Age-Specific Association Between Visit-to-Visit Blood Pressure Variability and Hearing Loss: A Population-Based Cohort Study.

Background and Objectives: Hearing loss is common and undertreated, and the impact of blood pressure variability (BPV) on the development of hearing loss remains unclear. We aimed to examine the age-specific association between visit-to-visit BPV and hearing loss. Research Design and Methods: This nationally representative cohort study included 3,939 adults over 50 years from the Health and Retirement Study in the United States. Variabilities of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were assessed by standard deviation (SD), coefficient of variation, and variability independent of the mean (VIM), using SBP and DBP from 3 visits. Hearing loss was assessed by self-rated questions. Cox proportional risk models were used to evaluate age-specific associations (50-64, 65-79, and ≥80 years) between BPV and hearing loss. The generalized additive Cox models were further used to visualize the combined effect of age and BPV. Results: During the follow-up up to 7.0 years, 700 participants developed hearing loss. Among people aged under 65 years, we observed a 36% increased risk of hearing loss with per-SD increment in VIM of SBP (hazard ratio [HR] per SD 1.36, 95% confidence interval [CI] 1.13-1.63) and a slightly significant association between VIM of DBP (HR per SD 1.21, 95% CI 1.01-1.45) and hearing loss. We did not observe significant associations among groups aged over 65 years (p > .05). The generalized additive Cox models also showed younger participants had stronger associations between BPV and hearing loss. Discussion and Implications: Higher visit-to-visit variabilities of SBP were associated with an increased risk of hearing loss in middle-aged adults (50-65 years). Intervention in early BPV may help decrease hearing loss in adults aged over 50 years.

Characteristics and phylogenetic analysis of the complete chloroplast genome of Cornus hongkongensis Hemsl. 1888 (Cornaceae).

Cornus hongkongensis Hemsl. 1888, native to Hong Kong, belongs to the subgenus Syncarpea within the Cornus genus of the Cornaceae family. The complete chloroplast genome of C. hongkongensis spans 156,954 bp, comprising four subregions: a large single-copy region (86,290 bp), a small single-copy region (18,394 bp), and a pair of inverted repeats (26,135 bp). Within the chloroplast genome of C. hongkongensis, we identified 113 unique genes, including 80 protein-encoding genes, four ribosomal RNA (rRNA) genes, and 30 transfer RNA (tRNA) genes. Phylogenetic analysis based on the complete chloroplast genome of 30 related taxa of the Cornus genus indicates that C. hongkongensis has not formed a monophyletic lineage. Analyses of sequence divergence found three intergenic regions including rps19-rpl22, ccsA-ndhD, and atpH-atpI, exhibiting a high degree of variations. The first chloroplast genome of C. hongkongensis was reported in this work contributes to the enrichment of genomic data for the genus Cornus.

A High-Tryptophan Diet Alleviated Cognitive Impairment and Neuroinflammation in APP/PS1 Mice through Activating Aryl Hydrocarbon Receptor via the Regulation of Gut Microbiota.

SCOPE: Recent studies have highlighted the vital role of gut microbiota in the pathogenesis of Alzheimer's disease (AD). However, the effect of the regulation of gut microbiota by dietary components on AD remains unknown. Thus, the study explored that a high-tryptophan (Trp) diet alleviates cognitive impairment by regulating microbiota. METHODS AND RESULTS: Male APP/PS1 mice are fed 0.5% Trp diet for 4 weeks, and then cognitive function, amyloid-ß (Aß) deposition, microglial activation, proinflammatory cytokines production, and gut microbiota are detected. Moreover, the level of aryl hydrocarbon receptor (AhR) and NF-κB pathway related protein are determined. The results show that high-Trp diet significantly alleviates cognitive impairment and Aß deposits. Moreover, high-Trp diet significantly inhibits activation of microglia, decreases the level of cluster of differentiation 11b (CD11b), and restrains the activation markers of microglia, such as cyclooxygenase-2 (Cox-2), interleukin (IL)-1ß, and IL-6. Notably, high-Trp diet significantly activates AhR, inhibits the phosphorylation of p65, and improves microbiota dysbiosis. CONCLUSIONS: These findings demonstrated that high-Trp diet exerts anti-inflammatory effects via upregulating AhR and suppressing NF-κB pathway, and its mechanisms may be mediated by regulating gut microbiota, suggesting that Trp diet may be a potential strategy for AD intervention.

