Biodegradable and Efficient Charge-Migrated Z-Scheme Heterojunction Amplifies Cancer Ferroptosis by Blocking Defensive Redox System.

Ferroptosis is an emerging non-apoptotic death process, mainly involving lipid peroxidation (LPO) caused by iron accumulation, which is potentially lethal to the intrinsically apoptotic-resistant malignant tumor. However, it is still restricted by the inherent antioxidant systems of tumor cells and the poor efficacy of traditional iron-based ferroptosis initiators. Herein, the study develops a novel ferroptosis-inducing agent based on PEGylated Cu+/Cu2+-doped black phosphorus@polypyrrole heterojunction (BP@CPP), which is constructed by utilizing the phosphate on the surface of BP to chelate Cu ions and initiating subsequent in situ polymerization of pyrrole. As a novel Z-scheme heterojunction, BP@CPP possesses an excellent photocatalytic activity in which the separated electron-hole pairs under laser irradiation endow it with powerful oxidizing and reducing capacities, which synergy with Cu+/Cu2+ self-cycling catalyzing Fenton-like reaction to further strengthen reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, and glutathione peroxidase 4 (GPX4) inactivation, ultimately leading to efficient ferroptosis. Systematic in vitro and in vivo evaluations demonstrate that BP@CPP effectively inhibit tumor growth by inducing desired ferroptosis while maintaining a favorable biosafety in the body. Therefore, the developed BP@CPP-based ferroptosis initiator provides a promising strategy for ferroptosis-like cancer therapy.

Three-stage Dynamic Brain-cognitive Model of Understanding Action Intention Displayed by Human Body Movements.

The ability to comprehend the intention conveyed through human body movements is crucial for effective interpersonal interactions. If people can't understand the intention behind other individuals' isolated or interactive actions, their actions will become meaningless. Psychologists have investigated the cognitive processes and neural representations involved in understanding action intention, yet a cohesive theoretical explanation remains elusive. Hence, we mainly review existing literature related to neural correlates of action intention, and primarily propose a putative Three-stage Dynamic Brain-cognitive Model of understanding action intention, which involves body perception, action identification and intention understanding. Specifically, at the first stage, body parts/shapes are processed by those brain regions such as extrastriate and fusiform body areas; During the second stage, differentiating observed actions relies on configuring relationships between body parts, facilitated by the activation of the Mirror Neuron System; The last stage involves identifying various intention categories, utilizing the Mentalizing System for recruitment, and different activation patterns concerning the nature of the intentions participants dealing with. Finally, we delves into the clinical practice, like intervention training based on a theoretical model for individuals with autism spectrum disorders who encounter difficulties in interpersonal communication.

Environmental BaP/BPDE suppressed trophoblast cell invasion/migration and induced miscarriage by down-regulating lnc-HZ01/MEST/VIM axis.

Environmental benzo(a)pyrene (BaP) and itsmetabolite benzo(a)pyrene-7, 8-dihydrodiol-9, 10-epoxide (BPDE), classic endocrine disrupting chemical and persistent organic pollutant, could cause miscarriage. However, the detailed mechanisms are still largely unclear and should be further explored. In this study, we discovered that exposure of trophoblast cells with BPDE could suppressed cell invasion/migration by inhibiting MEST/VIM (Vimentin) pathway. Moreover, BPDE exposure also increased lnc-HZ01 expression level, which further inhibited MEST/VIM pathway and then suppressed invasion/migration. Knockdown of lnc-HZ01 or overexpression of MEST could efficiently rescue invasion/migration of BPDE-exposed Swan 71 cells. Furthermore, lnc-HZ01 was highly expressed and MEST/VIM were lowly expressed in recurrent miscarriage (RM) villous tissues compared with healthy control (HC) group. Finally, we also found that BaP exposure inhibited murine Mest/Vim pathway in placental tissues and induced miscarriage in BaP-exposed mice. Therefore, the regulatory mechanisms were similar in BPDE-exposed human trophoblast cells, RM villous tissues, and placental tissues of BaP-exposed mice with miscarriage, building a bridge to connect BaP/BPDE exposure, invasion/migration, and miscarriage. This study provided novel insights in the toxicological effects and molecular mechanisms of BaP/BPDE-induced miscarriage, which is helpful for better elucidating the toxicological risks of BaP/BPDE on female reproduction.

