Causal relationship between gut microbiota and functional outcomes after ischemic stroke: A comprehensive Mendelian randomization study.

AIMS: To investigate the association of the genetic predisposition of specific gut microbiotas with the clinical outcome of ischemic stroke. METHODS: We leveraged publicly available genome-wide association study (GWAS) data to perform Mendelian randomization (MR) analysis. The gut microbiota-related GWAS data from 18,340 individuals from the international consortium MiBioGen was used. The summary data for functional outcomes after ischemic stroke was obtained from the Genetics of Ischemic Stroke Functional Outcome (GISCOME) network meta-analysis. The primary outcomes were judged by the modified Rankin Scale (mRS). The principal analyses were conducted using the inverse-variance weighted (IVW) MR method. The Cochran's Q test, weighted median, MR-Egger regression, leave-one-SNP-out analysis, MR-Pleiotropy Residual Sum, and Outlier methods were adopted as sensitivity analyses. Furthermore, we performed bi-directional MR analysis and the MR Steiger directionality test to examine the direction of the causal relations. RESULTS: The results demonstrated that the genetic predisposition of genus Lactococcus, genus Ruminococcaceae NK4A214 group, family Peptostreptococcaceae, and genus Odoribacter was positively associated with favorable functional outcome after ischemic stroke. Genus Collinsella, genus Ruminococcaceae UCG005, genus Akkermansia, genus Eubacterium oxidoreducens group, and family Verrucomicrobiaceae were identified to be associated with worse functional outcomes after ischemic stroke. Our results showed no evidence of heterogeneity, directional pleiotropic effects, or collider bias, and the sensitivity of our analysis was acceptable. CONCLUSION: The genetic predisposition of different gut microbiotas was associated with the clinical outcome of ischemic stroke. Microbiota adjustment was a promising method to improve the clinical outcome of ischemic stroke.

Antioxidants and the risk of stroke: results from NHANES and two-sample Mendelian randomization study.

BACKGROUND: Stroke is the second leading cause of death worldwide, and observational studies have suggested a correlation between antioxidants and reduced stroke risk. However, it remains unclear whether causal relationships exist. METHODS: This study first performed a cross-sectional study of the association between the Composite Dietary Antioxidant Index (CDAI) and stroke using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Second, a two-sample univariable Mendelian Randomization (MR) was performed to analyze the causal effect of circulating levels of antioxidants on different subtypes of stroke. RESULTS: The cross-sectional study included a total of 24,892 participants representing more than 200 million US non-institutionalized residents, a multivariable logistic regression model revealed that the risk of stroke decreased by 3.4% for each unit increase in CDAI (P = 0.017), with a non-linear association found, indicating a reduction in stroke risk before an inflection point of 3.078. MR analysis revealed that genetically determined levels of retinol had a suggestive protective effect on subarachnoid hemorrhage (SAH) (OR = 0.348, P = 0.025), and genetically determined levels of selenium had a suggestive protective effect against SAH (OR = 0.826, P = 0.007). However, no causal relationship was found between antioxidants and ischemic stroke or intracranial hemorrhage risk. CONCLUSIONS: Evidence suggests that diet-derived antioxidants may reduce the risk of stroke, as indicated by the protective effects of retinol and selenium against SAH. However, more research is needed to fully understand how antioxidants prevent stroke.

The functions of exosomes targeting astrocytes and astrocyte-derived exosomes targeting other cell types.

Astrocytes are the most abundant glial cells in the central nervous system; they participate in crucial biological processes, maintain brain structure, and regulate nervous system function. Exosomes are cell-derived extracellular vesicles containing various bioactive molecules including proteins, peptides, nucleotides, and lipids secreted from their cellular sources. Increasing evidence shows that exosomes participate in a communication network in the nervous system, in which astrocyte-derived exosomes play important roles. In this review, we have summarized the effects of exosomes targeting astrocytes and the astrocyte-derived exosomes targeting other cell types in the central nervous system. We also discuss the potential research directions of the exosome-based communication network in the nervous system. The exosome-based intercellular communication focused on astrocytes is of great significance to the biological and/or pathological processes in different conditions in the brain. New strategies may be developed for the diagnosis and treatment of neurological disorders by focusing on astrocytes as the central cells and utilizing exosomes as communication mediators.

