Berbamine targets cancer stem cells and reverses cabazitaxel resistance via inhibiting IGF2BP1 and p‐STAT3 in prostate cancer

Background Cancer stem cells (CSCs) are a small subpopulation of tumor cells with the capability of self-renewal and drug resistance, leading to tumor progression and disease relapse. Our study aimed to investigate the antitumor effect of berbamine, extracted from berberis amurensis, on prostate CSCs. Methods Sphere formation was used to collect prostate CSCs. The viability, proliferation, invasion, migration, and apoptosis assays were used to evaluate the antitumor effect of berbamine on prostate CSCs. Prostate CSC markers were analyzed by flow cytometry and qRT-PCR. Small RNA sequencing analysis was conducted to analyse miRNAs. Exosomes were extracted using the ExoQuick-TC kit and verified by testing exosomal markers using western blot. Results Berbamine targets prostate CSCs. Additionally, berbamine enhanced the antitumor effect of cabazitaxel, a second-line chemotherapeutic drug for advanced prostate cancer, and re-sensitized Cabazitaxel-resistant PCa cells (CabaR-DU145) to cabazitaxel by inhibiting ABCG2, CXCR4, IGF2BP1, and p-STAT3. Berbamine enhanced the expression of let-7 miRNA family and miR-26b and influenced the downstream targets IGF2BP1 and p-STAT3, respectively. Silencing CXCR4 and ABCG2 downregulated the expression of IGF2BP1 and p-STAT3, respectively. Importantly, berbamine enhanced also levels of exosomal let-7 family and miR-26b, suggesting that berbamine possibly influences the expression of let-7 family and miR-26b through exosome delivery. Exosomes derived from berbamine-treated CabaR-DU145 cells re-sensitized the cells to cabazitaxel. Conclusion Berbamine enhanced the toxic activity of cabazitaxel and reversed cabazitaxel resistance potentially through CXCR4/exosomal let-7/IGF2BP1 and ABCG2/exosomal miR-26b/p-STAT3 axes

Bureaucratic overload and organizational policy triage: A comparative study of implementation agencies in five European countries

Research on policy implementation traditionally has focused on understanding the success or failure of individual policies within specific contexts. Little attention has been given to the challenges that emerge from the cumulative growth of policy portfolios over time. This paper is addressing this research gap by examining the phenomenon of organizational policy triage, which occurs when implementation organizations face overload and are forced to make trade-off decisions between the implementation of the different policies in their portfolios. We investigate empirical patterns of policy triage across 16 social and environmental implementation agencies in five European countries (Denmark, Germany, Ireland, Italy, and UK). We show that variation in policy triage can be explained by the combination of three central factors: blame-shifting opportunities, the mobilization of external resources, and the commitment to compensate for overload by implementation authorities

Multicationic Tetrahedra Networks: Alkaline‐Earth‐Centered Polyhedra and Non‐Condensed AlN6‐Octahedra in the Imidonitridophosphates AE2AlP8N15(NH) (AE=Ca, Sr, Ba)

A series of isostructural imidonitridophosphates AE2AlP8N15(NH) (AE=Ca, Sr, Ba) was synthesized at high-pressure/high-temperature conditions (1400 °C and 5–9 GPa) from alkaline-earth metal nitrides or azides Ca3N2/Sr(N3)2/Ba(N3)2 and the binary nitrides AlN and P3N5. NH4F served as a hydrogen source and mineralizing agent. The crystal structures were determined by single-crystal X-ray diffraction and feature a three-dimensional network of vertex-sharing PN4-tetrahedra forming diverse-sized rings that are occupied by aluminum and alkaline earth ions. These structures represent another example of nitridophosphate-based networks that simultaneously incorporate AlN6-octahedra and alkaline-earth-centered polyhedra, with aluminum not participating in the tetrahedra network. They differ from previously reported ones by incorporating non-condensed octahedra instead of strongly condensed octahedra units and contribute to the diversity of multicationic nitridophosphate network structures. The results are supported by atomic resolution EDX mapping, solid-state NMR and FTIR measurements. Eu2+-doped samples show strong luminescence with narrow emissions in the range of green to blue under UV excitation, marking another instance of Eu2+-luminescence within imidonitridophosphates

N‐Azidoethyl azoles through N‐alkylation under highly harmonized reaction conditions: Synthesis, characterization, and complexation as energetic coordination compounds

Organic azides are universally important in many areas of chemistry, particularly in organic synthesis. The availability of these azides often depends on specific transfer reagents and reaction conditions, or only work with certain substrates. Customizable transfer reagents offer a safe and direct pathway to desired compounds, thereby increasing the availability of N-alkyl-azides. In an effort to streamline the synthesis and broaden the scope of N-azidoethyl-containing molecules, three different versatile azidoethyl transfer reagents were synthesized and a uniform reaction protocol with azoles as substrates, including imidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole, and tetrazole was established. The resulting azidoethyl-azoles were further used as ligands for energetic coordination compounds in an effort to create new lead-free primary explosives. A comprehensive characterization of the transfer reagents, the azidoethyl-containing products, and energetic coordination compounds was conducted using multinuclear nuclear magnetic resonance (NMR), elemental analysis, mass spectrometry, and infrared spectroscopy (IR). Furthermore, their thermal stability and sensitivity toward friction and impact were determined as well as the detonation properties were calculated by using the EXPLO5 code

