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The potential adverse effects of 2,2′,4,4′-tetrabromodiphenyl ether (PBDE-47) on neurons are extensively studied, and mitochondria are identified as critical targets. This study aimed to investigate whether PBDE-47 impairs mitochondrial biogenesis via the miR-128-3p/PGC-1α axis to trigger mitochondrial dysfunction-related neuronal damage. In vitro neuroendocrine pheochromocytoma (PC12) cells and in vivo Sprague Dawley rat model were adopted. In this study, biochemical methods were used to examine mitochondrial ATP content, cell viability, and expressions of key mitochondrial biogenesis regulators, including peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). Mimics and inhibitors of miR-128-3p were employed to explore its role in PBDE-47-induced neurotoxicity. Both in vivo and in vitro evidences suggested that PBDE-47 suppressed PGC-1α/NRF1/TFAM signaling pathways and mitochondrial DNA (mtDNA) encoding proteins synthesis. PBDE-47 also suppressed the relative mtDNA content, mRNA levels of mtDNA-encoded subunits, and mitochondrial ATP levels in vitro. Specifically, 2-(4-tert-butylphenyl) benzimidazole (ZLN005) alleviated PBDE-47-induced neuronal death through the improvement of mitochondrial function by activating PGC-1α/NRF1/TFAM signaling pathways. Mechanistically, PBDE-47 dramatically upregulated miR-128-3p expression. Furthermore, miR-128-3p inhibition enhanced PGC-1α/NRF1/TFAM signaling and abolished PBDE-47-induced impairment of mitochondrial biogenesis. In summary, this study provides in vitro evidence to reveal the role of mitochondrial biogenesis in PBDE-47-induced mitochondrial dysfunction and related neurotoxicity and suggests that miR-128-3p/PGC-1α axis may be a therapeutic target for PBDE-47 neurotoxicity.

Soil erodibility (K factor) mapping has been accomplished mainly by soil map-linked or geo-statistical interpolation. However, the resulting maps usually have coarse spatial resolution at a regional scale. The objectives of this study were a) to map the K factors using a set of environmental variables and random forest (RF) model, and b) to identify the important environmental variables in the predictive mapping on a regional scale. We collected 101 surface soil samples across southeast China in the summer of 2019. For each sample, we measured the particle size distribution and organic matter content, and calculated the K factors using the nomograph equation. The hyperparameters of RF were optimized through 5-fold cross validation (mtry = 2, ntree = 500, p = 63), and a digital map with 250 m resolution was generated for the K factor. The lower and upper limits of a 90% prediction interval were also produced for uncertainty analysis. It was found that the important environmental variables for the K factor prediction were relief, climate, land surface temperature and vegetation indexes. Since the existing K factor map has an average polygonal area of 6.8 km2, our approach dramatically improves the spatial resolution of the K factor to 0.0625 km2. The new method captures more distinct differences in spatial details, and the spatial distribution of the K factor derived from RF prediction followed a similar pattern with kriging interpolation. This suggests the presented approach in this study is effective for mapping the K factor with limited sampling data.

A new type of polymeric nanomicelle-based nanoagent (denoted as PT@MFH hereafter) capable of the highly sensitive release of the chemotherapeutic drug paclitaxel (PTX) upon exposure to a near-infrared (NIR) laser trigger was developed. Specifically, PTX and a photothermal polymer (T-DPPT) were encapsulated in the cavity of nanomicelles, which were constructed from an amphiphilic block copolymer (PCL-PEEP) with a lower critical solution temperature (LCST) of ∼54 °C. Owing to the unprecedented ability of the T-DPPT moiety to harvest near-infrared light, with a mass extinction coefficient at 808 nm of up to ∼80.8 L g

The change of refractive index resulting from the isomerization of photochromic molecules under light irradiation reconfigures lattice plasmon resonances, which allows for the realization of dynamically and continuously tunable plasmonic lasers.