The relationship between plasma prolactin levels and clinical manifestations with neuromyelitis optica spectrum disorders.

INTRODUCTION: Systemic prolactin levels have been found to increase in 19 patients diagnosed with neuromyelitis optica spectrum disorders (NMOSD). However, the relationship between plasma prolactin levels and clinical manifestations in NMOSD patients remains unclear. METHODS: This cross-sectional study was conducted as part of a Registered Cohort Study of Inflammatory Demyelination Disease (NCT04386018). A total of 95 patients diagnosed with central nervous system demyelinating diseases and 43 healthy controls were recruited between May 2020 and February 2022 at the First Affiliated Hospital of Fujian Medical University. Plasma samples were collected from all participants and analyzed for prolactin levels using electrochemiluminescence immunoassay. The study aimed to investigate the correlation between plasma prolactin levels and clinical features in patients with central nervous system demyelinating diseases. RESULTS: Plasma prolactin levels in NMOSD patients were significantly higher than those in multiple sclerosis/myelin oligodendrocyte glycoprotein antibody-associated diseases patients and controls (p<0.05, respectively), and were found to be correlated with disease activity, sensory abnormalities, thoracic spinal cord lesions, and MR lesion enhancement (p<0.05). A total of 16.28% of NMOSD patients exhibited macroprolactinemia. However, there was no correlation found between macroprolactin levels and disease activity (p>0.05). CONCLUSION: Prolactin may play a role in the pro-inflammatory regulation mechanism of NMOSD.

Genetically determined blood pressure, antihypertensive medications, and risk of intracranial aneurysms and aneurysmal subarachnoid hemorrhage: A Mendelian randomization study.

INTRODUCTION: Observational studies suggest that different classes of antihypertensive drugs may have different effects on the occurrence of intracranial aneurysms (IA) and subarachnoid hemorrhage (SAH). However, the reported results in previous studies are inconsistent, and randomized data are absent. We performed a two-sample Mendelian randomization (MR) analysis to study the causal effects of genetically determined blood pressure (BP) and genetic proxies for antihypertensive drug classes on the risk of IA and SAH. MATERIALS AND METHODS: Genetic instruments and outcome data were obtained from independent genome-wide association studies (GWAS) or published data, which were exclusively restricted to European ancestry. Causal relationships were identified using inverse-variance weighted MR analyses and a series of statistical sensitivity analyses. The FinnGen consortium was used for repeated analysis to verify results obtained from the above GWAS. RESULTS: Two-sample MR analysis showed that genetically determined Systolic BP, Dystolic BP, and Pulse Pressure were related to a higher risk of IA and SAH. Based on identified single nucleotide polymorphisms (SNPs) that influence the effect of calcium channel blockers (CCB, 42 SNPs), beta-blockers (BB, 8 SNPs), angiotensin-converting enzyme inhibitors (ACEI, 2 SNPs), angiotensin receptor blockers (ARB, 1 SNPs), and thiazides (5 SNPs), genetically determined effect of CCBs was associated with a higher risk of IA (OR, 1.07 [95% CI, 1.03-1.10], p = 5.02 × 10-5) and SAH (OR, 1.06 [95% CI, 1.03-1.09], p = 1.84 × 10-3). No associations were found between other antihypertensive drugs and the risk of IA or SAH. The effect of CCBs on SAH was confirmed in FinnGenconsortium samples (OR, 1.04 [95% CI, 1.00-1.08], p = 0.042). DISCUSSION AND CONCLUSION: This MR analysis supports the role of elevated blood pressure in the occurrence of intracranial aneurysms and subarachnoid hemorrhage. However, genetic proxies for calcium channel blockers were associated with an increased risk of intracranial aneurysms and subarachnoid hemorrhage. Further studies are required to confirm these findings and investigate the underlying mechanisms.

