The HIV-1 restriction factor SAMHD11,2 is proposed to inhibit HIV-1 replication by depleting the intracellular dNTP pool3-5. However, the phosphorylation of SAMHD1 regulates its ability to restrict HIV-1 without decreasing cellular dNTP levels6-8, which is not consistent with a role for SAMHD1 dNTPase activity in HIV-1 restriction. Here, we show that SAMHD1 possesses RNase activity and that the RNase but not the dNTPase function is essential for HIV-1 restriction. By enzymatically characterizing Aicardi-Goutières syndrome (AGS)-associated SAMHD1 mutations and mutations in the allosteric dGTP-binding site of SAMHD1, we identify SAMHD1 mutants that are RNase-positive but dNTPase-negative (SAMHD1D137N) or RNase-negative but dNTPase-positive (SAMHD1Q548A). The allosteric mutant SAMHD1D137N is able to restrict HIV-1 infection, whereas the AGS mutant SAMHD1Q548A is defective for HIV-1 restriction. SAMHD1 associates with HIV-1 RNA and degrades it during the early phases of infection. SAMHD1 silencing in macrophages and CD4+ T cells from healthy donors increases HIV-1 RNA stability, rendering the cells permissive for HIV-1 infection. Furthermore, the phosphorylation of SAMHD1 at T592 negatively regulates its RNase activity in vivo and impedes HIV-1 restriction. Our results reveal that the RNase activity of SAMHD1 is responsible for preventing HIV-1 infection by directly degrading the HIV-1 RNA.

The purpose of this study was to examine the levels of Internet addiction and interpersonal problems, explore the relationship between the two, and identify the relevant factors of Internet addiction in Korean middle school students. A cross-sectional survey design was used. The participants were 676 middle school students. A Korean version of the Internet addiction self-test scale and a Korean version of the Inventory of Interpersonal Problems were used. Among the participants, 547 (80.9%) were identified as general users, 108 (16%) were potential risk users, and 21 (3.1%) were high-risk users. There were statistically significant positive correlations between Internet addiction and interpersonal problems (r = 0.425, P = .000). There were significant positive correlations between Internet addiction and hours spent playing games. Internet-addicted adolescents also had more interpersonal problems. It is important to raise awareness about Internet addiction, and close attention must be paid not only to students at risk of Internet addiction but also to students at low risk to prevent students from becoming addicted to the Internet.

The addition of SWE to B-mode US improved diagnostic performance with increased specificity for screening US-detected breast masses. BI-RADS category 4a masses detected at US screening that showed a dark blue color or a maximum elasticity value of 30 kPa or less on SWE images can be safely followed up instead of performing biopsy.

Background Hydroxychloroquine (HCQ) is regarded as a mainstay in the treatment of systemic lupus erythematosus (SLE) because of its efficacy in preventing flares, achieving remission, and reducing overall mortality. However, the impact of HCQ on pregnancy outcomes remains controversial. Objective We aimed to investigate the effect of HCQ on pregnancy outcomes in patients with SLE. Methods We performed a retrospective cohort study of 151 pregnancies in 122 patients with SLE (80 pregnancies in the HCQ treatment group and 71 pregnancies in the HCQ nontreatment group). We reviewed baseline characteristics including maternal comorbidities such as antiphospholipid syndrome, lupus nephritis, and autoimmune hepatitis. Pregnancy outcomes (preeclampsia, preterm delivery, and fetal growth restriction) and neonatal outcomes (gestational age at delivery and birth weight) were compared between HCQ treatment and nontreatment groups. Results Preeclampsia was significantly less complicated (7.5% vs 19.7%, p = 0.032) and neonatal birth weight was significantly greater (2757.0 ± 583.5 g vs 2542.3 ± 908.3 g, p = 0.001) in the HCQ treatment group than in the HCQ nontreatment group. Multiple logistic analysis adjusting for body mass index (BMI), lupus nephritis, serum uric acid, and estimated glomerular filtration rate revealed HCQ treatment was associated with exceedingly lower risk of preeclampsia in SLE pregnancy (odds ratio (OR) 0.106 (confidence interval (CI) 0.017–0.671)). Other independent risk factors for preeclampsia were a high prepregnancy BMI (OR 1.575 (CI 1.114–2.227)) and low eGFR level (OR 0.931 (CI 0.886–0.979)) before pregnancy. Conclusion Our data showed pregnancy outcomes in SLE patients can be improved in the HCQ treatment group with about 90% reduction of preeclampsia.