Association of nocturnal sleep duration and midday napping with subjective poor hearing among middle-aged and older adults in China.

Background: Hearing loss has occurred as a critical concern for aging and health. However, it remains unknown whether nocturnal sleep and midday napping duration are associated with hearing loss in middle-aged and older adults. Methods: The study comprised 9,573 adults from China Health and Retirement Longitudinal Study, who have completed the survey for sleep characteristics and subjective functional hearing. We collected self-reported nocturnal sleep duration (<5, 5 to <6, 6 to <7, 7 to <9, ≥9 h/night) and midday napping duration (≤5, 5 to ≤30, and >30 min). The sleep information was classified into different sleep patterns. The primary outcome was self-reported hearing loss events. Multivariate Cox regression models and restricted cubic splines were used to investigate the longitudinal association of sleep characteristics with hearing loss. We applied Cox generalized additive models and bivariate exposure-response surface diagrams to visualize the effects of different sleep patterns on hearing loss. Results: We confirmed 1,073 cases of hearing loss (55.1% female) during the follow-up. After adjusting for demographic characteristics, lifestyle factors and health condition, nocturnal sleep with < 5 h was positively associated with hearing loss [hazard ratio (HR): 1.45, 95% confidence interval [CI]: 1.20, 1.75]. Individuals with napping for 5 to ≤30 min had a 20% (HR: 0.80, 95%CI: 0.63, 1.00) lower risk of hearing loss compared with those with napping ≤ 5 min. Restrictive cubic splines showed the reverse J-shaped association between nocturnal sleep and hearing loss. Moreover, we found significant joint effects of sleeping < 7 h/night and midday napping ≤ 5 min (HR: 1.27, 95% CI: 1.06, 1.52) on hearing loss. Bivariate exposure-response surface diagrams also reflected the finding that short sleep without napping existed the highest risk of hearing loss. Compared with persistently sleeping moderately (7-9 h/night), those who persistently slept < 7 h/night or shifted from < 7 h/night to moderate or > 9 h/night had higher risks of hearing loss. Conclusion: Inadequate nocturnal sleep was associated with an elevated risk of poor subjective hearing in middle-aged and older adults, while moderate napping decreased the risk of hearing loss. Keeping sleep stable within recommendation duration may be a useful strategy for preventing poor hearing loss.

Prevalence of Hypertension and Its Association with Cardiovascular Risk Factors in College Students in Hunan, China.

Background: Although the prevalence of hypertension has been well studied in middle age and elderly populations, few studies have systematically investigated the prevalence of hypertension and its association with cardiovascular and cerebrovascular risk factors in young populations. Objective: This study examined the prevalence of hypertension in college students and its correlation with cardiovascular and cerebrovascular risk factors, such as neck circumference and body mass index (BMI). Methods: This population-based study recruited a total of 1719 students (723 were junior, 502 were sophomore, and 494 were freshman), including 996 males (average age: 20.8 years) and 723 females (average age: 20.4 years). Hypertension was defined by the 2018 revised edition of the Chinese Guidelines for Prevention and Treatment of Hypertension. Blood and pulse pressure were measured using standard protocols. Circulating levels of lipids, glucose, glycosylated hemoglobin (GHb), leptin, and adiponectin were determined using standard methods. The Chi-squared (χ2) test was used for comparison of significant differences between groups. Linear and logistic regression analyses were used to explore risk factors that significantly influence hypertension. Findings: The prevalence of hypertension was 10.59% in the total cohort, and sophomores had a higher prevalence of hypertension than freshmen and juniors (χ2 = 19.372; P < 0.001). In addition, male students had a significantly higher prevalence of hypertension (10.24%) and abnormal pulse pressure (8.13%) than female students (1.4% and 0.83%) (χ2 = 327.424, P < 0.001 for high SBP and χ2 = 60.49, P < 0.001 for high DBP, respectively). Correlation analysis revealed that hypertension was significantly correlated with neck circumference and BMI (r = 0.509, P < 0.001; r = 0.474, P < 0.001), but not significantly correlated with the other parameters examined. Conclusion: The prevalence of hypertension in college students is closely correlated with two obesity indicators, neck circumference and BMI.

