For a representative number of approved or investigational anticancer metallodrugs varying in lipophilicity, unspecific adsorption onto ultracentrifugal filter units was studied. It was found that for fairly hydrophilic compounds, such as cisplatin and oxaliplatin, the binding to filters does not substantially affect their amount measured (by ICP-MS) after ultrafiltration (>95%). learn more In the case of metal complexes with moderate lipophilicity (log P > -0.1), adsorption effects turn out to be substantial. This might impede using ultrafiltration for studying the transformations of such drugs in human serum, unless they are rapidly converted into the protein adducts. The adsorption-suppressing effect of proteins was proved for indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] whose recovery from the filters was 61 and 14% in free and HSA-bound form, respectively. BACKGROUND Haploidentical stem cell transplantation (haplo-SCT) is an option for patients without human leukocyte antigen-matched related or unrelated donor. Post-transplantation cyclophosphamide (PTCy) is an effective method of graft versus host disease (GVHD) prophylaxis and permits the use of T-cell replete grafts in settings were ex vivo manipulation is not feasible. METHODS A retrospective study among patients younger than 18 years, with a history of hematologic malignancies who underwent haplo-SCT between 2012 and 2016. All patients received a preparative regimen of fludarabine, busulfan, and 400 cGy total body irradiation or melphalan. Post-transplant GvHD prophylaxis consisted either of PTCy (50 mg/kg on Days + 3 and + 4) and cyclosporine (CSA) plus mycophenolate (MMF) (15 mg/kg/dose, thrice daily, per os), or mini-dose methotrexate (MTX; 5 mg/m2 dose) on Days + 5, +7, +10, and + 15. RESULTS A total of 52 children were included, whose median age was 9 years (interquartile range, 4.9-14; range, 1.2-17 years), and 63% were males. The most common complications were cytomegalovirus reactivation (57%) and hemorrhagic cystitis (36%). The acute GVHD prophylaxis was PTCy, CSA, and mini-dose MTX in 42 (81%) patients, and 10 (19%) patients received PTCy, CSA, and MMF. The cumulative incidence of acute GvHD II-IV, acute GvHD III-IV, and chronic GvHD were 42%, 8.5%, and 19%, respectively. Grades I-IV acute GvHD occurred in 100% of the patients who received prophylaxis with CSA and MMF, and 62% who received CSA and mini-dose MTX (p = .055). The transplant-related mortality at 100 days was 18%. The 5-year overall and event-free survival were 59% and 57%, respectively. CONCLUSIONS Haplo-SCT with PT/Cy can be an available, safe, and feasible option for children with hematologic malignancies; meanwhile, the use of mini-dose of MTX was associated with lower rates of acute GVHD. However, our results require further support from prospective randomized studies to improve the efficacy of this prophylactic strategy. Cytolytic (Cyt)-like genes are known by omics analyses to exist widely in bacterial and fungal pathogens, but their insecticidal activities in fungi remains unknown. A full-length coding sequence of a Cyt-like gene was first amplified from Conidiobolus obscurus (an obligate aphid-pathogenic fungus) through RACE (rapid-amplification of cDNA ends). The deduced protein structure was structurally characterized by a single Cyt-typical α/β domain. The expression level of the Cyt-like gene in conidia correlated well with the fungal virulence against aphids (r2 = 0.97). The results demonstrate the Cyt-like gene acts as an important virulence factor of C. obscurus against aphids, and has potential for exploitation in aphid control. Latent HIV reservoirs are the main obstacle to eradicate HIV infection. One strategy proposes to eliminate these viral reservoirs by pharmacologically reactivating the latently infected T cells. We show here that a 4-deoxyphorbol ester derivative isolated from Euphorbia amygdaloides ssp. semiperfoliata, 4β-dPE A, reactivates HIV-1 from latency and could potentially contribute to decrease the viral reservoir. 4β-dPE A shows two effects in the HIV replication cycle, infection inhibition and HIV transactivation, similarly to other phorboids PKC agonists such PMA and prostratin and to other diterpene esters such SJ23B. Our data suggest 4β-dPE A is non-tumorigenic, unlike the related compound PMA. As the compounds are highly similar, the lack of tumorigenicity by 4β-dPE A could be due to the lack of a long side lipophilic chain that is present in PMA. 4β-dPE activates HIV transcription at nanomolar concentrations, lower than the concentration needed by other latency reversing agents (LRAs) such as prostratin and sfect, suggesting that the combination would not interefer with antiretroviral therapy (ART). Finally, 4β-dPE A induced latent HIV reactivation in CD4 + T cells of infected patients under ART at similar levels than the tumorigenic phorbol derivative PMA, showing a clear reactivation effect. In summary, we describe here the mechanism of action of a new potent deoxyphorbol derivative as a latency reversing agent candidate to decrease the size of HIV reservoirs. Ketamine, an anesthetic developed in the early 1960s, is also a popular abused drug among young people at dance parties and raves and among spiritual seekers, because it produces schizophrenia-like symptoms and dissociation (i.e., out-of-body experience). Regarding mood disorders, ketamine exerts robust antidepressant actions in treatment-resistant patients with depression. Ketamine is a racemic mixture comprising equal parts of (R)-ketamine (or arketamine) and (S)-ketamine (or esketamine). The United States (US) Food and Drug Administration approved the J&J (S)-ketamine nasal spray for treatment-resistant depression on March 5, 2019; the spray was then approved in Europe (December 19, 2019). Although (R)-ketamine has lower affinity for the N-methyl-d-aspartate receptor (NMDAR) vs. (S)-ketamine, (R)-ketamine has greater potency and longer-lasting antidepressant-like actions in animal models of depression. Importantly, (R)-ketamine has less detrimental side effects than does (R,S)-ketamine or (S)-ketamine in rodents, monkeys, and humans.