Cell-Cycle-Specific Autoencoding Improves Cluster Analysis of Cycling Cardiomyocytes.

BACKGROUND: Our previous analyses of cardiomyocyte single-nucleus RNA sequencing (snRNAseq) data from the hearts of fetal pigs and pigs that underwent apical resection surgery on postnatal day (P) 1 (ARP1), myocardial infarction (MI) surgery on P28 (MIP28), both ARP1 and MIP28 (ARP1MIP28), or controls (no surgical procedure or CTL) identified 10 cardiomyocyte subpopulations (clusters), one of which appeared to be primed to proliferate in response to MI. However, the clusters composed of primarily proliferating cardiomyocytes still contained noncycling cells, and we were unable to distinguish between cardiomyocytes in different phases of the cell cycle. Here, we improved the precision of our assessments by conducting similar analyses with snRNAseq data for only the 1646 genes included under the Gene Ontology term "cell cycle." METHODS: Two cardiac snRNAseq datasets, one from mice (GEO dataset number GSE130699) and one from pigs (GEO dataset number GSE185289), were evaluated via our cell-cycle-specific analytical pipeline. Cycling cells were identified via the co-expression of 5 proliferation markers (AURKB, MKI67, INCENP, CDCA8, and BIRC5). RESULTS: The cell-cycle-specific autoencoder (CSA) algorithm identified 7 cardiomyocyte clusters in mouse hearts (mCM1 and mCM3-mCM8), including one prominent cluster of cycling cardiomyocytes in animals that underwent MI or Sham surgery on P1. Five cardiomyocyte clusters (pCM1, pCM3-pCM6) were identified in pig hearts, 2 of which (pCM1 and pCM4) displayed evidence of cell cycle activity; pCM4 was found primarily in hearts from fetal pigs, while pCM1 comprised a small proportion of cardiomyocytes in both fetal hearts and hearts from ARP1MIP28 pigs during the 2 weeks after MI induction, but was nearly undetectable in all other experimental groups and at all other time points. Furthermore, pseudotime trajectory analysis of snRNAseq data from fetal pig cardiomyocytes identified a pathway that began at pCM3, passed through pCM2, and ended at pCM1, whereas pCM3 was enriched for the expression of a cell cycle activator that regulates the G1/S phase transition (cyclin D2), pCM2 was enriched for an S-phase regulator (CCNE2), and pCM1 was enriched for the expression of a gene that regulates the G2M phase transition and mitosis (cyclin B2). We also identified 4 transcription factors (E2F8, FOXM1, GLI3, and RAD51) that were more abundantly expressed in cardiomyocytes from regenerative mouse hearts than from nonregenerative mouse hearts, from the hearts of fetal pigs than from CTL pig hearts, and from ARP1MIP28 pig hearts than from MIP28 pig hearts during the 2 weeks after MI induction. CONCLUSIONS: The CSA algorithm improved the precision of our assessments of cell cycle activity in cardiomyocyte subpopulations and enabled us to identify a trajectory across 3 clusters that appeared to track the onset and progression of cell cycle activity in cardiomyocytes from fetal pigs.

eIF2α incites photoreceptor cell and retina damage by all-trans-retinal.

Dry age-related macular degeneration (AMD) and recessive Stargardt's disease (STGD1) lead to irreversible blindness in humans. The accumulation of all-trans-retinal (atRAL) induced by chaos in visual cycle is closely associated with retinal atrophy in dry AMD and STGD1 but its critical downstream signaling molecules remain ambiguous. Here, we reported that activation of eukaryotic translation initiation factor 2α (eIF2α) by atRAL promoted retinal degeneration and photoreceptor loss through activating c-Jun N-terminal kinase (JNK) signaling-dependent apoptosis and gasdermin E (GSDME)-mediated pyroptosis. We determined that eIF2α activation by atRAL in photoreceptor cells resulted from endoplasmic reticulum homeostasis disruption caused at least in part by reactive oxygen species production, and it activated JNK signaling independent of and dependent on activating transcription factor 4 and the activating transcription factor 4/transcription factor C/EBP homologous protein (CHOP) axis. CHOP overexpression induced apoptosis of atRAL-loaded photoreceptor cells through activating JNK signaling rather than inhibiting the expression of antiapoptotic gene Bcl2. JNK activation by eIF2α facilitated photoreceptor cell apoptosis caused by atRAL via caspase-3 activation and DNA damage. Additionally, we demonstrated that eIF2α was activated in neural retina of light-exposed Abca4-/-Rdh8-/- mice, a model that shows severe defects in atRAL clearance and displays primary features of human dry AMD and STGD1. Of note, inhibition of eIF2α activation by salubrinal effectively ameliorated retinal degeneration and photoreceptor apoptosis in Abca4-/-Rdh8-/- mice upon light exposure. The results of this study suggest that eIF2α is an important target to develop drug therapies for the treatment of dry AMD and STGD1.

