Identification of Sodium- and Chloride-Sensitive Sites in the Slack Channel.

The Slack channel (KCNT1, Slo2.2) is a sodium-activated and chloride-activated potassium channel that regulates heart rate and maintains the normal excitability of the nervous system. Despite intense interest in the sodium gating mechanism, a comprehensive investigation to identify the sodium-sensitive and chloride-sensitive sites has been missing. In the present study, we identified two potential sodium-binding sites in the C-terminal domain of the rat Slack channel by conducting electrophysical recordings and systematic mutagenesis of cytosolic acidic residues in the rat Slack channel C terminus. In particular, by taking advantage of the M335A mutant, which results in the opening of the Slack channel in the absence of cytosolic sodium, we found that among the 92 screened negatively charged amino acids, E373 mutants could completely remove sodium sensitivity of the Slack channel. In contrast, several other mutants showed dramatic decreases in sodium sensitivity but did not abolish it altogether. Furthermore, molecular dynamics (MD) simulations performed at the hundreds of nanoseconds timescale revealed one or two sodium ions at the E373 position or an acidic pocket composed of several negatively charged residues. Moreover, the MD simulations predicted possible chloride interaction sites. By screening predicted positively charged residues, we identified R379 as a chloride interaction site. Thus, we conclude that the E373 site and the D863/E865 pocket are two potential sodium-sensitive sites, while R379 is a chloride interaction site in the Slack channel.SIGNIFICANCE STATEMENT The research presented here identified two distinct sodium and one chloride interaction sites located in the intracellular C-terminal domain of the Slack (Slo2.2, KCNT1) channel. Identification of the sites responsible for the sodium and chloride activation of the Slack channel sets its gating property apart from other potassium channels in the BK channel family. This finding sets the stage for future functional and pharmacological studies of this channel.

Urolithin A promotes atherosclerotic plaque stability by limiting inflammation and hypercholesteremia in Apolipoprotein E-deficient mice.

Urolithin A (UroA), a dietary phytochemical, is produced by gut bacteria from fruits rich in natural polyphenols ellagitannins (ETs). The efficiency of ETs metabolism to UroA in humans depends on gut microbiota. UroA has shown a variety of pharmacological activities. In this study we investigated the effects of UroA on atherosclerotic lesion development and stability. Apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat and high-cholesterol diet for 3 months to establish atherosclerosis model. Meanwhile the mice were administered UroA (50 mg·kg-1·d-1, i.g.). We showed that UroA administration significantly decreased diet-induced atherosclerotic lesions in brachiocephalic arteries, macrophage content in plaques, expression of endothelial adhesion molecules, intraplaque hemorrhage and size of necrotic core, while increased the expression of smooth muscle actin and the thickness of fibrous cap, implying features of plaque stabilization. The underlying mechanisms were elucidated using TNF-α-stimulated human endothelial cells. Pretreatment with UroA (10, 25, 50 µM) dose-dependently inhibited TNF-α-induced endothelial cell activation and monocyte adhesion. However, the anti-inflammatory effects of UroA in TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) were independent of NF-κB p65 pathway. We conducted RNA-sequencing profiling analysis to identify the differential expression of genes (DEGs) associated with vascular function, inflammatory responses, cell adhesion and thrombosis in UroA-pretreated HUVECs. Human disease enrichment analysis revealed that the DEGs were significantly correlated with cardiovascular diseases. We demonstrated that UroA pretreatment mitigated endothelial inflammation by promoting NO production and decreasing YAP/TAZ protein expression and TEAD transcriptional activity in TNF-α-stimulated HUVECs. On the other hand, we found that UroA administration modulated the transcription and cleavage of lipogenic transcription factors SREBP1/2 in the liver to ameliorate cholesterol metabolism in ApoE-/- mice. This study provides an experimental basis for new dietary therapeutic option to prevent atherosclerosis.

A 2-oxoglutarate-dependent dioxygenase converts dihydrofuran to furan in Salvia diterpenoids.