Soil erodibility (K) is a key factor of soil erosion, and its appropriate quantification and interpolation are vitally important for soil and water conservation. The traditional point-represent-polygon approaches and common kriging method for the estimation of K, however, do not sufficiently represent the original data. The objectives of this study were to simulate the spatial distribution of K using a sequential Gaussian algorithm and analyze the uncertainty in evaluating the risk of soil erodibility in southeastern China. We determined 101 sampling points in the area and collected disturbed soil samples from the 0–20 cm layer at each point. Soil properties were determined, and K was calculated using five common models: the EPIC (Erosion/Productivity Impact Calculator), approximate nomograph, Torri, Shirazi, and Wang models. Among the chosen models, the EPIC model performed the best at estimating K(KEPIC), which ranged from 0.019 to 0.060 t ha h (ha MJ mm)−1, with a mean of 0.043 t ha h (ha MJ mm)−1. The KEPIC was moderately spatially variable and had a limited spatial structure, increasing from south to north in our study area, and all spatial simulations using the cooperative kriging (CK) interpolation and the sequential Gaussian simulation (SGS) with 10, 25, 50, 100, 200, and 500 realizations had acceptable accuracies. The CK interpolation narrowed the range, and the SGS maintained the original characteristics of the calculated data. The proportions of the risk area were 38.0% and 10.1%, when the risk probability for K was 60% and 80%, respectively, and high risk areas were mostly located in the north. The results provide scientific guidance for managing the risk of soil erodibility in southeastern China.

Room temperature phosphorescence (RTP) materials are characterized with emission after removing the excitation source. Such long-lived emission feature possesses great potential in biological fluorescence imaging because it enables a way regarding temporal dimension for separating the interference of autofluorescence and common noises typically encountered in conventional fluorescence imaging. Herein, we constructed a new type of mesoporous silica nanoparticles (MSNs)-based composite nanoparticles (NPs) with dual-color long-lived emission, namely millisecond-level green phosphorescence and sub-millisecond-level delayed red fluorescence by encapsulating a typical RTP dye and Rhodamine dye in the cavities of the MSNs with the former acting as energy donor (D) while the latter as acceptor (A). Benefiting from the close D-A proximity, energy match between the donor and the acceptor and the optimized D/A ratio in the composite NPs, efficient triplet-to-singlet Fӧrster resonance energy transfer (TS-FRET) in the NPs occurred upon exciting the donor, which enabled dual-color long-lived emission. The preliminary results of dual-color correlation imaging of live cells based on such emission feature unequivocally verified the unique ability of such NPs for distinguishing the false positive generated by common emitters with single-color emission feature.

The oilfield is unable to carry out normal temperature gathering and transportation (NTGT) process, since the feasibility has not been verified and the minimum flowable temperature (MFT) calculations have not been proposed. In this paper, the simulation of parameters such as temperature and pressure of the pipeline network are performed based on the production data of the oilfield during the period of unheated gathering. It is verified that the temperature and pressure errors of the simulation results are less than 0.79 °C and 0.1 MPa, respectively. It is found that the gathering network of this oilfield can operate normally in winter, which proves the feasibility of NTGT theoretically. Through calculating the flow parameters of the gathering network under extreme cold conditions in winter, a novel formula for calculating the MFT of oil-gas-water three-phase mixed transmission process is proposed, where the shearing effect of gas on fluid has been extra considered. The fitting effect of MFT formula on a single well is better than that on multiple wells. The application of the fitted MFT formula in situ as well as the corresponding preliminary oilfield tests has proved the feasibility of the NTGT process. Thus, the oilfield gathering network is successfully guided to change from a heated gathering process to a NTGT process.