Reperfusion status and postoperative blood pressure in acute stroke patients after endovascular treatment.

Background and purpose: An aggressive lowering of blood pressure (BP) could lead to neurological worsening, particularly of the area that has not been reperfused in acute stroke patients with large vessel occlusion (LVO). We sought to investigate the association of reperfusion status and BP course following mechanical thrombectomy (MT) with outcomes in LVO. Materials and methods: Consecutive patients with LVO treated with MT between Jan 2020 to Jun 2021 were enrolled in a retrospective cohort study. Hourly systolic BP (SBP) and diastolic BP (DBP) were recorded for 72 h following MT and maximum SBP and DBP levels were identified. The Extended Thrombolysis in Cerebral Infarction (eTICI) scale was used to assess reperfusion extent. LVO patients were stratified in 2 groups based on reperfusion status: complete reperfusion (eTICI 3) and incomplete reperfusion (eTICI 2b/c). Three-month functional independence was defined as a modified Rankin Scale score of 0-2. Results: A total of 263 acute ischemic stroke patients with LVO were retrospectively evaluated. Complete reperfusion was achieved in 210 patients (79.8%). Post-MT maximum SBP over 160 mmHg was significantly related to worse functional outcome (38.1% vs. 55.7%, p = 0.006), higher likelihood of in-hospital mortality and 3-month mortality (19.0% vs. 6.9%, p = 0.004, 27.4% vs. 14.3%, p = 0.012). No statistical correlation was found between reperfusion status and blood pressure level (p > 0.05). In patients with complete reperfusion, patients with an average BP 120-140 mmHg tends to have worse functional outcome compared with 100-120 mmHg (OR = 1.77, 95%CI: 0.97-3.23, p = 0.061). Conclusion: High maximum SBP levels following MT are associated with an increased likelihood of 3-month functional dependence and mortality. An average BP of 100-120 mmHg tends to have better functional independence in completely reperfused patients. The effect of intensive BP control on incomplete reperfusion still warrants further investigations.

Atomic Layer Deposition of Titanium Oxide-Based Films for Semiconductor Applications-Effects of Precursor and Operating Conditions.

Two widely used atomic layer deposition precursors, Tetrakis (dimethylamido) titanium (TDMA-Ti) and titanium tetrachloride (TiCl4), were investigated for use in the deposition of TiOx-based thin films as a passivating contact material for solar cells. This study revealed that both precursors are suited to similar deposition temperatures (150 °C). Post-deposition annealing plays a major role in optimising the titanium oxide (TiOx) film passivation properties, improving minority carrier lifetime (τeff) by more than 200 µs. Aluminium oxide deposited together with titanium oxide (AlOy/TiOx) reduced the sheet resistance by 40% compared with pure TiOx. It was also revealed that the passivation quality of the (AlOy/TiOx) stack depends on the precursor and ratio of AlOy to TiOx deposition cycles.

Association between blood pressure and different antihypertensive drugs with outcome after ischemic stroke: A Mendelian randomization study.

