Community-based Intervention for Obstructive Sleep Apnea in the General Population: A Randomized Controlled Trial.

STUDY OBJECTIVES: To investigate the engagement and health outcomes of community-based intervention for obstructive sleep apnea (OSA) in the general population. METHODS: We conducted a 3-month randomized controlled trial in two communities in southern China. We initially screened the general population for high-risk OSA and further diagnosis using home sleep testing. Eligible participants were randomly (1:1) assigned to either a control or continuous positive airway pressure-based integrated intervention group. The primary outcomes were multimodal indicators reflecting health outcomes, including health-related quality of life (Short Form-36 [SF-36]), sleep-related symptoms, and cardiometabolic risk. RESULTS: Of the 2,484 participants screened, 1,423 identified as having high-risk OSA were considered for telephone invitations to participate in the trial. Of these, 401 participants responded positively (28.2%), 279 were diagnosed with OSA, and 212 were randomized. The intervention significantly improved several domains of SF-36, including physical functioning (intergroup difference, 2.8; P=0.003), vitality (2.3; P=0.031), and reported health transition (6.8; P=0.005). Sleep-related symptoms, including Epworth Sleepiness Scale (-0.7; P=0.017), Fatigue Severity Scale (-3.0; P=0.022), Insomnia Severity Index (-1.8; P<0.001), and Pittsburgh Sleep Quality Index (-0.7; P=0.032), also showed significant improvements. Although the intervention did not significantly alter glycolipid metabolism, ventricular function, or cardiac structural remodeling, it achieved a significant reduction in systolic (-4.5 mmHg; P=0.004) and diastolic blood pressure (-3.7 mmHg; P<0.001). CONCLUSIONS: Community-based intervention for previously undiagnosed OSA in the general population yielded improvements in health-related quality of life, sleep-related symptoms, and blood pressure. However, engagement in the intervention program was low.

OsJAB1 Positively Regulates Ascorbate Biosynthesis and Negatively Regulates Salt Tolerance Due to Inhibiting Early-Stage Salt-Induced ROS Accumulation in Rice.

Reactive oxygen species (ROS) play dual roles in plant stress response, but how plants modulate the dual roles of ROS in stress response is still obscure. OsJAB1 (JUN-activation-domain-binding protein 1) encodes the rice CSN5 (COP9 signalsome subunit 5). This study showed that, similar to the Arabidopsis homolog gene CSN5B, OsJAB1-overexpressing (driven by a CaMV 35S promoter) plants (OEs) impaired rice salt stress tolerance; in contrast, OsJAB1-inhibited-expression (using RNA-interfering technology) plants (RIs) enhanced rice salt stress tolerance. Differing from CSN5B that negatively regulated ascorbate (Asc) biosynthesis, Asc content increased in OEs and decreased in RIs. ROS analysis showed that RIs clearly increased, but OEs inhibited ROS accumulation at the early stage of salt treatment; in contrast, RIs clearly decreased, but OEs promoted ROS accumulation at the late stage of salt treatment. The qPCR revealed that OEs decreased but RIs enhanced the expressions of ROS-scavenging genes. This indicated that OsJAB1 negatively regulated rice salt stress tolerance by suppressing the expression of ROS-scavenging genes. This study provided new insights into the CSN5 homologous protein named OsJAB1 in rice, which developed different functions during long-term evolution. How OsJAB1 regulates the Asc biosynthesis that coordinates the balance between cell redox signaling and ROS scavenging needs to be investigated in the future.

Knockdown of lncRNA SNHG15 Ameliorates Oxygen and Glucose Deprivation (OGD)-Induced Neuronal Injury via Regulating the miR-9-5p/TIPARP Axis.

Stroke is a cerebrovascular disease with impaired nerve function. Long non-coding RNA (lncRNA) is considered to be an important regulator of various diseases. Nevertheless, the role of lncRNA small nucleolar RNA host gene 15 (SNHG15) in cerebral ischemia injury induced by stroke is still unclear. Cell-counting kit 8 assay and flow cytometry were used to detect cell viability and apoptosis, respectively. The caspase3 activity of cells was measured using Caspase3 Activity Assay Kit. Besides, the protein levels of apoptosis markers and TCCD-induced poly (ADP)-ribose polymerase (TIPARP) were determined using western blot analysis. Moreover, quantitative real-time polymerase chain reaction was employed to examine the relative expression of SNHG15 and miR-9-5p. Furthermore, dual-luciferase reporter assay was used to assess the interaction between miR-9-5p and SNHG15 or TIPARP. In addition, biotin-labeled RNA pull-down assay was performed to evaluate the interaction between miR-9-5p and SNHG15 further. Middle cerebral artery occlusion (MCAO) model was constructed to further explore the role of SNHG15 in neuronal injury in vivo. Our data showed that oxygen and glucose deprivation (OGD) could induce N-2a cell injury and enhance SNHG15 expression. Silenced SNHG15 could promote the viability and suppress the apoptosis of OGD-induced N-2a cells. Also, SNHG15 knockdown also could alleviate the neuronal injury of MCAO mice. Mechanistically, SNHG15 could sponge miR-9-5p, and miR-9-5p could target TIPARP. Further experiments revealed that miR-9-5p inhibition or TIPARP overexpression could reverse the suppressive effect of SNHG15 knockdown on OGD-induced N-2a cell injury. Our findings indicated that SNHG15 knockdown inhibited neuronal injury through the miR-9-5p/TIPARP axis, suggesting that SNHG15 might be a potential target for cerebral ischemia injury induced by stroke.