Tanshinone ⅡA (TⅡA), a diterpene quinone with a furan ring, is a bioactive compound found in the medicinal herb redroot sage (Salvia miltiorrhiza Bunge), in which both furan and dihydrofuran analogs are present in abundance. Progress has been made recently in elucidating the tanshinone biosynthetic pathway, including heterocyclization of the dihydrofuran D-ring by cytochrome P450s; however, dehydrogenation of dihydrofuran to furan, a key step of furan ring formation, remains uncharacterized. Here, by differential transcriptome mining, we identified six 2-oxoglutarate-dependent dioxygenase (2-ODD) genes whose expressions corresponded to tanshinone biosynthesis. We showed that Sm2-ODD14 acts as a dehydrogenase catalyzing the furan ring aromatization. In vitro Sm2-ODD14 converted cryptotanshinone to TⅡA and thus was designated TⅡA synthase (SmTⅡAS). Furthermore, SmTⅡAS showed a strict substrate specificity, and repression of SmTⅡAS expression in hairy root by RNAi led to increased accumulation of total dihydrofuran-tanshinones and decreased production of furan-tanshinones. We conclude that SmTⅡAS controls the metabolite flux from dihydrofuran- to furan-tanshinones, which influences medicinal properties of S. miltiorrhiza.

Effects of Particulate Matter on the Risk of Gestational Hypertensive Disorders and Their Progression.

Associations between particulate matter (PM) and gestational hypertensive disorders (GHDs) are well documented, but there is no evidence on the associations between PM and GHD progression, especially among those with assisted reproductive technology (ART) conceptions. To explore the effects of PM on the risk of GHDs and their progression among pregnant women with natural or ART conception, we enrolled 185,140 pregnant women during 2014-2020 in Shanghai and estimated the associations during different periods using multivariate logistic regression. During the 3 months of preconception, 10 µg/m3 increases in PM concentrations were associated with increased risks of gestational hypertension (GH) (PM2.5: aOR = 1.076, 95% CI: 1.034-1.120; PM10: aOR = 1.042, 95% CI: 1.006-1.079) and preeclampsia (PM2.5: aOR = 1.064, 95% CI: 1.008-1.122; PM10: aOR = 1.048, 95% CI: 1.006-1.092 ) among women with natural conception. Furthermore, for women with ART conceptions who suffered current GHD, 10 µg/m3 increases in PM concentrations in the third trimester elevated the risk of progression (PM2.5: aOR = 1.156, 95% CI: 1.022-1.306 ; PM10: aOR = 1.134, 95% CI: 1.013-1.270). In summary, women with natural conception should avoid preconceptional PM exposure to protect themselves from GH and preeclampsia. For women with ART conceptions suffering from GHD, it is necessary to avoid PM exposure in late pregnancy to prevent the disease from progressing.

Interactive effects of ambient air pollution and sunshine duration on the risk of intrahepatic cholestasis of pregnancy.

INTRODUCTION: While the associations among ambient pollutants and various pregnancy complications are well documented, the effect of ambient pollutants on intrahepatic cholestasis of pregnancy (ICP) has not been examined. This study aimed to explore the effects of ambient pollutants and sunshine duration on ICP. METHODS: The study enrolled 169,971 pregnant women who delivered between 2015 and 2020 in two hospitals. The associations between ICP and exposure to ambient pollutants and sunshine duration, averaged throughout different periods (including the 3 months before conception, 1st trimester and 2nd trimester), were estimated using a generalized linear model. The interaction effects of ambient pollutants and sunshine duration on ICP were estimated. RESULTS: The fitted curves for ICP incidence were similar to the temporal trends of PM2.5, PM10, SO2, CO and NO2 but not that of O3. The risk of ICP was significantly elevated following a 10-µg/m3 increase in PM2.5 (aOR [adjusted odds ratio] = 1.057, 95% CI [confidence interval]: 1.017-1.099) and PM10 (aOR = 1.043, 95% CI: 1.013-1.074) and a 1-h decrease in sunshine duration (aOR = 1.039, 95% CI: 1.011-1.068) during the 3 months before conception. In the second trimester, a 1-µg/m3 increase in the concentration of SO2 was associated with an increased risk of ICP (aOR = 1.011, 95% CI: 1.001-1.021). Increased concentrations of PM2.5 and PM10 had interactive effects with reduced sunshine duration during the 3 months before conception on increasing the risk of ICP. CONCLUSIONS: Exposure to PM2.5 and PM10 during the 3 months before conception and exposure to SO2 in the second trimester were associated with an increased ICP risk. Reduced sunshine duration had an interactive effect with increased concentrations of PM2.5 and PM10 during the 3 months before conception on the occurrence of ICP.