For long-distance natural gas pipes crossing highway, the changing load of vehicles is the most important and frequently acting-live load on buried pipes, which poses a serious threat to the integrity of the pipe. This study has designed and built a buried pipe stress test experimental system. The experimental system is mainly composed of a sealed pipe, an air compressor, and a stress-strain testing system. In this study, a total of 24 sets of stress test experiments are carried out. The research conclusions are as follows. The maximum stress of the pipe occurs at the 12 o’clock position of the pipe when the vehicle load is rolled at the middle. The increase in vehicle load results in an increasing pipe stress value. Both of the vehicle speed and the internal pressure play a certain role in protecting the pipe. After carrying out a real experimental case via Sinopec’s natural gas pipe crossing the highway, we have found that it can withstand the rolling load of a heavy vehicle of 78t, when the L325 steel pipe section that crossing the Grade-4 highway has a buried depth of 0.8m, a diameter of 355.6 × 5.6mm, and a internal pressure of 1.03MPa.

Hydrogen sulfide (H2S) typically plays biphasic biological roles in living organisms with subnormal H2S exerting cytoprotective effects such as participating in cardioprotective signaling pathways while H2S with higher-than-normal concentrations in localized tissues acting the opposite way such as inhibiting mitochondrial respiration. Such concentration-dependent biological and pathological roles of H2S with the wide involvement of mitochondria and the elusive feature of H2S definitely highlight the vital significance of fast and precise estimation of the physiological level of H2S in specific microenvironments, particularly within cellular mitochondria. In this work, we developed a new type of fluorescent probe (QcyCHO) featured with H2S-triggered off-to-on near-infrared (NIR) fluorescence conversion within ~ 10 min, limit of detection (LOD) down to 8.3 nM, and high recognition specificity over other similarly interfering species. The ideal mitochondrion-targeting ability, high recognition specificity over typical interfering substances and other physiologically relevant species, and the ability for mapping intracellular H2S in living cells of QcyCHO probe were also unequivocally confirmed, which imply its potential for shedding light on the biology of H2S and therapeutic development in H2S-associated diseases by identifying the specific physiological stimuli inducing H2S production and determining the levels of H2S at the location and time of stimulation.

Xiguajiang (XGJ) is one kind of Chinese traditionally fermented soybean food. The aim of this study was to identify core bacterial communities and volatile compounds and explore their relationships in XGJ samples obtained from different manufacturers. Results showed that Bacillus, Staphylococcus, Weissella, and Chromohalobacter were the predominant bacterial genus, although their relative abundance is quite diverse. Larger relative contents of esters and alcohols were detected in XGJ. Moreover, the results of E-nose analysis indicated that nitrogen oxides compounds, pyrazines, and ketones compounds also played a critical role in XGJ unique flavor. The correlation analysis suggested that 3-methyl-butanol, ethoxybenzene, ethyl acetate, acetaldehyde, and 2-(4-methyl-3-cyclohexen-1-yl)-2-propanyl acetate had a significant correlation with Enterobacter, Clostridium, Pseudomonas, Streptomyces, Weissella, Staphylococcus, and Bacillus. These results may provide vital information to understand the role of the microbiota in developing flavor in XGJ products, and improve the quality and safety of XGJ production in industries.

The optimal storage temperature for vaccines ranges from 2 °C to 8 °C. Electronic thermometers can provide real-time and remote temperature monitoring but are not applicable for individual packages. However, it is known that few alkanes have melting points in this range. The photo-induced conversion of colorless spiropyran to blue merocyanine can be thermally reversed, resulting in decoloration. By dispersing spiropyran in a mixture of n-tetradecane and n-pentadecane with the melting point of 8 °C, an accurate and low-cost thermochromism indicator to record temperature abuse has been designed. The results showed that the thin label based on this system has taken a permanent decoloration within 10 min of the temperature exceeding 8 °C.