Effect of interpregnancy interval on the risk of gestational diabetes mellitus during a second pregnancy.

BACKGROUND: Interpregnancy interval (IPI) is associated with the risk of GDM in a second pregnancy. However, an optimal IPI is still need to be determined based on the characteristics of the population. This study aimed to analyze the effect of interpregnancy interval (IPI) on the risk of gestational diabetes mellitus (GDM) in the Chinese population. METHODS: We conducted a retrospective cohort study on female participants who had consecutive deliveries at Peking University Shenzhen Hospital from 2013 to 2021. The IPI was categorized into 7 groups and included into the multivariate logistic regression model with other confound factors. Analysis was also stratified based on age of first pregnancy, BMI, and history of GDM. Adjusted OR values (aOR) and 95% confidence intervals (CI) calculated. The regression coefficient of IPI months on GDM prediction risk was analyzed using a linear regression model. RESULTS: A total of 2,392 participants were enrolled. The IPI of the GDM group was significantly greater than that of the non-GDM group (P < 0.05). Compared with the 18-24 months IPI category, participants with longer IPIs (24-36 months, 36-48 months, 48-60 months, and ≥ 60 months) had a higher risk of GDM (aOR:1.585, 2.381, 2.488, and 2.565; 95% CI: 1.021-2.462, 1.489-3.809, 1.441-4.298, and 1.294-5.087, respectively). For participants aged < 30 years or ≥ 30 years or without GDM history, all longer IPIs (≥ 36 months) were all significantly associated with the GDM risk in the second pregnancy (P < 0.05), while any shorter IPIs (< 18 months) was not significantly associated with GDM risk (P > 0.05). For participants with GDM history, IPI 12-18 months, 24-36 months, 36-48 months, and ≥ 60 months were all significantly associated with the GDM risk (aOR: 2.619, 3.747, 4.356, and 5.373; 95% CI: 1.074-6.386, 1.652-8.499, 1.724-11.005, and 1.078-26.793, respectively), and the slope value of linear regression (0.5161) was significantly higher compared to participants without a history of GDM (0.1891) (F = 284.168, P < 0.001). CONCLUSIONS: Long IPI increases the risk of GDM in a second pregnancy, but this risk is independent of maternal age. The risk of developing GDM in a second pregnancy for women with GDM history is more significantly affected by IPI.

Hypoadiponectinemia-induced upregulation of microRNA449b downregulating Nrf-1 aggravates cardiac ischemia-reperfusion injury in diabetic mice.

Diabetes enhances myocardial ischemic/reperfusion (MI/R) injury via an incompletely understood mechanism. Adiponectin (APN) is a cardioprotective adipokine suppressed by diabetes. However, how hypoadiponectinemia exacerbates cardiac injury remains incompletely understood. Dysregulation of miRNAs plays a significant role in disease development. However, whether hypoadiponectinemia alters cardiac miRNA profile, contributing to diabetic heart injury, remains unclear. Methods and Results: Wild-type (WT) and APN knockout (APN-KO) mice were subjected to MI/R. A cardiac microRNA profile was determined. Among 23 miRNAs increased in APN-KO mice following MI/R, miR-449b was most significantly upregulated (3.98-fold over WT mice). Administrating miR-449b mimic increased apoptosis, enlarged infarct size, and impaired cardiac function in WT mice. In contrast, anti-miR-449b decreased apoptosis, reduced infarct size, and improved cardiac function in APN-KO mice. Bioinformatic analysis predicted 73 miR-449b targeting genes, and GO analysis revealed oxidative stress as the top pathway regulated by these genes. Venn analysis followed by luciferase assay identified Nrf-1 and Ucp3 as the two most important miR-449b targets. In vivo administration of anti-miR-449b in APN-KO mice attenuated MI/R-stimulated superoxide overproduction. In vitro experiments demonstrated that high glucose/high lipid and simulated ischemia/reperfusion upregulated miR-449b and inhibited Nrf-1 and Ucp3 expression. These pathological effects were attenuated by anti-miR-449b or Nrf-1 overexpression. In a final attempt to validate our finding in a clinically relevant model, high-fat diet (HFD)-induced diabetic mice were subjected to MI/R and treated with anti-miR-449b or APN. Diabetes significantly increased miR-449b expression and downregulated Nrf-1 and Ucp3 expression. Administration of anti-miR-449b or APN preserved cardiac Nrf-1 expression, reduced cardiac oxidative stress, decreased apoptosis and infarct size, and improved cardiac function. Conclusion: We demonstrated for the first time that hypoadiponectinemia upregulates miR-449b and suppresses Nrf-1/Ucp3 expression, promoting oxidative stress and exacerbating MI/R injury in this population. Dysregulated APN/miR-449b/oxidative stress pathway is a potential therapeutic target against diabetic MI/R injury.