Association of depression with all-cause and cardiovascular mortality among US adults with high and low baseline risk of cardiovascular disease.

The intervention of depression was considered a prevention and treatment option for cardiovascular disease (CVD). However, evidence regarding whether association of depression with mortality differed among people at high or low risk of CVD yielded conflicting results. We aimed to investigate associations between depression and all-cause and CVD mortality among 3854 and 3044 US adults at high and low baseline risk of CVD, respectively. Among participants at high risk of CVD, depression and per 5-point increase in PHQ-9 score were associated with 81% (HR=1.81, 95%CI: 1.15-2.86) and 33% (HR=1.33, 95%CI: 1.14-1.55) increased all-cause mortality, respectively. We did not find statistically significant associations between depression (HR=1.40, 95%CI: 0.67-2.95) and PHQ-9 score (HR=1.28, 95%CI: 1.00-1.63) with CVD mortality due to a small number of mortality events. Among people with low risk of CVD, each 5-point increment in PHQ-9 score was associated with all-cause mortality (HR=1.26, 95%CI: 1.02-1.56), while there was no statistically significant association of depression with all-cause mortality (HR=1.69, 95%CI: 0.75-3.81) and CVD mortality (HR=1.99, 95%CI: 0.83-4.81). This study found that depression was associated with all-cause mortality among individuals at a high baseline risk of CVD, but no significant association was observed in people at a low baseline risk of CVD.

Long-term fasting glucose variability and risk of cancer in patients with type 2 diabetes mellitus: A retrospective population-based cohort study in Shanghai.

BACKGROUNDS: Fasting blood glucose (FBG) variability may make an impact on adverse events in patients with diabetes mellitus. However, the association between long-term changes in FBG and cancer remains unclear. We aimed to investigate this association in a large-scale longitudinal study. METHODS: Data were collected from 46 761 patients with type 2 diabetes mellitus aged 20-80 years who participated in the Diabetes Standardized Management Program in Shanghai, China. We adopted four indicators, including standard deviation (SD), coefficient of variation (CV), variation independent of the mean (VIM), and average real variability (ARV) to describe FBG variability. Adjusted multivariable Cox regression analyses and restricted cubic splines were used to investigate the association between long-term FBG variability and cancer risk. We also determined the interactive effect of FBG variability with hypertension and FBG-mean with hypertension on cancer risk, respectively. RESULTS: In this study, we confirmed 2218 cancer cases (51.1% male) over a median follow-up of 2.86 years. In the multivariable-adjusted models, participants in the highest quartile of FBG variability had an increased risk of cancer compared with those in the lowest quartile. The nonlinear association was found when using FBG-VIM, FBG-ARV, and FBG-SD in restricted cubic spline plots. There was a significant interaction effect of FBG variability with hypertension on cancer, whereas the effect of FBG-mean with hypertension did not attain significance. CONCLUSIONS: Our retrospective cohort study demonstrated a positive association between the long-term changes in FBG and cancer risk in patients with type 2 diabetes mellitus. FBG variability may independently predict cancer incidence.

Probiotic Pediococcus pentosaceus ameliorates MPTP-induced oxidative stress via regulating the gut microbiota-gut-brain axis.

Recent evidence demonstrated that functional bacteria were involved in the regulation of Parkinson's disease (PD). However, the mechanism of probiotics in improving PD was unclear. Here the antioxidant effect and the mechanism of probiotics Pediococcus pentosaceus (PP) on PD were studied by regulating the gut-brain axis. In this study, male C57BL/6J mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally to establish a PD model and were then treated with PP for 4 weeks. Subsequently, a series of neurobehavioral tests to evaluate the motor function of the mice was performed. Additionally, degeneration of dopaminergic neurons, accumulation of α-synuclein, the production of an oxidative stress response, and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway-related proteins were evaluated. Moreover, the gut microbial composition and the level of metabolite γ-aminobutyric acid (GABA) were assessed. The results showed that PP treatment could improve MPTP-induced motor deficits, the degeneration of dopaminergic neurons, and the accumulation of α-synuclein. Moreover, PP treatment significantly increased the levels of SOD1, Gpx1, and Nrf2, while it decreased the levels of Keap1 in the brain of MPTP-induced mice. Notably, PP treatment improved the gut microbial dysbiosis and increased the level of GABA in MPTP-induced mice. These findings indicated that PP might represent a promising candidate, due to the metabolite of GABA, that could be used for the treatment of PD.