2,2',4,4'-tetrabromodiphenyl ether (PBDE-47), the widely used brominated flame retardant, has remarkable neurotoxicity which is associated with autophagy disorder. However, the mechanism remains unclear. The results showed that PBDE-47 damaged lysosomal biogenesis and interfered with autophagy-lysosome fusion both in vivo and in vitro. Our investigation further demonstrated that PBDE-47 could downregulate TFEB expression and inhibit the nuclear translocation of TFEB. Knockdown of TFEB in PC12 cells increased the reduction of lysosomal-associated proteins and the expression of STX17-SNAP29-VAMP8 proteins involved in autophagy-lysosomal fusion. Conversely, Overexpression TFEB in vitro significantly improved lysosomal abundance and ameliorated the autophagosome-lysosome fusion inhibition, thus restoring autophagic flux and improving PC12 cells survival. In addition, TFEB biologically interacted with STX17 by not inducing or inducing TFEB overexpression. Collectively, our results indicate that the autophagy flux compromised by PBDE-47 is related to the defective fusion of autophagosome and lysosome. TFEB may serve as a promising molecular target for future study of PBDE-47 developmental neurotoxicity.

A single-chromophore-based photoactive agent (MB-DOPA) capable of rapid sensing of nanomolar hypochlorous acid (HOCl) and in-situ generating photocytotoxicity to cancer cells was developed using dopamine moiety as the recognition unit and methylene blue (MB) moiety as the fluorescence signaling unit. Specifically, HOCl triggered conversion of the nonfluorescent MB-DOPA to MB enabling far-red fluorescence emission (λmax ∼ 683 nm) and additional ability to photogenerate 1O2 species. Owing to the catechol nature of dopamine characterized with strong electron-donating property, MB-DOPA underwent HOCl-mediated conversion with response time of ∼20 s and a strong fluorescence OFF-to-ON contrast by a factor of more than 3000. The preliminary bioimaging results confirmed the intracellular HOCl sensing ability of MB-DOPA and the in-situ photodynamic therapy (PDT) effectiveness for inducing massive apoptosis of cancer cells. The figure of merits of MB-DOPA, including ability for sensing of nanomolar HOCl with high specificity, rapid response, practicality for intracellular fluorescence imaging, and the in-situ generation of 1O2 for killing tumor cells, is expected to enable diagnosis of early-stage oncogenesis based on the highly specific detection of abnormal HOCl levels in the transformed cells and the simultaneous treatment in biomedical applications.

A new type of single-chromophore-based photoactivatable prodrug (B-Cbl-3) enabling green-light-triggered chemotherapy and simultaneous photodynamic therapy with superb therapeutic efficacy was developed by conjugating a photoactive BODIPY derivative with an antitumor chlorambucil moiety. The optimized BODIPY moiety markedly enabled high efficient photogeneration of 1O2 and fluorescence emission with distinct colors before and after photorelease of chlorambucil. The preliminary biological experiment results have verified the efficient photorelease of chlorambucil from B-Cbl-3 and the huge contrast in cytotoxicity between them, superior combined therapeutic performance based on extraordinary low doses of drug and light irradiation, and ratiometric fluorescence imaging for in situ monitoring drug release. The salient superiority of B-Cbl-3 regarding alleviating the attenuation of triggering light caused by optically turbid tissue that short-wavelength lights typically encounters has also been verified.

