Organ-Specific Gene Expression Control Using DNA Origami-Based Nanodevices.

Nanodevices that function in specific organs or cells are one of the ultimate goals of synthetic biology. The recent progress in DNA nanotechnology such as DNA origami has allowed us to construct nanodevices to deliver a payload (e.g., drug) to the tumor. However, delivery to specific organs remains difficult due to the fragility of the DNA nanostructure and the low targeting capability of the DNA nanostructure. Here, we constructed tough DNA origami that allowed us to encapsulate the DNA origami into lipid-based nanoparticles (LNPs) under harsh conditions (low pH), harnessing organ-specific delivery of the gene of interest (GOI). We found that DNA origami-encapsulated LNPs can increase the functionality of payload GOIs (mRNA and siRNA) inside mouse organs through the contribution from different LNP structures revealed by cryogenic electron microscope (Cryo-EM). These data should be the basis for future organ-specific gene expression control using DNA origami nanodevices.

Comprehensive Proteomics Analysis Reveals Dynamic Phenotypes of Tumor-Associated Macrophages and Their Precursor Cells in Tumor Progression.

Tumor-associated macrophages (TAMs) are key regulators in tumor progression, but the precise role of bone marrow-derived monocytes (Mons) as TAM precursors and their dynamic phenotypes regulated by the tumor microenvironment (TME) remain unclear. Here, we developed an optimized microproteomics workflow to analyze low-cell-number mouse myeloid cells. We sorted TAMs and their corresponding Mons (1 × 105 per sample) from individual melanoma mouse models at both the early and late stages. We established the protein expression profiles for these cells by mass spectrometry. Subsequently, we analyzed the dynamics phenotypes of TAMs and identified a characteristic protein expression profile characterized by upregulated cholesterol metabolism and downregulated immune responses during tumor progression. Moreover, we found the downregulation of both STAT5 and PYCARD expression not only in late-stage TAMs but also in late-stage Mons, indicating a loss of the ability to induce inflammatory responses prior to Mons infiltration into TME. Taken together, our study provides valuable insights into the progression-dependent transitions between TAMs and their precursor cells, as well as the cross-organ communications of tumor and bone marrow.

Puerarin mitigated LPS-ATP or HG-primed endothelial cells damage and diabetes-associated cardiovascular disease via ROS-NLRP3 signalling.

The occurrence and development of diabetic vascular diseases are closely linked to inflammation-induced endothelial dysfunction. Puerarin (Pue), the primary component of Pueraria lobata, possesses potent anti-inflammatory properties. However, its vasoprotective role remains elusive. Therefore, we investigated whether Pue can effectively protect against vascular damage induced by diabetes. In the study, Pue ameliorated lipopolysaccharide-adenosine triphosphate (LPS-ATP) or HG-primed cytotoxicity and apoptosis, while inhibited reactive oxygen species (ROS)-mediated NLR family pyrin domain containing 3 (NLRP3) inflammasome in HUVECs, as evidenced by significantly decreased ROS level, NOX4, Caspase-1 activity and expression of NLRP3, GSDMD, cleaved caspase-1, IL-1ß and IL-18. Meanwhile, ROS inducer CoCI2 efficiently weakened the effects of Pue against LPS-ATP-primed pyroptosis. In addition, NLRP3 knockdown notably enhanced Pue's ability to suppress pyroptosis in LPS-ATP-primed HUVECs, whereas overexpression of NLRP3 reversed the inhibitory effects of Pue. Furthermore, Pue inhibited the expression of ROS and NLRP3 inflammasome-associated proteins on the aorta in type 2 diabetes mellitus rats. Our findings indicated that Pue might ameliorate LPS-ATP or HG-primed damage in HUVECs by inactivating the ROS-NLRP3 signalling pathway.

Methyltransferase like-14 suppresses growth and metastasis of non-small-cell lung cancer by decreasing LINC02747.