In Situ Separable Nanovaccines with Stealthy Bioadhesive Capability for Durable Cancer Immunotherapy.

Because of tumor heterogeneity and the immunosuppressive tumor microenvironment, most cancer vaccines typically do not elicit robust antitumor immunological responses in clinical trials. In this paper, we report findings about a bioadhesive nanoparticle (BNP)-based separable cancer vaccine, FeSHK@B-ovalbumin (OVA), to target multi-epitope antigens and exert effective cancer immunotherapy. After the FeSHK@B-OVA "nanorocket" initiates the "satellite-rocket separation" procedure in the acidic tumor microenvironment, the FeSHK@B "launch vehicle" can amplify intracellular oxidative stress persistently. This procedure allows for bioadhesiveness-mediated prolonged drug retention within the tumor tissue and triggers the immunogenic death of tumor cells that transforms the primary tumors into antigen depots, which acts synergistically with the OVA "satellite" to trigger robust antigen-specific antitumor immunity. The cooperation of these two immunostimulants not only efficiently inhibits the primary tumor growth and provokes durable antigen-specific immune activation in vivo but also activates a long-term and robust immune memory effect to resist tumor rechallenge and metastasis. These results highlight the enormous potential of FeSHK@B-OVA to serve as an excellent therapeutic and prophylactic cancer nanovaccine. By leveraging the antigen depots in situ and the synergistic effect among multi-epitope antigens, such a nanovaccine strategy with stealthy bioadhesion may offer a straightforward and efficient approach to developing various cancer vaccines for different types of tumors.

Radiometric cross-calibration of Sentinel-2B MSI with HY-1C SCS based on the near simultaneous imaging of common ground targets.

To simplify the cross-calibration process and improve calibration frequency and accuracy, this paper proposes a cross-calibration method for the multispectral remote sensor Multi-Spectral Instrument (MSI) carried by Sentinel-2B using the hyperspectral remote sensor, that is, the satellite calibration spectrometer (SCS) carried by Hai Yang (HY)-1C, as the reference sensor and establishes the calibration process. Precise spectral response matching between SCS and MSI spectral channels is performed by the interpolation and iteration of hyperspectral data to eliminate the difference in band settings and significantly improve the accuracy of cross-calibration coefficients. The SNO-x inherited from the simultaneous nadir overpass (SNO) method is used as a prediction method to carry out cross-calibration imaging in mid- and low-latitude regions, which improves the cross-calibration frequency and broadens the dynamic range of calibration. The cross-calibration coefficients and offsets of MSI B1∼B7 and B8a were obtained by processing the earth observation images of the MSI and SCS on January 24, 2019. Then, the cross-calibration coefficients and offsets are applied to the ocean, farmland and other ground objects with different reflectance, and the reliability and accuracy of the cross-calibration results are evaluated with the Moderate-resolution Imaging Spectroradiometer (MODIS) carried by Terra as a reference. To improve the accuracy of the evaluation, the spectral band adjustment factor between the corresponding channels of MSI and MODIS is used to correct the measured reflectance of MODIS based on the satellite calibration coefficient. The reflectance directly obtained by processing the MSI image is used as the MSI-measured reflectance, the reflectance obtained based on the cross-calibration coefficient is used as the MSI-calculated reflectance, and the reflectance corrected by the spectral band adjustment factor (SBAF) is used as the MODIS-calculated reflectance. The results show that the mean root-mean-square relative error (RMSRE) between the MODIS-calculated reflectance and the MSI-calculated reflectance is 2.16% and that the mean RMSRE between the MODIS-calculated reflectance and the MSI-measured reflectance is 3.05%, indicating that the reflectance corrected based on calibration coefficients is closer to the MODIS-calculated reflectance. Finally, each uncertainty source in the cross-calibration is analyzed, and the comprehensive uncertainty is found to be 4.03%, indicating that SCS can be used as a reference for MSI cross-calibration.