Association between prenatal exposure to ambient air pollutants and postpartum depressive symptoms: A multi-city cohort study.

BACKGROUND: Women are vulnerable to depression during postpartum period. While several studies have shown associations between ambient air pollution exposure and depression in general population, there was few studies focused on the effect of various air pollutants on postpartum depression (PPD). OBJECTIVE: This study is designed to explore the association between prenatal exposure to air pollutants and PPD, and to reveal the potential vulnerable exposure time point. METHODS: The study enrolled 10,209 pregnant women who delivered between October 2019 and February 2021 in 5 participating hospitals from 3 cities in China. Edinburgh Postnatal Depression Scale (EPDS) was administered at 6 weeks postpartum to identify PPD symptoms. Associations between PPD symptoms and exposure levels in PM2.5, PM10, SO2, CO, NO2, and O3 averaged over the whole pregnancy and each trimester were estimated using logistic regression models after adjusting for potential confounding factors. Distributed lag models (DLMs) were used to determine the relevant associations in each gestational week. RESULTS: The risk for developing PPD symptoms was significant following a 10 µg/m3 increase in PM10 (aOR = 1.47, 95%CI:1.36-1.59), NO2 (aOR = 1.63, 95%CI:1.44-1.85), and 0.1 mg/m3 increase in CO (aOR = 2.31, 95%CI: 1.99-2.69) during the whole pregnancy. Similar results were also found in exposure during each trimester of pregnancy. Besides, SO2 exposure during the second trimester was a major risk factor for developing PPD symptoms (aOR = 1.10, 95%CI:1.03-1.18). Consistent effects were also observed in DLMs, except for PM2.5 and O3, which showed no significant sensitive windows throughout pregnancy period. CONCLUSION: Exposure to PM10, CO, NO2, and SO2 in pregnancy is associated with increased risks of developing depression at 6 weeks postpartum. Our findings reveal the importance of air pollution control for preventing maternal mental health disorders among the public.

Antepartum sleep quality, mental status, and postpartum depressive symptoms: a mediation analysis.

BACKGROUND: Poor sleep quality and maternal mood disturbances are common during pregnancy and may play pivotal roles in the development of postpartum depression. We aim to examine the trajectories of sleep quality and mental health in women from early pregnancy to delivery and explore the mediating effects of sleep quality and mental status on the link between antepartum depressive symptoms and postpartum depressive symptoms. METHODS: In an ongoing prospective birth cohort, 1301 women completed questionnaires in the first, second and third trimesters and at 6 weeks postpartum. In each trimester, sleep quality was measured utilizing the Pittsburgh Sleep Quality Index (PSQI), and mental health was assessed with the Center for Epidemiologic Studies Depression Scale (CES-D), the Self-Rating Anxiety Scale (SAS) and the Perceived Stress Scale (PSS). Postpartum depressive symptoms were evaluated by the Edinburgh Postnatal Depression Scale (EPDS). The bootstrap method was used to test the mediation effect. RESULTS: The PSQI, CES-D, and SAS scores presented U-shaped curves across the antenatal period while the PSS score followed a descending trend. Antenatal sleep quality, depressive symptoms, anxiety symptoms and perceived stress all predicted depressive symptoms at 6 weeks postpartum. The influence of antepartum depressive symptoms on postpartum depressive symptoms was mediated by antepartum sleep quality and anxiety symptoms, which accounted for 32.14%, 39.25% and 31.25% in the first, second and third trimesters (P = 0.002, P = 0.001, P = 0.001, respectively). CONCLUSIONS: Poor sleep quality and anxiety symptoms in pregnancy mediated the relationship between antepartum depressive symptoms and postpartum depressive symptoms. Interventions aimed at detecting and managing sleep quality and elevated anxiety among depressed women in pregnancy warrant further investigation as preventative strategies for postpartum depression.