Multiple epigenetic regulatory mechanisms exert critical roles in tumor development, and understanding the interactions and impact of diverse epigenetic modifications on gene expression in cancer is crucial for the development of precision medicine. We found that methyltransferase-like 14 (METTL14) was significantly downregulated in non-small-cell lung cancer (NSCLC) tissues. Functional experiments demonstrated that overexpression of METTL14 inhibited the proliferation and migration of NSCLC cells both in vivo and in vitro, and the colorimetric m6A quantification assay also showed that knockdown of METTL14 notably reduced global m6A modification levels in NSCLC cells. By using the methylated-RNA immunoprecipitation-qPCR and dual-luciferase reporter assays, we verified that long noncoding RNA LINC02747 was a target of METTL14 and was regulated by METTL14-mediated m6A modification, and silencing LINC02747 inhibited the malignant progression of NSCLC by modulating the PI3K/Akt and CDK4/Cyclin D1 signaling pathway. Further studies revealed that overexpression of METTL14 promoted m6A methylation and accelerated the decay of LINC02747 mRNA via increased recognition of the "GAACU" binding site by YTHDC2. Additionally, histone demethylase lysine-specific histone demethylase 5B (KDM5B) mediated the demethylation of histone H3 lysine 4 tri-methylation (H3K4me3) in the METTL14 promoter region and repressed its transcription. In summary, KDM5B downregulated METTL14 expression at the transcriptional level in a H3K4me3-dependent manner, while METTL14 modulated LINC02747 expression via m6A modification. Our results demonstrate a synergy of multiple mechanisms in regulating the malignant phenotype of NSCLC, revealing the complex regulation involved in the occurrence and development of cancer.

Interpretable artificial intelligence-based app assists inexperienced radiologists in diagnosing biliary atresia from sonographic gallbladder images.

BACKGROUND: A previously trained deep learning-based smartphone app provides an artificial intelligence solution to help diagnose biliary atresia from sonographic gallbladder images, but it might be impractical to launch it in real clinical settings. This study aimed to redevelop a new model using original sonographic images and their derived smartphone photos and then test the new model's performance in assisting radiologists with different experiences to detect biliary atresia in real-world mimic settings. METHODS: A new model was first trained retrospectively using 3659 original sonographic gallbladder images and their derived 51,226 smartphone photos and tested on 11,410 external validation smartphone photos. Afterward, the new model was tested in 333 prospectively collected sonographic gallbladder videos from 207 infants by 14 inexperienced radiologists (9 juniors and 5 seniors) and 4 experienced pediatric radiologists in real-world mimic settings. Diagnostic performance was expressed as the area under the receiver operating characteristic curve (AUC). RESULTS: The new model outperformed the previously published model in diagnosing BA on the external validation set (AUC 0.924 vs 0.908, P = 0.004) with higher consistency (kappa value 0.708 vs 0.609). When tested in real-world mimic settings using 333 sonographic gallbladder videos, the new model performed comparable to experienced pediatric radiologists (average AUC 0.860 vs 0.876) and outperformed junior radiologists (average AUC 0.838 vs 0.773) and senior radiologists (average AUC 0.829 vs 0.749). Furthermore, the new model could aid both junior and senior radiologists to improve their diagnostic performances, with the average AUC increasing from 0.773 to 0.835 for junior radiologists and from 0.749 to 0.805 for senior radiologists. CONCLUSIONS: The interpretable app-based model showed robust and satisfactory performance in diagnosing biliary atresia, and it could aid radiologists with limited experiences to improve their diagnostic performances in real-world mimic settings.

Exploring gut-lung axis crosstalk in SARS-CoV-2 infection: Insights from a hACE2 mouse model.

Based on the forefront of clinical research, there is a growing recognition that the gut microbiota, which plays a pivotal role in shaping both the innate and adaptive immune systems, may significantly contribute to the pathogenesis of coronavirus disease 2019 (COVID-19). Although an association between altered gut microbiota and COVID-19 pathogenesis has been established, the causative mechanisms remain incompletely understood. Additionally, the validation of the precise functional alterations within the gut microbiota relevant to COVID-19 pathogenesis has been limited by a scarcity of suitable animal experimental models. In the present investigation, we employed a newly developed humanized ACE2 knock-in (hACE2-KI) mouse model, capable of recapitulating critical aspects of pulmonary and intestinal infection, to explore the modifications in the gut microbiota following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Examination of fecal samples using 16S rRNA gene profiling unveiled a notable reduction in species richness and conspicuous alterations in microbiota composition at 6 days postinfection (dpi). These alterations were primarily characterized by a decline in beneficial bacterial species and an escalation in certain opportunistic pathogens. Moreover, our analysis entailed a correlation study between the gut microbiota and plasma cytokine concentrations, revealing the potential involvement of the Lachnospiraceae_NK4A136_group and unclassified_f_Lachnospiraceae genera in attenuating hyperinflammatory responses triggered by the infection. Furthermore, integration of gut microbiota data with RNA-seq analysis results suggested that the increased presence of Staphylococcus in fecal samples may signify the potential for bacterial coinfection in lung tissues via gut translocation. In summary, our hACE2-KI mouse model effectively recapitulated the observed alterations in the gut microbiota during SARS-CoV-2 infection. This model presents a valuable tool for elucidating gut microbiota-targeted strategies aimed at mitigating COVID-19.