BACKGROUND: Observational studies suggest an association between blood pressure (BP) and functional outcomes in ischemic stroke patients but whether this is causal or due to confounding is uncertain. We used Mendelian randomization (MR) to assess causality, and also explore whether particular classes of anti-hypertensives were associated with a better outcome after ischemic stroke. METHODS: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drugs from genome-wide association studies (GWAS) on 757,601 individuals. The primary outcome was 3-month dependence or death defined as a modified Rankin Scale (mRS) of 3-6. The secondary outcome was disability or death after 90 days defined as mRS 2-6. Cochran's Q statistic in the inverse variance weighted (IVW) model, the weighted median, MR-Egger regression, leave-one-single-nucleotide polymorphism (SNP)-out analysis, MR-Pleiotropy Residual Sum and Outlier methods were adopted as sensitivity analyses. To validate our primary results, we performed independent repeat analyses and Bi-directional MR analyses. RESULTS: Genetic predisposition to higher systolic and diastolic BP was associated with disability or death after ischemic stroke in univariable IVW MR analysis (odds ratio (OR) 1.29, 95% confidence interval (CI): 1.05-1.59, p = 0.014; OR 1.27, 95% CI: 1.07-1.51, p = 0.006, respectively). Pulse pressure was associated with both dependence or death and disability or death after ischemic stroke (OR = 1.05, 95% CI: 1.02-1.08, p = 0.002; OR = 1.04, 95% CI = 1.01-1.07, p = 0.009, respectively). Angiotensin-converting enzyme inhibitor (ACEI) and calcium channel blocker (CCB) were significantly associated with improved functional outcomes (dependence or death, OR 0.76, 95% CI: 0.62-0.94, p = 0.009; OR 0.89, 95% CI: 0.83-0.97, p = 0.005). Proxies for ß-blockers, angiotensin receptor blockers (ARB), and thiazides failed to show associations with functional outcomes (p > 0.05). CONCLUSION: We provide evidence for an association of genetic predisposition to higher BP with a higher risk of 3-month functional dependence after ischemic stroke. Our findings support ACEI and CCB as promising antihypertensive drugs for improving functional outcomes in ischemic stroke.

Optical Simulation-Aided Design and Engineering of Monolithic Perovskite/Silicon Tandem Solar Cells.

Monolithic perovskite/c-Si tandem solar cells have attracted enormous research attention and have achieved efficiencies above 30%. This work describes the development of monolithic tandem solar cells based on silicon heterojunction (SHJ) bottom- and perovskite top-cells and highlights light management techniques assisted by optical simulation. We first engineered (i)a-Si:H passivating layers for (100)-oriented flat c-Si surfaces and combined them with various (n)a-Si:H, (n)nc-Si:H, and (n)nc-SiOx:H interfacial layers for SHJ bottom-cells. In a symmetrical configuration, a long minority carrier lifetime of 16.9 ms was achieved when combining (i)a-Si:H bilayers with (n)nc-Si:H (extracted at the minority carrier density of 1015 cm-3). The perovskite sub-cell uses a photostable mixed-halide composition and surface passivation strategies to minimize energetic losses at charge-transport interfaces. This allows tandem efficiencies above 23% (a maximum of 24.6%) to be achieved using all three types of (n)-layers. Observations from experimentally prepared devices and optical simulations indicate that both (n)nc-SiOx:H and (n)nc-Si:H are promising for use in high-efficiency tandem solar cells. This is possible due to minimized reflection at the interfaces between the perovskite and SHJ sub-cells by optimized interference effects, demonstrating the applicability of such light management techniques to various tandem structures.

Microglia Exhibit Distinct Heterogeneity Rather than M1/M2 Polarization within the Early Stage of Acute Ischemic Stroke.

The classification of microglial M1/M2 polarization in the acute phase of ischemic stroke remains controversial, which has limited further advances in neuroprotective strategy. To thoroughly assess the microglial phenotypes, we made the middle cerebral artery occlusion model in mice to simulate the acute pathological processes of ischemic stroke from normal conditions to acute cerebral ischemia and then to the early reperfusion period. The temporal changes in gene profiles, cell subtypes, and microglial function were comprehensively analyzed using single-cell RNA sequencing. We identified 37,614 microglial cells and divided them into eight distinct subpopulations. Mic_home, Mic_pre1, and Mic_pre2 subpopulations were three clusters mainly composed of cells from the control samples, in which Mic_home was a homeostatic subpopulation characterized by high expression of Hpgd and Tagap, and Mic_pre1 and Mic_pre2 were two clusters with preliminary inflammatory activation characteristics marked by P2ry13 and Wsb1 respectively. Mic_M1L1 and Mic_M1L2 subpopulations exhibited M1-like polarization manifested by the upregulation of inflammatory genes after ischemic stroke, while the intrinsic heterogeneity on the level of inflammatory responses and neurotrophic support properties was observed. Moreover, we identified three unique clusters of cells with low inflammation levels. Mic_np1, Mic_np2, and Mic_np3 were characterized by high expression of Arhgap45, Rgs10, and Pkm respectively. However, these cells did not show significant M2-like characteristics and their classic microglia function was also attenuated. These subpopulations exhibited higher activation of neuropeptide functional pathways. At last, we performed cell-cell communication analysis and identified major couplings contributing to the interaction between microglia and other cell populations. In summary, our study elucidated the temporal heterogeneity of microglia in the acute phase of ischemic stroke, which may facilitate the identification of effective neuroprotective targets to curb ischemic damage at an early stage.

