Personal Insolvency in China: Necessities, Difficulties, and Possibilities

There has long been demand for personal insolvency laws in China, yet such laws have hitherto been unavailable, in part due to ideological resistance. In more recent years there has been an increase in borrowing by individuals, which has led to increased calls for honest but unfortunate debtors to be able to obtain a fresh start. Yet there is significant public mistrust of defaulting debtors and in particular there is a shadow cast by those termed the Lao Lai that has led many to question the desirability of such a reform. There has also been a need for change in the development of an infrastructure to support a personal insolvency system, such as a social security, property registration and credit information systems, and although progress has been made in these regards there is still a need for further development. However, there has been case law progress in one province enabling collective resolutions of claims against insolvent debtors, and judicial guidance from senior courts has expanded on this. More recently, the COVID-19 pandemic has accelerated progress towards the enactment of personal insolvency laws on a local level in Shenzhen. This article considers the need for personal insolvency laws in China, identifies the obstacles that have hitherto stood in the way of such laws and discusses the momentum which has been recently gained towards the enactment of personal insolvency laws

Relative Quantification of Protein-Protein Interactions Using a Dual Luciferase Reporter Pull-Down Assay System

The identification and quantitative analysis of protein-protein interactions are essential to the functional characterization of proteins in the post-proteomics era. The methods currently available are generally time-consuming, technically complicated, insensitive and/or semi-quantitative. The lack of simple, sensitive approaches to precisely quantify protein-protein interactions still prevents our understanding of the functions of many proteins. Here, we develop a novel dual luciferase reporter pull-down assay by combining a biotinylated Firefly luciferase pull-down assay with a dual luciferase reporter assay. The biotinylated Firefly luciferase-tagged protein enables rapid and efficient isolation of a putative Renilla luciferase-tagged binding protein from a relatively small amount of sample. Both of these proteins can be quantitatively detected using the dual luciferase reporter assay system. Protein-protein interactions, including Fos-Jun located in the nucleus; MAVS-TRAF3 in cytoplasm; inducible IRF3 dimerization; viral protein-regulated interactions, such as MAVS-MAVS and MAVS-TRAF3; IRF3 dimerization; and protein interaction domain mapping, are studied using this novel assay system. Herein, we demonstrate that this dual luciferase reporter pull-down assay enables the quantification of the relative amounts of interacting proteins that bind to streptavidin-coupled beads for protein purification. This study provides a simple, rapid, sensitive, and efficient approach to identify and quantify relative protein-protein interactions. Importantly, the dual luciferase reporter pull-down method will facilitate the functional determination of proteins

About AGN ionization echoes, thermal echoes, and ionization deficits in low redshift Lyman-alpha blobs

We report the discovery of 14 Lyα blobs (LABs) at z ∼ 0.3, existing at least 4–7 billion years later in the Universe than all other LABs known. Their optical diameters are 20–70 kpc, and GALEX data imply Lyα luminosities of (0.4–6.3) × 1043 erg s−1. Contrary to high-z LABs, they live in low-density areas. They are ionized by AGN, suggesting that cold accretion streams as a power source must deplete between z = 2 and 0.3. We also show that transient AGN naturally explain the ionization deficits observed in many LABs. Their Lyα and X-ray fluxes decorrelate below ≲106 years because of the delayed escape of resonantly scattering Lyα photons. High Lyα luminosities do not require currently powerful AGN, independent of obscuration. Chandra X-ray data reveal intrinsically weak AGN, confirming the luminous optical nebulae as impressive ionization echoes. For the first time, we also report mid-infrared thermal echoes from the dusty tori. We conclude that the AGN have faded by three to four orders of magnitude within the last 104–5 years, leaving fossil UV, optical and thermal radiation behind. The host galaxies belong to the group of previously discovered Green Bean galaxies (GBs). Gemini optical imaging reveals smooth spheres, mergers, spectacular outflows and ionization cones. Because of their proximity and high flux densities, GBs are perfect targets to study AGN feedback, mode switching and the Lyα escape. The fully calibrated, co-added optical FITS images are publicly available

Exogenously scavenged and endogenously synthesized heme are differentially utilized by Mycobacterium tuberculosis

Heme is both an essential cofactor and an abundant source of nutritional iron for the human pathogen Mycobacterium tuberculosis. While heme is required for M. tuberculosis survival and virulence, it is also potentially cytotoxic. Since M. tuberculosis can both synthesize and take up heme, the de novo synthesis of heme and its acquisition from the host may need to be coordinated in order to mitigate heme toxicity. However, the mechanisms employed by M. tuberculosis to regulate heme uptake, synthesis, and bioavailability are poorly understood. By integrating ratiometric heme sensors with mycobacterial genetics, cell biology, and biochemistry, we determined that de novo-synthesized heme is more bioavailable than exogenously scavenged heme, and heme availability signals the downregulation of heme biosynthetic enzyme gene expression. Ablation of heme synthesis does not result in the upregulation of known heme import proteins. Moreover, we found that de novo heme synthesis is critical for survival from macrophage assault. Altogether, our data suggest that mycobacteria utilize heme from endogenous and exogenous sources differently and that targeting heme synthesis may be an effective therapeutic strategy to treat mycobacterial infections. IMPORTANCE Mycobacterium tuberculosis infects ~25% of the world's population and causes tuberculosis (TB), the second leading cause of death from infectious disease. Heme is an essential metabolite for M. tuberculosis, and targeting the unique heme biosynthetic pathway of M. tuberculosis could serve as an effective therapeutic strategy. However, since M. tuberculosis can both synthesize and scavenge heme, it was unclear if inhibiting heme synthesis alone could serve as a viable approach to suppress M. tuberculosis growth and virulence. The importance of this work lies in the development and application of genetically encoded fluorescent heme sensors to probe bioavailable heme in M. tuberculosis and the discovery that endogenously synthesized heme is more bioavailable than exogenously scavenged heme. Moreover, it was found that heme synthesis protected M. tuberculosis from macrophage killing, and bioavailable heme in M. tuberculosis is diminished during macrophage infection. Altogether, these findings suggest that targeting M. tuberculosis heme synthesis is an effective approach to combat M. tuberculosis infections.Microbiology and Molecular Genetic

Asymmetric triplex metallohelices with high and selective activity against cancer cells

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and ​p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 ​p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli. At a glanc