Presence of CoV-2 antibody in vitreous humor after Cov-2 infection.

Purpose: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a life-threatening disease with largely unknown intraocular pathogenesis. Herein, we determined the presence of SARS-CoV-2-specific ribonucleic acid (RNA) and virus-associated antibodies in the vitreous humor of people who have recently recovered from SARS-CoV-2 infection. Design: This cross-sectional study included 33 patients (33 eyes) who have recently recovered from SARS-CoV-2 infection. Vitreous humor and blood serum samples were tested for the SARS-CoV-2 RNA and virus-associated antibodies. Results: Among 33 participants, blood serum and vitreous humor were all tested negative for SARS-CoV-2 RNA. SARS-CoV-2-specific IgM was detected in 87.88 % (29/33) patients in blood serum and 6.10 % (2/33) in vitreous humor; SARS-CoV-2-specific IgG was detected in 96.97 % (32/33) patient in blood serum and 81.82 % (27/33) in vitreous humor. Statistical significance was found for IgM expression between blood serum and vitreous humor (P < 0.01), while IgG was not (P = 0.11). The days after recovery were statistically longer both in IgM-positive blood serum samples group and IgG-positive vitreous humor samples group compared with negative samples of each group (P < 0.01). Additionally, no statistical difference could be detected in antibody expression in vitreous humor between different groups divided on the condition of the risk of blood-retina-barrier (BRB) failure (P = 0.49 for IgM; P = 0.37 for IgG). Conclusion: After recovering from COVID-19, no SARS-CoV-2 RNA was detected in vitreous humor, but anti-CoV-2 IgM was detected in 6.1 % and IgG in approximately 80 % of vitreous humor samples of participants. We also found that the positivety rate of SARS-CoV-2-specific antibodies in the blood serum and vitreous humor were both correlated with the days after recovery since the infection.

Room Temperature Ionic Liquid Capping Layer for High Efficiency FAPbI3 Perovskite Solar Cells with Long-Term Stability.

Ionic liquid salts (ILs) are generally recognized as additives in perovskite precursor solutions to enhance the efficiency and stability of solar cells. However, the success of ILs incorporation as additives is highly dependent on the precursor formulation and perovskite crystallization process, posing challenges for industrial-scale implementation. In this study, a room-temperature spin-coated IL, n-butylamine acetate (BAAc), is identified as an ideal passivation agent for formamidinium lead iodide (FAPbI3) films. Compared with other passivation methods, the room-temperature BAAc capping layer (BAAc RT) demonstrates more uniform and thorough passivation of surface defects in the FAPbI3 perovskite. Additionally, it provides better energy level alignment for hole extraction. As a result, the champion n-i-p perovskite solar cell with a BAAc capping layer exhibits a power conversion efficiency (PCE) of 24.76%, with an open-circuit voltage (Voc) of 1.19 V, and a Voc loss of ≈330 mV. The PCE of the perovskite mini-module with BAAc RT reaches 20.47%, showcasing the effectiveness and viability of this method for manufacturing large-area perovskite solar cells. Moreover, the BAAc passivation layer also improves the long-term stability of unencapsulated FAPbI3 perovskite solar cells, enabling a T80 lifetime of  3500 h when stored at 35% relative humidity at room temperature in an air atmosphere.

A 4.43 TΩ ZIN 0.0128 mm2 Cascaded Instrumentation Amplifier with Input-biased Pseudo Resistor for Implantable Brain Machine Interfaces.

A cascaded instrumentation amplifier (CaIA) with input-biased pseudo resistors (IBPR) is presented for implantable brain machine interfaces (BMI). The gain distribution of two-stage cascaded amplifiers, instead of a single-stage amplifier, helps to achieve an input impedance of 4.43TΩ at 100Hz, and maintain the small active area (0.0128 mm2). The input-biased pseudo resistors contribute to a much lower high-pass corner (fHP=0.00011Hz) compared with the conventional structure, the input-referred noise is only 3.836µVrms integrated from 0.5Hz to 10kHz with 0.98µW power consumption.Clinical Relevance- This establishes an area-efficient amplifier design with ultra-high input impedance (4.43TΩ at 100Hz) and hyper-low high-pass corner frequency (fHP=0.00011Hz), which is suitable for long-term monitoring of neural activities (including slow oscillations) in implantable brain-machine interfaces.