Learning-based adaptive under-sampling for Fourier single-pixel imaging.

In this Letter, we present a learning-based method for efficient Fourier single-pixel imaging (FSI). Based on the auto-encoder, the proposed adaptive under-sampling technique (AuSamNet) manages to optimize a sampling mask and a deep neural network at the same time to achieve both under-sampling of the object image's Fourier spectrum and high-quality reconstruction from the under-sampled measurements. It is thus helpful in determining the best encoding and decoding scheme for FSI. Simulation and experiments demonstrate that AuSamNet can reconstruct high-quality natural color images even when the sampling ratio is as low as 7.5%. The proposed adaptive under-sampling strategy can be used for other computational imaging modalities, such as tomography and ptychography. We have released our source code.

Curcumin Attenuates Periodontal Injury via Inhibiting Ferroptosis of Ligature-Induced Periodontitis in Mice.

Periodontitis is a chronic infectious disease characterized by the destruction of connective tissue and alveolar bone that eventually leads to tooth loss. Ferroptosis is an iron-dependent regulated cell death and is involved in ligature-induced periodontitis in vivo. Studies have demonstrated that curcumin has a potential therapeutic effect on periodontitis, but the mechanism is still unclear. The purpose of this study was to investigate the protective effects of curcumin on alleviating ferroptosis in periodontitis. Ligature-induced periodontal-diseased mice were used to detect the protective effect of curcumin. The level of superoxide dismutase (SOD), malondialdehyde (MDA) and total glutathione (GSH) in gingiva and alveolar bone were assayed. Furthermore, the mRNA expression levels of acsl4, slc7a11, gpx4 and tfr1 were measured using qPCR and the protein expression of ACSL4, SLC7A11, GPX4 and TfR1 were investigated by Western blot and immunocytochemistry (IHC). Curcumin reduced the level of MDA and increased the level of GSH. Additionally, curcumin was proven to significantly increase the expression levels of SLC7A11 and GPX4 and inhibit the expression of ACSL4 and TfR1. In conclusion, curcumin plays a protective role by inhibiting ferroptosis in ligature-induced periodontal-diseased mice.

Onboard spectral calibration and validation of the satellite calibration spectrometer on HY-1C.

To monitor the spectral position drift, expansion and contraction of the full width at half maximum (FWHM) of the satellite calibration spectrometer (SCS) of the HY-1C satellite during on-orbit operation, an onboard spectral calibration method based on a wavelength diffuser is proposed in this paper. This method uses the wavelength diffuser reflectance measured prelaunch as the standard spectrum, convolves it with the spectral response function of the SCS to obtain a reference spectrum, uses the measured data of the onboard SCS as the measured spectrum, and obtains the spectral drift and variation of the FWHM through spectral line matching. Generally, the spectral response function of a hyperspectral remote sensor follows a Gaussian model, and so does that of the SCS. The spectral calibration results obtained based on the onboard wavelength diffuser are validated and evaluated in comparison to calibration based on an oxygen absorption line. Preliminary results show that (1) the SCS spectral drift is negative, indicating a shift in the shortwave direction, and its absolute value is gradually decreasing with increasing on-orbit operation time; (2) the mean values of the central wavelength and FWHM errors between the two calibration methods are 0.08 nm and 0.20 nm, respectively, indicating that the spectral calibration method based on the wavelength diffuser has high accuracy and reliability; and (3) the SCS spaceborne spectral calibration error has the greatest impact on radiometric calibration in Band 18, with an uncertainty of 0.99%, while the uncertainty in the other bands is less than 0.33%, indicating that the spectral calibration uncertainty meets radiometric calibration accuracy requirements.

Novel lncRNA-HZ04 promotes BPDE-induced human trophoblast cell apoptosis and miscarriage by upregulating IP3 R1 /CaMKII/SGCB pathway by competitively binding with miR-hz04.