Effects of Neuromuscular Electrical Stimulation Combined with Repetitive Transcranial Magnetic Stimulation on Upper Limb Motor Function Rehabilitation in Stroke Patients with Hemiplegia.

OBJECTIVE: To investigate the effect of neuromuscular electrical stimulation (NMES) combined with repetitive transcranial magnetic stimulation (rTMS) on upper limb motor dysfunction in stroke patients with hemiplegia. METHODS: A total of 240 stroke patients with hemiplegia who met the inclusion criteria were selected and randomly divided into 4 groups (60 cases in each group): control group, NMES group, rTMS group, and NMES + rTMS group. Before treatment and 4 weeks after treatment, we evaluated and compared the results including Fugl-Meyer assessment of upper extremity (FMA-UE) motor function, modified Barthel index (MBI), modified Ashworth scale (MAS), and motor nerve electrophysiological results among the 4 groups. RESULTS: Before treatment, there was no significant difference in the scores of FMA-UE, MBI, MAS, and motor nerve electrophysiological indexes among the four groups, with comparability. Compared with those before treatment, the scores of the four groups were significantly increased and improved after treatment. And the score of the NMES + rTMS group was notably higher than those in the other three groups. CONCLUSION: NMES combined with rTMS can conspicuously improve the upper extremity motor function and activities of daily life of stroke patients with hemiplegia, which is worthy of clinical application and promotion.

Neuroprotective Effect of Optogenetics Varies With Distance From Channelrhodopsin-2 Expression in an Amyloid-ß-Injected Mouse Model of Alzheimer's Disease.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease that is the most common cause of dementia. Optogenetics uses a combination of genetic engineering and light to activate or inhibit specific neurons in the brain. Objective: The objective of the study was to examine the effect of activation of glutamatergic neurons in the hippocampus of mice injected with Aß1-42 on memory function and biomarkers of neuroinflammation and neuroprotection in the brain to elucidate the clinical utility of optogenetic neuromodulation in AD. Methods: AAV5-CaMKII-channelrhodopsin-2 (CHR2)-mCherry (Aß-CHR2 mice) or AAV5-CaMKII-mCherry (Aß-non-CHR2 mice) was injected into the dentate gyrus (DG) of the bilateral hippocampus of an Aß1-42-injected mouse model of AD. The novel object recognition test was used to investigate working memory (M1), short-term memory (M2), and long-term memory (M3) after Aß1-42 injection. Hippocampus tissues were collected for immunohistochemical analysis. Results: Compared to controls, M1 and M2 were significantly higher in Aß-CHR2 mice, but there was no significant difference in M3; NeuN and synapsin expression were significantly increased in the DG of Aß-CHR2 mice, but not in CA1, CA3, the subventricular zone (SVZ), or the entorhinal cortex (ENT); GluR2 and IL-10 expressions were significantly increased, and GFAP expression was significantly decreased, in CA1, CA3, the DG, and the SVZ of Aß-CHR2 mice, but not in the ENT. Conclusion: Activation of glutamatergic neurons by optogenetics in the bilateral DG of an Aß-injected mouse model of AD improved M1 and M2, but not M3. A single-target optogenetics strategy has spatial limitations; therefore, a multiple targeted optogenetics approach to AD therapy should be explored.

Gray Matter Atrophy in Parkinson's Disease and the Parkinsonian Variant of Multiple System Atrophy: A Combined ROI- and Voxel-Based Morphometric Study.

