequence of novel therapeutic options in patients with advanced prostate cancer (PCa). Objective To systematically review contemporary data regarding HRQOL outcomes in patients with advanced PCa. Evidence acquisition A systematic review of the literature published between January 2011 and March 2019 was performed using the PubMed/Medline Database. In total, 873 articles were screened, and 14 articles including 12 661 patients were selected for synthesis and included in the current analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) and European Association of Urology recommendations. Evidence synthesis Regarding HRQOL assessment, the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire was used in 11 of 14 studies, the European Quality of Life 5-Dimensions (EQ-5D) questionnaire in six of 14 studies, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) in two of 14, and its prostate-specific amendment QLQ-PR25 was used in one of 14 studies. Three studies included patients with metastatic castration-sensitive prostate PCa, and found beneficial HRQOL effects for abiraterone acetate and docetaxel compared with standard androgen deprivation therapy. Two studies included patients with nonmetastatic castration-resistant PCa, and positive HRQOL effects for enzalutamide and apalutamide were observed. Nine studies focused on patients with metastatic castration-resistant PCa. Hereby, beneficial HRQOL outcomes were described for enzalutamide, abiraterone acetate, and radium-223. Evidence synthesis was mostly based on studies with a low risk of bias based on standardized risk of bias assessment. Limitations include hampered comparability between different validated questionnaires, lack of baseline values, and unclear impact of supportive care on HRQOL outcomes. Conclusions There is strong evidence from several phase III trials supporting a beneficial effect of current systemic treatment options on HRQOL outcomes in patients with advanced PCa compared with standard androgen deprivation therapy. Patient summary In this systematic review, we provide an overview of contemporary data from large clinical trials on the effect of current treatment strategies on patients’ health-related quality of life (HRQOL). We summarize the assessment tools that have been used to measure HRQOL and show that there are robust data for positive HRQOL effects of numerous agents in different clinical stages of advanced prostate cancer.

The high natural abundance of aluminium makes the respective fluorophores attractive for various optical applications, but photoluminescence quantum yields above 0.7 have yet not been reported for solutions of aluminium complexes. In this contribution, a dinuclear aluminium(III) complex featuring enhanced photoluminescence properties is described. Its facile one-pot synthesis originates from a readily available precursor and trimethyl aluminium. In solution, the complex exhibits an unprecedented photoluminescence quantum yield near unity (Φabsolute 1.0 ± 0.1) and an excited-state lifetime of 2.3 ns. In the solid state, J-aggregation and aggregation-caused quenching are noticed, but still quantum yields of 0.6 are observed. Embedding the complex in electrospun nonwoven fabrics yields a highly fluorescent fleece possessing a quantum yield of 0.9 ± 0.04.