Midazolam is one of top three drugs used in palliative care. Its use increases in the last days of hospice patients' lives while safe dosage can be challenging. Equations currently used to estimate glomerular filtration rate, e.g the Cockroft-Gault (eGFR
  ) and the Modification of Diet in Renal Disease (eGFR
  ) ones, do not generate precise calculations, especially in palliative patients exhibiting variations in body parameters. Our aim was to seek new relationships between mean midazolam (M
  ) and alfahydroxymidazolam (OH-M
  ) concentrations in plasma, and selected biochemical and physiological parameters of palliative patients, to enable optimal midazolam pharmacotherapy.
 
  The pilot study included 11 Caucasians, aged 42-95, with advanced cancer disease, receiving midazolam in a hospice in-patient unit. We tested correlations among M
  , BMI, eGFR
  , midazolam clearance (CL), OH-M
  , bilirubin (Bil) and blood creatinine concentration (Cr). F test and leave-one out (LOO) validation was applied to verify themidazolam metabolism depends. Two of ten correlations proposed came close to meet all LOO validation criteria. Current findings can help optimize midazolam treatment in palliative therapy.Chimeric antigen receptor T cells (CAR-T) immunotherapy has shown promising clinical results in the treatment of leukemia and lymphoma, but the effectiveness is limited for solid tumors. The PD-1/PD-L1 pathway is a key immunosuppressive mechanism for cancer cells to avoid eradication by CAR-T cells. In this study, the shRNA (short hair RNA) gene-silencing technique was used to construct the third-generation of CAR-T cells with PD-1 silencing which targeted CD19 antigen (CD19/△PD-1 CAR-T) and prostate stem cell antigen (PSCA/△PD-1 CAR-T), thereby blocking the PD-1/PD-L1 pathway in treatment of lymphoma and prostate subcutaneous xenograft and enhancing the anti-tumor effect of CAR-T cells. The cell experiments showed that PD-1 silencing in CAR-T cells effectively blocked the PD-1 / PD-L1 pathway. When the ratio of effector to target cell is 81, △PD-1 CAR-T cells exhibited higher killing ability and cytokine releasing ability than normal CAR-T cells did. The subcutaneous tumor models were constructed using humantumor effect of CAR-T cells on subcutaneous xenograft.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causal factor of the coronavirus disease 2019 (COVID-19). Drug repurposing, portraying patented drugs as a successful drug development technique, could shorten the period and minimize costs relative to de novo drug exploration. Recently several drugs have been used as anti-SARS-CoV-2 such as Remdesivir, Favipiravir, Hydroxychloroquine, Azithromycin, Lopinavir/Ritonavir, Nafamostat mesylate and so on. Despite such efforts, there is currently no successful broad-spectrum antiviral countermeasures to combat SARS-CoV-2 or possibly potential CoVs pandemic. Therefore it is desperately important to recognize and test widely efficient, reliable anti-CoV therapies now and in the future. Remdesivir and Favipiravir were more promising despite having side effects; it had prominent efficacy and efficiency while still not yet approved as the official anti-viral drug for SARS CoV-2. In this review, we summarizes the current drug and vaccine discovery status against SARS-CoV-2, predicting that these efforts will help create effective drugs and vaccines for SARS-CoV-2.During the past decades, tryptophan metabolism disorder was discovered to play a vital and complex role in the development of cancer.  https://www.selleckchem.com/products/SB-202190.html  Indoleamine 2,3-dioxygenase 2 (IDO2) is one of the initial and rate-limiting enzymes of the kynurenine pathway of tryptophan catabolism. Increasing evidence indicates that IDO2 is upregulated in some tumors and plays a role in the development of cancer. In spite of the growing body of research, few reviews focused on the role of IDO2 in cancer. Here, we review the emerging knowledge on the roles of IDO2 in cancer and its potential as a therapeutic target. Firstly, the main biological features and regulatory mechanisms are reviewed, after which we focus on the expression and roles of IDO2 in cancer. Finally, we discuss the potential of IDO2 as a therapeutic target for cancer treatment.Although Pseudoalteromonas is an abundant, ubiquitous, marine algae-associated bacterial genus, there is still little information on their phages. In the present study, a marine phage AL, infecting Pseudoalteromonas marina, was isolated from the coastal waters off Qingdao. The AL phage is a siphovirus with an icosahedral head of 53 ± 1 nm and a non-contractile tail, length of 99 ± 1 nm. A one-step growth curve showed that the latent period was approximately 70 min, the rise period was 50 min, and the burst size was 227 pfu/cell. The genome sequence of this phage is a 33,582 bp double-stranded DNA molecule with a GC content of 40.1 %, encoding 52 open reading frames (ORFs). The order of the functional genes, especially those related to the structure module, is highly conserved and basically follows the common pattern used by siphovirus. The stable order has been formed during the long-term evolution of phages in the siphovirus group, which has helped the phages to maintain their normal morphology and function. Phylogenetic trees based on the major capsid protein (mcp) and genome-wide sequence have shown that the AL phage is closely related to four Pseudoalteromonas phages, including PHS21, PHS3, SL25 and Pq0. Further analysis using all-to-all BLASTP also confirmed that this phage shared high sequence homology with the same four Pseudoalteromonas phages, with amino acid sequence identities ranging from 44 % to 71 %. In particular, their similarity in virion structure module may imply that these phages share common assembly mechanism characteristics and infection pathways. Pseudoalteromonas phage AL not only provides basic information for the further study of the evolution of Pseudoalteromonas phages and interactions between marine phage and host but also helps to explain the unknown viral sequences in the metagenomic databases.Low permeability zones (LPZs) are major sources of groundwater contamination after active remediation to remove pollutants in adjacent high permeability zones (HPZs). Slow back diffusion from LPZs to HPZs can extend management of polluted sites by decades. Numerical models are often used to simulate back diffusion, estimate cleanup times, and develop site management strategies. Sharp concentration gradients of pollutants are present at the interface between HPZs and LPZs, and hence accurate simulation requires fine grid sizes resulting in high computational burden. Since the MODFLOW family of codes is widely used in practice, we develop a new approach for modeling pollutant back diffusion using MODFLOW/RT3D that eliminates the need for fine discretization of the LPZ. Instead, the LPZ is treated as an impermeable region in MODFLOW, while in RT3D the LPZ is conceptualized as a series of immobile zones coupled with a mobile zone at the HPZ/LPZ interface. Finite volume discretization of diffusion and reaction within the LPZ is then modeled as mass transfer and reaction among several immobile species.