OBJECTIVES: Parkinson's disease (PD) and the parkinsonian variant of multiple system atrophy (MSA-P) are distinct neurodegenerative disorders that share similar clinical features of parkinsonism. The morphological alterations of these diseases have yet to be understood. The purpose of this study was to evaluate gray matter atrophy in PD and MSA-P using regions of interest (ROI)-based measurements and voxel-based morphometry (VBM). METHODS: We studied 41 patients with PD, 20 patients with MSA-P, and 39 controls matched for age, sex, and handedness using an improved T1-weighted sequence that eased gray matter segmentation. The gray matter volumes were measured using ROI and VBM. RESULTS: ROI volumetric measurements showed significantly reduced bilateral putamen volumes in MSA-P patients compared with those in PD patients and controls (p<0.05), and the volumes of the bilateral caudate nucleus were significantly reduced in both MSA-P and PD patients compared with those in the controls (p<0.05). VBM analysis revealed multifocal cortical and subcortical atrophy in both MSA-P and PD patients, and the volumes of the cerebellum and temporal lobes were remarkably reduced in MSA-P patients compared with the volumes in PD patients (p<0.05). CONCLUSIONS: Both PD and MSA-P are associated with gray matter atrophy, which mainly involves the bilateral putamen, caudate nucleus, cerebellum, and temporal lobes. ROI and VBM can be used to identify these morphological alterations, and VBM is more sensitive and repeatable and less time-consuming, which may have potential diagnostic value.

MiR-302b-5p enhances the neuroprotective effect of IGF-1 in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease by regulating inducible nitric-oxide synthase.

Parkinson's disease (PD) is a neurodegenerative disease which results in damage in neuronal cells. Insulin-like growth factor (IGF)-1 was previously reported to play a role of neuroprotection in some diseases. Nitric oxide (NO) can also regulate neuronal cells. However, the mechanisms underlying IGF-1 and NO in PD still need to be elucidated. In present study, we explored the interaction between IGF-1 and inducible Nitric-Oxide Synthase (iNOS) in PD progression. We firstly constructed PD models by methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or MPP+ treatment. Then RT-qPCR revealed that IGF-1 expression was downregulated while iNOS expression was upregulated in MPTP model. Moreover, IGF-1 elevation or iNOS depletion enhanced cell viability and blocked cell apoptosis. Rescue assay disclosed iNOS overexpression reversed the effect on viability and apoptosis mediated by IGF-1 upregulation. Furthermore, IGF-1 was identified to positively regulate miR-302b-5p which could target iNOS. MiR-302b-5p could abolish the inhibitory function IGF-1 exerted on cell apoptosis and iNOS could counteract miR-302b-5p upregulation-triggered inhibition on cell apoptosis as well. Besides, we observed the deficiency of miR-302b-5p improved the lesioned neurobehavior of MPTP-treated mice. To sum up, present study proved that miR-302b-5p enhanced the neuroprotective effect of IGF-1 in MPTP-induced PD by regulating iNOS, recommending a novel therapeutic target for PD treatment. SIGNIFICANCE OF THE STUDY: In this study, we mainly explored that IGF-1 was decreased while iNOS was boosted in MPTP-induced PD mice model; IGF-1 suppressed while iNOS promoted MPP+ -induced toxicity and apoptosis in SH-SY5Y cells; miR-302b-5p ehanhced the neuroprotective effect of IGF-1 via targeting Inos; deficiency of miR-302b-5p improved the lesioned neurobehavior of MPTP-treated mice.

High-Ge-Content SiGe Alloy Single Crystals Using the Nanomembrane Platform.

The growth of single crystals of Ge-rich SiGe alloys in an extended composition range is demonstrated using the nanomembrane (NM) platform and III-V growth substrates. Thin films of high-Ge-content SiGe films are grown on GaAs(001) to below the kinetic critical thickness and released from the growth substrate by selectively etching a release layer to relax the strain. The resulting crystalline nanomembranes at the natural lattice constant of the alloy are transferred to a new host and epitaxially overgrown at similar compositions to make a thicker single crystal. Straightforward critical-thickness calculations demonstrate that a very wide range of group IV alloys, including those involving Sn, can be fabricated using the NM platform and the proper choice of III-V substrate. Motivations for making new group IV alloys center on band gap engineering for the development of novel group IV optoelectronic structures and devices.

Effects of electron-beam irradiation on inoculated Listeria innocua, microbiological and physicochemical quality of fresh noodles during refrigerated storage.