Normal pregnancy is essential for human reproduction. However, BaP (benzo(a)pyrene) and its metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) could cause dysfunctions of human trophoblast cells and might further induce miscarriage. Yet, the underlying mechanisms remain largely unknown. Herein, we identified a novel upregulated lnc-HZ04 and a novel downregulated miR-hz04 in villous tissues of unexplained recurrent miscarriage (RM) relative to those in healthy control tissues and also in BPDE-treated human trophoblast cells. Lnc-HZ04 directly and specifically bound with miR-hz04, diminished the reduction effects of miR-hz04 on IP3 R1 mRNA expression level and on IP3 R1 mRNA stability, and then activated the Ca2+ -mediated IP3 R1 /p-CaMKII/SGCB pathway, which further promoted trophoblast cell apoptosis. The miR-hz04 target site on lnc-HZ04 played crucial roles in these regulations. In normal trophoblast, relatively less lnc-HZ04 and more miR-hz04 suppressed this apoptosis pathway and gave normal pregnancy. After exposure to BPDE or in RM tissues, p53 was upregulated, which might promote p53-mediated lnc-HZ04 transcription. Relatively more lnc-HZ04 and less miR-hz04 activated this apoptosis pathway and might further induce miscarriage. BaP could also induce mice miscarriage by upregulating its corresponding murine apoptosis pathway. Therefore, BPDE-induced apoptosis of human trophoblast cells was associated with the occurrence of miscarriage. This work discovered the regulation roles of lnc-HZ04 and miR-hz04 and provided scientific and clinical understanding of the occurrence of unexplained miscarriage.

Regulatory roles of extracellular vesicles in adverse pregnancy outcomes exposed with environmental toxicants.

Extracellular vesicles (EVs) derived from parental cells could communicate with neighboring or distant recipient cells. The components in EVs, especially non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, could regulate the functions of the recipient cells. Meanwhile, EVs could also be used as valuable biomarkers and drug delivery carriers. Moreover, environmental toxicants may alter EVs components and regulate EVs-mediated pathogenesis of various diseases. In this review, we mainly summarized the roles of EV-derived non-coding RNAs in the regulation of cell dysfunctions in various adverse pregnancy outcomes, such as preeclampsia (PE), gestational diabetes mellitus (GDM), and miscarriage. Moreover, the effects of environmental toxicants on the components and functions of EVs, as well as on their regulatory roles in these diseases, were also discussed.

Lnc-HZ05 regulates BPDE-inhibited human trophoblast cell proliferation and affects the occurrence of miscarriage by directly binding with miR-hz05.

Approximately 15-25% pregnant women end with miscarriage in the world. Environmental BaP (benzo(a)pyrene) and its terminal metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) may result in the dysfunctions of trophoblast cells, which might further lead to RM (recurrent miscarriage). However, potential mechanisms remain unelucidated. In this work, we identified a novel lnc-HZ05 highly expressed and a novel miR-hz05 lowly expressed in both trophoblast cells exposed to BPDE and human RM tissues. MiR-hz05 reduces FOXO3a mRNA level by weakening its mRNA stability. Lnc-HZ05 increases the expression of FOXO3a by acting as a ceRNA for miR-hz05, and then increases P21 level and reduces CDK2 level. Thus, cell cycle is arrested at G0/G1 phase and trophoblast proliferation is inhibited. Lnc-HZ05 harboring wild-type binding site for miR-hz05, but not its mutant site, could upregulate FOXO3a expression. In normal trophoblast cells, relatively less lnc-HZ05 and more miR-hz05 activate FOXO3a/P21/CDK2 pathway and promote trophoblast proliferation, giving normal pregnancy. In RM tissues and BPDE-treated human trophoblast cells, lnc-HZ05 is increased and miR-hz05 is reduced, both of which suppress this pathway and inhibit cell proliferation, and finally lead to miscarriage. Thus, lnc-HZ05 and miR-hz05 simultaneously regulate cell cycle and proliferation of BPDE-exposed trophoblast cells and miscarriage, providing new perspectives and clinical understandings in the occurrence of unexplained miscarriage.