Demonstration of 4H-silicon carbide on an aluminum nitride integrated photonic platform.

The existing silicon-carbide-on-insulator photonic platform utilizes a thin layer of silicon dioxide under silicon carbide (SiC) to provide optical confinement and mode isolation. Here, we replace the underneath silicon dioxide layer with 1-µm-thick aluminum nitride and demonstrate a 4H-silicon-carbide-on-aluminum-nitride integrated photonic platform for the first time to our knowledge. Efficient grating couplers, low-loss waveguides, and compact microring resonators with intrinsic quality factors up to 210,000 are fabricated. In addition, by undercutting the aluminum nitride layer, the intrinsic quality factor of the silicon carbide microring is improved by nearly one order of magnitude (1.8 million). Finally, an optical pump-probe method is developed to measure the thermal conductivity of the aluminum nitride layer, which is estimated to be over 30 times of that of silicon dioxide.

Drp1-dependent mitochondrial fragmentation mediates photoreceptor abnormalities in type 1 diabetic retina.

Recent studies have highlighted that retinal neurodegeneration precedes microvascular changes in diabetic retinopathy (DR), but the specific mechanisms remain unclear. Given the pivotal role of dysfunctional mitochondria and oxidative stress in early DR, our objective was to observe mitochondria-related alterations in the neural retina of type one diabetic mellitus mice with no evidence of DR (T1DM-NDR). We aimed to identify the key mitochondrial-related proteins contributing to mitochondrial injury. Our study revealed that T1DM-NDR mice exhibited outer retina thinning, including the ellipsoid zone, inner segment, and outer segment. Additionally, there was an impaired amplitude of the b-wave in electroretinogram (ERG) and a disorganized arrangement of the photoreceptor layer. In both the retina of DM mice and high glucose (HG)-treated 661w cells, mitochondria appeared swollen and fragmented, with disrupted cristae, disorganized or shortened branches in the mitochondrial network, and decreased mitochondrial membrane potential. Among the mitochondrial-related proteins, dynamin-related protein 1 (Drp1) was upregulated, and the ratio of phosphorylated Drp1 protein at serine 616 (S616) and serine 637 (S637) sites significantly increased in the retina of DM mice. The administration of Mdivi-1 ameliorated high-glucose-induced dysfunctional mitochondria, thereby protecting T1DM-NDR mice retina from morphological and functional injuries. Our findings suggest that hyperglycemia promotes Drp1-mediated mitochondrial dysfunction, which may be a significant factor in the development of DR. The inhibition of high-glucose-induced mitochondrial fission emerges as a potential and innovative intervention strategy for preventing DR.

Bone morphogenetic protein 4 derived from the cerebrospinal fluid in patients with postherpetic neuralgia induces allodynia via the crosstalk between microglia and astrocyte.