Efficient surface passivation of germanium nanostructures with 1% reflectance.

Germanium (Ge) is a vital element for applications that operate in near-infrared wavelengths. Recent progress in developing nanostructured Ge surfaces has resulted in >99% absorption in a wide wavelength range (300-1700 nm), promising unprecedented performance for optoelectronic devices. However, excellent optics alone is not enough for most of the devices (e.g. PIN photodiodes and solar cells) but efficient surface passivation is also essential. In this work, we tackle this challenge by applying extensive surface and interface characterization including transmission electron microscopy and x-ray photoelectron spectroscopy, which reveals the limiting factors for surface recombination velocity (SRV) of the nanostructures. With the help of the obtained results, we develop a surface passivation scheme consisting of atomic-layer-deposited aluminum oxide and sequential chemical treatment. We achieve SRV as low as 30 cm s-1combined with ∼1% reflectance all the way from ultraviolet to NIR. Finally, we discuss the impact of the achieved results on the performance of Ge-based optoelectronic applications, such as photodetectors and thermophotovoltaic cells.

Preliminary study of the toxicity and radioprotective effects of zymosan in vitro and in vivo.

BACKGROUND: This study aimed to confirm the cytotoxicity of zymosan in vitro and in vivo and determine the appropriate treatment time and the dose of zymosan. METHODS: AHH-1 cells and HIECs were administered by 0, 20, 40, 80 or 160 µg/mL zymosan. The CCK-8 assay and flow cytometry were used to evaluate the cell viability and apoptosis 24 h, 48 h, and 72 h after administration. Furthermore, 12 h before irradiation, the cells were treated with 0, 5, 10, or 20 µg/mL zymosan and then irradiated with 4 Gy X-rays. Cell viability and apoptosis were measured by the CCK-8 assay and flow cytometry at 24 h. In addition, the protective effect of zymosan against radiation in vitro was compared to that of 20 µg/mL LPS. In vivo, weight, the spleen index, and the thymus index were measured to evaluate the toxicity of 0, 5, 10, 20, and 10 mg/kg zymosan. In addition, rats were treated with 0, 2, 4, 8, or 10 mg/kg zymosan and then irradiated with 7 Gy X-rays. The survival rate, organ index were evaluated. The protective effect of zymosan against radiation in vivo was compared to that of 10 mg/kg LPS a positive control. RESULTS: The viability and apoptosis of cells treated with different doses and treatment times of zymosan were not different from those of control cells (p < 0.05). Furthermore, cell viability and apoptosis were clearly improved after zymosan preadministration (p < 0.05). The radioprotective effect of zymosan was dose-dependent. In addition, the viability of cells pretreated with zymosan was higher than that of cells pretreated with LPS, and the apoptosis rate of zymosan-treated cells was lower than that of cells pretreated with LPS (p < 0.05). In vivo, weight, the spleen index and the thymus index were significantly decreased by zymosan at a concentration of 20 mg/kg (p < 0.05). Further experiments showed that the concentration at which zymosan exerted radioprotective effects was 10 mg/kg. The survival curves in the irradiated rats were barely separated between the LPS treatment and zymosan treatment. CONCLUSION: Zymosan administration before radiation exposure significantly increased cell viability and the survival rates of rats.

Epitranscriptomic 5-Methylcytosine Profile in PM2.5-induced Mouse Pulmonary Fibrosis.