Gasdermin E mediates photoreceptor damage by all-trans-retinal in the mouse retina.

The breakdown of all-trans-retinal (atRAL) clearance is closely associated with photoreceptor cell death in dry age-related macular degeneration (AMD) and autosomal recessive Stargardt's disease (STGD1), but its mechanisms remain elusive. Here, we demonstrate that activation of gasdermin E (GSDME) but not gasdermin D promotes atRAL-induced photoreceptor damage by activating pyroptosis and aggravating apoptosis through a mitochondria-mediated caspase-3-dependent signaling pathway. Activation of c-Jun N-terminal kinase was identified as one of the major causes of mitochondrial membrane rupture in atRAL-loaded photoreceptor cells, resulting in the release of cytochrome c from mitochondria to the cytosol, where it stimulated caspase-3 activation required for cleavage of GSDME. Aggregation of the N-terminal fragment of GSDME in the mitochondria revealed that GSDME was likely to penetrate mitochondrial membranes in photoreceptor cells after atRAL exposure. ABC (subfamily A, member 4) and all-trans-retinol dehydrogenase 8 are two key proteins responsible for clearing atRAL in the retina. Abca4-/-Rdh8-/- mice exhibit serious defects in atRAL clearance upon light exposure and serve as an acute model for dry AMD and STGD1. We found that N-terminal fragment of GSDME was distinctly localized in the photoreceptor outer nuclear layer of light-exposed Abca4-/-Rdh8-/- mice. Of note, degeneration and caspase-3 activation in photoreceptors were significantly alleviated in Abca4-/-Rdh8-/-Gsdme-/- mice after exposure to light. The results of this study indicate that GSDME is a common causative factor of photoreceptor pyroptosis and apoptosis arising from atRAL overload, suggesting that repressing GSDME may represent a potential treatment of photoreceptor atrophy in dry AMD and STGD1.

Gut microbial signatures of patients with primary hepatocellular carcinoma and their healthy first-degree relatives.

AIMS: The gut microbiome has been recognized as a significant contributor to primary hepatocellular carcinoma (HCC), with mounting evidence indicating associations between bacterial components and cancers of the digestive system. METHODS AND RESULTS: Here, to characterize gut bacterial signature in patients with primary HCC and to assess the diagnostic potential of bacterial taxa for primary HCC, 21 HCC patients and 21 healthy first-degree relatives (control group) were enrolled in this study. Bacterial DNA in the fecal samples was quantified by 16S rRNA gene sequencing. We found that 743 operational taxonomic units (OTUs) were shared between patients with primary HCC and healthy controls. Of these, 197 OTUs were unique to patients with primary HCC, while 95 OTUs were unique to healthy subjects. Additionally, we observed significant differences in the abundance of Ruminococcaceae_UCG-014 and Romboutsia between patients with primary HCC and their healthy first-degree relatives. Besides, the relative abundance of Ruminococcaceae_UCG-014 and Prevotella_9 was positively correlated with physiological indicators including AST, ALT, ALB, or TBIL. Signature bacterial taxa could serve as non-invasive biomarkers, of which Romboutsia and Veillonella were identified as differential taxa in fecal samples from patients with HCC compared to healthy controls. Romboutsia showed a strong association with HCC (AUC = 0.802). Additionally, the combination of Romboutsia and Veillonella (AUC = 0.812) or the grouping of Fusobacterium, Faccalibacterium, and Peptostreptococcacae together (AUC = 0.762) exhibited promising outcomes for the diagnosis of HCC. CONCLUSIONS: The composition of gut microbes in patients with HCC was found to be significantly altered. Differential taxa Romboutsia, Veillonella, and Peptostreptococcacae could be tested for identification of HCC.