INTRODUCTION: During postherpetic neuralgia (PHN), the cerebral spinal fluid (CSF) possesses the capability to trigger glial activation and inflammation, yet the specific changes in its composition remain unclear. Recent findings from our research indicate elevations of central bone morphogenetic protein 4 (BMP4) during neuropathic pain (NP), serving as an independent modulator of glial cells. Herein, the aim of the present study is to test the CSF-BMP4 expressions and its role in the glial modulation in the process of PHN. METHODS: CSF samples were collected from both PHN patients and non-painful individuals (Control) to assess BMP4 and its antagonist Noggin levels. Besides, intrathecal administration of both CSF types was conducted in normal rats to evaluate the impact on pain behavior, glial activity, and inflammation.; Additionally, both Noggin and STAT3 antagonist-Stattic were employed to treat the PHN-CSF or exogenous BMP4 challenged cultured astrocytes to explore downstream signals. Finally, microglial depletion was performed prior to the PHN-CSF intervention so as to elucidate the microglia-astrocyte crosstalk. RESULTS: BMP4 levels were significantly higher in PHN-CSF compared to Control-CSF (P < 0.001), with a positive correlation with pain duration (P < 0.05, r = 0.502). Comparing with the Control-CSF producing moderate paw withdrawal threshold (PWT) decline and microglial activation, PHN-CSF further exacerbated allodynia and triggered both microglial and astrocytic activation (P < 0.05). Moreover, PHN-CSF rather than Control-CSF evoked microglial proliferation and pro-inflammatory transformation, reinforced iron storage, and activated astrocytes possibly through both SMAD159 and STAT3 signaling, which were all mitigated by the Noggin application (P < 0.05). Next, both Noggin and Stattic effectively attenuated BMP4-induced GFAP and IL-6 upregulation, as well as SMAD159 and STAT3 phosphorylation in the cultured astrocytes (P < 0.05). Finally, microglial depletion diminished PHN-CSF induced astrogliosis, inflammation and endogenous BMP4 expression (P < 0.05). CONCLUSION: Our study highlights the role of CSF-BMP4 elevation in glial activation and allodynia during PHN, suggesting a potential therapeutic avenue for future exploration.

Prevalence of Underreported Nicotine Exposure Among US Nonsmoking Adults: A Comparison of Self-Reported Exposure and Serum Cotinine Levels From NHANES 2013-2020.

INTRODUCTION: Secondhand smoke (SHS) poses a significant health risk. However, individuals who do not smoke may be unaware of their exposure, thereby failing to take protective actions promptly. AIMS AND METHODS: We assessed the prevalence of underreported nicotine exposure in a nationally representative sample of US nonsmoking adults using data from the US National Health and Examination Survey. Individuals with underreported nicotine exposure were defined as those who reported no exposure to all tobacco products (traditional tobacco, nicotine replacements, and e-cigarettes) or SHS, yet had detectable levels of serum cotinine (>0.015 ng/mL). We fitted logistic regression models to determine sociodemographic and chronic condition factors associated with underreported nicotine exposure. RESULTS: Our analysis included 13 503 adults aged 18 years and older. Between 2013 and 2020, the prevalence of self-reported SHS exposure, serum cotinine-assessed nicotine exposure, and underreported nicotine exposure among US nonsmokers were 22.0%, 51.2%, and 34.6%, respectively. Remarkably, 67.6% with detectable serum cotinine reported no SHS exposure. Males, non-Hispanic blacks, individuals of other races (including Asian Americans, Native Americans, and Pacific Islanders), and those without cardiovascular diseases were more likely to underreport nicotine exposure than their counterparts. The median serum cotinine value was higher in respondents who reported SHS exposure (0.107 ng/mL) than in those who reported no exposure (0.035 ng/mL). We estimate that approximately 56 million US residents had underreported nicotine exposure. CONCLUSIONS: Over a third of US nonsmokers underreport their nicotine exposure, underlining the urgent need for comprehensive public awareness campaigns and interventions. Further research into sociodemographic determinants influencing this underreporting is needed. IMPLICATIONS: Understanding the extent of underreported nicotine exposure is crucial for developing effective public health strategies and interventions. It is imperative to bolster public consciousness about the risks associated with SHS. Additionally, surveillance tools should also incorporate measures of exposure to outdoor SHS and e-cigarette vapor to enhance the quality of data monitoring. Findings from this study can guide tobacco control initiatives and inform smoke-free air legislation.

Association of food insecurity with overall and disease-specific mortality among cancer survivors in the US.

