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We aimed to evaluate the influence of early pregnancy stage 1 hypertension and mean arterial pressure (MAP) on the risk of pregnancy complications, including gestational diabetes mellitus (GDM) and adverse pregnancy outcomes. Pregnant women without early pregnancy hypertension were consecutively recruited in 2010 in Shanghai, China. Total 6104 women with blood pressure (BP) <140/90 mmHg were categorized according to early pregnancy BP and MAP levels, respectively. Multivariate adjusted logistic regression and cox regression was used to test the potential associations. Finally 313 (5.1%) pregnant women identified as stage 1 hypertension. Compared with normotensive women, women with early pregnancy stage 1 hypertension increased the risk of gestational hypertension (GH) [Adjust odds ratio (AOR) 2.295, 95% confidence interval (CI) 1.578-3.338], GDM [AOR 1.185, 95% CI 1.010-1.391], preeclampsia [AOR 2.295 95% CI 1.578-3.338], preterm delivery [AOR 1.326, 95% CI 1.026-1.713]and infants with low-birth weight [AOR 1.487, 95% CI 1.082-2.045]; Compared women with MAP < 76 mmHg, the risk of GDM increased, with an adjust hazard ratio (AHR) of 1.387 (95%CI 1.048-1.835) for 76 ≤ MAP < 88 mmHg and an AHR of 1.451 (95%CI 1.053-1.998) for MAP ≥ 88 mmHg. Especially, high MAP levels (≥ 88 mmHg) are associated with GH [AOR 2.775, 95%CI 1.805-4.266], preeclampsia [AOR 3.936, 95%CI 2.358-6.570] and preterm delivery [AOR 1.412, 95%CI 1.035-1.926]. In summary early pregnancy stage 1 hypertension is associated with adverse pregnancy outcomes. Relative higher BP levels in early pregnancy, especially elevated MAP levels should be aware by clinicians to decrease the risk of pregnancy complications., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

African swine fever virus (ASFV) is highly contagious and can cause lethal disease in pigs. ASFV is primarily replicated in the cytoplasm of pig macrophages, which is oxidative and caused constant damage to ASFV genome. ASFV AP endonuclease ( Asfv AP) catalyzes DNA cleavage reaction at the abasic site and is a key enzyme of ASFV base excision repair (BER) system. Although it plays an essential role in ASFV survival in host cells, the basis underlying substrate binding and cleavage by Asfv AP remains unclear. Here, we reported the structural and functional studies of Asfv AP, showing that Asfv AP adopts a novel DNA-binding mode distinct from other APs. Asfv AP possesses many unique structural features, including one narrower nucleotide-binding pocket at the active site, the C16-C20 disulfide bond-containing region, and histidine-rich loop. As indicated by our mutagenesis, in vitro binding and cleavage assays, these features are important for Asfv AP to suit the acidic and oxidative environment. Owing to their functional importance, these unique features could serve as targets for designing small molecule inhibitors that could disrupt the repair process of ASFV genome and help fight against this deadly virus in the future., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

S -adenosyl-1-methionine (SAM)-dependent enzymes regulate various disease-related behaviors in all organisms. Recently, the leporin biosynthesis enzyme LepI, a SAM-dependent enzyme, was reported to catalyze pericyclic reactions in leporin biosynthesis; however, the mechanisms underlying LepI activation and catalysis remain unclear. This study aimed to investigate the molecular mechanisms of LepI. Here, we reported crystal structures of LepI bound to SAM/5'-deoxy-5'-(methylthio) adenosine (MTA), S -adenosyl-homocysteine (SAH), and SAM/substrate states. Structural and biochemical analysis revealed that MTA or SAH inhibited the enzyme activities, whereas SAM activated the enzyme. The analysis of the substrate-bound structure of LepI demonstrated that this enzymatic retro-Claisen rearrangement was primarily driven by three critical polar residues His133, Arg197, Arg295 around the active site and assisted by SAM with unclear mechanism. The present studies indicate that the unique mechanisms underlying regulatory and catalysis of the unusual SAM-dependent enzyme LepI, not only strengthening current understanding of the fundamentally biochemical catalysis, but also providing novel insights into the design of SAM-dependent enzyme-specific small molecules., Competing Interests: Competing interestsThe authors declare no competing interests.