As a nonthermal sterilization technology, electron-beam irradiation (EBI) has attracted great interests for microbial inactivation in food preservation. In this study, the inactivation of inoculated Listeria innocua, natural microbiota, and quality of fresh noodles treated by EBI during refrigerated storage were evaluated. Results showed that the initial L. innocua population (6.38 log CFU/g) was significantly reduced to an undetectable level by treatment with 3.0 kGy EBI. Moreover, treatment with 3 kGy EBI significantly reduced the initial total bacteria counts and fungal counts (mold and yeast) from 5.66 and 3.15 log CFU/g to 2.90 and 2.11 log CFU/g, respectively. However, along with the storage process, the inoculated L. innocua and natural microbiota were recovered resulting in the increased populations of the spoilage microorganisms. Increasing the dose of EBI to 4.0 kGy or 5.0 kGy, the L. innocua population was inhibited to the undetectable level and the microbiological quality of the fresh noodles was kept in the acceptable level during the 28 day storage. In addition, changes of the physicochemical indicators including pH value, color, cooking characteristics, texture, and sensory of fresh noodles treated with EBI were delayed during storage. These results reveal that EBI treatment can improve the microbiological safety and shelf life of fresh noodles without impairing quality.

Gray matter atrophy in parkinsons disease and the parkinsonian variant of multiple system atrophy: a combined roi- and voxel-based morphometric study

OBJECTIVES: Parkinson's disease (PD) and the parkinsonian variant of multiple system atrophy (MSA-P) are distinct neurodegenerative disorders that share similar clinical features of parkinsonism. The morphological alterations of these diseases have yet to be understood. The purpose of this study was to evaluate gray matter atrophy in PD and MSA-P using regions of interest (ROI)-based measurements and voxel-based morphometry (VBM). METHODS: We studied 41 patients with PD, 20 patients with MSA-P, and 39 controls matched for age, sex, and handedness using an improved T1-weighted sequence that eased gray matter segmentation. The gray matter volumes were measured using ROI and VBM. RESULTS: ROI volumetric measurements showed significantly reduced bilateral putamen volumes in MSA-P patients compared with those in PD patients and controls (p<0.05), and the volumes of the bilateral caudate nucleus were significantly reduced in both MSA-P and PD patients compared with those in the controls (p<0.05). VBM analysis revealed multifocal cortical and subcortical atrophy in both MSA-P and PD patients, and the volumes of the cerebellum and temporal lobes were remarkably reduced in MSA-P patients compared with the volumes in PD patients (p<0.05). CONCLUSIONS: Both PD and MSA-P are associated with gray matter atrophy, which mainly involves the bilateral putamen, caudate nucleus, cerebellum, and temporal lobes. ROI and VBM can be used to identify these morphological alterations, and VBM is more sensitive and repeatable and less time-consuming, which may have potential diagnostic value.

Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1.

Foot-and-mouth disease virus (FMDV) can result in economical destruction of cloven-hoofed animals. FMDV infection has been reported to induce macroautophagy/autophagy; however, the precise molecular mechanisms of autophagy induction and effect of FMDV capsid protein on autophagy remain unknown. In the present study, we report that FMDV infection induced a complete autophagy process in the natural host cells of FMDV, and inhibition of autophagy significantly decreased FMDV production, suggesting that FMDV-induced autophagy facilitates viral replication. We found that the EIF2S1-ATF4 pathway was activated and the AKT-MTOR signaling pathway was inhibited by FMDV infection. We also observed that ultraviolet (UV)-inactivated FMDV can induce autophagy. Importantly, our work provides the first piece of evidence that expression of FMDV capsid protein VP2 can induce autophagy through the EIF2S1-ATF4-AKT-MTOR cascade, and we found that VP2 interacted with HSPB1 (heat shock protein family B [small] member 1) and activated the EIF2S1-ATF4 pathway, resulting in autophagy and enhanced FMDV replication. In addition, we show that VP2 induced autophagy in a variety of mammalian cell lines and decreased aggregates of a model mutant HTT (huntingtin) polyglutamine expansion protein (HTT103Q). Overall, our results demonstrate that FMDV capsid protein VP2 induces autophagy through interaction with HSPB1 and activation of the EIF2S1-ATF4 pathway.

Electronic Transport Properties of Epitaxial Si/SiGe Heterostructures Grown on Single-Crystal SiGe Nanomembranes.