PURPOSE: To investigate the association of food insecurity with overall and disease-specific mortality among US cancer survivors. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES 1999-2018) were used to examine the impact of food insecurity on mortality risks among cancer survivors in the US. Study participants aged ≥ 20 years who had a history of cancer and completed the Adult Food Security Survey Module were included. Mortality data [all-cause, cancer, and cardiovascular (CVD) specific] through December 31, 2019 were obtained through linkage to the National Death Index. Using multivariable Cox proportional hazard regression, hazard ratios of mortality based on food security status were estimated. RESULTS: Among 5032 cancer survivors (mean age 62.5 years; 58.0% women; 86.2% non-Hispanic White), 596 (8.8%) reported food insecurity. Overall, 1913 deaths occurred (609 cancer deaths and 420 CVD deaths) during the median follow-up of 6.8 years. After adjusting for age, food insecurity was associated with a higher risk of overall (HR = 1.93; 95% CI = 1.56-2.39), CVD-specific (HR = 1.95; 95% CI = 1.24-3.05), and cancer-specific (HR = 1.70; 95% CI = 1.20-2.42) mortality (P < 0.001). However, after adjusting for socioeconomic characteristics and health-related factors (physical activity, diet quality measured by healthy eating index), the association between food insecurity and overall mortality was no longer statistically significant. CONCLUSIONS: Food insecurity was associated with a greater risk of overall mortality among cancer survivors. Further studies are needed to confirm these findings and evaluate whether the observed association represents a causal phenomenon and, if so, whether the effect is modifiable with food assistance programs.

Valproic acid regulates the miR-155/Jarid2 axis by affecting miR-155 promoter methylation in glioma.

The most frequent primary brain tumor in adults is glioma, yet no effective curative treatments are currently available. Our previous study demonstrated the enhancing effects of JARID2 on glioma sensitivity to TMZ treatment. In this study, miR-155 is predicted to target JARID2. miR-155 is overexpressed in clinical glioma specimens and cell lines. miR-155 overexpression in glioma cells enhances cell viability and represses cell apoptosis. Through targeting, miR-155 inhibits JARID2 expression. miR-155 inhibition inhibits glioma cell viability and enhances cell apoptosis, whereas JARID2 knockdown enhances cell viability and inhibits cell apoptosis; JARID2 knockdown partially reverses miR-155 inhibition effects on glioma phenotypes. miR-155 inhibition reduces but knockdown of JARID2 promotes the tumor formation ability of glioma cells in vivo. Valproic acid (VPA) upregulates JARID2 expression, inhibits glioma cell viability and enhances cell apoptosis. VPA downregulates the expression level of miR-155 by increasing the methylation level of the miR-155 promoter, suggesting that the miR-155/JARID2 axis is implicated in VPA inhibition of glioma cell viability and enhancement of glioma cell apoptosis. This study demonstrates a new mechanism of VPA treatment of gliomas by affecting the miR-155/JARID2 axis, which could be regarded as a new strategy for the prevention and treatment of glioma.

Spatiotemporally resolved subcellular phosphoproteomics.

Proteome-wide profiling of protein phosphorylation has been widely used to reveal the underlying mechanism of diverse cellular signaling events. Yet, characterizing subcellular phosphoproteome with high spatial-temporal resolution has remained challenging. Herein, we developed a subcellular-specific uncaging-assisted biotinylation and mapping of phosphoproteome (SubMAPP) strategy to monitor the phosphorylation dynamics of subcellular proteome in living cells and animals. Our method capitalizes on the genetically encoded bioorthogonal decaging strategy, which enables the rapid activation of subcellular localized proximity labeling biotin ligase through either light illumination or small-molecule triggers. By further adopting an integrated orthogonal pull-down strategy with quantitative mass spectrometry, SubMAPP allowed for the investigation of subcellular phosphoproteome dynamics, revealing the altered phosphorylation patterns of endoplasmic reticulum (ER) luminal proteins under ER stress. Finally, we further expanded the scope of the SubMAPP strategy to primary neuron culture and living mice.

Nucleocytoplasmic trafficking and turnover mechanisms of BRASSINAZOLE RESISTANT1 in Arabidopsis thaliana.

