Potential Role of Decoy B7-H4 in the Pathogenesis of Rheumatoid Arthritis: A Mouse Model Informed by Clinical Data

Finding an association between soluble B7-H4 and rheumatoid arthritis severity, Lieping Chen and colleagues use a mouse model to show that the soluble form blocks the inhibitory function of cell-surface B7-H4

Integrated Design of Emergency Medical and Material Distribution Networks During the Epidemic Outbreak Period

During the epidemic outbreak period, the number of infected people increased explosively. In order to effectively contain the further spread of the epidemic and treat infected people, it is necessary to make reasonable planning for the treatment of infected people and the distribution of materials. In this paper, a multi-objective mixed-integer programming model for the integrated design of emergency medical and material distribution networks is developed, in which the location of medical points, the allocation of infected people, and the distribution of medical materials are addressed in the multi-stage planning. Then, the multi-objective model is solved by the augmented $\varepsilon$ -constraint method. A realistic case study on Huangpu District of Shanghai in China is conducted to demonstrate the validity of the developed model. The results show that the integrated consideration of the emergency medical network and the material distribution network is more capable of reducing the total transportation distance and decreasing the total operating cost

The complete mitochondrial genome of Pareuchiloglanis myzostoma (Teleostei, Siluriformes)

Pareuchiloglanis myzostoma is a key-listed protected indigenous fish species in Nujiang, Yunnan, China. In this study, we firstly reported the complete mitochondrial genome of P. myzostoma, which was 16,584 bp in length, containing 13 protein-coding genes, 22 transfer RNAs (tRNAs), 2 ribosomal RNA genes (rRNAs), and a non-coding control region (D-loop). The overall base composition of P. myzostoma was 30.7% for A, 24.2% for T, 16.0% for G, and 29.1% for C. Phylogenetic analysis showed that all Sisoridae species clustered together formed a monophyletic group. This work would provide a set of useful data on further molecular evolution studies of this precious species

Irregular rhythm adversely influences calcium handling in ventricular myocardium: implications for the interaction between heart failure and atrial fibrillation

Background-Despite adequate rate control, the combination of atrial fibrillation with heart failure (HF) has been shown, in a number of studies, to hasten HF progression. In this context, we aimed to test the hypothesis that an irregular ventricular rhythm causes an alteration in ventricular cardiomyocyte excitation-contraction coupling which contributes to the progression of HF. Methods and Results-We investigated the effects of electrical field stimulation (average frequency 2 Hz) in an irregular versus regular drive train pattern on the expression of calcium-handling genes and proteins in rat ventricular myocytes. The effect of rhythm on intracellular calcium transients was examined using Fura-2AM fluorescence spectroscopy. In conjunction, calcium-handling protein expression was examined in left ventricular samples obtained from end-stage HF patients, in patients with either persistent atrial fibrillation or sinus rhythm. Compared with regularly paced ventricular cardiomyocytes, in cells paced irregularly for 24 hours, there was a significant reduction in the expression of sarcoplasmic reticulum calcium (Ca2+) ATPase together with reduced serine-16 phosphorylation of phospholamban. These findings were accompanied by a 59% reduction (

Quantitative Proteomic Analysis of Tumor Reversion in Multiple Myeloma Cells

Tumor reversion is defined as the process by which cancer cells lose their malignant phenotype. However, relatively little is known about the cellular proteome changes that occur during the reversion process. A biological model of multiple myelonna (MM) reversion was established by using the H-1 parvovirus as a tool to select for revertant cells from MM cells. Isolated revertant cells displayed a strongly suppressed malignant phenotype both in vitro and in vivo. To explore possible mechanisms of MM reversion, the protein profiles of the revertant and parental MM cells were compared using a quantitative proteomic strategy termed SILAC-MS. Our results revealed that 379 proteins were either activated or inhibited during the reversion process, with a much greater proportion of the proteins, including STAT3, TCTP, CDC2, BAG2, and PCNA, being inhibited. Of these, STAT3, which is significantly down regulated, was selected for further functional studies. Inhibition of STAT3 expression by RNA interference resulted in suppression of the malignant phenotype and concomitant down regulation of TCTP expression, suggesting that myeloma reversion operates, at least in part, through inhibition of STAT3. Our results provide novel insights into the mechanisms of tumor reversion and suggest new alternative approaches for MM treatment

Proteomic analysis of multiple myeloma: Current status and future perspectives

Multiple myeloma (MM) is a malignant plasma cell neoplasm that accounts for slightly more than 10% of all hematologic cancers and remains incurable. The major challenge remains the identification of better diagnosis and prognostic biomarkers. The advent of proteomic technologies creates new opportunities and challenges for those seeking to gain greater understanding of MM. Although there is a limited number of proteomic studies to date in MM, those performed highlight the potential impact of these technologies in our understanding of MM pathogenesis and the identification of novel therapeutic targets. In this review, we introduce the proteomic technologies available for the study of MM, summarize results of the published proteomic studies on MM, and discuss the novel developments and applications for the analysis of protein PTM in MM. The application of proteomic technologies will be valuable to better understand the pathogenesis of MM and may in the future open novel avenues in the treatment of MM

Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy

The immature and dysfunctional vascular network within solid tumors poses a substantial obstacle to immunotherapy because it creates a hypoxic tumor microenvironment that actively limits immune cell infiltration. The molecular basis underpinning this vascular dysfunction is not fully understood. Using genome-scale receptor array technology, we showed here that insulin-like growth factor binding protein 7 (IGFBP7) interacts with its receptor CD93, and we subsequently demonstrated that this interaction contributes to abnormal tumor vasculature. Both CD93 and IGFBP7 were up-regulated in tumor-associated endothelial cells. IGFBP7 interacted with CD93 via a domain different from multimerin-2, the known ligand for CD93. In two mouse tumor models, blockade of the CD93/IGFBP7 interaction by monoclonal antibodies promoted vascular maturation to reduce leakage, leading to reduced tumor hypoxia and increased tumor perfusion. CD93 blockade in mice increased drug delivery, resulting in an improved antitumor response to gemcitabine or fluorouracil. Blockade of the CD93 pathway triggered a substantial increase in intratumoral effector T cells, thereby sensitizing mouse tumors to immune checkpoint therapy. Last, analysis of samples from patients with cancer under anti-programmed death 1/programmed death-ligand 1 treatment revealed that overexpression of the IGFBP7/CD93 pathway was associated with poor response to therapy. Thus, our study identified a molecular interaction involved in tumor vascular dysfunction and revealed an approach to promote a favorable tumor microenvironment for therapeutic intervention