Fluorinated Graphene-Lewis-Base Polymer Composites as a Multifunctional Passivation Layer for High-Performance Perovskite Solar Cells.

Increasing the open-circuit voltage (Voc) stands as a critical strategy for further improving the efficiency of organic-inorganic halide perovskite solar cells (PSCs). Lewis basic polymers, such as polymethyl methacrylate (PMMA), are considered as an effective approach to reduce the nonradiative recombination at the perovskite surface and protect the photoactive layer against moisture. However, the insulating nature of PMMA inherently leads to increased series resistance in PSCs. Here, we propose a multifunctional passivation layer (FG-PMMA) composed of fluorinated graphene (FG) and PMMA, offering high conductivity, a good passivation effect, and excellent hole transportation capabilities. The introduction of FG not only reduces the resistance of the PMMA layer but also improves its hydrophobicity. More importantly, we found that fluoride, which acts as a p-type dopant in graphene, can further reduce the nonradiative recombination centers by forming PbF2 with uncoordinated Pb0 at the perovskite/hole transport layer interface. As a result, the introduction of FG-PMMA significantly enhances the photovoltaic performance, with a record-high open-circuit voltage (Voc) of 1.247 V and an average power conversion efficiency of 22.91%, higher than those of PMMA-based devices (20.75%, 1.210 V), as well as increasing the device's moisture stability, with over 90% of the initial efficiency maintained after 1200 h of aging at room temperature and a relative humidity of 35%.

Contribution of Tibetan Plateau ecosystems to local and remote precipitation through moisture recycling.

The ecosystems of the Tibetan Plateau (TP) provide multiple important ecosystem services that benefit both local populations and those beyond, such as through climate regulation services on precipitation for East Asia and China. However, the precipitation regulation service of the TP ecosystems for supplying moisture and maintaining precipitation is yet to be evaluated. In this study, we used the moisture recycling framework and a moisture tracking model to quantify the precipitation regulation services of TP ecosystems for their contribution to precipitation. We found TP ecosystems contributed substantially to local and downwind precipitation, with a contribution of 221 mm/year for the TP and neighboring areas through evapotranspiration (ET) (104 mm/year through transpiration), declined to <10 mm/year for eastern China and other surrounding countries. Among ecosystem types, grassland contributed most to precipitation, followed by barren and snow lands, forests, and shrublands. In terms of seasonality, precipitation contribution from TP ecosystems was greater in summer months than in non-summer months for western China, while the opposite was true for eastern China-although the magnitude was much smaller. Over the past two decades, the significant ET increases in TP translated to a widespread increase in precipitation contribution for TP and downwind beneficiary regions from 2000 to 2020. Our study provides a quantitative way to understand the precipitation regulation services of TP ecosystems through moisture recycling, substantiating their key role to maintain precipitation and the water cycle for downwind regions-effectively acting as an ecological safeguard that could be perceived by the public.

Integrated profiling uncovers prognostic, immunological, and pharmacogenomic features of ferroptosis in triple-negative breast cancer.