Regulation of the nucleocytoplasmic trafficking of signaling components, especially transcription factors, is a key step of signal transduction in response to extracellular stimuli. In the brassinosteroid (BR) signal transduction pathway, transcription factors from the BRASSINAZOLE RESISTANT1 (BZR1) family are essential in mediating BR-regulated gene expression. The subcellular localization and transcriptional activity of BZR1 are tightly regulated by reversible protein phosphorylation; however, the underlying mechanism is not well understood. Here, we provide evidence that both BZR1 phosphorylation and dephosphorylation occur in the nucleus and that BR-regulated nuclear localization of BZR1 is independent from its interaction with, or dephosphorylation by, protein phosphatase 2A. Using a photoconvertible fluorescent protein, Kaede, as a living tag to distinguish newly synthesized BZR1 from existing BZR1, we demonstrated that BR treatment recruits cytosolic BZR1 to the nucleus, which could explain the fast responses of plants to BR. Additionally, we obtained evidence for two types of protein turnover mechanisms that regulate BZR1 abundance in plant cells: a BR- and 26S proteosome-independent constitutive degradation mechanism and a BR-activated 26S proteosome-dependent proteolytic mechanism. Finally, treating plant cells with inhibitors of 26S proteosome induces the nuclear localization and dephosphorylation of BZR1, even in the absence of BR signaling. Based on these results, we propose a model to explain how BR signaling regulates the nucleocytoplasmic trafficking and reversible phosphorylation of BZR1.

Cerebrospinal Fluid Proteomic Profiles in Patients with Postherpetic Neuralgia.

The intrinsic mechanism of postherpetic neuralgia (PHN) remains unclear. Herein, we aimed to seek the hub proteins in the cerebrospinal fluid (CSF), which display significant changes between the PHN and nonpainful patients (Control). First, the proteomic results showed that compared with the Control-CSF, there were 100 upregulated and 50 downregulated differentially expressed proteins (DEPs) in the PHN-CSF. Besides, functional analyses including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) revealed that biological processes and pathways including complement activation, infection, coagulation, and lipid metabolism were activated, while synaptic organization was suppressed. Next, the protein-protein interaction (PPI) analysis indicated that increased PLG, F2, APOA1, APOA2, SERPINC1, and KNG1 and reduced APOE, which were all enriched in the top pathways according to the KEGG analysis, were defined as hub proteins. Finally, three of the hub proteins, such as PLG, APOA1, and APOE, were reconfirmed in a larger cohort using both enzyme-linked immunosorbent assay (ELISA) and Western blotting methods. Above all, the results indicated that PLG, APOA1, and APOE and their involved processes such as infection, inflammation, cholesterol metabolism, and coagulation shall be potential therapeutic approaches. (The raw mass spectrometry proteome data and search results have been deposited to the iProx-integrated Proteome Resources (http://www.iprox.cn) with the data set identifier IPX0007372000.).

Trends and factors associated with secondhand smoke exposure among US cancer survivors, 2013-2020.

BACKGROUND: Secondhand smoke (SHS) poses a significant public health threat. Cancer survivors are at a greater risk of adverse health outcomes from SHS because of its association with poor prognosis and other downstream clinical events. METHODS: A nationally representative sample of US adults aged 20 years and older was analyzed from the National Health and Nutrition Examination Survey between 2013 and 2020. Data on indoor SHS exposure were reported by 16,778 adults who were not currently smoking (1775 cancer survivors; 15,003 individuals without a cancer history). The weighted prevalence of SHS exposure was estimated and compared across sociodemographic and health-related characteristics. Multivariable logistic regression models were fitted to identify correlates of SHS exposure. RESULTS: Of the 1775 nonsmoking cancer survivors (mean age, 64.9 years; 57.0% female; 84.4% non-Hispanic Whites), 15.8% reported SHS exposure. No significant change in trends of SHS exposure was observed during the study period. The prevalence of SHS exposure was higher in cancer survivors who were younger, racial minorities, and had a household income below 130% of the federal poverty level. After adjustment for multiple correlates, age below 40 years, low income, smoking history, and diagnosis within 2 years were associated with SHS exposure. Cancer survivors were most likely to report that SHS exposure occurred at home or in a car. CONCLUSIONS: The prevalence of SHS exposure among cancer survivors remained steady in the past decade. However, disparities exist in SHS exposure among cancer survivors across sociodemographic characteristics and smoking status. Smoking cessation programs should be promoted among caregivers and families of cancer survivors.

Deletion of BACH1 alleviates ferroptosis and protects against LPS-triggered acute lung injury by activating Nrf2/HO-1 signaling pathway.