LncRNA BCYRN1 promotes cell migration and invasion of non-small cell lung cancer via the miR-30b-3p/ROCK1 axis.

Long non-coding RNA brain cytoplasmic RNA 1 (LncRNA BCYRN1) has been proved to participate in the cancer cell metastasis process, including non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms involved in the BCYRN1-mediated function remain largely unknown. The qRT-PCR analysis was carried out to examine the relative expressions of BCYRN1, microRNA-30b-3p (miR-30b-3p), and Rho-associated coiled-coil protein kinase 1 (ROCK1). ROCK1 protein level was detected via western blot assay. The migrative and invasive abilities of H520 and A549 cells were evaluated via Transwell assay. The relationships between BCYRN1 and miR-30b-3p or ROCK1 and miR-30b-3p were examined by luciferase reporter assay. The expression levels of BCYRN1 and ROCK1 were upregulated in NSCLC tissues and cells, while miR-30b-3p was downregulated. Higher BCYRN1 expression indicated lymph node metastasis and advanced tumor-node-metastasis (TNM) stage of NSCLC patients. Loss of BCYRN1 suppressed cell migration and invasion. More importantly, miR-30b-3p possessed the binding sites with BCYRN1. Besides, BCYRN1 negatively regulated the expression level of miR-30b-3p. Meanwhile, ROCK1 was proven to be directly targeted by miR-30b-3p. In addition, the silencing of miR-30b-3p also weakened the effect of BCYRN1 knockdown on cell migration and invasion. In vivo, BCYRN1 silencing reduced the growth of A549 cells. LncRNA BCYRN1 was involved in the metastasis of NSCLC through modulating the miR-30b-3p/ROCK1 axis.

Remodeling of occluded internal carotid artery in vessel wall magnetic resonance imaging.

OBJECTIVE: The purpose of the present study was to investigate the remodeling pattern of the extracranial occluded internal carotid artery (OICA) by vessel wall magnetic resonance imaging (VWI). METHODS: Thirty-nine atherosclerotic OICAs from 32 consecutive cases underwent 3-Tesla VWI to acquire pre- and post-contrast T1-weighted two-dimensional fluid-attenuated inversion recovery fast spin echo sequences. 25 symptomatic CAs exhibited ipsilateral downstream cerebral ischemia or ophthalmic artery embolism within last three months. The 14 remaining CAs were asymptomatic. Twenty-four CAs from 22 patients with atherosclerosis but no stenosis were recruited as control group. The outer wall area (OWA) was calculated based on the outer contour of the carotid artery drawn on the pre-contrast VWI. Negative remodeling was defined as a lower OWA compared to that of control group. RESULTS: Clinical characteristics including age, sex and vascular risk factors showed no significant difference between the occluded and control group. However, the OWA was lower in the occluded group than in the control group (0.63 versus 0.90 cm2, p = 0.004). For all OICAs, the OWA was larger in symptomatic cases than asymptomatic cases (0.71 versus 0.49cm2, p = 0.025). Using a cutoff value of 0.44, the sensitivity and specificity of OWA for detecting symptomatic OICA were 0.88 and 0.57, respectively. Heterogeneous signal intensity and enhancement were more often observed at the proximal than the distal segment of occlusion (p < 0.001). The inter-observer agreement regarding the evaluation of VWI characteristics was desirable (κ = 0.805 ∼ 0.847). CONCLUSIONS: Negative remodeling is prevalent in OICA, especially in asymptomatic cases.