Objective: Ferroptosis is an iron-dependent type of regulated cell death triggered by the toxic buildup of lipid peroxides on cell membranes. Nonetheless, the implication of ferroptosis in triple-negative breast cancer (TNBC), which is the most aggressive subtype of breast carcinoma, remains unexplored. Methods: Three TNBC cohorts-TCGA-TNBC, GSE58812, and METABRIC-were adopted. Consensus molecular subtyping on prognostic ferroptosis-related genes was implemented across TNBC. Ferroptosis classification-relevant genes were selected through weighted co-expression network analysis (WGCNA), and a ferroptosis-relevant scoring system was proposed through the LASSO approach. Prognostic and immunological traits, transcriptional and post-transcriptional modulation, therapeutic response, and prediction of potential small-molecule agents were conducted. Results: Three disparate ferroptosis patterns were identified across TNBC, with prognostic and immunological traits in each pattern. The ferroptosis-relevant scoring system was proposed, with poorer overall survival in high-risk patients. This risk score was strongly linked to transcriptional and post-transcriptional mechanisms. The high-risk group had a higher response to anti-PD-1 blockade or sunitinib, and the low-risk group had higher sensitivity to cisplatin. High relationships of risk score with immunological features were observed across pan-cancer. Two Cancer Therapeutics Response Portal (CTRP)-derived agents (SNX-2112 and brefeldin A) and PRISM-derived agents (MEK162, PD-0325901, PD-318088, Ro-4987655, and SAR131675) were predicted, which were intended for high-risk patients. Conclusion: Altogether, our findings unveil prognostic, immunological, and pharmacogenomic features of ferroptosis in TNBC, highlighting the potential clinical utility of ferroptosis in TNBC therapy.

A Nontoxic NFM Solvent for High-Efficiency Perovskite Solar Cells with a Widened Processing Window.

With the steady industrialization process of the perovskite solar cells (PSCs), the toxicity of the used solvents has become a pivotal issue that needs to be addressed. Especially, the usage of N,N-dimethylformamide (DMF) solvent would pose serious environmental and health concerns. Herein, we have reported a nontoxic solvent N-formylmorpholine (NFM) to replace the toxic DMF and have achieved a higher PCE of 22.78% compared to 21.97% when DMF was adopted. Moreover, with NFM, a widened antisolvent processing window was observed, facilitating the fabrication of PSCs with high reproducibility. This solvent engineering strategy offers an important solution to prepare eco-friendly, efficient, and stable perovskite solar cells.

Thermal Annealing-Free SnO2 for Fully Room-Temperature-Processed Perovskite Solar Cells.

The SnO2 electron transport layer (ETL) for perovskite solar cells (PSCs) has been recognized as one of the most reported protocols due to its processing convenience, high reproducibility, and excellence in device performance. To date, the thermal annealing (TA) process is still an essential step for a high-quality SnO2 ETL to reduce the surface trap density. This however could restrict its processing with high thermal energy input and set a barrier to the easiness of manufacturing such as processing under room-temperature conditions. Herein, we report a thermal annealing-free (TAF) SnO2 ETL by an alternative UV-ozone (UVO) treatment. This technique simultaneously endows the SnO2 ETL with a deeper valence band maximum (EVB) and lower defect density. Furthermore, with this SnO2 ETL, a power conversion efficiency (PCE) of 21.46 and 22.26% was achieved based on MAPbI3 and Cs0.05(FA0.85MA0.15)0.95Pb(I0.85Br0.15)3 absorbers, respectively. Importantly, a fully room-temperature-processed (RTP) PSC based on the TAF-SnO2 ETL has been demonstrated with a PCE of 20.88% on a rigid substrate and 15.92% on a flexible substrate, which are the highest values for RTP solar cells.

Double-Layer Solid Composite Electrolytes Enabling Improved Room-Temperature Cycling Performance for High-Voltage Lithium Metal Batteries.

The development of solid-state electrolytes (SSEs) for high energy density lithium metal batteries (LMBs) usually needs to take into account of the interfacial compatibility against lithium metal and the electrolyte stability suitable for a high-potential cathode. In this study, through a facile two-step coating process, novel double-layer solid composite electrolytes (SCEs) with Janus characteristics are customized for the high-voltage LMBs with improved room-temperature cycling performance. Among which, high-voltage resistant poly(vinylidene fluoride) (PVDF) is adopted here for the construction of an electrolyte layer facing the cathode, while the other layer against the lithium anode is composed of the polymer matrix of poly(ethylene oxide) (PEO) blended with PVDF to obtain a lithium metal-friendly interface. With the further incorporation of Laponite clay, the PVDF/(PEO+PVDF)-L SCEs not only exhibit improved mechanical properties, but also achieve a highly increased ionic conductivity (5.2 × 10-4 S cm-1) and lithium ion migration number (0.471) at room temperature. The assembled NCM523|PVDF/(PEO+PVDF)-L SCEs|Li cells thus are able to deliver the initial discharge capacity of 153.9 mAh g-1 with 80.8% capacity retention after 200 cycles at 0.3 C. Such easily manufactured double-layer SCEs capable of operating steadily at room temperature provide a competitive electrolyte option for high-voltage solid-state LMBs.