Tissue perfusion of the kurtosis/diffusion mismatch differs from the central core and peripheral regions in acute cerebral infarction patients.

BACKGROUND: Despite its wide adoption in stroke imaging, the diffusion-weighted imaging (DWI) lesion is heterogeneous. The emerging diffusion kurtosis imaging (DKI) has been postulated to resolve the graded DWI lesion. PURPOSE: To determine the perfusion characteristics of the central infarction core, kurtosis/diffusion mismatch, and peripheral regions. MATERIAL AND METHODS: Patients with acute ischemic stroke underwent DWI, DKI, and perfusion-weighted imaging (PWI) scans. The patients were divided into mean kurtosis (MK)/mean diffusivity (MD) match and mismatch groups. Perfusion parameters were measured in the MK/MD lesion and peripheral areas in the MK/MD match group. We also analyzed perfusion status in the MK/MD lesion mismatch area for the mismatch group. RESULTS: A total of 40 eligible patients (24 MK/MD match and 16 MK/MD mismatch) were enrolled in the final data analysis. The MTT and TTP progressively decreased, while the cerebral blood flow (CBF) and cerebral blood volume (CBV) increased from the central to peripheral areas. In addition, CBF in the MK/MD mismatch region was significantly higher than that in the central region (P < 0.05), but similar to the peripheral region. Furthermore, CBV in the MK/MD mismatch region did not differ significantly from that of the central region, but both were significantly lower than that of the peripheral area (P < 0.05). CONCLUSION: The MK/MD mismatch region had blood flow similar to the peripheral region but with a reduced blood volume, indicating that it was less ischemic from the infarction core, albeit insufficient collateral circulation.

Association between sodium and potassium intake levels and body compositions of Chinese college students.

BACKGROUND AND OBJECTIVES: To investigate the relationship between sodium (Na) and potassium (K) nutritional condition and body compositions in youth aiming to give target population reasonable diet recommendations. METHODS AND STUDY DESIGN: The cross-sectional study was conducted involving 512 healthy youth aged 18 to 31 years from universities in Beijing. Food frequency questionnaire (FFQ) and bioelectrical impedance analyzer (BIA) were used to collect dietary intake information and body compositions. RESULTS: There was an increasing tendency in fat-related indicators and muscle-related indicators of the dietary Na tertile group (p <0.05). Additionally, Weight, body mass index (BMI), waist circumference (WC), and muscle-related indicators increased with the dietary K tertile group (p <0.05). Across increasing tertiles of dietary Na intake, the odds ratio (OR) was increased significantly (p < 0.05) in fat-related indicators. On the contrary, with the increased dietary Na intake, the OR decreased (p < 0.05) in appendicular skeletal muscle mass index (ASMI) and body lean mass. As tertiles of dietary K intake increased, the OR in both skeletal muscle mass index (SMMI) and lean mass index (LMI) decreased. CONCLUSIONS: High dietary Na is a risk factor for abnormal lipid distribution in college students. High dietary K can maintain skeletal muscle mass and reduce the risk of obesity. Na in the diet has a greater impact on the body composition of young people than K. Low dietary Na and high dietary K still need to be strengthened in science popularization and practice among more college students.

Ferroptosis drives photoreceptor degeneration in mice with defects in all-trans-retinal clearance.