Multiple lines of evidences have unraveled the emerging role of ferroptosis in the pathophysiological process of acute lung injury (ALI). In this study, we aimed to decipher the role of BACH1 in the onset and progression of ALI with a focus on ferroptosis and elucidated potential molecular mechanism. We observed that BACH1 expression was drastically elevated in BEAS-2B cells upon exposure to LPS. In the functional aspect, BACH1 deletion exerted an anti-inflammatory property, featured by decreased the secretion of several cytokines including TNF-α, IL-1ß and IL-6 in the face of LPS challenge. What's more important, BACH1 knockout evidently repressed LPS-triggered oxidative stress damage, as evidenced by reduced reactive oxygen species (ROS) production and malondialdehyde (MDA) generation, accompanied with the elevated the activities of superoxide dismutase (SOD), GSH-Px and CAT. Meanwhile, ablation of BACH1 restrained LPS-elicited ferroptosis, as characterized by decreased iron content and PTGS2 expression, accompanied with increased expression of SLC7A11 and GPX4. In terms of mechanism, Nrf2/HO-1 signaling inhibitor effectively abrogated the beneficial effects of BACH1 inhibition on LPS-stimulated inflammation, oxidative damage and ferroptosis. Taken together, these preceding outcomes strongly illuminated that BACH1 was a novel regulator of LPS-evoked injury through regulation of inflammation response, oxidative stress and ferroptosis via activation Nrf2/HO-1 signaling, indicating that BACH1 may represent as a promising novel therapeutic candidate for ALI treatment.

Monocrystalline Labeling Enables Stable Plasmonic Enhancement for Isolation-Free Extracellular Vesicle Analysis.

Sensitive detection of extracellular vesicles (EVs) as emerging biomarkers has shown great promises for disease diagnosis. Plasmonic metal nanostructures conjugated with molecules that bind specific biomarker targets are widely used for EVs sensing but involve tradeoffs between particle-size-dependent signal intensity and conjugation efficiency. One solution to this problem would be to induce nucleation on nanoparticles that have successfully bound a target biomarker to permit in situ nanoparticle growth for signal amplification, but approaches that are evaluated to date require harsh conditions or lack nucleation specificity, prohibiting their effective use with most biological specimens. This study describes a one-step in situ strategy to induce monocrystalline copper shell growth on gold nanorod probes without decreasing signal by disrupting probe-target interactions or lipid bilayer integrity to enable EV biomarker detections. This approach increases the detected nanoparticle signal about two orders of magnitude after a 10 min copper nanoshell growth reaction. This has significant implications for improved disease detection, as indicated by the ability of a novel immunoassay using this approach to detect low abundance EVs carrying a pathogen-derived biomarker, after their direct capture from serum, to facilitate the diagnosis of tuberculosis cases in a diagnostically challenging pediatric cohort.

Microwave photonic radar system with improved SNR performance utilizing optical resonant amplification and random Fourier coefficient waveforms.

A microwave photonic (MWP) radar system with improved signal-to-noise ratio (SNR) performance is proposed and experimentally demonstrated. By improving the SNR of echoes through properly designed radar waveforms and resonant amplification in the optical domain, the proposed radar system can detect and image weak targets that were previously hidden in noise. Echoes with a common low-level SNR obtain high optical gain and the in-band noise is suppressed during resonant amplification. The designed radar waveforms, based on random Fourier coefficients, reduce the effect of optical nonlinearity while providing reconfigurable waveform performance parameters for different scenarios. A series of experiments are developed to verify the feasibility of the SNR improvement of the proposed system. Experimental results show a maximum SNR improvement of 3.6 dB with an optical gain of 28.6 dB for the proposed waveforms over a wide input SNR range. From a comparison with linear frequency modulated signals in microwave imaging of rotating targets, significant quality enhancement is observed. The results confirm the ability of the proposed system to improve SNR performance of MWP radars and its great application potential in SNR-sensitive scenarios.

Investigation of the electro-optic effect in high-Q 4H-SiC microresonators.

Silicon carbide (SiC) recently emerged as a promising photonic and quantum material owing to its unique material properties. In this work, we carried out an exploratory investigation of the Pockels effect in high-quality-factor (high-Q) 4H-SiC microresonators and demonstrated gigahertz-level electro-optic modulation for the first time. The extracted Pockels coefficients show certain variations among 4H-SiC wafers from different manufacturers, with the magnitudes of r 13 and r 33 estimated to be in the range of (0.3-0.7) pm/V and (0-0.03) pm/V, respectively.