Apoptosis is involved in 2,2',4,4'- tetrabromodiphenyl ether (PBDE-47)-induced developmental neurotoxicity. However, little is known about the role of autophagy, especially its relationship with apoptosis underlying such neurotoxic process. Methods: Using female Sprague-Dawley rats exposed to low-dose PBDE-47 (0.1, 1.0 and 10 mg/kg/day) from pre-pregnancy until weaning of offspring to mimic human exposure, we investigated the effects of PBDE-47 on autophagy and apoptosis in relation to cognitive impairment of adult offspring rats. We also evaluated relationship between autophagy and apoptosis using neuroendocrine pheochromocytoma (PC12) cells, a widely used neuron-like cell line for neuronal development. Results: In vivo, perinatal exposure to PBDE-47 induced memory deficits in adult rats. This is accompanied by hippocampal neuronal loss partly as a result of apoptosis, as evidenced by caspase-3 activation and PARP cleavage. Further study identified that PBDE-47 triggered autophagic vesicles accumulation, increased levels of microtubule-associated protein 1 light chain 3 (LC3)-II, an essential protein for autophagosomes formation, and autophagy substrate sequestosome 1 (SQSTM1/p62), but reduced levels of autophagy-related protein (ATG) 7, a key protein for autophagosomes elongation, suggestive of autophagy impairment. These findings were further demonstrated by an in vitro model of PBDE-47-treated PC12 cells. Mechanistically, autophagy alteration is more sensitive to PBDE-47 treatment than apoptosis induction. Importantly, while stimulation of autophagy by the chemical inducer rapamycin and adenovirus-mediated Atg7 overexpression aggravated PBDE-47-induced apoptosis and cell death, inhibition of autophagy by the chemical inhibitor wortmannin and siRNA knockdown of Atg7 reversed PBDE-47-produced detrimental outcomes. Interestingly, blockage of apoptosis by caspase-3 inhibitor Ac-DEVD-CHO ameliorated PBDE-47-exerted autophagy impairment and cell death, though in combination with autophagy inhibitor did not further promote cell survival. Conclusion: Our data suggest that autophagy impairment facilitates apoptosis, which, in turn, disrupts autophagy, ultimately resulting in cell death, and that autophagy may act as a promising therapeutic target for PBDE-47-induced developmental neurotoxicity.

Novel hybrid fluorescent nanoparticles (NPs) characterized with salient features of fluorescence brightness, photostability and fluorescence lifetime were fabricated based on fluorescent dyes (DBQ-3PXZ) with thermal activation delayed fluorescence (TADF) and aggregation-induced emission (AIE) characteristics (aggregation-induced delayed fluorescence, AIDF). An amphiphilic polymer with oxygen-blocking properties was used as the host matrix, while small-molecular-weight antifade agents (singlet oxygen quencher and antioxidant) and a triplet energy barrier were incorporated in the hybrid NPs. The matrix polymer, which is capable of separating DBQ-3PXZ molecules from molecular oxygen, and the incorporated antifade agents, which are capable of suppressing the oxygen-mediated photodegradation of DBQ-3PXZ, contributed to the excellent photostability of the target hybrid NPs. The intrinsic AIE properties and the triplet energy barrier capable of confining the triplet excitons within the dye molecules jointly enabled the high fluorescing ability of DBQ-3PXZ dyes residing in the core part of the NPs. Additionally, the TADF nature of DBQ-3PXZ dye together with the protective role of the matrix polymer and antifade agents imparted long fluorescence lifetimes to the target NPs. The preliminary cell fluorescence imaging results verified the practicability of these feature-packed NPs for highlighting regions of interest and enabling high-resolution visualization of fine subcellular architectures; this unequivocally proclaims this probe to be an ideal tag for biological fluorescence imaging.

We herein developed a core-shell type antitumor nanoagent based on the synergistically reinforced oxidative stress and calcium overload to mitochondria, both of which were triggered by near-infrared (NIR) light. The folic acid (FA) moiety decorated on MOF shells enabled efficient cellular uptake of nanoagents. The upconversion nanoparticle (UCNP) core converted NIR light to ultraviolet (UV) light with the latter catalyzed Fe3+-to-Fe2+ reduction and simultaneously activated the photoacid generator encapsulated in the cavities of MOFs, which enabled the release of free Fe2+ and photoacidification of intracellular microenvironment, respectively. The overexpressed H2O2 in the mitochondria, highly reactive Fe2+ and acidic milieu synergistically reinforced Fenton reactions for producing lethal hydroxyl radicals in mitochondria. Moreover, the photoacidification of plasma induced calcium influx, leading to calcium overload in the mitochondria. The therapeutic potency of the nanoagent based on the dual mitochondrial damage has been unequivocally confirmed in cell- and patient-derived tumor xenograft models in vivo.