Lnc-HZ08 regulates BPDE-induced trophoblast cell dysfunctions by promoting PI3K ubiquitin degradation and is associated with miscarriage.

Increasing evidences have shown that pregnant women might miscarry after exposure with environmental BaP (benzo(a)pyrene). Additionally, BPDE (benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide), the ultimate metabolite of BaP, could induce dysfunctions of human trophoblast cells. However, it is rarely correlated between miscarriage and trophoblast dysfunctions. Moreover, their underlying mechanisms are still largely unidentified. In this study, a novel lncRNA (long non-coding RNA), lnc-HZ08, was identified to be highly expressed in human recurrent miscarriage (RM) tissues and in BPDE-treated human trophoblast cells. Lnc-HZ08 acts as a RNA scaffold to interact with both PI3K and its ubiquitin ligase CBL (Cbl proto-oncogene), enhances their protein interactions, and promotes PI3K ubiquitin degradation. In RM tissues and BPDE-treated trophoblast cells, DNA methylation level in lnc-HZ08 promoter region was reduced, which promotes estrogen receptor 1 (ER)-mediated lnc-HZ08 transcription. Subsequently, this upregulated lnc-HZ08 downregulated PI3K level, suppressed PI3K/p-AKT/p-P21/CDK2 pathway, and thus weakened proliferation, migration, and invasion of human trophoblast cells, which further induces miscarriage. These results may provide novel scientific and clinical insights in the occurrence of unexplained miscarriage. A novel lncRNA (lnc-HZ08) regulates the functions of human trophoblast cells and affects miscarriage. Lnc-HZ08 promotes PI3K ubiquitin degradation by enhancing CBL and PI3K interactions, downregulates PI3K/p-AKT/p-P21/CDK2 pathway, and weakens proliferation, migration, and invasion of trophoblast cells. BPDE exposure reduces the DNA methylation level in lnc-HZ08 promoter region and promotes estrogen receptor 1 (ER)-mediated lnc-HZ08 transcription. The suppressed PI3K/p-AKT/p-P21/CDK2 pathway regulated by increased lnc-HZ08 is associated with miscarriage. These results provide novel insights in the occurrence of unexplained miscarriage. Graphical Headlights • Lnc-HZ08 downregulates PI3K/p-AKT/p-P21/CDK2 pathway to suppress proliferation, migration, and invasion of human trophoblast cells, and affects miscarriage. • Lnc-HZ08 acts as a RNA scaffold to enhance the protein interaction of PI3K and its ubiquitin ligase CBL, which increases PI3K ubiquitination and degradation. • Lnc-HZ08 transcription is associated with DNA methylation on its promoter region and transcription factor ER.

Environmental BPDE induced human trophoblast cell apoptosis by up-regulating lnc-HZ01/p53 positive feedback loop.

Human trophoblast cell apoptosis may induce miscarriage. Trophoblast cells are sensitive to environmental BaP-7,8-dihydrodiol-9,10-epoxide (BPDE). However, how BPDE induces human trophoblast cell apoptosis is still largely elusive. In this work, we used BPDE-treated human trophoblast cells and villous tissues collected from recurrent miscarriage and health control groups to explore the underlying mechanism of BPDE-induced human trophoblast cell apoptosis. Continued with our recent work, we found that lncRNA HZ01 (lnc-HZ01) could induce human trophoblast cell apoptosis. In mechanism, lnc-HZ01 up-regulated p53 expression level by suppressing its MDM2-mediated proteasomal degradation. Meanwhile, we found that p53 acted as lnc-HZ01 transcription factor and promoted lnc-HZ01 transcription. Thus, lnc-HZ01 and p53 composed a positive feedback loop in human trophoblast cells. In normal trophoblast cells, relatively low levels of lnc-HZ01 and p53 suppressed p53/caspase-3 apoptosis pathway, giving normal pregnancy. Upon BPDE exposure, BPDE up-regulated the expression levels of lnc-HZ01 and p53, triggered this positive feedback loop, activated the p53/caspase-3 apoptosis pathway, and then induced miscarriage. Collectively, we discovered new mechanism by which lnc-HZ01 regulated BPDE-induced human trophoblast cell apoptosis, providing scientific basis for the diagnosis and treatment of unexplained recurrent miscarriage.