To assess possible improvements in the electronic performance of two-dimensional electron gases (2DEGs) in silicon, SiGe/Si/SiGe heterostructures are grown on fully elastically relaxed single-crystal SiGe nanomembranes produced through a strain engineering approach. This procedure eliminates the formation of dislocations in the heterostructure. Top-gated Hall bar devices are fabricated to enable magnetoresistivity and Hall effect measurements. Both Shubnikov-de Haas oscillations and the quantum Hall effect are observed at low temperatures, demonstrating the formation of high-quality 2DEGs. Values of charge carrier mobility as a function of carrier density extracted from these measurements are at least as high or higher than those obtained from companion measurements made on heterostructures grown on conventional strain graded substrates. In all samples, impurity scattering appears to limit the mobility.

Differential regulation of glucose transporters mediated by CRH receptor type 1 and type 2 in human placental trophoblasts.

Glucose transport across the placenta is mediated by glucose transporters (GLUT), which is critical for normal development and survival of the fetus. Regulatory mechanisms of GLUT in placenta have not been elucidated. Placental CRH has been implicated to play a key role in the control of fetal growth and development. We hypothesized that CRH, produced locally in placenta, could act to modulate GLUT in placenta. To investigate this, we obtained human placentas from uncomplicated term pregnancies and isolated and cultured trophoblast cells. GLUT1 and GLUT3 expressions in placenta were determined, and effects of CRH on GLUT1 and GLUT3 were examined. GLUT1 and GLUT3 were identified in placental villous syncytiotrophoblasts and the endothelium of vessels. Treatment of cultured placental trophoblasts with CRH resulted in an increase in GLUT1 expression while a decrease in GLUT3 expression in a dose-dependent manner. Cells treated with either CRH antibody or nonselective CRH receptor (CRH-R) antagonist astressin showed a decrease in GLUT1 and an increase in GLUT3 expression. CRH-R1 antagonist antalarmin decreased GLUT1 expression while increased GLUT3 expression. CRH-R2 antagonist astressin2b increased the expression of both GLUT1 and GLUT3. Knockdown of CRH-R1 decreased GLUT1 expression while increased GLUT3 expression. CRH-R2 knockdown caused an increase in both GLUT1 and GLUT3 expression. Our data suggest that, in placenta, CRH produced locally regulates GLUT1 and GLUT3 expression, CRHR1 and CRHR2-mediated differential regulation of GLUT1 and GLUT3 expression. Placental CRH may regulate the growth of fetus and placenta by modulating the expression of GLUT in placenta during pregnancy.

Expression of cystathionine ß-synthase and cystathionine γ-lyase in human pregnant myometrium and their roles in the control of uterine contractility.

BACKGROUND: Human uterus undergoes distinct molecular and functional changes during pregnancy and parturition. Hydrogen sulfide (H(2)S) has recently been shown to play a key role in the control of smooth muscle tension. The role of endogenous H(2)S produced locally in the control of uterine contractility during labour is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Human myometrium biopsies were obtained from pregnant women undergoing cesarean section at term. Immunohistochemistry analysis showed that cystathionine-γ-lyase (CSE) and cystathionine-ß-synthetase (CBS), the principle enzymes responsible for H(2)S generation, were mainly localized to smooth muscle cells of human pregnant myometrium. The mRNA and protein expression of CBS as well as H(2)S production rate were down-regulated in labouring tissues compared to nonlabouring tissues. Cumulative administration of L-cysteine (10(-7)-10(-2) mol/L), a precursor of H(2)S, caused a dose-dependent decrease in the amplitude of spontaneous contractions in nonlabouring and labouring myometrium strips. L-cysteine at high concentration (10(-3) mol/L) increased the frequency of spontaneous contractions and induced tonic contraction. These effects of L-cysteine were blocked by the inhibitors of CBS and CSE. Pre-treatment of myometrium strips with glibenclamide, an inhibitor of ATP-sensitive potassium (K(ATP)) channels, abolished the inhibitory effect of L-cysteine on spontaneous contraction amplitude. The effects of L-cysteine on the amplitude of spontaneous contractions and baseline muscle tone were less potent in labouring tissues than that in nonlabouring strips. CONCLUSION/SIGNIFICANCE: H(2)S generated by CSE and CBS locally exerts dual effects on the contractility of pregnant myometrium. Expression of H(2)S synthetic enzymes is down-regulated during labour, suggesting that H(2)S is one of the factors involved in the transition of pregnant uterus from quiescence to contractile state after onset of parturition.