Targeting subcellular organelle with multilevel damage has shown great promise for antitumor therapy. Here, we report a core-shell type of nanoagent with iron (III) carboxylate metal-organic frameworks (MOFs) as shell while upconversion nanoparticles (UCNPs) as core, which enables near-infrared (NIR) light-triggered synergistically reinforced oxidative stress and calcium overload to mitochondria. The folate decoration on MOFs shells enables efficient cellular uptake of nanoagents. Based on the upconversion ability of UCNPs, NIR light mediates Fe3+-to-Fe2+ reduction and simultaneously activates the photoacid generator (pHP) encapsulated in MOFs cavities, which enables release of free Fe2+ and acidification of intracellular microenvironment, respectively. The overexpressed H2O2 in mitochondria, highly reactive Fe2+ and acidic milieu synergistically reinforce Fenton reactions for producing lethal hydroxyl radicals (•OH) while plasma photoacidification inducing calcium influx, leading to mitochondria calcium overload. The dual-mitochondria-damage-based therapeutic potency of the nanoagent has been unequivocally confirmed in cell- and patient-derived tumor xenograft models in vivo., Targeting damage to mitochondria has become an effective strategy antitumor therapies. Here, the authors report on nanoagents with upconversion nanoparticles as cores and photoacid-loaded MOFs as shells for NIR triggered Fenton reaction, acidification and calcium overload to provide synergistic mitochondrial damage.

A new hydrophilic polyurethane polymer, W-OH, has recently been widely used in southern China to control soil erosion, but the theory of its effectiveness lags behind the practice. We used two typically erodible soils, red clay soil (RCS) from sloping farmland and benggang sandy soil (BSS) from collapsing gullies, in southern China as test objects to analyze the effect of spraying W-OH on the characteristics of soil aggregates, infiltration, runoff, and sediment transport in indoor controlled experiments and outdoor simulated rainfall experiments. The mean diameter of the aggregate increased, the fractal dimension decreased, and the water-stable aggregate content increased in RCS and BSS as the concentration of W-OH increased from 0 to 7%. Spraying 5% W-OH significantly decreased the infiltration rate for both soils. Spraying W-OH increased the mean RCS and BSS runoff rates by 190 and 37.3% but decreased the sediment yields by 74.1 and 62.1%, respectively, and showed a good soil erosion control effect. Spraying W-OH also affected the leaching of nutrients, increasing total organic carbon content by 170 and 330% for RCS and BSS, respectively. This study provides theoretical supplementation for the application of W-OH for controlling soil erosion from sloping farmland and benggangs in southern China.

There is a practical motivation for correlating different types of microscopy for revealing complementary information of ultrastructures with resolution beyond the diffraction limit. The correlative microscopy strategy based on the combination of super-resolution fluorescence imaging with atomic force microscopy (AFM) is expected to provide both the specificity and three-dimensional structural information of nanomaterials. Herein we synthesized a dual-alternating-color photoswitchable fluorescent probe based on a naphthalimide-spiropyran dyad (NI-SP) and explored the capability of such correlative microscopy for visualizing nanostructures with complex structural hierarchy. NI-SP underwent reversible photoswitching between green and red fluorescence based on a reversible photochemical reaction and such reaction-linked correlation between two distinct types of fluorescence signals intrinsically enabled mutual authentication in super-resolution fluorescence imaging. Additionally, such correlative microscopy also demonstrated mutual complementation between different pieces of structural information of the target acquired via fluorescence imaging and AFM, respectively, in which the former reveals spatial distribution of fluorescent dyes in the nanoscale polymer fibroid micelles while the latter maps the topographical structure of the target with complex structural hierarchy. The results obtained in this work proclaimed that the combination of such correlative microscopy with our NI-SP probe is an effective modality for ultrastructural analysis and has future applications in various complex systems such as tissue/organ imaging.