Comprehensive Analysis of Ferroptosis-Related LncRNAs in Breast Cancer Patients Reveals Prognostic Value and Relationship With Tumor Immune Microenvironment.

Background: Breast cancer (BC) is a heterogeneous malignant tumor, leading to the second major cause of female mortality. This study aimed to establish an in-depth relationship between ferroptosis-related LncRNA (FRlncRNA) and the prognosis as well as immune microenvironment of the patients with BC. Methods: We downloaded and integrated the gene expression data and the clinical information of the patients with BC from The Cancer Genome Atlas (TCGA) database. The co-expression network analysis and univariate Cox regression analysis were performed to screen out the FRlncRNAs related to prognosis. A cluster analysis was adopted to explore the difference of immune microenvironment between the clusters. Furthermore, we determined the optimal survival-related FRLncRNAs for final signature by LASSO Cox regression analysis. Afterward, we constructed and validated the prediction models, which were further tested in different subgroups. Results: A total of 31 FRLncRNAs were filtrated as prognostic biomarkers. Two clusters were determined, and C1 showed better prognosis and higher infiltration level of immune cells, such as B cells naive, plasma cells, T cells CD8, and T cells CD4 memory activated. However, there were no significantly different clinical characters between the clusters. Gene Set Enrichment Analysis (GSEA) revealed that some metabolism-related pathways and immune-associated pathways were exposed. In addition, 12 FRLncRNAs were determined by LASSO analysis and used to construct a prognostic signature. In both the training and testing sets, patients in the high-risk group had a worse survival than the low-risk patients. The area under the curves (AUCs) of receiver operator characteristic (ROC) curves were about 0.700, showing positive prognostic capacity. More notably, through the comprehensive analysis of heatmap, we regarded LINC01871, LINC02384, LIPE-AS1, and HSD11B1-AS1 as protective LncRNAs, while LINC00393, AC121247.2, AC010655.2, LINC01419, PTPRD-AS1, AC099329.2, OTUD6B-AS1, and LINC02266 were classified as risk LncRNAs. At the same time, the patients in the low-risk groups were more likely to be assigned to C1 and had a higher immune score, which were consistent with a better prognosis. Conclusion: Our research indicated that the ferroptosis-related prognostic signature could be used as novel biomarkers for predicting the prognosis of BC. The differences in the immune microenvironment exhibited by BC patients with different risks and clusters suggested that there may be a complementary synergistic effect between ferroptosis and immunotherapy.

Sodium butyrate alleviates cholesterol gallstones by regulating bile acid metabolism.

Cholesterol overloading and bile acid metabolic disorders play an important role in the onset of cholesterol gallstone (CGS). Short-chain fatty acids (SCFAs) can regulate bile acid metabolism by modulating the gut microbiota. However, the role and mechanism by which sodium butyrate (NaB) targets bile acids to attenuate CGS are still unknown. In this study, continuous administration of 12 mg/day for 8 weeks was decreased the incidence of gallstones induced by lithogenic diet (LD) from 100% to 25%. NaB modulated SCFAs and improved the gut microbiota. The remodeling of the gut microbiota changed the bile acid compositions and decreased cecal tauro-α-muricholic acid (T-α-MCA) and tauro-ß-muricholic acid (T-ß-MCA) which are effective farnesoid X receptor (FXR) antagonists. The quantitative real-time PCR examination showed that NaB significantly increased levels of ileal Fxr, fibroblast growth factor-15 (Fgf-15) and small heterodimer partner (Shp) mRNA and subsequently inhibited bile acid synthesis. In addition, NaB enhanced bile acid excretion by increasing the levels of hepatic multidrug resistance protein 2 (Mdr2) and bile salt export pump (Bsep) mRNA, and it enhanced bile acid reabsorption in the intestine by increasing the levels of ileal bile acid transporter (Ibat) mRNA. In addition, NaB reduced the absorption of cholesterol in the intestine and inhibited the excretion of cholesterol in the liver, which reduced the cholesterol concentration in serum and bile. Furthermore, the protective effects of NaB administration were abolished by FXR antagonists. Taken together, our results suggest that NaB mitigates CGS by modulating the gut microbiota to regulate the FXR-FGF-15/SHP signaling pathway.