Three-Dimensional Encoding Approach for Wearable Tactile Communication Devices.

In this work, we presented a novel encoding method for tactile communication. This approach was based on several tactile sensory characteristics of human skin at different body parts, such as the head and neck, where location coordinates in the three-dimensional (3D) space were clearly mapped in the brain cortex, and gentle stimulations of vibrational touching with varied strengths were received instantly and precisely. For certain applications, such as playing cards or navigating walk paths for blinded people, we demonstrated specifically designed code lists with different patterns of tactile points in varied temporal sequences. By optimizing these codes, we achieved excellent efficiency and accuracy in our test experiments. As this method matched well with the natural habits of tactile sensory, it was easy to learn in a short training period. The results of the present work have offered a silent, efficient and accurate communication solution for visually impaired people or other users.

Boosted Inner Surface Charge Transfer in Perovskite Nanodots@Mesoporous Titania Frameworks for Efficient and Selective Photocatalytic CO2 Reduction to Methane.

Exploring high-efficiency and stable halide perovskite-based photocatalysts for the selective reduction of CO2 to methane is a challenge because of the intrinsic photo- and chemical instability of halide perovskites. In this study, halide perovskites (Cs3 Bi2 Br9 and Cs2 AgBiBr6 ) were grown in situ in mesoporous TiO2 frameworks for an efficient CO2 reduction. Benchmarked CH4 production rates of 32.9 and 24.2 µmol g-1 h-1 with selectivities of 88.7 % and 84.2 %, were achieved, respectively, which are better than most reported halide perovskite photocatalysts. Focused ion-beam sliced-imaging techniques were used to directly image the hyperdispersed perovskite nanodots confined in mesopores with tunable sizes ranging from 3.8 to 9.9 nm. In situ X-ray photoelectronic spectroscopy and Kelvin probe force microscopy showed that the built-in electric field between the perovskite nanodots and mesoporous titania channels efficiently promoted photo-induced charge transfer. Density functional theory calculations indicate that the high methane selectivity was attributed to the Bi-adsorption-mediated hydrogenation of *CO to *HCO that dominates CO desorption.

Engineering high coenzyme Q10 tomato.

Coenzyme Q (CoQ) is vital for energy metabolism in living organisms. In humans, CoQ10 deficiency causes diseases and must be replenished via diet; however, CoQ content in plant foods is primarily low. Here, we report the breeding of high CoQ10 tomato lines by expressing four enzymes with a fruit-specific promoter, which modifies the chloroplast chorismate pathway, enhances cytosolic isoprenoid biosynthesis, and up-regulates the first two reactions in mitochondrion that construct the CoQ10 polyisoprenoid tail. We show that, while the level of the aromatic precursor could be markedly elevated, head group prenylation is the key to increasing the final CoQ10 yield. In the HUCD lines expressing all four transgenes, the highest CoQ10 content (0.15 mg/g dry weight) shows a seven-fold increase from the wild-type level and reaches an extraordinarily rich CoQ10 food grade. Overviewing the changes in other terpenoids by transcriptome and metabolic analyses reveals variable contents of carotenoids and α-tocopherol in the HUCD lines. In addition to the enigmatic relations among different terpenoid pathways, high CoQ10 plants maintaining substantial levels of either vitamin can be selected. Our investigation paves the way for the development of CoQ10-enriched crops as dietary supplements.

Perinatal outcomes of neonates born from different endometrial preparation protocols after frozen embryo transfer: a retrospective cohort study.