Research on a Partial Aperture Factor Measurement Method for the AGRI Onboard Calibration Assembly.

A partial aperture onboard calibration method can solve the onboard calibration problems of some large aperture remote sensors, which is of great significance for the development trend of increasingly large apertures in optical remote sensors. In this paper, the solar diffuser reflectance degradation monitor (SDRDM) in the onboard calibration assembly (CA) of the FengYun-4 (FY-4) advanced geostationary radiance imager (AGRI) was used as the reference radiometer. It was designed for measuring the partial aperture factor (PAF) for the AGRI onboard calibration. First, the linear response count variation relationship between the two was established under the same radiance source input. Then, according to the known bidirectional reflection distribution function (BRDF) of the solar diffuser (SD) in the CA, the relative reflectance ratio coefficient between the AGRI observation direction and the SDRDM observation direction was calculated. On this basis, the response count value of the AGRI and the SDRDM was used to realize the high-precision measurement of the PAF of the AGRI B1~B3 bands by simulating the AGRI onboard calibration measurement under the illumination of a solar simulator in the laboratory. According to the determination process of the relevant parameters of the PAF, the measurement uncertainty of the PAF was analyzed; this uncertainty was greater than 2.04% and provided an important reference for the evaluation of the onboard absolute radiometric calibration uncertainty after launch.

Mitochondrial Metabolic Reprogramming by CD36 Signaling Drives Macrophage Inflammatory Responses.

RATIONALE: A hallmark of chronic inflammatory disorders is persistence of proinflammatory macrophages in diseased tissues. In atherosclerosis, this is associated with dyslipidemia and oxidative stress, but mechanisms linking these phenomena to macrophage activation remain incompletely understood. OBJECTIVE: To investigate mechanisms linking dyslipidemia, oxidative stress, and macrophage activation through modulation of immunometabolism and to explore therapeutic potential targeting specific metabolic pathways. METHODS AND RESULTS: Using a combination of biochemical, immunologic, and ex vivo cell metabolic studies, we report that CD36 mediates a mitochondrial metabolic switch from oxidative phosphorylation to superoxide production in response to its ligand, oxidized LDL (low-density lipoprotein). Mitochondrial-specific inhibition of superoxide inhibited oxidized LDL-induced NF-κB (nuclear factor-κB) activation and inflammatory cytokine generation. RNA sequencing, flow cytometry, 3H-labeled palmitic acid uptake, lipidomic analysis, confocal and electron microscopy imaging, and functional energetics revealed that oxidized LDL upregulated effectors of long-chain fatty acid uptake and mitochondrial import, while downregulating fatty acid oxidation and inhibiting ATP5A (ATP synthase F1 subunit alpha)-an electron transport chain component. The combined effect is long-chain fatty acid accumulation, alteration of mitochondrial structure and function, repurposing of the electron transport chain to superoxide production, and NF-κB activation. Apoe null mice challenged with high-fat diet showed similar metabolic changes in circulating Ly6C+ monocytes and peritoneal macrophages, along with increased CD36 expression. Moreover, mitochondrial reactive oxygen species were positively correlated with CD36 expression in aortic lesional macrophages. CONCLUSIONS: These findings reveal that oxidized LDL/CD36 signaling in macrophages links dysregulated fatty acid metabolism to oxidative stress from the mitochondria, which drives chronic inflammation. Thus, targeting to CD36 and its downstream effectors may serve as potential new strategies against chronic inflammatory diseases such as atherosclerosis.

Novel lnc-HZ03 and miR-hz03 promote BPDE-induced human trophoblastic cell apoptosis and induce miscarriage by upregulating p53/SAT1 pathway.