Exposure of airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 µm (PM2.5) is epidemiologically associated with lung dysfunction and respiratory symptoms, including pulmonary fibrosis. However, whether epigenetic mechanisms are involved in PM2.5-induced pulmonary fibrosis is currently poorly understood. Herein, using a PM2.5-induced pulmonary fibrosis mouse model, we found that PM2.5 exposure leads to aberrant mRNA 5-methylcytosine (m5C) gain and loss in fibrotic lung tissues. Moreover, we showed the m5C-mediated regulatory map of gene functions in pulmonary fibrosis after PM2.5 exposure. Several genes act as m5C gain-upregulated factors, probably critical for the development of PM2.5-induced fibrosis in mouse lungs. These genes, including Lcn2, Mmp9, Chi3l1, Adipoq, Atp5j2, Atp5l, Atpif1, Ndufb6, Fgr, Slc11a1, and Tyrobp, are highly related to oxidative stress response, inflammatory responses, and immune system processes. Our study illustrates the first epitranscriptomic RNA m5C profile in PM2.5-induced pulmonary fibrosis and will be valuable in identifying biomarkers for PM2.5 exposure-related lung pathogenesis with translational potential.

CXCL13/CXCR5 are potential biomarkers for diagnosis and prognosis for breast cancer.

PURPOSE: Breast cancer is known as the second frequent cancer in the world, even as the most common cancer among women. This study aimed to explore the correlation of CXCL13/CXCR5 expression with clinical characteristics in breast cancer and evaluate their potential to be used as biomarkers in diagnosis and prognosis of this disease. METHODS: A total of 133 female patients diagnosed with breast cancer were collected. The expression of CXCL13 and CXCR5 mRNA was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining. RESULTS: The expression of CXCL13 and CXCR5 was significantly higher in breast cancer tissue than in normal breast tissues, with a high correlation coefficient of 0.9973. Positive cell numbers and positive expression rates of CXCL13 and CXCR5 in cancer breast tissue were much higher than those in normal breast tissue, and raised with increase of cancer stage. The high expression of CXCL13 and CXCR5 in breast cancer tissue was notably associated with lymph node metastasis, distant metastasis, disease stage, but not with age, Her-2 status, histological type or tumor size. Immunohistochemistry analysis showed that the positive expression of CXCL13 and CXCR5 was related with cancer stage, Also, positive expression of CXCL13 was correlated with positive expression of CXCR5. Patient age, Her-2 status, tumor size, histological type, and lymph node metastasis were independent factors for the 5-year survival rate of breast cancer patients, whereas the 5-year survival was correlated with distant metastasis and expression of CXCL13 and CXCR5. CONCLUSIONS: These results suggested that CXCL13 and CXCR5 expressions could act as potential biomarkers for breast cancer diagnosis and prognosis.

Simulation and observation for volume emission rates emitted from O2(0-1) and O(1S) nightglow in northwest China.

Being susceptible to the change of atmospheric conditions, the volume emission rate (VER) is very suitable to be used as a light source by passive remote sensing for measuring atmospheric wind and temperature. Thus, the VERs emitted from O2(0-1) and O(S1) of the nightglow at 80-120 km are studied in this paper. Based on the Naval Research Laboratory Mass Spectrometer Incoherent Scatter (NRLMSISE-00) model data and the ground-based airglow imaging interferometer (GBAII) instrument observation for a local time and place, simulated VER profiles represented by four layers are obtained for the nightglow of O2(0-1) and O(S1). The O2(0-1) nightglow model peak values at 94 km on 6 December 2013 and 8 November 2011 are 8111 photons·cm-3·s-1 and 8406 photons·cm-3·s-1, respectively; however, the O(S1) VER peak at a higher altitude of about 96 km on 18 December 2011 is only 338 photons·cm-3·s-1. The upper atmospheric VER values have been derived to transfer into the ground-based detected column intensities by our GBAII prototype. The calculated column integrated emission rates (IERs) of O2(0-1) for 0° and 45° zenith angles are 1.48×107 and 1.91×107 photons·cm-2·s-1, respectively; the calculated column IERs of O(S1) are 5.53×105 and 7.03×105 photons·cm-2·s-1, respectively. Correspondingly, the detected column IERs obtained by GBAII are 2.43×107 for O2(0-1) and 6.57×105 photons·cm-2·s-1 for O(S1).