BACKGROUND: Previous studies have focused on pregnancy outcomes after frozen embryo transfer (FET) performed using different endometrial preparation protocols. Few studies have evaluated the effect of endometrial preparation on pregnancy-related complications. This study was designed to explore the association between different endometrial preparation protocols and adverse obstetric and perinatal complications after FET. METHODS: We retrospectively included all FET cycles (n = 12,950) in our hospital between 2010 and 2017, and categorized them into three groups, natural cycles (NC), hormone replacement therapy (HRT) and ovarian stimulation (OS) protocols. Pregnancy-related complications and subsequent neonatal outcomes were compared among groups. RESULTS: Among all 12,950 FET cycles, the live birth rate was slightly lower for HRT cycles than for NC (HRT vs. NC: 28.15% vs. 31.16%, p < 0.001). The pregnancy loss rate was significantly higher in OS or HRT cycles than in NC (HRT vs. NC: 17.14% vs. 10.89%, p < 0.001; OS vs. NC: 16.44% vs. 10.89%, p = 0.001). Among 3864 women with live birth, preparing the endometrium using OS or HRT protocols increased the risk of preeclampsia, and intrahepatic cholestasis of pregnancy (ICP) in both singleton and multiple deliveries. Additionally, OS and HRT protocols increased the risk of low birth weight (LBW) and small for gestational age (SGA) in both singletons and multiples after FET. CONCLUSION: Compared with HRT or OS protocols, preparing the endometrium with NC was associated with the decreased risk of pregnancy-related complications, as well as the decreased risk of LBW and SGA after FET.

Dynamic transcriptome landscape of Paragonimus proliferus developmental stages in the rat lungs.

Paragonimus proliferus, a lung fluke of the genus Paragonimus, was first reported in Yunnan province, China. P. proliferus can infect Sprague-Dawley (SD) rats and cause lung damage, but there is still no direct evidence of human infection. Until now, there has been a lack of studies on P. proliferus parasitism and development in mammalian lung tissue. The aim of this study was to perform transcriptomic profiling of P. proliferus at different developmental stages. SD rats were infected with P. proliferus metacercariae obtained from crabs; worms isolated from the lungs at different time points as well as metacercariae were subjected to whole transcriptome sequencing. Overall, 34,403 transcripts with the total length of 33,223,828 bp, average length of 965 bp, and N50 of 1833 bp were assembled. Comparative analysis indicated that P. proliferus, similar to other Paragonimus spp., expressed genes related to catabolism, whereas P. proliferus-specific transcripts were related to the maintenance of cellular redox homeostasis, sensitivity to bacteria, and immune response. Transcriptional dynamics analysis revealed that genes involved in the regulation of catabolism and apoptosis had stable expression over the P. proliferus life cycle, whereas those involved in development and immune response showed time-dependent changes. High expression of genes associated with immune response corresponded to that of genes regulating the sensitivity to bacteria and immune protection. We constructed a P. proliferus developmental model, including the development of the body, suckers, blood cells, reproductive and tracheal systems, lymph, skin, cartilage, and other tissues and organs, and an immune response model, which mainly involved T cells and macrophages. Our study provides a foundation for further research into the molecular biology and infection mechanism of P. proliferus.

Two single mutations in carboxylesterase 001C improve fenvalerate hydrolase activity in Helicoverpa armigera.

Carboxylesterases (CarEs) usually play critical roles in the detoxification of toxic chemicals and therefore may be involved in insecticide resistance in agricultural pests. Previous work has shown that CarE 001C from Helicoverpa armigera was able to metabolize the isomers of cypermethrin and fenvalerate. In this study, seven mutants of CarE 001C with single amino acid substitution were produced and expressed in the Escherichia coli. Enzyme kinetic analysis indicated that all seven mutations dramatically reduced enzymatic activities toward the generic substrate α-naphthyl acetate, but in vitro metabolism assay showed that two of the mutations, H423I and R322L, significantly improved hydrolase activities toward fenvalerate, with their recorded specific activities being 3.5 and 5.1 nM·s-1·mg -1 proteins, respectively. Further, thermostability assay showed that the stability of one mutant enzyme was enhanced. This study will help us better understand the potential of CarEs in insecticide detoxification and resistance in H. armigera.

[Risk Factors for Patients Using Intraoperative Vasopressor Infusions During Carotid Body Tumor Excision].