A Safe Flexible Self-Powered Wristband System by Integrating Defective MnO2-x Nanosheet-Based Zinc-Ion Batteries with Perovskite Solar Cells.

The booming market of portable and wearable electronics has aroused the requests for advanced flexible self-powered energy systems featuring both excellent performance and high safety. Herein, we report a safe, flexible, self-powered wristband system by integrating high-performance zinc-ion batteries (ZIBs) with perovskite solar cells (PSCs). ZIBs were first fabricated on the basis of a defective MnO2-x nanosheet-grown carbon cloth (MnO2-x@CC), which was obtained via the simple lithium treatment of the MnO2 nanosheets to slightly expand the interlayer spacing and generate rich oxygen vacancies. When used as a ZIB cathode, the MnO2-x@CC with a ultrahigh mass loading (up to 25.5 mg cm-2) exhibits a much enhanced specific capacity (3.63 mAh cm-2 at current density of 3.93 mA cm-2), rate performance, and long cycle stability (no obvious degradation after 5000 cycles) than those of the MnO2@CC. Importantly, the MnO2-x@CC-based quasi-solid-state ZIB not only achieves excellent flexibility and an ultrahigh energy density of 5.11 mWh cm-2 (59.42 mWh cm-3) but also presents a high safety under a wide temperature range and various severe conditions. More importantly, the flexible ZIBs can be integrated with flexible PSCs to construct a safe, self-powered wristband, which is able to harvest light energy and power a commercial smart bracelet. This work sheds light on the development of high-performance ZIB cathodes and thus offers a good strategy to construct wearable self-powered energy systems for wearable electronics.

lncRNA FGD5­AS1 promotes breast cancer progression by regulating the hsa­miR­195­5p/NUAK2 axis.

Breast cancer is the second most prevalent cancer in women worldwide. Long non­coding RNAs (lncRNAs) have been identified as important regulators of tumorigenesis and tumor metastasis. lncRNA FGD5­AS1 has been previously reported as a carcinogenic gene, however its role in breast cancer has yet to be investigated. The present study aimed to understand the function of lncRNA FGD5­AS1 in breast cancer and examine the underlying molecular mechanisms. Sample tissues for downstream gene expression profiling were collected from patients with breast cancer (n=23). The effect of FGD5­AS1 overexpression on cell viability, invasion and migration has been studied in breast cancer cells (MDA­MB­231). Changes in glycolysis were monitored by comparing glucose consumption, lactate production and ATP levels. Using StarBase and TargetScan databases a putative interaction between FGD5­AS1, miR­195­5p and SNF1­like kinase 2 (NUAK2) was predicted in silico. Expression levels of FGD5­AS1, has­miR­195­5p and NUAK2 were validated by reverse transcription­quantitative PCR and interactions were validated using dual­luciferase reporter assays and RNA pull­down. High expression of lncRNA FGD5­AS1 was detected in breast cancer tissue samples and disease model cell lines. Silencing of FGD5­AS1 led to decreased cell proliferation, migration and invasion. It was identified that at a molecular level FGD5­AS1 serves as a sponge of miR­195­5p and alters the expression of its downstream target gene NUAK2. In breast cancer lncRNA FGD5­AS1 serve a key role in glycolysis and tumor progression via the miR­195­5p/NUAK2 axis. The findings of the present study indicated FGD5­AS1 as a candidate target for intervention in patients with breast cancer.