Nrf2 deficiency exacerbates PM2.5-induced olfactory bulb injury.

Recent studies have demonstrated that long-term exposure to fine particulate matter (PM2.5) increases the risk of central nervous (CNS) diseases. As a basic region-leucine zipper (bZip) transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) is essential for protection against chemically induced oxidative stress to restore cellular redox balance. However, the impact of Nrf2 on the neurotoxic effects of PM2.5 remains to understand. In this study, we exposed wild-type (WT) and Nrf2 knockout (Nrf2-/-) mice to 1 mg/kg PM2.5 or deionized water by intranasal instillation for 28 days. After PM2.5 exposure, Nrf2-/- mice exhibited severe nerve injury in olfactory bulb (OB) of mice. In PM2.5-treated OBs, Nrf2 deficiency resulted in lower levels of antioxidant enzymes, greater induction of oxidative stress, microglia activation, inflammation and nuclear factor kappa B (NF-κB) activation compared to the OBs of WT mice. In PM2.5-treated BV2 cells, inhibition of Nrf2 activity significantly decreased cell viability and increased the intracellular reactive oxygen species (ROS) generation and nuclear factor kappa B (NF-κB) phosphorylation. Taken together, our results provide the role Nrf2-reuglated antioxidant and cytoprotective enzymes in protective responses to PM2.5-induced neurotoxicity. Our findings suggest Nrf2-mediated defenses against oxidative stress will help develop new strategies for the prevention and treatment of diseases associated with airborne pollution.

Astilbin ameliorates pulmonary fibrosis via blockade of Hedgehog signaling pathway.

BACKGROUND AND OBJECTIVE: The nature of pulmonary fibrosis involves inadequate repair of the epithelial cell barrier accompanied by impaired regulation of the fibroblast. Moreover, pulmonary fibrosis currently lacks an effective therapeutic drug. This study targets the protection of the epithelial cell and fibroblast to identify a novel, potentially therapeutic drug (i.e., astilbin). METHODS: In this study, the cytotoxicity of astilbin was firstly detected using CCK-8. A real-time proliferation/migration analysis system was used to test the inhibitory proliferation and migration of astilbin in vitro. The expression of mesenchymal markers and the loss of epithelial cell markers were analyzed to evaluate the antifibrotic activity of astilbin on TGF-ß1-treated AEC-II and L929 cells and bleomycin-treated mice. Then, in fibrosis-associated signaling pathways, the regulation of astilbin was tested using RNA sequencing and Cignal Finder 45-Pathway system. Rescue and other experiments were used to confirm this pathway regulation further. RESULTS: The data showed that astilbin inhibited proliferation and migration of cell samples. Its treatment resulted in the reduction of pathological score and collagen deposition, with a decrease in α-SMA and Snail and an increase in E-cadherin and SP-C in vivo and in vitro. The fibrosis-associated aberrant genes are some of the most notable components of the Hedgehog signaling pathway. CONCLUSIONS: Astilbin ameliorates pulmonary fibrosis via blockade of Hedgehog signaling pathway and has potential therapeutic value for lung fibrosis treatment.

Controllable switch of a transmittance signal via polarization combination manipulation.

We propose and experimentally demonstrate a process in which we can control the behavior of an atomic medium to switch on or off transmittance signals at multiple frequencies in ladder-type electromagnetically induced transparency (EIT) of 5S1/2-5P3/2-5D3/2 transition of Rb87 atoms. By adjusting the polarizations of the applied optical fields, the amplitudes of the transmittance spectra at multiple frequency channels can be controlled. This mechanism originates from the competition between EIT subsystems and single-photon absorption with a contribution from different transition strengths. Moreover, we also analyze the influences of the intensity and detuning of the coupling field on the transmitted signals when two lasers are perpendicular, linearly polarized lights, and observe electromagnetically induced absorption due to quantum constructive interference. Detailed theoretical analyses, including the different strengths in different transitions and Doppler broadening, agree with the experimental observations.