The death of photoreceptor cells in dry age-related macular degeneration (AMD) and autosomal recessive Stargardt disease (STGD1) is closely associated with disruption in all-trans-retinal (atRAL) clearance in neural retina. In this study, we reveal that the overload of atRAL leads to photoreceptor degeneration through activating ferroptosis, a nonapoptotic form of cell death. Ferroptosis of photoreceptor cells induced by atRAL resulted from increased ferrous ion (Fe2+), elevated ACSL4 expression, system Xc- inhibition, and mitochondrial destruction. Fe2+ overload, tripeptide glutathione (GSH) depletion, and damaged mitochondria in photoreceptor cells exposed to atRAL provoked reactive oxygen species (ROS) production, which, together with ACSL4 activation, promoted lipid peroxidation and thereby evoked ferroptotic cell death. Moreover, exposure of photoreceptor cells to atRAL activated COX2, a well-accepted biomarker for ferroptosis onset. In addition to GSH supplement, inhibiting either Fe2+ by deferoxamine mesylate salt (DFO) or lipid peroxidation with ferrostatin-1 (Fer-1) protected photoreceptor cells from ferroptosis caused by atRAL. Abca4-/-Rdh8-/- mice exhibiting defects in atRAL clearance is an animal model for dry AMD and STGD1. We observed that ferroptosis was indeed present in neural retina of Abca4-/-Rdh8-/- mice after light exposure. More importantly, photoreceptor atrophy and ferroptosis in light-exposed Abca4-/-Rdh8-/- mice were effectively alleviated by intraperitoneally injected Fer-1, a selective inhibitor of ferroptosis. Our study suggests that ferroptosis is one of the important pathways of photoreceptor cell death in retinopathies arising from excess atRAL accumulation and should be pursued as a novel target for protection against dry AMD and STGD1.

All-sapphire fiber-optic pressure sensors for extreme harsh environments.

In this paper, an all-sapphire fiber-optic Fabry-Perot (F-P) pressure sensor is proposed. The sapphire pressure-sensitive diaphragm with low surface roughness is fabricated by MEMS wet etching. The direct bonding process is adopted to bond the sapphire-sensitive diaphragm and substrate together. And the sapphire fiber is adopted to be the lead-in fiber to ensure the sensor's resistance to high temperature. The performance of the sensor is tested within a pressure range of 0.1∼5 MPa and within the temperature range from room temperature to 1200°C. Experimental results show that the sensor could work stably at the temperature of 1200°C. The pressure sensitivity reaches up to 15nm/MPa. The nonlinearity of the sensor is 0.96% FS (full scale), and the relative resolution reaches 0.12%FS. The all-sapphire F-P sensor could be used for high-pressure testing in a high-temperature environment.

Repressing c-Jun N-terminal kinase signaling mitigates retinal pigment epithelium degeneration in mice with failure to clear all-trans-retinal.

Retinal pigment epithelium (RPE) cell apoptosis arising from all-trans-retinal (atRAL) is in close contact with the etiology of dry age-related macular degeneration (AMD) and autosomal recessive Stargardt's disease (STGD1), but its underlying mechanisms remain elusive. In this study, we reported that c-Jun N-terminal kinase (JNK) activation facilitated atRAL-induced apoptosis of RPE cells. Reactive oxygen species production and endoplasmic reticulum stress were identified as two of major upstream events responsible for activating JNK signaling in atRAL-loaded RPE cells. Inhibiting JNK signaling rescued RPE cells from apoptosis induced by atRAL through attenuating caspase-3 activation leading to poly-ADP-ribose polymerase (PARP) cleavage, and DNA damage response. Abca4-/-Rdh8-/- mice upon light exposure exhibit rapidly increased accumulation of atRAL in the retina, and display severe RPE degeneration, a primary attribute of dry AMD and STGD1. Reducing JNK signaling by intraperitoneally injected JNK-IN-8 was highly effective in preventing RPE atrophy and apoptosis in light-exposed Abca4-/-Rdh8-/- mice. These findings afford a further understanding for contribution of JNK activation by atRAL to retinal damage.

Quantitative breast density measurement based on three-dimensional images: a study on cone-beam breast computed tomography.

BACKGROUND: Breast density is an independent predictor of breast cancer risk. Quantitative volumetric breast density (QVBD) is expected to provide more information on the prediction of breast cancer risk. PURPOSE: To evaluate the reliability of QVBD measurements based on cone-beam breast computed tomography (CBBCT) images. MATERIAL AND METHODS: A total of 216 breasts were used to evaluate the stability of QVBD measurements based on CBBCT images and the correlations between this volumetric measurement and visual and area-based measurement methods. The intra- and inter-observer consistency of QVBD measurements were compared. Visual breast density (VBD) was evaluated with Breast Imaging Reporting and Data System (BI-RADS) standard on CBBCT images. The correlation between QVBD and VBD was evaluated by Spearman correlation coefficient. Receiver operating characteristic (ROC) curve was used to assess the sensitivity and specificity of the volumetric method in distinguishing dense and non-dense breasts. The correlation between QVBD and quantitative area-based breast density (QABD) was determined with Pearson correlation coefficient. Then, the breast volume measured with CBBCT images was compared with the breast specimen obtained during nipple-sparing mastectomy (NSM) by Pearson correlation coefficient and linear regression. RESULTS: Excellent intra- and inter-observer consistency was found from QVBD measurements. The volumetric method distinguished dense and non-dense breasts at a cutoff value of 9.5%, with 94.5% sensitivity and 77.1% specificity. Positive correlations were found between QVBD and QABD (r=0.890; P<0.001) and between the volume measured with CBBCT images and Archimedes method (r=0.969; P<0.001). CONCLUSION: CBBCT images can evaluate breast density reliably on a continuous scale.

