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Highlights d SARS-CoV-2 genome sequencing and phylogenetic analyses identify 35 recurrent mutations d Association with 117 clinical phenotypes reveals potentially important mutations d D500-532 in Nsp1 coding region correlates with lower viral load and serum IFN-b d Viral isolates with D500-532 mutation induce lower IFN-I response in the infected cells

Objective: With the introduction of iodized salt worldwide, more and more people are exposed to more than adequate iodine intake levels with median urinary iodine excretion (MUI 200-300 mg/l) or excessive iodine intake levels (MUI O300 mg/l). The objective of this study was to explore the associations between more than adequate iodine intake levels and the development of thyroid diseases (e.g. thyroid dysfunction, thyroid autoimmunity, and thyroid structure) in two Chinese populations. Design: A population-based cross-sectional study was conducted in two areas in which people are exposed to different levels of iodine intake (Rongxing, MUI 261 mg/l; Chengshan, MUI 145 mg/l). A total of 3813 individuals were recruited by random sampling. Thyroid hormones, thyroid autoantibodies in serum, and iodine levels in urine were measured. B-mode ultrasonography of the thyroid was also performed for each participant. Results: The prevalence of subclinical hypothyroidism was significantly higher for subjects who live in Rongxing than those who live in Chengshan (5.03 vs 1.99%, P!0.001). The prevalence of positive anti-thyroid peroxidase antibody (TPOAb) and positive anti-thyroglobulin antibody (TgAb) was significantly higher for subjects in Rongxing than those in Chengshan (TPOAb: 10.64 vs 8.4%, PZ0.02; TgAb: 10.27 vs 7.93%, PZ0.01). The increase in thyroid antibodies was most pronounced in the high concentrations of TPOAb (TPOAb: R500 IU/ml) and low concentrations of TgAb (TgAb: 40-99 IU/ml) in Rongxing. Conclusions: More than adequate iodine intake could be a public health concern in terms of thyroid function and thyroid autoimmunity in the Chinese populations.European Journal of Endocrinology 164 943-950

During gestation, Toxoplasma gondii infection produces a series of complications including stillbirths, abortions, and congenital malformations. The inhibitory receptor, LILRB4, which is mainly expressed by professional antigen-presenting cells (especially macrophages and dendritic cells) may play an important immune-regulatory role at the maternal–fetal interface. To assess the role of LILRB4 during T. gondii infection, LILRB4−/− and T. gondii infected pregnant mouse models were established. Further, human primary-decidual macrophages were treated with anti-LILRB4 neutralizing antibody and then infected with T. gondii. These in vivo and in vitro models were used to explore the role of LILRB4 in T. gondii-mediated abnormal pregnancy outcomes. The results showed that abnormal pregnancy outcomes were more prevalent in LILRB4−/− infected pregnant mice than in wild-type infected pregnant mice. In subsequent experiments, expression levels of LILRB4, M1, and M2 membrane-functional molecules, arginine metabolic enzymes, and related cytokines were assessed in uninfected, infected, LILRB4-neutralized infected, and LILRB4−/− infected models. The results demonstrated T. gondii infection to downregulate LILRB4 on decidual macrophages, which strengthened M1 activation functions and weakened M2 tolerance functions by changing M1 and M2 membrane molecule expression, synthesis of arginine metabolic enzymes, and cytokine secretion profiles. These changes contributed to abnormal pregnancy outcomes. The results of this study provide not only a deeper understanding of the immune mechanisms operational during abnormal pregnancy, induced by T. gondii infection, but also identify potential avenues for therapeutic and preventive treatment of congenital toxoplasmosis.

Attribute-based encryption (ABE) is a promising cryptographic tool for data owner (DO) to realize fine-grained date sharing in the cloud computing. In the encryption of most existing ABE schemes, a substantial number of modular exponentiations are often required; the computational cost of it is growing linearly with the complexity of the access policy. Besides, in the most existing ABE with outsourced decryption, the computation cost of generating transformation key is growing linearly with the number of attributes associated with user private key; these computations are prohibitively high for mobile device users, which becomes a bottleneck limiting its application. To address the above issues, we propose a secure outsourcing algorithm for modular exponentiation in one single untrusted server model and a new method to generate the transformation key. Based on these techniques and Brent Waters's ciphertext-policy ABE scheme, we propose an ABE scheme with verifiable outsourced both encryption and decryption, which can securely outsource encryption and decryption to untrusted encryption service provider (ESP) and decryption service provider (DSP), respectively, leaving only a constant number of simple operations for the DO and eligible users to perform locally. In addition, both DO and the eligible users can check the correctness of results returned from the ESP and the DSP with a probability, respectively. Finally, we provide the experimental evaluation and security analysis of our scheme, which indicates that our construction is suitable for the mobile environment.

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Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis.

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