Objective To investigate the risk factors for patients using intraoperative vasopressor infusions during carotid body tumor(CBT)excision.Patients' mean arterial pressure(MAP)and heart rate(HR)fluctuations as well as their requirements for vasoactive agents during surgery were assessed. Methods The patients receiving CBT excision in Peking Union Medical College Hospital from May 1,2013 to July 31,2017 were included for a retrospective cohort study.The potential factors of intraoperative requirement for vasopressor infusions were investigated using univariate analysis and Logistic multivariate analysis.Furthermore,the relationships of Shamblin types of CBT with intraoperative MAP/HR fluctuations and requirements for vasoactive agents were analyzed. Results A total of 108 patients with 116 CBTs were included.Univariate analysis revealed that maximum tumor diameter >4 cm,intraoperative internal carotid artery injury,internal carotid artery reconstruction,malignant pathology,advanced Shamblin types(type Ⅱ and Ⅲ),estimated blood loss ≥400 ml,and operation duration >4 hours were associated with intraoperative requirements for vasopressor infusions.Logistic analysis showed that Shamblin type Ⅲ(OR=2.286,95% CI=1.324-14.926,P=0.016)and operation duration >4 hours(OR=3.874,95% CI=1.020-14.623,P=0.046)were risk factors for intraoperative requirements for vasopressor infusions during CBT surgery.In addition,Shamblin type Ⅲ was associated with intraoperative abnormal HR elevation and requirements for vasopressors.Conclusions Shamblin type Ⅲ and operation duration>4 hours are risk factors for intraoperative requirements of patients for using vasopressor infusions during CBT surgery.Shamblin type Ⅲ is associated with intraoperative abnormal HR elevation and requirements for vasopressors.

Neonatal outcome in 29 pregnant women with COVID-19: A retrospective study in Wuhan, China.

BACKGROUND: As of June 1, 2020, coronavirus disease 2019 (COVID-19) has caused more than 6,000,000 infected persons and 360,000 deaths globally. Previous studies revealed pregnant women with COVID-19 had similar clinical manifestations to nonpregnant women. However, little is known about the outcome of neonates born to infected women. METHODS AND FINDINGS: In this retrospective study, we studied 29 pregnant women with COVID-19 infection delivered in 2 designated general hospitals in Wuhan, China between January 30 and March 10, 2020, and 30 neonates (1 set of twins). Maternal demographic characteristics, delivery course, symptoms, and laboratory tests from hospital records were extracted. Neonates were hospitalized if they had symptoms (5 cases) or their guardians agreed to a hospitalized quarantine (13 cases), whereas symptom-free neonates also could be discharged after birth and followed up through telephone (12 cases). For hospitalized neonates, laboratory test results and chest X-ray or computed tomography (CT) were extracted from hospital records. The presence of antibody of SARS-CoV-2 was assessed in the serum of 4 neonates. Among 29 pregnant COVID-19-infected women (13 confirmed and 16 clinical diagnosed), the majority had higher education (56.6%), half were employed (51.7%), and their mean age was 29 years. Fourteen women experienced mild symptoms including fever (8), cough (9), shortness of breath (3), diarrhea (2), vomiting (1), and 15 were symptom-free. Eleven of 29 women had pregnancy complications, and 27 elected to have a cesarean section delivery. Of 30 neonates, 18 were admitted to Wuhan Children's Hospital for quarantine and care, whereas the other 12 neonates discharged after birth without any symptoms and had normal follow-up. Five hospitalized neonates were diagnosed as COVID-19 infection (2 confirmed and 3 suspected). In addition, 12 of 13 other hospitalized neonates presented with radiological features for pneumonia through X-ray or CT screening, 1 with occasional cough and the others without associated symptoms. SARS-CoV-2 specific serum immunoglobulin M (IgM) and immunoglobulin G (IgG) were measured in 4 neonates and 2 were positive. The limited sample size limited statistical comparison between groups. CONCLUSIONS: In this study, we observed COVID-19 or radiological features of pneumonia in some, but not all, neonates born to women with COVID-19 infection. These findings suggest that intrauterine or intrapartum transmission is possible and warrants clinical caution and further investigation. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000031954 (Maternal and Perinatal Outcomes of Women with coronavirus disease 2019 (COVID-19): a multicenter retrospective cohort study).