Activation of JNK signaling promotes all-trans-retinal-induced photoreceptor apoptosis in mice.

Disrupted clearance of all-trans-retinal (atRAL), a component of the visual (retinoid) cycle in the retina, may cause photoreceptor atrophy in autosomal recessive Stargardt disease (STGD1) and dry age-related macular degeneration (AMD). However, the mechanisms underlying atRAL-induced photoreceptor loss remain elusive. Here, we report that atRAL activates c-Jun N-terminal kinase (JNK) signaling at least partially through reactive oxygen species production, which promoted mitochondria-mediated caspase- and DNA damage-dependent apoptosis in photoreceptor cells. Damage to mitochondria in atRAL-exposed photoreceptor cells resulted from JNK activation, leading to decreased expression of Bcl2 apoptosis regulator (Bcl2), increased Bcl2 antagonist/killer (Bak) levels, and cytochrome c (Cyt c) release into the cytosol. Cytosolic Cyt c specifically provoked caspase-9 and caspase-3 activation and thereby initiated apoptosis. Phosphorylation of JNK in atRAL-loaded photoreceptor cells induced the appearance of γH2AX, a sensitive marker for DNA damage, and was also associated with apoptosis onset. Suppression of JNK signaling protected photoreceptor cells against atRAL-induced apoptosis. Moreover, photoreceptor cells lacking Jnk1 and Jnk2 genes were more resistant to atRAL-associated cytotoxicity. The Abca4-/-Rdh8-/- mouse model displays defects in atRAL clearance that are characteristic of STGD1 and dry AMD. We found that JNK signaling was activated in the neural retina of light-exposed Abca4-/-Rdh8-/- mice. Of note, intraperitoneal administration of JNK-IN-8, which inhibits JNK signaling, effectively ameliorated photoreceptor degeneration and apoptosis in light-exposed Abca4-/-Rdh8-/- mice. We propose that pharmacological inhibition of JNK signaling may represent a therapeutic strategy for preventing photoreceptor loss in retinopathies arising from atRAL overload.

IL-1/IL-1R signaling induced by all-trans-retinal contributes to complement alternative pathway activation in retinal pigment epithelium.

The underlying mechanisms of complement activation in Stargardt disease type 1 (STGD1) and age-related macular degeneration (AMD) are not fully understood. Overaccumulation of all-trans-retinal (atRAL) has been proposed as the pathogenic factor in both diseases. By incubating retinal pigment epithelium (RPE) cells with atRAL, we showed that C5b-9 membrane attack complexes (MACs) were generated mainly through complement alternative pathway. An increase in complement factor B (CFB) expression as well as downregulation of complement regulatory proteins CD46, CD55, CD59, and CFH were observed in RPE cells after atRAL treatment. Furthermore, interleukin-1ß production was provoked in both atRAL-treated RPE cells and microglia/macrophages. Coincubation of RPE cells with interleukin-1 receptor antagonist (IL1Ra) and atRAL ameliorated complement activation and downregulated CFB expression by attenuating both p38 and c-Jun N-terminal kinase (JNK) signaling pathways. Our findings demonstrate that atRAL induces an autocrine/paracrine IL-1/IL-1R signaling to promote complement alternative pathway activation in RPE cells and provide a novel perspective on the pathomechanism of macular degeneration.

Excellent repeatability, all-sapphire Fabry Perot optical Pressure sensor based on wet etching and direct bonding for Harsh Environment Applications.

In this paper, we proposed an all-sapphire-based extrinsic Fabry-Perot interferometer (EFPI) sensor based on wet etching and the direct bonding process. Temperature measured by the EFPI is used to calibrate pressure measurement. The problem of repeatable measurement of dynamic pressure in a harsh environment is solved. The EFPI sensor can be applied in the temperature range of 25°C to 800°C and the pressure range environment of 0MPa to 5MPa. The pressure sensitivity of 355.8nm/MPa and the temperature sensitivity of 1.64nm/°C are obtained by a cross-correlation function (CCF) algorithm to interrogate the optical sensing system. Therefore, the proposed sensor has a great potential for pressure monitoring, such as jet engines, industrial gas turbine, and so on due to its 8×8mm size and compact structure.