Novel High-Sensitivity Racetrack Surface Plasmon Resonance Sensor Modified by Graphene.

In order to overcome the existing challenges presented by conventional sensors, including their large size, a complicated preparation process, and difficulties filling the sensing media, a novel high-sensitivity plasmonic resonator sensor which is composed of two graphene-modified straight waveguides, two metallic layers, and a racetrack nanodisk resonator is proposed in this study. The transmission characteristics, which were calculated by the finite element theory, were used to further analyze the sensing properties. The results of quantitative analysis show that the proposed plasmonic sensor generates two resonance peaks for the different incident wavelengths, and both resonance peaks can be tuned by temperature. In addition, after optimizing the structural parameters of the resonator, the Q value and the refractive sensitivity reached 21.5 and 1666.67 nmRIU⁻1, respectively. Compared with other studies, these values translate to a better performance. Furthermore, a temperature sensitivity of 2.33 nm/5°C was achieved, which allows the sensor to be easily applied to practical detection. The results of this study can broaden the useful range for a nanometer-scale temperature sensor with ultrafast real-time detection and resistance to electromagnetic interference.

Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population.

AIM: To assess disease-specific circulating microRNAs (miRNAs) in non-alcoholic steatohepatitis (NASH) patients. METHODS: A total of 111 biopsy-proven non-alcoholic fatty liver disease (NAFLD) or chronic hepatitis B (CHB) patients and healthy controls from mainland China were enrolled to measure their serum levels of miR-122, -125b, -146b, -16, -21, -192, -27b and -34a. The correlations between serum miRNAs and histological features of NAFLD were determined. The diagnostic value of miRNA in NASH and significant fibrosis was analyzed and compared with that of cytokeratin-18 (CK-18), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI), respectively. RESULTS: Circulating miR-122, -16, -192 and -34a showed differential expression levels between NAFLD and CHB patients, and miR-34a had an approximately 2-fold increase in NAFLD samples compared with that of CHB samples (P < 0.01). Serum miR-122, -192 and -34a levels were correlated with steatosis (R = 0.302, 0.323 and 0.470, respectively, P < 0.05) and inflammatory activity (R = 0.445, 0.447 and 0.517, respectively, P < 0.01); only serum miR-16 levels were associated with fibrosis (R = 0.350, P < 0.05) in patients with NAFLD. The diagnostic value of miR-34a for NASH (area under the receiver operating characteristic, 0.811, 95%CI: 0.670-0.953) was superior to that of alanine aminotransferase, CK-18, FIB-4 and APRI in NAFLD, but miR-16 showed a limited performance in the diagnosis of significant fibrosis in NASH. CONCLUSION: Circulating miR-34a may serve as a disease-specific noninvasive biomarker for the diagnosis of NASH.

Evaluating the Relationship Between Metabolic Syndrome and Liver Biopsy-Proven Non-Alcoholic Steatohepatitis in China: A Multicenter Cross-Sectional Study Design.

INTRODUCTION: Non-alcoholic steatohepatitis (NASH) is a serious form of non-alcoholic fatty liver disease (NAFLD) that can progress to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Differentiating between non-alcoholic fatty liver (NAFL) and NASH/advanced fibrosis is an important step in the management of NAFLD. Metabolic syndrome (MS) and its components are important risk factors for NAFLD, and NASH is thought to be the hepatic injury of MS. The prevalence of NASH among NAFLD patients with MS is thought to be high. In China, NAFLD is a relatively new public health concern, and the current prevalence of NASH among Chinese liver biopsy-proven NAFLD patients with and without MS is not known. METHODS: This multicenter, cross-sectional study will investigate the prevalence of NASH in approximately 480 Chinese NAFLD patients. Patients will be eligible for enrollment if they have biopsy-proven NAFLD and if their liver biopsies are available for rereading. For our analysis, patients will be stratified according to the presence/absence of MS, and the prevalence of NASH in the subgroups will be compared. Other possible tests that could indicate a risk of NASH, including transient elastography, ultrasonography, cytokeratin-18, liver function tests, and others, will be studied in an effort to derive a practical, noninvasive predictive model for NASH. DISCUSSION: Patients with NAFL who have MS may also have a very high risk of developing NASH. The present study will inform about the risk of NASH in Chinese liver biopsy-proven NAFLD patients with and without MS. TRIAL REGISTRATION: This study registered at http://www.chictr.org.cn (registration number: ChiCTR-OOC-16007902). FUNDING: Sanofi (China) Investment Co., Ltd.

