The glycosylation deficiency of flavivirus NS1 attenuates virus replication through interfering with the formation of viral replication compartments.

BACKGROUND: Flavivirus is a challenge all over the world. The replication of flavivirus takes place within membranous replication compartments (RCs) derived from endoplasmic reticulum (ER). Flavivirus NS1 proteins have been proven essential for the formation of viral RCs by remodeling the ER. The glycosylation of flavivirus NS1 proteins is important for viral replication, yet the underlying mechanism remains unclear. METHODS: HeLa cells were used to visualize the ER remodeling effects induced by NS1 expression. ZIKV replicon luciferase assay was performed with BHK-21 cells. rZIKV was generated from BHK-21 cells and the plaque assay was done with Vero Cells. Liposome co-floating assay was performed with purified NS1 proteins from 293T cells. RESULTS: We found that the glycosylation of flavivirus NS1 contributes to its ER remodeling activity. Glycosylation deficiency of NS1, either through N-glycosylation sites mutations or tunicamycin treatment, compromises its ER remodeling activity and interferes with viral RCs formation. Disruption of NS1 glycosylation results in abnormal aggregation of NS1, rather than reducing its membrane-binding activity. Consequently, deficiency in NS1 glycosylation impairs virus replication. CONCLUSIONS: In summary, our results highlight the significance of NS1 glycosylation in flavivirus replication and elucidate the underlying mechanism. This provides a new strategy for combating flavivirus infections.

Photothermoelectric Synergistic Hydrovoltaic Effect: A Flexible Photothermoelectric Yarn Panel for Multiple Renewable-Energy Harvesting.

The human body is in a complex environment affected by body heat, light, and sweat, requiring the development of a wearable multifunctional textile for human utilization. Meanwhile, the traditional thermoelectric yarn is limited by expensive and scarce inorganic thermoelectric materials, which restricts the development of thermoelectric textiles. Therefore, in this paper, photothermoelectric yarns (PPDA-PPy-PEDOT/CuI) using organic poly(3,4-ethylenedioxythiophene) (PEDOT) and inorganic thermoelectric material cuprous iodide (CuI) are used for the thermoelectric layer and poly(pyrrole) (PPy) for the light-absorbing layer. With the introduction of PPy, the temperature difference of the photothermoelectric yarn can be increased for a better voltage output. Subsequently synergizing the photothermoelectric effect with the hydrovoltaic effect to create higher electric potentials, a single wet photothermoelectric yarn obtained by preparation can be irradiated under an infrared lamp at a voltage of up to 0.47 V. Finally, the photothermoelectric yarn PPDA-PPy-PEDOT/CuI was assembled in a series and parallel to obtain a photothermoelectric yarn panel, which was able to output 41.19 mV under an infrared lamp, and the synergistic photothermoelectric and hydrovoltaic effects of the photothermoelectric panel were tested outdoors on human body, and we found that the voltage was able to reach approximately 0.16 V under sunlight. Therefore, the voltage values obtained from the photothermoelectric yarns in this study are competitive and provide a new research idea for the study of photothermoelectric yarns.

Associations of prenatal exposure to bisphenols with BMI growth trajectories in offspring within the first two years: evidence from a birth cohort study in China.

BACKGROUND: Prenatal bisphenol exposure has been reported to be associated with lower birth weight and obesity-related indicators in early childhood. These findings warrant an investigation of the relationship between prenatal bisphenol exposure and the dynamic growth of offspring. This study aimed to evaluate the relationship of maternal bisphenol concentration in urine with the body mass index (BMI) growth trajectory of children aged up to two years and to identify the critical exposure periods. METHODS: A total of 826 mother-offspring pairs were recruited from Wuhan Children's Hospital between November 2013 and March 2015. Maternal urine samples collected during the first, second, and third trimesters were analyzed for bisphenol A (BPA), bisphenol S, and bisphenol F (BPF) concentrations. Measurements of length and weight were taken at 0, 1, 3, 6, 8, 12, 18, and 24 months. Children's BMI was standardized using the World Health Organization reference, and group-based trajectory modeling was used to identify BMI growth trajectories. The associations between prenatal bisphenol exposure and BMI growth trajectory patterns were assessed using multinomial logistic regression models. RESULTS: The BMI growth trajectories of the 826 children were categorized into four patterns: low-stable (n = 134, 16.2%), low-increasing (n = 142, 17.2%), moderate-stable (n = 350, 42.4%), and moderate-increasing (n = 200, 24.2%). After adjusting for potential confounders, we observed that prenatal exposure to BPA during the second trimester [odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.09-4.43] and BPF during the third trimester (OR = 3.28, 95% CI = 1.55-6.95) at the highest quartile concentration were associated with an increased likelihood of the low-increasing BMI trajectory. Furthermore, in the subgroup analysis by infant sex, the positive association between the highest quartile of prenatal average urinary BPF concentration during the whole pregnancy and the low-increasing BMI trajectory was found only in girls (OR = 2.82, 95% CI = 1.04-7.68). CONCLUSION: Our study findings suggest that prenatal exposure to BPA and BPF (a commonly used substitute for BPA) is associated with BMI growth trajectories in offspring during the first two years, increasing the likelihood of the low-increasing pattern. Video Abstract (MP4 120033 kb).