Communication is vital for all organisms including microorganisms, which is clearly demonstrated by the bacterial quorum-sensing system. However, the molecular mechanisms underlying communication among viruses (phages) via the quorum-sensing-like 'arbitrium' system remain unclear. Viral or host densities are known to be related to an increased prevalence of lysogeny; however, how the switch from the lytic to the lysogenic pathway occurs is unknown. Thus, we sought to reveal mechanisms of communication among viruses and determine the lysogenic dynamics involved. Structural and functional analyses of the phage-derived SAIRGA and GMPRGA peptides and their corresponding receptors, phAimR and spAimR, indicated that SAIRGA directs the lysis-lysogeny decision of phi3T by modulating conformational changes in phAimR, whereas GMPRGA regulates the lysis-lysogeny pathway by stabilizing spAimR in the dimeric state. Although temperate viruses are thought to share a similar lytic-lysogenic cycle switch model, our study suggests the existence of alternative strain-specific mechanisms that regulate the lysis-lysogeny decision. Collectively, these findings provide insights into the molecular mechanisms underlying communication among viruses, offering theoretical applications for the treatment of infectious viral diseases.

To investigate the prevalence of cognitive impairment and its risk factors among Chinese elders aged over 80 years, a community-based, cross-sectional study was conducted from May to June 2016 in Shanghai, China. Cognitive function was measured by using Mini-Mental Status Examination. Multiple logistic regression assessed associations between risk factors and cognitive impairment. Of 480 participants, 30% were diagnosed with cognitive impairment. Women [adjusted odds ratio (AOR): 1.71, 95% confidence interval (CI): 1.03-2.83], solitary life (AOR: 3.15, 1.89-5.26), monthly income less than 2000 Chinese yuan (AOR: 3.47, 1.18-10.23) were significantly associated with increased risk of cognitive impairment, compared with men, non-solitary life, and monthly income greater than 4000 Chinese yuan, respectively. Overweight (AOR: 0.59, 0.36-0.97), being physically active at least 60 minutes per day (AOR: 0.59, 0.35-0.95), antihypertensive drugs users (AOR: 0.45, 0.28-0.72), and lipid lowering drugs users (AOR: 0.21, 0.06-0.76) significantly lowered the risk of cognitive impairment, compared with normal weight, inadequate outdoor activity, and non-medication users, respectively. Accordingly, this study found that women, solitary life, lower income was associated with increased risk of cognitive impairment, while overweight, being physically active, and antihypertensive and lipid lowering drugs usage might lower the risk.

Bioactivity focus on α-cyano-4-hydroxycinnamic acid (CHCA) scaffold results in a small library of novel multifunctional aldose reductase (ALR2) inhibitors. All the entities displayed good to excellent inhibition with IC50 72-405 nM. (R,E)-N-(3-(2-acetamido-3-(benzyloxy)propanamido)propyl)-2-cyano-3-(4-hydroxy phenyl)acrylamide (5f) was confirmed as the most active inhibitor (IC50 72.7 ± 1.6 nM), and the best antioxidant. 5f bound to ALR2 with new mode without affecting the aldehyde reductase (ALR1) activity, implicating high selectivity to ALR2. 5f was demonstrated as both an effective ALR2 inhibitor (ARI) and antioxidant in a chick embryo model of hyperglycemia. It attenuated hyperglycemia-induced incidence of neural tube defects (NTD) and death rate, and significantly improved the body weight and morphology of the embryos. 5f restored the expression of paired box type 3 transcription factor (Pax3), and reduced the hyperglycemia-induced increase of ALR2 activity, sorbitol accumulation, and the generation of ROS and MDA to normal levels. All the evidences support that 5f may be a potential agent to treat diabetic complications.

Reprogramming of somatic cells in the enucleated egg made Dolly, the sheep, the first successfully cloned mammal in 1996. However, the mechanism of sheep somatic cell reprogramming has not yet been addressed. Moreover, sheep embryonic stem (ES) cells are still not available, which limits the generation of precise gene-modified sheep. In this study, we report that sheep somatic cells can be directly reprogrammed to induced pluripotent stem (iPS) cells using defined factors (Oct4, Sox2, c-Myc, Klf4, Nanog, Lin28, SV40 large T and hTERT). Our observations indicated that somatic cells from sheep are more difficult to reprogram than somatic cells from other species, in which iPS cells have been reported. We demonstrated that sheep iPS cells express ES cell markers, including alkaline phosphatase, Oct4, Nanog, Sox2, Rex1, stage-specific embryonic antigen-1, TRA-1-60, TRA-1-81 and E-cadherin. Sheep iPS cells exhibited normal karyotypes and were able to differentiate into all three germ layers both in vitro and in teratomas. Our study may help to reveal the mechanism of somatic cell reprogramming in sheep and provide a platform to explore the culture conditions for sheep ES cells. Moreover, sheep iPS cells may be directly used to generate precise gene-modified sheep.