Normal pregnancy is essential for human reproduction. However, environmental BaP (benzo(a)pyrene) and its metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) induce dysfunctions of human trophoblastic cells, which could further result in miscarriage. Yet, the molecular mechanisms remain poorly understood. In this work, a novel lnc-HZ03 and a novel miR-hz03 were identified. Both lnc-HZ03 and miR-hz03 were highly expressed in human recurrent miscarriage villous tissues and in BPDE-exposed trophoblastic cells. Lnc-HZ03 and miR-hz03 upregulated each other, forming a positive feedback loop. MiR-hz03 could also upregulate p53 level by enhancing its mRNA stability. Both lnc-HZ03 and p53 mRNA contained the target site for miR-hz03 and could directly interact with miR-hz03. It was this target site instead of its mutant on lnc-HZ03 that regulated p53 expression. Subsequently, the upregulated p53 facilitated SAT1 transcription and enhanced SAT1-catalyzed spermine metabolism, which further resulted in trophoblastic cell apoptosis and induced miscarriage. All together, the p53/SAT1 pathway upregulated by lnc-HZ03 and miR-hz03 could promote BPDE-induced human trophoblastic cell apoptosis and the occurrence of miscarriage, shedding novel light on the causes of miscarriage. Graphical abstract Lnc-HZ03 and miR-hz03 regulate the occurrence of recurrent miscarriage (RM). In human trophoblastic cells, lnc-HZ03 upregulates miR-hz03 level. MiR-hz03 increases the RNA stability of lnc-HZ03 and p53 mRNA. P53 promotes SAT1 transcription and reduces its cellular spermine content, resulting in cell apoptosis. Under normal conditions, lnc-HZ03/miR-hz03 and p53/SAT1 pathways are downregulated, maintaining normal pregnancy. After exposure to BPDE, lnc-HZ03/miR-hz03 and p53/SAT1 pathways are upregulated and finally induce miscarriage.

Onboard absolute radiometric calibration and validation of the satellite calibration spectrometer on HY-1C.

As the reference radiometric calibration standard of sensors on the Haiyang-1C (HY-1C) satellite platform, the satellite calibration spectrometer (SCS) is equipped with an onboard calibration system composed of double solar diffusers and an erbium-doped diffuser to monitor the postlaunch radiometric response change. Herein, through onboard calibration data analysis, the calibration diffuser performance remains stable without degradation, and the Moderate Resolution Imaging Spectroradiometer (MODIS) on Terra is adopted as a reference to repeatedly verify onboard radiometric calibration results by selecting different dates and reflectance scenes. The SCS equivalent reflectance is obtained by combining the mean digital number (DN) of the SCS crossing area image with the radiometric calibration coefficient. The spectral reflectance is obtained via interpolation and iteration, which is adopted as the actual MODIS incident pupil spectral reflectance because the small imaging time interval can be ignored and almost vertically observed, and it is convoluted with the MODIS spectral response function to obtain the predicted equivalent reflectance. Validation is completed by comparing the predicted MODIS equivalent reflectance to the measured value based on the onboard calibration coefficient. The results show that (1) the difference between the measured and predicted MODIS band equivalent reflectance is between -0.00466 and 0.0039, and (2) the percentage difference between the measured and predicted MODIS band equivalent reflectance ranges from 4.17% and 1.24%, indicating that the calibration system carried on HY-1C can perform high-precision SCS radiometric calibration, meeting the cross-calibration accuracy requirements of other loads on the same platform.

Epigenetic DNA modification N6-methyladenine inhibits DNA replication by Sulfolobus solfataricus Y-family DNA polymerase Dpo4.