The casein kinase 2α promotes the occurrence polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease characterized by hyperandrogenism, polycystic ovaries, and anovulation. Previous studies have revealed that androgen receptors (ARs) are strongly associated with hyperandrogenism and abnormalities in folliculogenesis in patients with PCOS. However, the kinases responsible for androgen receptor activity, especially in granulosa cells, and the role of casein kinase 2α (CK2α) specifically in the pathogenesis of PCOS, remain unknown. Here, we show that both CK2α protein and mRNA levels were higher in luteinized granulosa cells of patients with PCOS compared with non-PCOS, as well as in the ovarian tissues of mice with a dehydroepiandrosterone-induced PCOS-like phenotype, compared with controls. In addition, CK2α not only interacted with AR in vivo and in vitro, but it also phosphorylated and stabilized AR, triggering AR and ovulation related genes excessive expression. CK2α also promoted cell proliferation in the KGN cell line and inhibited apoptosis. Collectively, the finding highlighted that the CK2α-AR axis probably caused the etiology of the PCOS. Thus, CK2α might be a promising clinical therapeutic target for PCOS treatment.

Tumor-suppressive activity of sTRAIL on circulating CD44+ cells in patients with non-small cell lung cancer.

Circulating CD44+ cells have been identified as a prognostic marker for patients with non-small cell lung cancer (NSCLC). Serum tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) is involved in the pathophysiology of many cancers. However, no previous studies have shown the roles of sTRAIL in circulating CD44+ cells in the blood of NSCLC patients. We detected circulating CD44+ cells and sTRAIL levels in blood samples from NSCLC patients using flow cytometry and an enzyme-linked immunosorbent assay (ELISA). Anti-tumor roles of TRAIL in CD44+ cells were confirmed using a CCK-8 assay and mouse models. A higher number of circulating CD44+ cells were identified in NSCLC patients compared with healthy control individuals. In addition, we confirmed the anti-tumor roles and mechanisms of TRAIL in CD44+ cells both in vitro and in vivo. Our results indicate that (1) there is a negative correlation between sTRAIL and circulating CD44+ cells in NSCLC patients and (2) CD44+ cells have cancer stem cell properties and are more sensitive than CD44- cells to TRAIL.

Differential Diagnosis, Clinical Characteristics, and Interventions of Braid-Like Coronary Artery: Case Series Analysis Based on Optical Coherence Tomography.

AIM: Based on optical coherence tomography (OCT), we aimed to determine the diagnosis, clinical characteristics, and interventions of braid-like coronary arteries, which are rare and tend to be diagnosed as a woven coronary artery (WCA) anomaly. METHODS AND RESULTS: We identified braid-like lesions on coronary angiography (CAG) in 7 patients (6 men; median age 47 years; age range 26 to 57 years). All patients were heavy smokers. Four patients were diagnosed with an old myocardial infarction and the other 3 with unstable angina. The braid-like lesions were located in the left anterior descending arteries in 2 patients and in the right coronary arteries in the other 5. TIMI grade 2 flow was observed in all involved vessels. OCT findings of all lesions were consistent with recanalization of organized thrombi, which consisted of septa that divided the lumen into multiple small cavities communicating with each other. No separate three-layered structure could be defined. Based on the significance of the stenosis and its related symptoms, drug-eluting stents were implanted in all of the lesions. All patients experienced symptomatic improvement after the intervention and were followed up event-free for 12 months. CONCLUSIONS: Braid-like coronary arteries are likely to undergo recanalization of organized thrombi rather than WCA according to our OCT findings. The majority of cases affect men who smoke heavily. Percutaneous stent implantation may be beneficial in selected patients when feasible.