Long non-coding RNA ZFAS1 exerts a protective role to alleviate oxygen and glucose deprivation-mediated injury in ischemic stroke cell model through targeting miR-186-5p/MCL1 axis.

In recent years, accumulating articles have revealed that long non-coding RNAs (lncRNAs) play crucial roles in ischemic stroke (IS). A previous study found that lncRNA zinc finger antisense 1 (ZFAS1) was down-regulated in IS patients compared with healthy controls. However, the precise function of ZFAS1 in IS and its associated mechanism remain unclear. Cell viability was assessed by cell counting kit-8 (CCK8) assay. Cell apoptosis was analyzed by flow cytometry. Western blot assay and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to measure protein and RNA expression. The interaction between microRNA-186-5p (miR-186-5p) and ZFAS1 or MCL1 apoptosis regulator, BCL2 family member (MCL1) was confirmed by dual-luciferase reporter assay, RNA-pull down assay and RNA immunoprecipitation (RIP) assay. IS cell model was established through exposing N2a cells to oxygen and glucose deprivation (OGD). OGD exposure restrained the viability and induced the apoptosis of N2a cells. OGD exposure down-regulated the expression of ZFAS1 and up-regulated the level of miR-186-5p in a time-dependent manner. ZFAS1 overexpression alleviated OGD-mediated injury in IS cell model. MiR-186-5p was identified as a direct target of ZFAS1, and OGD-induced injury in IS cell model was attenuated by the silence of miR-186-5p. MiR-186-5p interacted with the 3' untranslated region (3'UTR) of MCL1 messenger RNA (mRNA). ZFAS1 positively regulated MCL1 mRNA expression by sequestering miR-186-5p in N2a cells. ZFAS1 overexpression-mediated protective effects in IS cell model were partly overturned by the overexpression of miR-186-5p. MCL1 silencing partly counteracted the protective effects mediated by miR-186-5p silencing in IS cell model. In conclusion, ZFAS1 overexpression exerted a protective role in IS cell model to attenuate OGD-induced injury through targeting miR-186-5p/MCL1 axis. ZFAS1/miR-186-5p/MCL1 signaling might be a novel diagnostic marker and promising treatment target for IS patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-021-00481-4.

LncRNA GAS5 Silencing Attenuates Oxygen-Glucose Deprivation/Reperfusion-Induced Injury in Brain Microvascular Endothelial Cells via miR-34b-3p-Dependent Regulation of EPHA4.

BACKGROUND: The aim of our study was to explore the role of long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) in ischemic stroke using oxygen-glucose deprivation/reperfusion (OGD/R)-induced bEnd.3 cells as in vitro cell model. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were adopted to analyze RNA and protein expression. Cell viability and apoptosis were analyzed by Cell Counting Kit-8 (CCK8) assay and flow cytometry. The levels of nitric oxide (NO) and endothelin-1 (ET-1) in culture supernatant were examined by their matching commercial kits. The intermolecular target interaction was predicted by starBase software and tested by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: OGD/R-induced apoptosis and dysregulation in vascular endocrine system were largely alleviated by the knockdown of GAS5. GAS5 interacted with microRNA-34b-3p (miR-34b-3p), and GAS5 silencing protected bEnd.3 cells from OGD/R-induced injury partly through up-regulating miR-34b-3p. EPH receptor A4 (EPHA4) was a target of miR-34b-3p. GAS5 acted as the molecular sponge of miR-34b-3p to up-regulate EPHA4 in bEnd.3 cells. GAS5 interference protected against OGD/R-induced damage in bEnd.3 cells partly through down-regulating EPHA4. CONCLUSION: LncRNA GAS5 knockdown protected brain microvascular endothelial cells bEnd.3 from OGD/R-induced injury depending on the regulation of miR-34b-3p/EPHA4 axis.

Feeding behavior of honey bees on dry sugar.

The feeding habits of insects can be influenced by food abundance, nutrition, physical forces, and many other variables, which is why this topic is multidisciplinary and perennially fascinating. Although honey bees primarily feed on liquid nectar, they also can feed on dry sugar; however, the feeding mechanism for feeding on dry substances by a primarily fluid-feeding insect remains unexplored. We observed that, when honey bees are accessible to both dry sugar and liquid nectar, they prefer to feed on the latter. To elucidate the diet preference, we conducted a comparative study between feeding on dry-sugar and drawing up liquid-nectar, from the tongue kinematics and dynamic configuration, friction force, glossal durability, and feeding efficiency. Using a high-speed camera, we discovered that the hairy tongue of the honey bee uses back-and-forth movements to furrow a groove on pieces of dry sugar, with saliva simultaneously dissolving the sugar. We found that the lapping frequency of the tongue on dry sugar reduces from 4.5 Hz to 1.6 Hz when compared to feeding on the liquid diet; a 64% decrease in average tongue speed. Through tribological tests, we revealed that the friction forces when feeding on dry sugar is approximately 5 times that of dipping nectar, and the glossal hairs wear 4 times faster when feeding on dry sugar compared to the sucrose solution. We built a mathematical model to bridge the gap between energy intake rate and tongue dynamics of these two feeding modes. The theoretical net energy intake rate of feeding on dry sugar is 50% lower than when feeding on sucrose solutions. Both experimental and theoretical discoveries revealed that although honey bees can feed on dry substances, natural selection has forged their tongue structures primarily for a liquid diet. This study combined behavioral and mechanical tests with mathematical modeling, which highlights the advantages of using multidisciplinary approaches for uncovering the feeding physiology of insects.