Nontraumatic convexal subarachnoid hemorrhage: A case report.

BACKGROUND: Nontraumatic convexal subarachnoid hemorrhage (cSAH) is a rare type of atypical subarachnoid hemorrhage. It mainly presents as a focal and transient neurological deficit with similar manifestations as transient ischemic attack. CASE SUMMARY: We report a case of a 64-year-old man who visited the hospital with paroxysmal left-sided numbness and weakness is presented in this study. Computed tomography examination indicated a high-density image of the right frontal-parietal sulcus. Digital subtraction angiography showed severe stenosis at the right anterior cerebral artery A2-A3 junction (stenosis rate approximately 70%). CONCLUSION: The findings of this case indicate that anterior cerebral artery stenosis may lead to the occurrence of cSAH.

Non-invasive Vagus Nerve Stimulation Protects Against Cerebral Ischemia/Reperfusion Injury and Promotes Microglial M2 Polarization Via Interleukin-17A Inhibition.

Microglia play an essential role during cerebral an ischemia/reperfusion (I/R)-related inflammatory process. Because the M2 phenotype of microglia exhibits anti-inflammation activity, it has become a promising target for anti-inflammatory therapy. Vagus nerve stimulation (VNS) reportedly has neuroprotective effects against cerebral I/R injuries via its anti-inflammatory action. The aim of this study was to investigate the ability of non-invasive VNS (nVNS) to alleviate cerebral I/R in mice by promoting microglial M2 polarization. Neurological scoring and cerebral infarct volume assessments were performed 72 h after a middle cerebral artery occlusion (MCAO)-induced stroke. M2 phenotype microglia were identified by immunohistochemistry staining using Arg-1 and Iba-1 antibodies. The protein expressions of Arg-1, IL-17A, IL-10, Bax, and Bcl-2 were detected by Western blot. Apoptotic cells were detected using TUNEL staining. According to our results, nVNS decreased infarct volume, improved neurological outcomes, reduced apoptotic neurons (TUNEL+NeuN+ cells), and promoted microglial M2 polarization as indicated by elevated Arg-1 protein expression and increased Arg-1+ cells after MCAO. Moreover, nVNS attenuated the increased levels of IL-17A protein expression after MCAO. To test the possible involvement of IL-17A in nVNS-induced neuroprotection and microglial M2 polarization, 1-µg recombinant IL-17A (rIL-17A) was intranasally administered once daily for three consecutive days after reperfusion. We found that the intranasal administration of rIL-17A nullified the nVNS-induced promotion of microglial M2 polarization. Furthermore, rIL-17A administration abolished the neuroprotective effect of nVNS. In conclusion, our study identifies microglial M2 polarization as an important mechanism underlying the nVNS-mediated neuroprotection against cerebral I/R. This effect of nVNS could be attributed to the inhibition of IL-17A expression.

Knockdown of RTN1-C attenuates traumatic neuronal injury through regulating intracellular Ca2+ homeostasis.

Reticulons (RTNs) are a family of membrane-bound proteins that are dominantly localized to the endoplasmic reticulum (ER) membrane. RTN1-C is one member of RTNs abundantly expressed in the brain and has been shown to mediate neuronal injury in cerebral ischemia models. In the present study, we investigated the role of RTN1-C in an in vitro brain trauma model mimicked by traumatic neuronal injury (TNI) in primary cultured cortical neurons. TNI increased the expression of RTN1-C in cortical neurons but had no effect on RTN1-A and RTN1-B. Knockdown of RTN1-C with specific siRNA (Si-RTN1-C) significantly decreased cytotoxicity and apoptosis after TNI. The results of Ca2+ imaging showed that intracellular Ca2+ overload induced by TNI was attenuated by RTN1-C knockdown. Furthermore, the activation of metabotropic glutamate receptor 1 (mGluR1)-induced Ca2+ response was partially prevented by Si-RTN1-C transfection. We also evaluated the role of RTN1-C in store-operated Ca2+ entry (SOCE) in cortical neurons using the ER Ca2+ inducer thapsigargin (Tg). The results showed that knockdown of RTN1-C alleviated the SOCE-mediated Ca2+ influx and decreased the expression of stromal interactive molecule 1 (STIM1). In summary, the present study found that knockdown of RTN1-C protected neurons against TNI via preservation of intracellular Ca2+ homeostasis, which was associated with the inhibition of mGluR1-mediated ER Ca2+ release and suppression of STIM1-related SOCE. Thus, RTN1-C might represent a therapeutic target for traumatic brain injury (TBI) research.