All-sapphire-based fiber-optic pressure sensor for high-temperature applications based on wet etching.

In this paper, we proposed an all-sapphire-based extrinsic Fabry-Perot interferometer (EFPI) pressure sensor based on an optimized wet etching process, aiming to improve the quality of the interference signal. The sapphire pressure sensitive diaphragm (SPSD) was fabricated by wet etching solutions with different mixture ratios of H3PO4 and H2SO4 at 280°C. The differences of mixture ratios affect the surface roughness of SPSD. SPSDs with surface roughness of 3.91nm and 0.39nm are obtained when the mixture ratios of H3PO4 and H2SO4 is 1:1 and 1:3, respectively. We constructed pressure sensing test system adopting these two kinds of SPSD and performed comparative test. The experiment results show that the demodulation jump can be solved and cavity length fluctuation is decreased to ±5nm when the surface roughness of SPSD is 0.39nm.

Gamma-aminobutyric acid (GABA) changes in the hippocampus and anterior cingulate cortex in patients with temporal lobe epilepsy.

PURPOSE: To explore the changes of gamma-aminobutyric acid (GABA) levels in the bilateral hippocampus and anterior cingulate cortex (ACC) of healthy control subjects and patients with temporal lobe epilepsy (TLE) and the correlation of GABA levels with the clinical symptoms by quantitative magnetic resonance spectroscopy (MRS). METHODS: N-acetylaspartate (NAA), creatine (Cr) as well as choline (Cho) and GABA levels in the bilateral hippocampus and ACC were measured in 40 patients with TLE and 26 healthy control (NC) subjects with quantitative Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS). The NAA/(Cho + Cr) and GABA/Cr ratios were compared between the NC and TLE groups. Comparisons were also made between the subgroups with lateralization (left TLE, right TLE and uncertain), short (<10 years) and longer (≥10 years) clinical seizure history (CSH), low (<1/month) and higher (≥1/month) seizure frequency (SF), with and without cognitive impairment (CI) in the patients with TLE, and by antiepileptic medications. Further analyses of the clinical information and metabolite ratios between the patients with TLE with and without CI were preformed. RESULTS: The GABA/Cr ratio was significantly decreased in the bilateral hippocampus (left: P = 0.028, right: P = 0.035), while the NAA/(Cho + Cr) ratio was decreased only in the right hippocampus (RH) (P = 0.004) in patients with TLE compared with that of the NCs. Whereas the NAA/(Cho + Cr) ratio showed a consistent decreasing trend in bilateral hippocampus during the CSH, it only showed a significant difference in the RH. The GABA changes in the hippocampal and ACC regions were not consistent during different stages of the disease. In the bilateral hippocampus, the GABA/Cr ratio was decreased in the short seizure history (<10 years) patients with TLE compared with NCs (left: P = 0.018, right: P = 0.012), whereas the long seizure history (≥10 years) patients with TLE showed no difference with the NCs. However, in the ACC, the GABA/Cr ratio of the CI group was significantly decreased compared with that of NCs (P = 0.015). Further analysis showed that the patients with TLE with CI had obvious atrophy of the gray matter volume (GMV) and total parenchymal brain volume (PBV); GABA/Cr ratio was decreased in ACC, but increased in bilateral hippocampus compared with that of the no cognitive impairment (NOCI) group. CONCLUSION: The GABA/Cr ratio was more valuable than the NAA/(Cho + Cr) ratio in evaluating the dynamic metabolite changes in patients with TLE. Importantly, the GABA changes in the hippocampal and ACC regions were not consistent during different stages of the disease. In the bilateral hippocampus, the GABA/Cr ratio was decreased at the early stage, but recovered to normal levels later. The decreased GABA/Cr ratio in the ACC might indicate more cerebral cortex was involved, resulting in more CI in patients with TLE.

Magnetic polyamidoamine dendrimers for magnetic separation and sensitive determination of organochlorine pesticides from water samples by high-performance liquid chromatography.

