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Tuberculosis (TB), an infectious bacterial disease caused by Mycobacterium tuberculosis (Mtb), is a major cause of death worldwide. Multidrug‐resistant TB remains a public health crisis and thus novel effective treatments, such as host‐directed therapies (HDTs), are urgently required to overcome the challenges of TB infection. In this study, we evaluated 4 calcium modulators for their effects on Mtb growth in macrophages. Only flunarizine enhanced the bactericidal ability of macrophages against Mtb, which was induced by an increase in phosphorylated calcium/calmodulin (CaM)‐dependent protein kinase II (pCaMKII) levels. We further discovered that the expression of CaM was decreased in Mtb‐infected macrophages and restored following flunarizine treatment; this was associated with phagolysosome maturation and acidification. Consistent with these findings, the anti‐TB ability of macrophages was reduced following the silencing of CaM or inhibition of CAMKII activity. In conclusion, our results demonstrated that flunarizine enhanced the bactericidal ability of macrophages and clarified its CaM–pCAMKII‐dependent mechanism. Therefore, our findings strongly support further studies of this currently approved drug as an HDT candidate for TB therapy. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that transforming growth factor (TGT) β1 plays an immunosuppressive role in clinical tuberculosis. However, the contribution of TGF-β1 gene polymorphisms to human tuberculosis susceptibility remains undetermined. In this study, we showed that single-nucleotide polymorphisms (SNPs) in TGF-β1 gene were associated with increased susceptibility to tuberculosis in the discovery cohort (1533 case patients and 1445 controls) and the validation cohort (832 case patients and 1084 controls), and 2 SNPs located in the promoter region (rs2317130 and rs4803457) are in strong linkage disequilibrium. The SNP rs2317130 was associated with the severity of tuberculosis. Further investigation demonstrated that rs2317130 CC genotype is associated with higher TGF-β1 and interleukin 17A production. The mechanistic study showed that rs2317130 C allele affected TGF-β1 promoter activity by regulating binding activity to nuclear extracts. These findings provide insights into the pathogenic role of TGF-β1 in human tuberculosis and reveal a function for the TGF-β1 promoter SNPs in regulating immune responses during Mycobacterium tuberculosis infection. [ABSTRACT FROM AUTHOR]

This paper proposes a novel multilevel gravity model of migration to study the under-researched topic of urban to urban migration in China. Many previous studies have looked at rural to urban migration in the context of urbanisation and economic development, and at return migration. Very few have looked at what is becoming more important in increasingly urbanised countries, which is the movement from one urban location to another. In the study, we develop a new method that allows for the interconnections between migration flows: between those that share an origin, those that share a destination, and where there is a reciprocal flow between places. A conventional gravity model of migration ignores those connections, risking erroneous estimation of the regression parameters and of their statistical significance. It also ignores that those connections are of substantive interest—they reveal the interconnections between places regarding the numbers of migrants that they send and receive. We motivate and illustrate the advantages of our approach using 2010 interprovincial migration census data for China. The results obtained from the model confirm the effect of distance, of population size and of regional income levels. They show that there is greater variation in the numbers of migrants received by provinces than there is in the numbers sent, and that reciprocal migration between pairs of provinces is an important feature of what is happening in China, especially between the neighbouring provinces of Sichuan and Tibet. [ABSTRACT FROM AUTHOR]