Dpo4 is a representative model of Y-family DNA polymerase and is therefore one of the most intensively studied DNA polymerase. 6 mA, an epigenetic marker, plays important roles in regulation of various biological processes. However, its effects on DNA replication by Dpo4 is completely unknown. Here, we found that 6 mA and its intermediate Hyp inhibits primer extension by Dpo4, showing an obvious blockage just one nucleotide before 6 mA or Hyp. 6 mA reduces dTTP incorporation efficiency, next-base extension efficiency, binding affinity of DNA to Dpo4, binding affinity of dTTP to Dpo4-DNA complex, the fraction of productive Dpo4 or productive ternary complex, and the burst incorporation rate, explaining the inhibition effects of 6 mA on DNA replication by Dpo4. Hyp is similar to G and dCTP is preferentially incorporated opposite Hyp by Dpo4, resulting in A:T to G:C mutation. Relative to dTTP incorporation opposite unmodified A, Hyp reduces dCTP incorporation efficiency, next-base extension efficiency, the priority in extension beyond correct pair, binding affinity of Dpo4 to DNA, binding of dCTP to Dpo4-DNA complex, and the burst incorporation efficiency, explaining the inhibition effects of Hyp on DNA replication by Dpo4. This work provides insight in the effects of epigenetically modified 6 mA and Hyp on DNA replication by a representative Y-family DNA polymerase Dpo4.

Thermoelectric properties of sorted semiconducting single-walled carbon nanotube sheets.

Single-walled carbon nanotubes (SWNTs), especially their semiconducting type, are promising thermoelectric (TE) materials due to their high Seebeck coefficient. In this study, the in-plane Seebeck coefficient (S), electrical conductivity (σ), and thermal conductivity (κ) of sorted semiconducting SWNT (s-SWNT) free-standing sheets with different s-SWNT purities are measured to determine the figure of merit ZT. We find that the ZT value of the sheets increases with increasing s-SWNT purity, mainly due to an increase in Seebeck coefficient while the thermal conductivity remaining constant, which experimentally proved the superiority of the high purity s-SWNT as TE materials for the first time. In addition, from the comparison between sorted and unsorted SWNT sheets, it is recognized that the difference of ZT between unsorted SWNT and high-purity s-SWNT sheet is not remarkable, which suggests the control of carrier density is necessary to further clarify the superiority of SWNT sorting for TE applications.

Cardiotonic Steroids Stimulate Macrophage Inflammatory Responses Through a Pathway Involving CD36, TLR4, and Na/K-ATPase.

OBJECTIVE: Circulating levels of cardiotonic steroids (CTS) are elevated in various chronic inflammatory conditions, but the role of CTS in inflammation remains largely unknown. We have previously shown that the CTS ouabain stimulates proinflammatory responses in murine macrophages. In this study, we aim to explore the mechanism how CTS induce proinflammatory responses in primary murine and human macrophages. APPROACH AND RESULTS: Using both murine peritoneal macrophages and human monocyte-derived macrophages, we demonstrated that ouabain activated NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), leading to proinflammatory cytokine (eg, MCP-1 [monocyte chemotactic protein 1], TNF-α [tumor necrosis factor-α], IL-1ß [interleukin-1ß], and IL-6) production. By applying siRNA techniques and murine peritoneal macrophages isolated from genetically modified mice, we showed that macrophages partially deficient in Na/K-ATPase, the receptor for CTS, or fully deficient in the scavenger receptor CD36 or TLR4 (Toll-like receptor) were resistant to ouabain-induced NF-κB activation, suggesting an indispensable role of these 3 receptors in this pathway. Mechanistically, this effect of ouabain was independent of the ion transport function of the Na/K-ATPase. Instead, ouabain stimulated a signaling complex, including Na/K-ATPase, CD36, and TLR4. Subsequently, TLR4 recruited MyD88 adaptor protein for NF-κB activation. Furthermore, intraperitoneal injection of ouabain into mice specifically recruited Ly6C+CCR2+ monocyte subtypes to the peritoneal cavities, indicating that the CTS ouabain triggers inflammation in vivo. CONCLUSIONS: CTS activate NF-κB leading to proinflammatory cytokine production in primary macrophages through a signaling complex, including CD36, TLR4, and Na/K-ATPase. These findings warrant further studies on endogenous CTS in chronic inflammatory diseases, such as atherosclerosis.