Raising awareness of uncertain choices in empirical data analysis: A teaching concept toward replicable research practices

Throughout their education and when reading the scientific literature, students may get the impression that there is a unique and correct analysis strategy for every data analysis task and that this analysis strategy will always yield a significant and noteworthy result. This expectation conflicts with a growing realization that there is a multiplicity of possible analysis strategies in empirical research, which will lead to overoptimism and nonreplicable research findings if it is combined with result-dependent selective reporting. Here, we argue that students are often ill-equipped for real-world data analysis tasks and unprepared for the dangers of selectively reporting the most promising results. We present a seminar course intended for advanced undergraduates and beginning graduate students of data analysis fields such as statistics, data science, or bioinformatics that aims to increase the awareness of uncertain choices in the analysis of empirical data and present ways to deal with these choices through theoretical modules and practical hands-on sessions

Long-term irradiation of an ATLAS NSW SM2 Micromegas quadruplet using an AmBe neutron source

The NSW Micromegas chambers in the ATLAS forward muon spectrometer are subject to background rates of 15-20 kHz/cm under HL-LHC conditions. The innermost detector area closest to the LHC beam pipe will accumulate a charge of C cm−2 year−1 under these rates. Due to the late change of the detector gas from non-aging Ar:CO 93:7 vol% to the more HV stable ternary mixture Ar:CO :iC H10 93:5:2 vol% and the known vulnerability of wire chambers to Hydrocarbon-containing gas mixtures a three-year-long aging study has been performed. An SM2 series module of the NSW Micromegas quadruplets was irradiated at LMU in Garching/Munich using a 10 GBq AmBe neutron source emitting MeV n/s as well as 4.4 MeV gammas/s and 60 keV gammas/s. The SM2 chamber was irradiated in a region of several 10 cm in size with a dose rate well exceeding the HL-LHC equivalent local charge densities for three years. In between the irradiation periods the performance of the SM2 chamber regarding spatial resolution and efficiency on cosmic muon tracking was tested several times. We report on the irradiation and the performance studies of the SM2 Micromegas quadruplet and conclude that no sign of loss in performance has been observed in contradiction to an earlier experience using drift tube wire chambers

Depression and vaccination behavior in patients with chronic physical illness – A cross-sectional survey

Objective: Chronically ill are vulnerable to vaccine preventable infections. Consequently, their vaccination behavior is highly relevant. Depressive comorbidities are frequent in these patients. Furthermore, these patients are mainly diagnosed, treated and vaccinated in primary care. Therefore, we aimed to investigate the associations between depression and vaccination behavior (COVID-19 and influenza) in adult chronically ill primary care patients. Methods: In a cross-sectional survey, we examined depression (PHQ9), psychological antecedents of vaccinations (Confidence and Constraints), health care utilization, and vaccination status. Based on an effect model, descriptive statistics and mixed linear/logistic models were calculated. (German Clinical Trials Register, DRKS00030042). Results: n = 795 patients were analyzed. Both psychological antecedents of vaccinations (Confidence and Constraints) mediated a negative association between depression and vaccination behavior, healthcare utilization mediated a positive association. The total effect of depression was negligible. Conclusions: As the effects of vaccination readiness and healthcare utilization are opposing, different total effects depending on the study population are possible. Further studies are needed to investigate additional predictors of vaccination behavior. Practice implications: We suggest tackling vaccine acceptance in chronically ill through increasing confidence using communication-based interventions, for which primary care is the suitable setting. Constraints might be reduced by reminder and recall systems

Comparison of veterinarians and a deep learning tool in the diagnosis of equine ophthalmic diseases

Background/Objectives The aim was to compare ophthalmic diagnoses made by veterinarians to a deep learning (artificial intelligence) software tool which was developed to aid in the diagnosis of equine ophthalmic diseases. As equine ophthalmology is a very specialised field in equine medicine, the tool may be able to help in diagnosing equine ophthalmic emergencies such as uveitis. Study design In silico tool development and assessment of diagnostic performance. Methods A deep learning tool which was developed and trained for classification of equine ophthalmic diseases was tested with 40 photographs displaying various equine ophthalmic diseases. The same data set was shown to different groups of veterinarians (equine, small animal, mixed practice, other) using an opinion poll to compare the results and evaluate the performance of the programme. Convolutional Neural Networks (CNN) were trained on 2346 photographs of equine eyes, which were augmented to 9384 images. Two hundred and sixty-one separate unmodified images were used to evaluate the trained network. The trained deep learning tool was used on 40 photographs of equine eyes (10 healthy, 12 uveitis, 18 other diseases). An opinion poll was used to evaluate the diagnostic performance of 148 veterinarians in comparison to the software tool. Results The probability for the correct answer was 93% for the AI programme. Equine veterinarians answered correctly in 76%, whereas other veterinarians reached 67% probability for the correct diagnosis. Main limitations Diagnosis was solely based on images of equine eyes without the possibility to evaluate the inner eye. Conclusions The deep learning tool proved to be at least equivalent to veterinarians in assessing ophthalmic diseases in photographs. We therefore conclude that the software tool may be useful in detecting potential emergency cases. In this context, blindness in horses may be prevented as the horse can receive accurate treatment or can be sent to an equine hospital. Furthermore, the tool gives less experienced veterinarians the opportunity to differentiate between uveitis and other ocular anterior segment disease and to support them in their decision-making regarding treatment