The aggregative instinct of platelets was exploited as a biomimetic strategy for synergistic combined therapy against cancer., To address long-standing issues with tumor penetration and targeting among cancer therapeutics, we developed an anticancer platelet-based biomimetic formulation (N+R@PLTs), integrating photothermal nanoparticles (N) and immunostimulator (R) into platelets (PLTs). Exploiting the aggregative properties of platelets and high photothermal capacity, N+R@PLTs functioned as an arsenal by targeting defective tumor vascular endothelial cells, accumulating in a positive feedback aggregation cascade at sites of acute vascular damage induced by N-generated local hyperthermia, and subsequently secreting nanosized proplatelets (nPLTs) to transport active components to deep tumor tissue. The immunostimulator augmented the immunogenicity of antigens released from ablated tumors, inducing a stronger immunological response to attack residual, metastatic, and recurrent tumors. Following activation by low-power near-infrared light irradiation, the photothermal and immunological components synergistically provide exceptionally high therapeutic efficacy across nine murine models that mimicked a range of clinical requirements, and, most notably, a sophisticated model based on humanized mouse and patient-derived tumor xenograft.

Brominated flame retardant 2,2′,4,4′‑tetrabromodiphenyl ether (PBDE-47) is known to induce developmental neurotoxicity by disturbing thyroid hormones (THs). Evidence shows that maternal THs are crucial for brain development and growth of fetuses and infants. However, little is known about the effects of PBDE-47 on maternal thyroid status and its mode of action. Here, using female Sprague-Dawley rats orally exposed to low doses of PBDE-47 (0.1, 1.0, 10 mg/kg/day) from pre-pregnancy until weaning of offspring to mimic human exposure, we show that perigestational exposure to PBDE-47 elevated serum triiodothyronine and thyroxine levels in mother rats. This is accompanied by disrupted thyroid follicle structure including expanded follicles, hyperplastic epithelial cells and shed cell remnants filled in the exhausted follicular lumen. Mechanistically, PBDE-47 enhanced apoptosis in thyroid tissue, as demonstrated by Caspase-3 activation, PARP cleavage and DNA fragmentation. Further study identified that PBDE-47 upregulated the levels of GRP78, ATF4, active Caspase-12 and CHOP, suggesting endoplasmic reticulum (ER) stress and unfolded protein response activation. Moreover, PBDE-47 reduced the levels of LC3-II, an autophagy marker protein essential for the autophagosomes formation, while increased the autophagy substrate p62 accumulation, indicating autophagy defect. Importantly, the colocalization of apoptotic cells with CHOP, a key mediator of ER stress-induced apoptosis, or p62, uncovered the contribution of excessive ER stress and defective autophagy to apoptosis. Collectively, our results suggest that excessive ER stress, defective autophagy and the resultant apoptosis are implicated in maternal thyroid injury following perigestational PBDE-47 exposure, which offers insight into a better understanding of PBDE-47-induced maternal thyroid toxicity.

A new type of xanthene-based fluorescent probe capable of intracellular subtle pH fluctuation sensing was developed. The probe underwent reversible deprotonation-protontation processes and therefore generated two states with distinct contrast in fluorescence emission features. In the physiological range (pH 7.0–8.0), the probe markedly presented 31.2% fluorescence signal change upon pH fluctuation of 0.1 pH unit, enabling sensitivity infinitely superior to previous fluorescent pH probes. The preliminary biological experiments revealed the large dynamic range of the probe for intracellular pH sensing within the range of pH 6.0–8.0. Owing to its sensitive responses to pH fluctuation in the physiological pH range, the probe definitely demonstrated its ability for “distinguishing” tumor from normal cells based on the difference in microenvironment pH level between the former and the latter. The figure of merits of the probe, including pKa (7.45) in the physiological pH range, excellent photostability, extraordinary large dynamic range for pH sensing, as well as the preliminary bioimaging results regarding differentiating tumor from normal cells are indicative of its potential for providing the microenvironment information regarding the interfacial features at the perimeter of tumor tissues by presenting high-contrast fluorescence images.