Organochlorine pesticides (OCPs) have received much attention due to their toxicity. Reliable methods to monitor their residues in the environment are needed. Here, magnetic polyamidoamine dendrimers were prepared by co-precipitation, Michael addition, and amidation. The magnetic polyamidoamine dendrimers demonstrated good adsorption ability for OCPs-this feature was utilized to construct a sensitive tool for monitoring OCPs in water samples. The proposed method provided remarkable linearity from 0.1 to 500 µg/L and satisfactory limits of detection from 0.012 to 0.029 µg/L. The spiked recoveries of the four target analytes were 91.8%-103.5% with relative standard deviations less than 4.5%. The magnetic materials had good reusability. The results indicated that the resulting method was an efficient, easy, rapid, economical, and eco-friendly tool for monitoring OCPs in aqueous samples.

Pathogenic role of human C-reactive protein in diabetic retinopathy.

PURPOSE: Elevated blood levels of C-reactive protein (CRP) are associated with both type 1 and type 2 diabetes and diabetic complications, such as diabetic retinopathy (DR). However, its pathogenic role in DR remains unknown. The present study aims to investigate the potential role of CRP in DR pathogenesis and explore its underlying mechanism. MATERIALS AND METHODS: Human CRP transgenic (hCRP-Tg) rats were employed for streptozotocin (STZ)-induced diabetic and oxygen-induced retinopathy (OIR) models. The retina function was monitored by electroretinography (ERG) and retinal thickness was measured by optical coherence tomography (OCT). TUNEL and cell death ELISA were performed to measure the apoptosis. Oxidative stress was detected by the measurement of reactive oxygen species (ROS) in cells and 3-Nitrotyrosine staining in tissue sections. RESULTS: In non-diabetic condition, hCRP-Tg with elevated hCRP levels in the retinas demonstrated declined ERG responses and decreased retinal thickness. In STZ-induced diabetic condition, overexpression of hCRP deteriorated retinal neurodegeneration as shown by ERG and apoptosis assays. hCRP also exacerbated retinal leukostasis and acellular capillary formation induced by diabetes. In the OIR model, overexpression of hCRP exacerbated retinal neovascularization (NV). In retinal cell lines, hCRP treatment induced cell death and over-production of ROS. Furthermore, hCRP-induced overexpression of pro-inflammatory, pro-oxidative, and pro-angiogenic factors was associated with up-regulation of CD32 and the NF-κB signaling in the retinas. CONCLUSIONS: Elevated hCRP levels play a pathogenic role in DR. Targeting the hCRP-CD32-NF-κB pathway may represent a novel therapeutic strategy for DR.

Conversion of all-trans-retinal into all-trans-retinal dimer reflects an alternative metabolic/antidotal pathway of all-trans-retinal in the retina.

Free all-trans-retinal (atRAL) and retinal pigment epithelium (RPE) lipofuscin are both considered to play etiological roles in Stargardt disease and age-related macular degeneration. A2E and all-trans-retinal dimer (atRAL-dimer) are two well characterized bisretinoid constituents of RPE lipofuscin. In this study, we found that, after treatment of primary porcine RPE (pRPE) cells with atRAL, atRAL-dimer readily formed and accumulated in a concentration- and time-dependent manner, but A2E was barely detected. Cell-based assays revealed that atRAL, the precursor of atRAL-dimer, significantly altered the morphology of primary pRPE cells and decreased cell viability at a concentration of 80 µm regardless of light exposure. By contrast, atRAL-dimer was not cytotoxic and phototoxic to primary pRPE cells. Compared with atRAL and A2E, atRAL-dimer was more vulnerable to light, followed by the generation of its photocleaved products. Moreover, we observed the presence of atRAL-dimer in reaction mixtures of atRAL with porcine rod outer segments (ROS), RPE/choroid, or neural retina. Taken together, we here proposed an alternative metabolic/antidotal pathway of atRAL in the retina: atRAL that evades participation of the visual (retinoid) cycle undergoes a condensation reaction to yield atRAL-dimer in both ROS and RPE. Translocation of atRAL, all-trans N-retinylidene-phosphatidylethanolamine (NR-PE), atRAL-dimer, and photocleavage products of atRAL-dimer from ROS into RPE is accomplished by phagocytosing shed ROS on a daily basis. Without causing damage to RPE cells, light breaks up total atRAL-dimer within RPE cells to release low-molecular-weight photocleavage fragments. The latter, together with ROS-atRAL-dimer photocleavage products, may easily move across membranes and thereby be metabolically eliminated.