Nucleotide oligomerization domain 2 contributes to the innate immune response in THCE cells stimulated by Aspergillus fumigatus conidia.

AIM: To investigate the expression of nucleotide oligomerization domain 2 (NOD2) in the immortalized human corneal epithelial cell line (THCE), and its role in the innate immune response triggered by inactive Aspergillus fumigatus (Af) conidia. METHODS: The normal THCE cells were investigated as controls. After incubation with inactive Af conidia for 0.5, 2, 4, 6, and 8 hours, THCE cells were harvested, mRNA expression of NOD2 and receptor interacting protein 2 (RIP2) was detected by RT-PCR. Intracellular proteins including NOD2, NF-κB and proinflammatory cytokines such as TNF-α, IL-8, IL-6 in the cell supernatant were analyzed by ELISA. RESULTS: Our data indicate that NOD2 expressed in the normal THCE cells. After triggered by the inactive Af conidia, the expression of NOD2, RIP2 mRNA and the secretion of NOD2, NF-κB, TNF-α, IL-8, IL-6 both increased in a time-depended manner, and reached the peak point at 4, 6, 6, 4, 6, 6, 4 hours, respectively. And after pretreated with NOD2 neutralizing antibody, the expression of RIP2, NF-κB, TNF-α, IL-8 both decreased dramatically at the peak point, while the secretion of IL-6 changed little. CONCLUSION: The results of this study suggest that NOD2 exists and expresses in the THCE cells, and contributes to the innate immune responses triggered by inactive Af conidia by induction of proinflammatory cytokines such as TNF-α and IL-8 through the NF-κB pathway.

Impaired iNOS-sGC-cGMP signalling contributes to chronic hypoxic and hypercapnic pulmonary hypertension in rat.

Nitric oxide (NO) is an important vascular modulator in the development of pulmonary hypertension. NO exerts its regulatory effect mainly by activating soluble guanylate cyclase (sGC) to synthesize cyclic guanosine monophosphate (cGMP). Exposure to hypoxia causes pulmonary hypertension. But in lung disease, hypoxia is commonly accompanied by hypercapnia. The aim of this study was to examine the changes of sGC enzyme activity and cGMP content in lung tissue, as well as the expression of inducible nitric oxide synthase (iNOS) and sGC in rat pulmonary artery after exposure to hypoxia and hypercapnia, and assess the role of iNOS-sGC-cGMP signal pathway in the development of hypoxic and hypercapnic pulmonary hypertension. Male Sprague-Dawley rats were exposed to hypoxia and hypercapnia for 4 weeks to establish model of chronic pulmonary hypertension. Weight-matched rats exposed to normoxia served as control. After exposure to hypoxia and hypercapnia, mean pulmonary artery pressure, the ratio of right ventricle/left ventricle+septum, and the ratio of right ventricle/body weight were significantly increased. iNOS mRNA and protein levels were significantly increased, but sGC α(1) mRNA and protein levels were significantly decreased in small pulmonary arteries of hypoxic and hypercapnic exposed rat. In addition, basal and stimulated sGC enzyme activity and cGMP content in lung tissue were significantly lower after exposure to hypoxia and hypercapnia. These results demonstrate that hypoxia and hypercapnia lead to the upregulation of iNOS expression, downregulation of sGC expression and activity, which then contribute to the development of pulmonary hypertension.